Flood Of Migrant Children To Put Estimated $2 Billion Strain On Public School System

 Last month, CBO Director Phill Swagel claimed that the influx of illegal immigrants into the United States will boost 2023-2034 GDP by "about 7 Trillion."

Yet while we wait for those unicorn farts to percolate, the Heritage Foundation estimates in a new report that the influx of migrants is costing American taxpayers billions of dollars, as most of the 470,000 unaccompanied migrant children who have entered the country since Joe Biden's 2021 inauguration have been enrolled in public schools.

In FY2023 alone, CBP encountered 145,474 accompanied and unaccompanied minors nationwide - which, based on the national average of $16,345 spent per student, would increase national education spending by more than $2 billion for one year, according to the Heritage report's fact sheet.

The report looked at instances in California, New York, Texas and Arizona where unaccompanied minors were sent to sponsors, according to data from the Office of Refugee Resettlement (ORR), a government agency under the Department of Health and Human Services (HHS). 

For example, in California, 11,121 unaccompanied migrant children were sent to sponsors. If all those children enrolled in public school, at the state average spending of $16,975 per pupil, that equates to an additional cost of about $189 million for one year.

The report similarly found that in New York, 8,477 unaccompanied migrant children were sent to sponsors. The state spends $28,261 on each pupil per year, making the total additional cost to taxpayers close to $240 million for one year. -Fox News

"Parents should not also have to worry about their kids going to the back of the line in terms of school resources, teacher attention, and academic rigor due to sudden and large influxes of illegal aliens into their schools and classrooms," Heritage scholars and two of the report's authors, Lindsey Burke and Lora Ries, told Fox News Digital.

The report also highlights the misuse of school property, classroom mismanagement and limited English proficiency, which is holding other students back.

As an example, Fox News cites the case of New York City parents who were furious with city officials after Brooklyn Hight School students were forced to stay home for virtual lessons so that migrants could pile into the school gymnasium. Other reports suggest that NY Public Schools have struggled to educate some 20,000 new migrant students

https://www.zerohedge.com/political/flood-migrant-children-put-estimated-2-billion-strain-public-school-system

Largest US Independent Primary Care Network Accused of Medicare Fraud

 A Maryland firm that oversees the nation's largest independent network of primary care medical practices is facing a whistleblower lawsuit alleging it cheated Medicare out of millions of dollars using billing software "rigged" to make patients appear sicker than they were.

The civil suit alleges that Aledade, Inc.'s, billing apps and other software and guidance provided to doctors improperly boosted revenues by adding overstated medical diagnoses to patients' electronic medical records.

"Aledade did whatever it took to make patients appear sicker than they were," according to the suit.

For example, the suit alleges that Aledade "conflated" anxiety into depression, which could boost payments by $3300 a year per patient. And Aledade decided that patients over 65 years old who said they had more than one drink per day had substance use issues, which could bring in $3680 extra per patient, the suit says.

The whistleblower case was filed by Khushwinder Singh in federal court in Seattle in 2021 but remained under seal until January of this year. Singh, a "senior medical director of risk and wellness product" at Aledade from January 2021 through May 2021, alleges the company fired him after he objected to its "fraudulent course of conduct," according to the suit. He declined to comment on the suit.

The case is pending, and Aledade has yet to file a legal response in court. Julie Bataille, Aledade's senior vice president for communications, denied the allegations, saying in an interview that "the whole case is totally baseless and meritless."

Based in Bethesda, Maryland, Aledade helps manage independent primary care clinics and medical offices in more than 40 states, serving some 2 million people.

Aledade is one of hundreds of groups known as accountable care organizations. ACOs enjoy strong support from federal health officials who hope they can keep people healthier and achieve measurable cost savings.

Aledade was co-founded in 2014 by Farzad Mostashari, a former health information technology chief in the Obama administration, and has welcomed other ex-government health figures into its ranks. In June 2023, President Joe Biden appointed Mandy Cohen, then executive vice president at Aledade, to head the Centers for Disease Control and Prevention in Atlanta.

Aledade has grown rapidly behind hundreds of millions of dollars in venture capital financing and was valued at $3.5 billion in 2023.

Mostashari, Aledade's chief executive officer, declined to be interviewed on the record.

"As this is an active legal matter, we will not respond to individual allegations in the complaint," Aledade said in a statement to KFF Health News. "We remain focused on our top priority of delivering high-quality, value-based care with our physician partners and will defend ourselves vigorously if needed in a court of law."

The lawsuit also names as defendants 19 independent physician practices, many in small cities in Delaware, Kansas, Louisiana, North Carolina, Pennsylvania, and West Virginia. According to the suit, the doctors knowingly used Aledade software to trigger illegal billings, a practice known in the medical industry as "upcoding." None has filed an answer in court.

More than two dozen whistleblower lawsuits, some dating back more than a decade, have accused Medicare health plans of overcharging the government by billing for medical conditions not supported by patient medical records. These cases have resulted in hundreds of millions of dollars in penalties. In September 2023, Cigna agreed to pay $37 million to settle one such case, for instance.

But the whistleblower suit filed against Aledade appears to be the first to allege upcoding within accountable care organizations, which describe part of their mission as foiling wasteful spending. ACOs including Aledade made headlines recently for helping to expose an alleged massive Medicare fraud involving urinary catheters, for instance.

Finding the 'Gravy'

Singh's suit targets Aledade's use of coding software and guidance to medical practices that joined its network. Some doctors treated patients on standard Medicare through the ACO networks, while others cared for seniors enrolled in Medicare Advantage plans, according to the suit.

Medicare Advantage is a privately run alternative to standard Medicare that has surged in popularity and now cares for more than 30 million people. Aledade has sought to expand its services to Medicare Advantage enrollees.

The lawsuit alleges Aledade encouraged doctors to tack on suspect medical diagnoses that paid extra money. Aledade called it finding "the gravy sitting in the [patient's] chart," according to the suit.

The company "instructed" providers to diagnose diabetes with complications, "even if the patient's diabetes was under control or the complicating factor no longer existed," according to the suit.

Some medical practices in Delaware, North Carolina, and West Virginia billed the inflated code for more than 90% of their Medicare Advantage patients with diabetes, according to the suit.

The lawsuit also alleges that Aledade "rigged" the software to change a diagnosis of overweight to "morbid obesity," which could pay about $2500 more per patient. Some providers coded morbid obesity for patients on traditional Medicare at 10 times the national average, according to the suit.

"This fraudulent coding guidance was known as 'Aledade gospel,'" according to the suit, and following it "paid dividends in the form of millions of dollars in increased revenue."

These tactics "usurped" the clinical judgment of doctors, according to the suit.

'No Diagnosis Left Behind'

In its statement to KFF Health News, Aledade said its software offers doctors a range of data and guidance that helps them evaluate and treat patients.

"Aledade's independent physicians remain solely responsible for all medical decision-making for their patients," the statement read.

The company said it will "continue to advocate for changes to improve Medicare's risk adjustment process to promote accuracy while also reducing unnecessary administrative burdens."

In a message to employees and partner practices sent on Feb. 29, Mostashari noted that the Justice Department had declined to take over the False Claims Act case.

"We recently learned that the federal government has declined to join the case U.S. ex rel. Khushwinder Singh v. Aledade, Inc., et al. That's good news, and a decision we wholeheartedly applaud given the baseless allegations about improper coding practices and wrongful termination brought by a former Aledade employee 3 years ago. We do not yet know how the full legal situation will play out but will defend ourselves vigorously if needed in a court of law," the statement said.

The Justice Department advised the Seattle court on Jan. 9 that it would not intervene in the case "at this time," which prompted an order to unseal it, court records show. Under the false claims law, whistleblowers can proceed with the case on their own. The Justice Department does not state a reason for declining a case but has said in other court cases that doing so has no bearing on its merits.

Singh argues in his complaint that many "unsupported" diagnosis codes were added during annual "wellness visits" and that they did not result in the patients receiving any additional medical care.

Aledade maintained Slack channels in which doctors could discuss the financial incentives for adding higher-paying diagnostic codes, according to the suit.

The company also closely monitored how doctors coded as part of an initiative dubbed "no diagnosis left behind," according to the suit.

https://www.medscape.com/s/viewarticle/largest-us-independent-primary-care-network-accused-medicare-2024a10004a8

How the Change Healthcare Cyberattack Affects Oncology Care

 An ongoing cyberattack, lasting more than 2 weeks, has had a substantial impact on cancer practices and their patients in the United States. Change Healthcare, a subsidiary of UnitedHealth, took its systems offline after a cyberattack by BlackCat/ALPHV ransomware group. 

The American Hospital Association said that this massive interruption is the "most significant cyberattack on the US healthcare system in American history." 

What Is the Change Healthcare Attack? 

On February 21, Change Healthcare experienced an outside cybersecurity threat. When it became aware of the issue, the company disconnected its systems to prevent any further issues. Change Healthcare said that it has a "high level" of confidence that the cyberattack did not affect Optum, UnitedHealthcare, and UnitedHealth Group systems, stating it was an isolated attack on Change Healthcare. However, Change Healthcare has not said whether patient information has been compromised. 

Who Is Behind the Attack? 

In a statement, Change Healthcare announced that BlackCat/ALPHV identified itself to the company, claiming responsibility for the cybercrime. According to the US Department of Justice, BlackCat/ALPHV is the second most prolific ransomware-as-a-service entity in the world, with over 1000 victims of cybercrimes across the globe. 

Medscape Medical News reached out to the Cybersecurity and Infrastructure Security Agency (CISA), a component of the US Department of Homeland Security, for comment on whether CISA or other agencies had taken any previous action to stop the group after other attacks. 

"CISA is working with our partners and Change Healthcare to support remediation, assist impacted organizations, and share timely information to reduce the likelihood of similar intrusions," Eric Goldstein, executive assistant director for cybersecurity, responded in a statement. 

How Has the Attack Affected Oncology Practices? 

Change Healthcare is a technology company that provides services to hospitals and clinics across the country, including pharmacy claims transactions, clinician claims processing, patient access and financial clearance, clinician payments, and prior authorizations. 

The Community Oncology Alliance (COA) said that the cyberattack has caused a massive disruption in claims processing. COA also said that practices have reported the disruption of benefits verification for patients, prior authorizations, and financial assistance from the attack. 

"It's impacting pretty much every facet of the practice and practice management," Nicolas Ferreyros, managing director of policy, advocacy, and communications at COA, told Medscape Medical News. "Right now, practices are making do, they're working around these challenges." 

However, Ferreyros cautioned, continuing to manage these challenges "is absolutely, 100% unsustainable" for oncology practices.

"Very soon you're going to find practices that are having to make tough decisions about what to do, how are they going to make payroll, are they going to take financial risks on filling prescriptions and treating patients?" he added.

What Are Current Workarounds for Clinicians? 

Change Healthcare recommends that clinicians use manual methods such as calling the payer's provider service line to check patients' claim status and complete eligibility verification and prior authorizations. 

The Department of Health & Human Services has issued guidance to Medicare Advantage organizations and Part D sponsors asking them to "remove or relax prior authorization, other utilization management, and timely filing requirements" while systems are offline. The department is also asking Medicare Advantage to offer advance funding to clinicians who have been affected the most. 

How Common Are Attacks Like These? 

In 2023, a record-setting 725 healthcare security breaches were reported to the Department of Health & Human Services Office for Civil Rights, according to a report from The HIPAA Journal. The number of breachers has increased yearly. Last year, an average of 370,000 healthcare records were breached every day.

https://www.medscape.com/viewarticle/how-change-healthcare-cyberattack-affects-oncology-care-2024a10004ca

'More Evidence Linking H. Pylori Infection to Colorectal Cancer'

 A history of Helicobacter pylori infection had a modest but statistically significant association with an increased risk of colorectal cancer (CRC), including fatal CRC, a large retrospective analysis showed.

Already a causative factor in gastric cancer, infection with H. pylori increased the likelihood of developing CRC by 18% and the risk of dying of CRC by 12% versus no history of the infection. Patients with infection confirmed by serologic testing had the highest risk.

Treatment of H. pylori infection reduced the risk of CRC and CRC mortality by a magnitude similar to that afforded by colonoscopy, reported Shailja C. Shah, MD, MPH, of the University of California San Diego and VA San Diego Healthcare System, and co-authors in the Journal of Clinical Oncologyopens in a new tab or window.

"While our data, supported by mechanistic studies, are compelling, more studies are needed to confirm the strength and consistency of these associations," the authors wrote in conclusion. "In the interim, on the basis of the data presented herein, we posit that testing and treating for H. pylori may reduce the risk not only for gastric cancer but also for CRC."

The findings added to evidence from observational studies implicating H. pylori in the development of CRC and showing a potentially beneficial effect of treatment for the infection, according to the authors of an accompanying editorialopens in a new tab or window.

"They found a small but significant reduction in both colorectal cancer incidence and mortality among H. pylori-positive individuals who received eradication therapy, compared with H. pylori-positive individuals who did not," wrote Julia Butt, PhD, of the German Cancer Research Center in Heidelberg, and Meira Epplein, PhD, of the Duke University Cancer Institute in Durham, North Carolina. "This specific benefit of H. pylori eradication has not been clearly demonstrated previously but is consistent with the general findings from observational studies of an increased risk of colorectal cancer among individuals with H. pylori."

"Although the statistically significant absolute risk reduction was small, the potential impact of a feasible, noninvasive interception strategy that could reduce both gastric and colorectal cancers is incredibly potent and should be considered in clinical care for individuals at high risk for GI [gastrointestinal] cancers," they added.

The most common chronic bacterial infection worldwideopens in a new tab or window, H. pylori has a group I carcinogen designation because of its causal association with gastric cancer. Treatment of the infection has been shown to reduce the risk of gastric canceropens in a new tab or window.

Meta-analyses have suggested that H. pylori also increases the risk of CRC, but the consistency and strength of the association has varied, the authors noted in their introduction. No randomized clinical trials or observational studies have evaluated the impact of treatment on CRC incidence or mortality.

To address the gaps in evidence, Shah and colleagues conducted a retrospective cohort study among U.S. military veterans who completed H. pylori testing from 1999 through 2018 and received care through the Veterans Health Administration (VHA). Investigators excluded patients with a history of total colectomy, inflammatory bowel disease-associated colitis, or CRC.

The primary exposures were H. pylori infection status and, among H. pylori-positive individuals, receipt of guideline-recommended treatment for the infection. The primary outcome was incident CRC, as identified by the VHA Central Cancer Registry and Oncology Domain or the National Death Index (NDI). Secondary outcomes included fatal CRC as defined by NDI code.

Data analysis included 812,736 individuals, 205,178 of whom tested positive for H. pylori. The analysis showed that H. pylori-positive status was associated with an adjusted hazard ratio of 1.18 for CRC versus H. pylori-negative status (95% CI 1.12-1.24) and an adjusted hazard ratio of 1.12 for CRC mortality (95% CI 1.03-1.21). Untreated patients had a 23% higher risk of developing CRC and a 40% higher risk of CRC death.

Stratification by race and ethnicity did not significantly alter the results for CRC incidence and mortality. The impact of untreated H. pylori infection was greater among non-Hispanic Black patients (aHR 1.61, 95% CI 1.23-2.10) and Hispanic patients (aHR 1.95, 95% CI 1.21-3.14) as compared with non-Hispanic white patients (aHR 1.19, 95% CI 0.99-1.43).

Treatment for H. pylori infection led to absolute risk reductions of CRC incidence and mortality of 0.23% to 0.35%.

"To put this into context, colonoscopy is associated with a 0.84%-1.22% absolute risk reduction in incident CRC (31% relative risk reduction) and 0.15%-0.30% absolute risk reduction in fatal CRC (50% relative risk reduction) among persons completing colonoscopy for CRC screening," the authors wrote. "H. pylori treatment is a noninvasive intervention that additionally reduces the risk of other complications, namely gastric cancer and peptic ulcer disease, further underscoring the clinical relevance of the findings presented herein."

Disclosures

This study was supported in part by a Veterans Affairs Career Development Award, the 2019 American Gastroenterological Association Research Scholar Award, the NIH, and the Intramural Research Program of the National Cancer Institute.

Shah reported relationships with Medscape, Phathom Pharmaceuticals, and RedHill Biopharma.

Several co-authors reported relationships with industry.

The editorialists had no disclosures.

Primary Source

Journal of Clinical Oncology

Source Reference: opens in a new tab or windowShah SC, et al "Impact of Helicobacter pylori infection and treatment on colorectal cancer in a large, nationwide cohort" J Clin Oncol 2024; DOI: 10.1200/JCO.23.00703.

Secondary Source

Journal of Clinical Oncology

Source Reference: opens in a new tab or windowButt J, Epplein M "Potent tool: Helicobacter pylori treatment to reduce the risk of both gastric and colorectal cancers" J Clin Oncol 2024; DOI: 10.1200/JCO.24.00019.

https://www.medpagetoday.com/hematologyoncology/coloncancer/109023

'Steep Decline in Chlamydia, Syphilis Rates 'Seals the Case' for DoxyPEP'

 Chlamydia and early syphilis cases among at-risk individuals were halved after the introduction of doxycycline post-exposure prophylaxis (doxyPEP), real-world data from San Francisco showed.

Over a 13-month period following the rollout of doxyPEP to high-risk men who have sex with men (MSM) and transgender women, monthly chlamydia cases decreased by 50% (95% CI 38-59) while syphilis cases decreased by 51% (95% CI 43-58) compared with projected numbers, according to Madeline Sankaran, MPH, of the San Francisco Department of Public Health, who presented the findings at the Conference on Retroviruses and Opportunistic Infections (CROI)opens in a new tab or window.

No difference, however, was observed for gonorrhea cases after the city's rollout of doxyPEP in 2022, when the cheap antibiotic was either recommended for MSM and transgender women with a bacterial sexually transmitted infection (STI) and history of condomless sex during the past year, or offered to this patient population if they'd had multiple sex partners over the prior year.

Another study presented during the same session at CROI reported high uptake of doxyPEP among people at a San Francisco clinic already taking HIV pre-exposure prophylaxis (PrEP), while yet a third study demonstrated sustained decreases in STI rates for randomized trial participants who used the antibiotic after condomless sex.

"DoxyPEP has really changed the face of STI prevention and control," commented Landon Myer, MD, of the University of Cape Town in South Africa, who moderated a press briefing highlighting the studies.

"It's not often that you have population health, in concordance with clinical service delivery cohorts, in concordance with clinical trial results, all at the same time," said Myer, who was not involved with the research. Together, the findings, "to my mind, seals the case. This is really unusual from a public health perspective for an intervention that is so new."

DoxyPEP Associated With Citywide Decrease in STIs

Following trial data showing the benefit of doxyPEP for reducing bacterial STI incidence, the San Francisco Department of Public Health in October 2022 became the first health departmentopens in a new tab or window to recommend doxyPEP for at-risk populations. The department issued guidelines and began distributing doxycycline, a tetracycline antibiotic, to MSM and transgender women through high-volume clinics to reduce the risks for syphilis, gonorrhea, and chlamydia.

These at-risk groups are disproportionately affected by San Francisco's high and growing burden of STIs, said Sankaran. From 2014 to 2019, for example, citywide surveillance data showed a 76% increase in chlamydia cases among these individuals, along with a 45% rise in early cases of syphilis and a 72% rise in gonorrhea.

To assess the impact of the doxyPEP intervention, the researchers estimated the number of predicted cases of chlamydia (~250 per month) and early syphilis (~90 per month) using an autoregressive integrated moving average model.

Following doxyPEP's introduction, reported STI cases from November 2022 to November 2023 in the city's MSM and transgender women population decreased by 6.6% monthly for chlamydia and by 2.7% for early syphilis when compared with the projections (P<0.0001 for both), said Sankaran.

The findings were further supported by increases in chlamydia among cisgender women during the study period.

"This is the first analysis to show that doxyPEP has the potential to have a population-level impact on STIs," Sankaran said at the press conference. "We're very encouraged by the findings, and we'll be following citywide STI trends closely to see if these positive trends continue."

Factors such as changes in screening and sexual practices -- for example, in response to the mpox outbreak -- may have contributed to the observed trends, Sankaran acknowledged.

DoxyPEP Uptake High Among PrEP Users

Following the health department's recommendation, a large sexual health clinic in the Castro neighborhood of San Francisco experienced a high uptake of doxyPEP among patients taking PrEP for HIV prevention, as well as an overall decline in STI incidence, reported Hyman Scott, MD, MPH, also of the San Francisco Department of Public Health.

Among 3,081 active PrEP users, 39% decided to take doxyPEP over the 9 months after being introduced at the clinic in December 2022.

"Over time, more and more of our clients decided to take doxyPEP," said Scott, noting that the rollout was facilitated by client-centered advertising, social media posts, and discussion at routine PrEP visits.

"We saw very high uptake of doxyPEP among our client population, reflecting a very strong demand among potential users," said Scott. "People wanted this and [were] waiting to be able to get it."

Uptake was largely consistent across race/ethnicity and age groups, though lower rates were observed among people ages 60 and up (27%) compared with younger adults (34% to 43%). The researchers also found uptake consistency across gender identities with the exception of the 14 cisgender women and the 32 transgender men (0% and 25% uptake, respectively).

The researchers also evaluated STI incidence at the clinic before and after offering doxyPEP. Among doxyPEP users, STIs declined from an absolute 18% during the first quarter of the study (June-August 2022, before the antibiotic was offered) to 7.5% in the last quarter of the study (June-August 2023).

Incidence among the doxyPEP users declined by a relative 58% for all STIs (incidence rate ratio [IRR] 0.42, 95% CI 0.24-0.74), by 78% for syphilis (IRR 0.22, 95% CI 0.09-0.54), and by 67% for chlamydia (IRR 0.33, 95% CI 0.23-0.46). No significant decline was observed with gonorrhea, possibly due to resistance to tetracycline, Scott said.

Among non-users of doxyPEP, the absolute incidence of all STIs showed a small decline during the study, from 7.5% in June-August 2022 to 6.5% in June-August 2023.

Open-Label Extension of DoxyPEP Trial Shows Sustained Benefit

New data from the open-label extension of the randomized DoxyPEP trialopens in a new tab or window showed that doxyPEP was associated with a sustained decrease in the incidence of STIs in MSM and transgender women, despite an increase in participants' sexual partners and condomless sex acts, Annie Luetkemeyer, MD, of the University of California San Francisco, reported at CROI.

Among participants initially assigned to standard care, the incidence of STIs per quarter decreased from 31% during the randomized part of the trial to 17% during the open-label extension when these participants started taking doxyPEP following condomless sex.

STI incidence per quarter was stable among participants initially assigned to doxyPEP who remained on doxyPEP during the open-label part of the trial as well (11% to 13%), Luetkemeyer told attendees.

Reported doxyPEP coverage per condomless sex act was high in both groups, at greater than 75%.

"The STI epidemic continues both in the U.S. and globally and has really impacted particularly men who have sex with men and trans women with really shocking increases in syphilis, but also sustained rises in chlamydia and gonorrhea," she told attendees.

The primary efficacy cohort for DoxyPEPopens in a new tab or window included 592 patients randomized 2:1 to either doxyPEP (doxycycline 200 mg within 72 hours of condomless sexual contact, one dose per day maximum) or standard care. The trial showed a 65% reduction in bacterial STIs each quarter of the study, with an 80% reduction in chlamydia and syphilis and a 50% reduction in gonorrhea.

Because doxyPEP was so effective, the study was terminated early and people randomized to the control group were offered doxyPEP. The open-label extension trial enrolled 289 participants, including 207 from the initial doxyPEP cohort and 82 control participants who chose to start doxyPEP.

Of note, Luetkemeyer reported that sexual partnerships and condomless sex acts increased in both groups during the open-label part of the trial, but especially among the standard-care group who switched to doxyPEP. The number of sex partners, condomless insertive sex, and receptive sex acts doubled in this group.

Disclosures

Sankaran had no disclosures.

Scott reported grants from Gilead Sciences and ViiV Healthcare.

Luetkemeyer's study was funded by the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and medicines and laboratory support were provided by Hologic, Cepheid, and Mayne Pharma. Luetkemeyer reported consulting fees from Vir Biotechnology and institutional grants from Gilead, Merck Sharp & Dohme, and ViiV.

Myer had no disclosures.

Primary Source

Conference on Retroviruses and Opportunistic Infections

Source Reference: opens in a new tab or windowSankaran M "Doxy-PEP associated with declines in chlamydia and syphilis in MSM and trans women in San Francisco" CROI 2024; Abstract 127.

Secondary Source

Conference on Retroviruses and Opportunistic Infections

Source Reference: opens in a new tab or windowScott H "Doxycycline PEP: high uptake and significant decline in STIs after clinical implementation" CROI 2024; Abstract 126.

Additional Source

Conference on Retroviruses and Opportunistic Infections

Source Reference: opens in a new tab or windowLuetkemeyer A "sustained reduction of bacterial STIs during the DoxyPEP study open-label extension" CROI 2024; Abstract 125.

https://www.medpagetoday.com/meetingcoverage/croi/109024

'Afib Might Be a Not-So-Pleasant Aftertaste of Sweetened Beverages'

   Overconsumption of beverages with added sugar or artificial sweetener, already associated with several cardiometabolic diseases, showed new links to atrial fibrillation (Afib or AF) in a prospective cohort study.

Within the U.K. Biobank, people who drank more than an estimated 2 L (~8.5 cups) of sugar-sweetened beverages (adjusted HR 1.10, 95% CI 1.01-1.20) or artificially sweetened beverages (adjusted HR 1.20, 95% CI 1.10-1.31) weekly had a greater risk of incident Afib within 10 years compared with nonconsumers.

Consuming 1 L or less of pure fruit juice, on the other hand, showed no such relationship and in fact appeared mildly protective against this established risk factor for stroke (adjusted HR 0.92, 95% CI 0.87-0.97), reported Ningjian Wang, MD, PhD, of Shanghai Ninth People's Hospital and Shanghai Jiao Tong University in China, and colleagues in Circulation: Arrhythmia and Electrophysiologyopens in a new tab or window.

The association between lots of sweetened beverages and Afib persisted after adjustment for genetic susceptibility to Afib. However, drinking less than the weekly 8.5 cups did not statistically correlate with Afib risk.

"To the best of our knowledge, this is the first study to estimate the associations of the consumption of different sweetened beverages with the risk of AF in a large prospective cohort," the authors wrote. "This study does not demonstrate that consumption of SSB [sugar-sweetened beverages] and ASB [artificially sweetened beverages] alters AF risk but rather that the consumption of SSB and ASB may predict AF risk beyond traditional risk factors."

The present findings on sweetened beverages thus add to the literature on diet and Afib, which has been dominated by studies on coffeeopens in a new tab or window and alcoholopens in a new tab or window.

Current federal dietary guidelinesopens in a new tab or window already urge limiting foods and beverages with added sugars to under 10% of daily calories.

"SSB are one of the largest sources of added sugar in the diet. They include energy-containing sweeteners, such as sucrose, high-fructose corn syrup, or fruit juice concentrates. High consumption of SSB is associated with a high risk of obesity, type 2 diabetes, cardiovascular diseases, and even all-cause mortality," Wang's group noted.

American guidelines do not endorse eating or drinking foods with low- and no-calorie sweeteners, either.

Recently marketed as a healthy, low-calorie artificial sweetener, even erythritolopens in a new tab or window, for example, has still been associated with cardiovascular disease. One study showed that erythritol-sweetened drinks increased plasma erythritol to levels that lingered above thresholds associated with heightened platelet reactivity and thrombosis potential.

Wang's team reported that the highest risk of Afib was observed in people at high genetic risk who also drank more than 8.5 cups of artificially sweetened -- not sugar-sweetened -- beverages per week.

"Somewhat surprising was that subjects with increased consumption of ASB were at the highest risk of incident AF. These findings raise the possibility that artificial sweeteners may have a more important role and contribute to the pathogenesis of AF," wrote Robert Koeth, MD, PhD, and two colleagues of Cleveland Clinic, in an accompanying editorialopens in a new tab or window.

Koeth's group said many questions surround the potential link between artificial sweeteners and Afib. The report by Wang and colleagues was unable to identify exact types of artificial sweeteners and other additives consumed by participants.

"Among ASB, what artificial sweetener(s) are associated with AF? What underlies the pathogenesis of this observation? Are there indirect or direct effects of artificial sweeteners on the myocardium? Finally, should longer term studies be required before the introduction of artificial nutrients into the food?" the editorialists asked.

Included in the present study were 201,856 U.K. Biobank participants (45.1% men, mean age 56 years) free of baseline Afib when they completed a 24-hour diet questionnaire. They were followed for a median 9.9 years, and some people answered multiple questionnaires during the study. Study authors sought records of incident Afib from primary care, hospital, and death records.

Diet questionnaires asked people to report various eating habits, including how many cups of beverages they drank the previous day. Wang's group extrapolated this information to weekly consumption estimates.

While a large majority of participants did not report drinking any sugar-sweetened or artificially sweetened beverages in their questionnaire, there were 6.6% and 5.5% of people reportedly drinking over 8.5 cups a week, respectively, of these drinks.

Heavy consumers tended to be young people with a higher BMI and a higher prevalence of coronary heart disease or diabetes.

A standard polygenic risk score was the basis for classifying people as high, intermediate, or low genetic risk for Afib.

Wang and colleagues acknowledged that their observational study left room for unmeasured confounding. Additionally, diet habits were possibly misreported or inherently biased in survey data, and the findings from relatively healthy participants from Britain may not apply to other groups.

"Despite these drawbacks, this study is the first to demonstrate a link between high consumption of SSB and ASB to AF. Further epidemiological and mechanistic studies are needed to confirm and extend these findings," Koeth's group wrote.

Disclosures

The study was supported by the National Natural Science Foundation of China, Shanghai Municipal Health Commission, Shanghai Municipal Human Resources and Social Security Bureau, Clinical Research Plan of Shanghai Hospital Development Center, Postdoctoral Scientific Research Foundation of Shanghai Ninth People's Hospital, and Shanghai Jiao Tong University School of Medicine.

Wang and Koeth's groups had no disclosures.

Primary Source

Circulation: Arrhythmia and Electrophysiology

Source Reference: opens in a new tab or windowSun Y, et al "Sweetened beverages, genetic susceptibility, and incident atrial fibrillation: a prospective cohort study" Circ Arrhythm Electrophysiol 2024; DOI: 10.1161/CIRCEP.123.012145.

Secondary Source

Circulation: Arrhythmia and Electrophysiology

Source Reference: opens in a new tab or windowKoeth RA, et al "Artificial sweeteners: A new dietary environmental risk factor for atrial fibrillation?" Circ Arrhythm Electrophysiol 2024; DOI: 10.1161/CIRCEP.124.012761.

https://www.medpagetoday.com/cardiology/prevention/109026

Novel Regimens Yield High Response Rates for Older, Hodgkin Lymphoma Patients

 Older patients with classical Hodgkin lymphoma unsuitable for conventional chemotherapy had high rates of durable responses with two brentuximab vedotin (BV; Adcetris) regimens, one that omitted chemotherapy, a small prospective study showed.

Brentuximab plus the alkylating agent dacarbazine (DTIC) produced an objective response rate (ORR) of 95% in 22 patients, whereas brentuximab plus nivolumab (Opdivo) led to responses in 86% of 21 patients. Two-thirds of patients achieved complete responses with each regimen.

Patients treated with the dacarbazine regimen had a median progression-free survival (PFS) of almost 4 years and the median had yet to be reached with the nivolumab regimen after 51.6 months of follow-up, reported Jonathan Friedberg, MD, MMSc, of the University of Rochester Wilmot Cancer Institute in New York, and co-authors in Bloodopens in a new tab or window.

"Despite a high median age, inclusion of patients up to 88 years, and frailty demonstrated on comprehensive geriatric assessment, our results compare favorably with our previous single-agent and combination studies in older patients incorporating BV," the authors wrote. "With a median follow-up of almost 4 years, the mDOR [median duration of response] and median PFS have not been reached, supporting the inference that some patients treated with this regimen may go on to be cured. Comprehensive geriatric assessments demonstrated similar rates of frailty and geriatric syndromes in the BV-nivolumab cohort compared with the BV-DTIC cohort."

The high response rates and durability of responses do raise the question of whether some patients with classical Hodgkin lymphoma, irrespective of age, might be cured without standard combination chemotherapy, agreed the author of an accompanying commentaryopens in a new tab or window.

"Traditionally, the dogma has been that a cure can only come from some combination of an anthracycline, a vinca alkaloid, and a drug that rhymes with -carbazine," wrote Ryan C. Lynch, MD, of the University of Washington and Fred Hutchinson Cancer Center in Seattle. "Personal anecdotes as well as emerging data from studies like this suggest there may be another way."

"Using noninvasive genotyping and circulating tumor DNA may help identify patients who are either at lower risk at baseline or perhaps cured far earlier during their treatment than anticipated," Lynch continued. "Given newer drugs and emerging technologies, we should resolve to design the next generation of studies with the goals of less or, dare I say, no chemotherapy at all, allowing us to reserve more toxic chemotherapy regimens for only those who truly need it."

Overall survival for adults with advanced classical Hodgkin lymphoma has improved dramatically over the past 2 decades, Friedberg and co-authors noted in their introduction. Nonetheless, older patients have inferior outcomes. A recent analysisopens in a new tab or window of Medicare patients showed that only a fourth received full-course chemotherapy, half received partial regimens or single-agent treatment, and the remaining fourth received no treatment at all.

Full-course therapy improves survival, but the observation is confounded by selection bias as frail patients and those with significant comorbidities are less likely to be treated with the regimens, the authors pointed out.

A recent studyopens in a new tab or window of brentuximab monotherapy in combination with dacarbazine led to objective responses exceeding 90%, which proved to be durable. The combination of brentuximab and nivolumabopens in a new tab or window has led to high rates of durable complete responses in younger patients. The cumulative results provided a rationale to evaluate brentuximab in combination with dacarbazine or nivolumab in older patients with previously untreated classical Hodgkin lymphoma.

In the non-comparative phase II studyopens in a new tab or window, the researchers enrolled patients ages 60 and older with untreated classical Hodgkin lymphoma who were considered unfit for conventional chemotherapy. Eligible patients had three or more general comorbidities or at least one significant comorbidity.

The 22 patients in the dacarbazine cohort had a median age of 69, 73% were men, 73% had stage III/IV disease, and three-fourths reported limitations in physical functioning.

The ORR of 95% included complete responses in 64% of patients. After a median follow-up of 63.6 months, median duration of response was 46 months, and median PFS was 47.2 months. Median duration of complete response and median overall survival had yet to be reached.

The most common treatment-emergent adverse events (TEAEs) were peripheral neuropathy (77%), constipation (45%), fatigue (45%), and nausea (41%). The most common grade ≥3 TEAEs were peripheral neuropathy (27%) and neutropenia (9%).

The 21 patients in the nivolumab cohort had a median age of 72, 71% were men, 77% had grade III/IV disease, and 43% reported limitations in physical functioning. The 86% ORR included complete responses in 67% of patients. After a median follow-up of 51.6 months, median duration of response, median duration of complete response, median PFS, and median overall survival had yet to be reached.

The most commonly reported TEAEs with brentuximab and nivolumab were fatigue (76%), peripheral neuropathy (48%), constipation (48%), nausea (48%), and diarrhea (48%). Grade ≥3 TEAEs included increased lipase (24%), motor peripheral neuropathy (19%), and sensory peripheral neuropathy (19%).

Disclosures

The trial was supported by Seagen.

Friedberg reported no relevant relationships with industry. Several co-authors disclosed relationships with multiple commercial interests.

Lynch disclosed relationships with TG Therapeutics, Incyte, Bayer, Cyteir, Genentech, Seagen, Rapt, Merck, Foresight Diagnostics, AbbVie, and Janssen.

Primary Source

Blood

Source Reference: opens in a new tab or windowFriedberg JW, et al "Brentuximab vedotin with dacarbazine or nivolumab as frontline cHL therapy for older patients ineligible for chemotherapy" Blood 2024; DOI: 10.1182/blood.2022019536.

Secondary Source

Blood

Source Reference: opens in a new tab or windowLynch RC "Toward a cure for cHL without chemotherapy" Blood 2024; DOI: 10.1182/blood.2023023108.

https://www.medpagetoday.com/hematologyoncology/lymphoma/109048