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Tuesday, November 5, 2024

Exact Sciences (EXAS) Misses Q3 EPS by 1c, Lowers Guidance

 Exact Sciences (NASDAQ: EXAS) reported Q3 EPS of ($0.21), $0.01 worse than the analyst estimate of ($0.20). Revenue for the quarter came in at $709 million versus the consensus estimate of $716.8 million.

GUIDANCE:

Exact Sciences sees FY2024 revenue of $2.73-2.75 billion, versus the consensus of $2.83 billion.

The Company has updated its full-year 2024 revenue and adjusted EBITDA guidance:

Prior guidance

November 5 update

Total revenue

$2.810 - $2.850 billion

$2.730 - $2.750 billion

Screening

$2.155 - $2.175 billion

$2.080 - $2.095 billion

Precision Oncology

$655 - $675 million

$650 - $655 million

Adjusted EBITDA

$335 - $355 million

$310 - $320 million


Migrant Caravan of 3,000 Heads North in Mexico as US Votes

 A caravan of approximately 3,000 migrants set off on Tuesday from southern Mexico, headed toward the United States on the day when U.S. voters were deciding between U.S. presidential candidates Kamala Harris and Donald Trump.

Immigration has been a key issue in the U.S. election campaign.

Before heading northward, the migrants gathered in Tapachula, the capital of the southern Chiapas state, carrying banners with messages such as "NO MORE MIGRANT BLOOD" and images of the Virgin of Guadalupe, an important religious and cultural symbol in Mexico, according to Reuters witnesses.

"We want U.S. authorities to see us, to see that we are people who want to work, not to harm anyone," said Honduran migrant Roy Murillo, who joined the caravan with his two children and his pregnant wife.

In recent years, several caravans with people hoping to enter the United States have attempted to reach the U.S.-Mexican border, traveling in mass groups for safety. Most have dispersed along the way. 

"I'm afraid to travel alone with my family. Here, the cartels either kidnap you or kill you. ... That's why we're coming in the caravan," Murillo said. 

Murillo recounted his unsuccessful attempts to secure an asylum appointment through a mobile app developed by the U.S. Customs and Border Protection agency.

Tapachula, a mandatory crossing point for tens of thousands of migrants, has become one of Mexico's most violent cities in recent months, with migrants frequently targeted by organized crime, according to official data.

"I feel suffocated here. That's why we decided to leave," said 28-year-old Venezuelan migrant Thais, who spoke on condition that her surname not be used due to safety concerns.

She joined the caravan with her husband and 3-year-old daughter.

"I wish Mr. Trump and Ms. Kamala would see that we are human beings, that we want to live and support our families," she added. 

Voters cast ballots on Tuesday in the race between Vice President Harris, a Democrat seeking to become the first female U.S. president, and Trump, a Republican immigration hard-liner aiming to regain the presidency.

https://www.usnews.com/news/world/articles/2024-11-05/migrant-caravan-of-3-000-heads-north-in-mexico-as-us-votes

Israeli Military Says Sirens Sounded in Eilat

 Israeli military said on Tuesday that sirens were sounded in the Red Sea port city of Eilat.

The Islamic Resistance in Iraq said in a statement that it targeted a "vital target" in Eilat by drones.

The Iraqi pro-Iran group has been launching attacks on Israel since the start of Israel's war in Gaza.

Arcus Combo Improved Overall Survival in Non-Small Cell Lung Cancer

 

  • Domvanalimab plus zimberelimab was associated with greater progression-free survival, overall survival, and objective response rate compared with those of zimberelimab or chemotherapy
  • A 36% reduction in risk of death (HR=0.64) was observed for domvanalimab plus zimberelimab compared to zimberelimab alone; zimberelimab reached a median overall survival of two years while the median overall survival for domvanalimab plus zimberelimab was not reached
  • Treatment-related adverse events leading to treatment discontinuation were low (10.5%) for the combination of domvanalimab and zimberelimab relative to chemotherapy (23.5%)
  • Arcus will discuss these results on its earnings call at 2:00 PM PT / 5:00 PM ET Wednesday, November 6, 2024

Alzheimer's Diagnosis Takes More Than Biomarkers, Working Group Says

 A definition of Alzheimer's disease -- one that requires objective cognitive deficits in addition to brain amyloid for Alzheimer's to be diagnosed -- was proposed by the International Working Group (IWG).

The proposal was presented at the Clinical Trials on Alzheimer's Diseaseopens in a new tab or window (CTAD) annual meeting in Madrid and published simultaneously in JAMA Neurologyopens in a new tab or window.

It's an extension of earlier positionsopens in a new tab or window by the IWG that for clinical use, cognitive symptoms must be present and a definition of Alzheimer's rooted only in biomarkers is not enough.

"Alzheimer's disease should be defined as a clinical-biological entity where a diagnosis is made in consideration of a clinical disorder supported by positive amyloid and tau biomarkers," said Howard Feldman, MD, of the University of California San Diego in La Jolla, who presented the IWG recommendations at CTAD.

This definition allows Alzheimer's to be diagnosed at an early prodromal stage once mild but definite clinical features are evident, he noted.

This viewpoint varies significantly from criteria published by the Alzheimer's Association (AA) workgroup earlier this year, Feldman told MedPage Today.

The AA criteria defined Alzheimer's diseaseopens in a new tab or window as a process that can be detected by abnormal biomarkers even when patients do not have cognitive symptoms. Defining diseases biologically is standard in cancer, heart disease, and diabetes, the AA workgroup noted.

A purely biological definition of Alzheimer's that diagnoses cognitively normal adults with one positive core biomarker as having Alzheimer's disease could lead to false positives and people living with a label of Alzheimer's disease even if they never have cognitive symptoms, Feldman maintained.

"The problem with the AA criteria is that they consider, in clinical settings, to make and to disclose the diagnosis of Alzheimer's disease in cognitively normal people who are biomarker-positive -- the majority of whom will never develop the disease clinically," IWG leading member Bruno Dubois, MD, MSc, of the Sorbonne University in Paris, told MedPage Today.

The IWG included 46 Alzheimer's experts from 17 countries who reviewed available evidence about biomarkers and diagnosing Alzheimer's disease from July 2020 to March 2024. Their goal was to evaluate the AA criteria and offer a different defining perspective of Alzheimer's for clinical use.

Based on their review, the IWG proposed:

  • Cognitively impaired people with specific clinical phenotypes and positive biomarkers would be classified as having Alzheimer's disease
  • Cognitively normal individuals with positive amyloid-related biomarkers only would be classified as "asymptomatic at risk of Alzheimer's disease," reflecting that these people have an increased lifetime risk of developing symptomatic disease
  • People with autosomal dominant genetic mutations, Down syndrome, or other distinct biomarker profiles associated with an almost deterministic and very high lifetime risk of Alzheimer's progression would be classified as having "presymptomatic Alzheimer's disease"

The AA group defined Alzheimer's by positive biomarkers, but it also advised against testing cognitively unimpaired individuals outside of research studies, noted Ronald Petersen, MD, PhD, of the Mayo Clinic in Rochester, Minnesota, and co-authors in a JAMA Neurology editorialopens in a new tab or window.

The AA group argued that "the application of biomarker-defined Alzheimer's disease to asymptomatic persons is a research construct," Petersen and colleagues wrote. However, it's reasonable to expect that many cognitively unimpaired people will soon have access to affordable Alzheimer's biomarker tests, the editorialists pointed out.

The IWG group argued that "labeling asymptomatic persons with Alzheimer's disease will do irrevocable harm to persons who may never become symptomatic," they added.

The importance of an incorrect diagnosis is well characterized by the IWG group, but lessons from other diseases like cancer may offer important guidance, the editorialists suggested: "The assumption that irrevocable damage would ensue if asymptomatic individuals receive a biomarker diagnosis of Alzheimer's disease may have elements of paternalism similar to avoiding the word 'cancer' in the past."

The conceptual approach proposed by the IWG is to maintain the essential clinical-pathological concept of Alzheimer's, Feldman noted.

"We separate asymptomatic at-risk individuals from those who already have the disease," he stated. "Predictive accuracy, cutoff points, and utility across diverse populations are still needed. Rather than applying a diagnostic label of Alzheimer's disease, we advocate for this being a state of risk."

Disclosures

Feldman reported relationships with Annovis, Vivoryon, AC Immune, Biohaven, LuMind Foundation, Novo Nordisk, Axon Neuroscience, Arrowhead, Roche/Genentech, Tau Consortium, Janssen, Epstein Family Alzheimer's Research Collaboration, and Royal Society of Canada, and having a patent with personal royalties received. Co-authors reported relationships with other pharmaceutical companies and nonprofit groups.

Petersen reported personal fees from Roche, Genentech, Eli Lilly, Eisai, and Novo Nordisk outside the submitted work. Other editorialists reported relationships with pharmaceutical companies and nonprofit groups.

Primary Source

JAMA Neurology

Source Reference: opens in a new tab or windowDubois B, et al "Alzheimer disease as a clinical-biological construct -- an international working group recommendation" JAMA Neurol 2024; DOI: 10.1001/jamaneurol.2024.3770.

Secondary Source

JAMA Neurology

Source Reference: opens in a new tab or windowPetersen RC, et al "Alzheimer disease -- what's in a name?" JAMA Neurol 2024; DOI: 10.1001/jamaneurol.2024.3766.


https://www.medpagetoday.com/meetingcoverage/ctad/112748

Dentists Pulling 'Healthy' and Treatable Teeth to Profit From Implants

 Becky Carroll was missing a few teeth, and others were stained or crooked. Ashamed, she smiled with lips pressed closed. Her dentist offered to fix most of her teeth with root canals and crowns, Carroll said, but she was wary of traveling a long road of dental work.

Then Carroll saw a TV commercial for another path: ClearChoice Dental Implant Centers. The company advertises that it can give patients "a new smile in as little as one dayopens in a new tab or window" by surgically replacing teeth instead of fixing them.

So Carroll saved and borrowed for the surgery, she said. In an interview and a lawsuit, Carroll said that at a ClearChoice clinic in New Jersey in 2021, she agreed to pay $31,000 to replace all her natural upper teeth with pearly-white prosthetic ones. What came next, Carroll said, was "like a horror movie."

Carroll alleged that her anesthesia wore off during implant surgery, so she became conscious as her teeth were removed and titanium screws were twisted into her jawbone. Afterward, Carroll's prosthetic teeth were so misaligned that she was largely unable to chew for more than 2 years until she could afford corrective surgery at another clinic, according to a sworn deposition from her lawsuit.

ClearChoice has denied Carroll's claims of malpractice and negligence in court filings and did not respond to requests for comment on the ongoing case.

"I thought implants would be easier, and all at once, so you didn't have to keep going back to the dentist," Carroll, 52, said in an interview. "But I should have asked more questions ... like, Can they save these teeth?"

Dental implants have been used for more than half a century to surgically replace missing or damaged teeth with artificial duplicates, often with picture-perfect results. While implant dentistry was once the domain of a small group of highly trained dentists and specialists, tens of thousands of dental providers now offer the surgery and place millions of implants each year in the U.S.

Amid this booming industry, some implant experts worry that many dentists are losing sight of dentistry's fundamental goal of preserving natural teeth and have become too willing to remove teeth to make room for expensive implants, according to a months-long investigation by KFF Health News and CBS News. In interviews, 10 experts said they had each given second opinions to multiple patients who had been recommended for mouths full of implants that the experts ultimately determined were not necessary. Separately, lawsuits filed across the country have alleged that implant patients like Carroll have experienced painful complications that have required corrective surgery, while other lawsuits alleged dentists at some implant clinics have persuaded, pressured, or forced patients to remove teeth unnecessarily.

The experts warn that implants, for a single tooth or an entire mouth, expose patients to costs and surgery complications, plus a new risk of future dental problems with fewer treatment options because their natural teeth are forever gone.

"There are many cases where teeth, they're perfectly fine, and they're being removed unnecessarily," said William Giannobile, DDS, dean of the Harvard School of Dental Medicineopens in a new tab or window. "I really hate to say it, but many of them are doing it because these procedures, from a monetary standpoint, they're much more beneficial to the practitioner."

Giannobile and nine other experts say they are combating a false public perception that implants are more durable and longer-lasting than natural teeth, which some believe stems in part from advertising on TV and social media. Implants require upkeep, and although they can't get cavities, studies have shownopens in a new tab or window that patients can be susceptible to infections in the gums and bone around their implants.

"Just because somebody can afford implants doesn't necessarily mean that they're a good candidate," said George Mandelaris, DDS, a Chicago-area periodontist and member of the American Academy of Periodontology Board of Trustees. "When an implant has infection, or when an implant has bone loss, an implant dies a much quicker death than do teeth."

In its simplest form, implant surgery involves extracting a single tooth and replacing it with a metal post that is screwed into the jaw and then affixed with a prosthetic tooth commonly made of porcelain, also known as a crown. Patients can also use "full-arch" or "All-on-4" implants to replace all their upper or lower teeth -- or all their teeth.

For this story, KFF Health News and CBS News sought interviews with large dental chains whose clinics offer implant surgery -- ClearChoice, Aspen Dental, Affordable Care, and Dental Care Alliance -- each of which declined to be interviewed or did not respond to multiple requests for comment. The Association of Dental Support Organizations, which represents these companies and others like them, also declined an interview request.

ClearChoice, which specializes in full-arch implants, did not answer more than two dozen questions submitted in writing. In an emailed statement, the company said full-arch implants "have become a well-accepted standard of care for patients with severe tooth loss and teeth with poor prognosis."

"The use of full-arch restorations reflects the evolution of modern dentistry, offering patients a solution that restores their ability to eat, speak, and live comfortably -- far beyond what traditional dentures can provide," the company said.

Carroll said she regrets not letting her dentist try to fix her teeth and rushing to ClearChoice for implants.

"Because it was a nightmare," she said.

'They Are Not Teeth'

Dental implant surgery can be a godsend for patients with unsalvageable teeth. Several experts said implants can be so transformative that their invention should have contended for a Nobel Prize. And yet, these experts still worry that implants are overused, because it is generally better for patients to have their natural teeth.

Paul Rosen, DMD, a Pennsylvania periodontist who said he has worked with implants for more than 3 decades, said many patients believe a "fallacy" that implants are "bulletproof."

"You can't just have an implant placed and go off riding into the sunset," Rosen said. "In many instances, they need more care than teeth because they are not teeth."

Generally, a single implant costs a few thousand dollars while full-arch implants cost tens of thousands. Neither procedure is well covered by dental insurance, so many clinics partner with credit companies that offer loans for implant surgeries. At ClearChoice, for example, loans can be as large as $65,000 paid off over 10 yearsopens in a new tab or window, according to the company's website.

Despite the price, implants are more popular than ever. Sales increased by more than 6% on average each year since 2010, culminating in more than 3.7 million implants sold in the U.S. in 2022, according to a 2023 report produced by iData Research, a healthcare market research firm.

Some worry implant dentistry has gone too far. In 10 interviews, dentists and dental specialists with expertise in implants said they had witnessed the overuse of implants firsthand. Each expert said they'd examined multiple patients in recent years who were recommended for full-arch implants by other dentists despite their teeth being treatable with conventional dentistry.

Giannobile, the Harvard dean, said he had given second opinions to "dozens" of patients who were recommended for implants they did not need.

"I see many of these patients now that are coming in and saying, 'I've been seen, and they are telling me to get my entire dentition -- all of my teeth -- extracted.' And then I'll take a look at them and say that we can preserve most of your teeth," Giannobile said.

Tim Kosinski, DDS, who is a representative of the Academy of General Dentistryopens in a new tab or window said he has placed more than 19,000 implants, and said he examines as many as five patients a month who have been recommended for full-arch implants that he deems unnecessary.

"There is a push in the profession to remove teeth that could be saved," Kosinski said. "But the public isn't aware."

Luiz Gonzaga, DDS, a periodontist and prosthodontist at the University of Florida, said he, too, had turned away patients who wanted most or all their teeth extracted. Gonzaga said some had received implant recommendations that he considered "an atrocity."

"You don't go to the hospital and tell them 'I broke my finger a couple of times. This is bothering me. Can you please cut my finger off?' No one will do that," Gonzaga said. "Why would I extract your tooth because you need a root canal?"

Jaime Lozada, DDS, director of an elite dental implant residency program at Loma Linda University, said he'd not only witnessed an increase in dentists extracting "perfectly healthy teeth" but also treated a rash of patients with mouths full of ill-fitting implants that had to be surgically replaced.

Lozada said in August that he'd treated seven such patients in just 3 months.

"When individuals just make a decision of extracting teeth to make it simple and make money quick, so to speak, that's where I have a problem," Lozada said. "And it happens quite often."

When full-arch implants fail, patients sometimes don't have enough jawbone left to anchor another set. These patients have little choice but to get implants that reach into cheekbones, said Sohail Saghezchi, an oral and maxillofacial surgeon at the University of California San Francisco.

"It's kind of like a last resort," Saghezchi said. "If those fail, you don't have anywhere else to go."

'It Was Horrendous Dentistry'

Most of the experts interviewed for this article said their rising alarm corresponded with big changes in the availability of dental implants. Implants are now offered by more than 70,000 dental providers nationwide, two-thirds of whom are general dentists, according to the iData Research report.

Dentists are not required to learn how to place implants in dental school, nor are they required to complete implant training before performing the surgery in nearly all states. This year, Oregon started requiring dentists to complete 56 hoursopens in a new tab or window of hands-on training before placing any implants. Stephen Prisby, RDH, executive director of the Oregon Board of Dentistry, said the requirement -- the first and only of its kind in the U.S. -- was a response to dozens of investigations in the state into botched surgeries and other implant failures, split evenly between general dentists and specialists.

"I was frankly stunned at how bad some of these dentists were practicing," Prisby said. "It was horrendous dentistry."

Many dental clinics that offer implants have consolidated into chains owned by private equity firms that have bought out much of implant dentistry. In healthcare, private equity investment is sometimes criticized for overtreatment and prioritizing short-term profit over patientsopens in a new tab or window.

Private equity firms have spent about $5 billion in recent years to buy large dental chains that offer implants at hundreds of clinics owned by individual dentists and dental specialists. ClearChoice was bought for an estimated $1.1 billion in 2020 by Aspen Dentalopens in a new tab or window, which is owned by three private equity firms, according to PitchBookopens in a new tab or window, a research firm focused on the private equity industry. Private equity firms also bought Affordable Care, whose largest clinic brand is Affordable Dentures & Implantsopens in a new tab or window, for an estimated $2.7 billion in 2021, according to PitchBook. And the private equity wing of the Abu Dhabi government bought Dental Care Allianceopens in a new tab or window, which offers implants at many of its affiliated clinics, for an estimated $1 billion in 2022, according to PitchBook.

ClearChoice and Aspen Dental each said in email statements that the companies' private equity owners "do not have influence or control over treatment recommendations." Both companies said dentists or dental specialists make all clinical decisions.

Private equity deals involving dental practices increased ninefold from 2011 to 2021, according to an American Dental Association studyopens in a new tab or window published in August. The study also said investors showed an interest in oral surgery, possibly because of the "high prices" of implants.

"Some argue this is a negative thing," said Marko Vujicic, PhD, vice president of the association's Health Policy Institute, who co-authored the study. "On the other hand, some would argue that involvement of private equity and outside capital brings economies of scale, it brings efficiency."

Edwin Zinman, DDS, JD, a San Francisco dental malpractice attorney and former periodontist who has filed hundreds of dental lawsuits over 4 decades, said he believed many of the worst fears about private equity owners had already come true in implant dentistry.

"They've sold a lot of [implants], and some of it unnecessarily, and too often done negligently, without having the dentists who are doing it have the necessary training and experience," Zinman said. "It's for five simple letters: M-O-N-E-Y."

Hundreds of Implant Clinics With No Specialists

For this article, journalists from KFF Health News and CBS News analyzed the webpages for more than 1,000 clinics in the nation's largest private equity-owned dental chains, all of which offer some implants. The analysis found that more than 70% of those clinics listed only general dentists on their websites and did not appear to employ the specialists -- oral surgeons, periodontists, or prosthodontists -- who traditionally have more training with implants.

Affordable Dentures & Implants listed specialists at fewer than 5% of its more than 400 clinics, according to the analysis. The rest were staffed by general dentists, most of whom did not list credentialing from implant training organizations, according to the analysis.

ClearChoice, on the other hand, employs at least one oral surgeon or prosthodontist at each of its more than 100 centers, according to the analysis. But its new parent company, Aspen Dental, which offers implants in many of its more than 1,100 clinics, does not list any specialists at many of those locations.

Not everyone is worried about private equity in implant dentistry. In interviews arranged by the American Academy of Implant Dentistryopens in a new tab or window, which trains dentists to use implants, two other implant experts did not express concerns about private equity firms.

Brian Jackson, DDS, a former academy president and implant specialist in New York, said he believed dentists are too ethical and patients are too smart to be pressured by private equity owners "who will never see a patient."

Jumoke Adedoyin, DDS, a chief clinical officer for Affordable Care, who has placed implants at an Affordable Dentures & Implants clinic in the Atlanta suburbs for 15 years, said she had never felt pressure from above to sell implants.

"I've actually felt more pressure sometimes from patients who have gone around and been told they need to take their teeth out," she said. "They come in and, honestly, taking a look at them, maybe they don't need to take all their teeth out."

Still, lawsuits filed across the country have alleged that dentists at implant clinics have extracted patients' teeth unnecessarily.

For example, in Texas, a patient alleged in a 2020 lawsuit that an Affordable Care dentist removed "every single tooth from her mouth when such was not necessary," then stuffed her mouth with gauze and left her waiting in the lobby as he and his staff left for lunch. In Maryland, a patient alleged in a 2021 lawsuit that ClearChoice "convinced" her to extract "eight healthy upper teeth," by "greatly downplay[ing] the risks." In Florida, a patient alleged in a 2023 lawsuit that ClearChoice provided her with no other treatment options before extracting all her teeth, "which was totally unnecessary."

ClearChoice and Affordable Care denied wrongdoing in their respective lawsuits, then privately settled out of court with each patient. ClearChoice and Affordable Care did not respond to requests for comment submitted to the companies or attorneys. Lawyers for all three plaintiffs declined to comment on these lawsuits or did not respond to requests for comment.

Fred Goldberg, JD, a Maryland dental malpractice attorney who said he has represented at least six clients who sued ClearChoice, said each of his clients agreed to get implants after meeting with a salesperson -- not a dentist.

"Every client I've had who has gone to ClearChoice has started off meeting a salesperson and actually signing up to get their financing through ClearChoice before they ever meet with a dentist," Goldberg said. "You meet with a salesperson who sells you on what they like to present as the best choice, which is almost always that they're going to take out all your natural teeth."

Becky Carroll, the ClearChoice patient from New Jersey, told a similar story.

Carroll said in her lawsuit that she met first with a ClearChoice salesperson referred to as a "patient education consultant." In an interview, Carroll said the salesperson encouraged her to borrow money from family members for the surgery, and it was not until after she agreed to a loan and passed a credit check that a ClearChoice dentist peered into her mouth.

"It seems way backwards," Carroll said. "They just want to know you're approved before you get to talk to a dentist."

https://www.medpagetoday.com/primarycare/dentalhealth/112740

Walgreens pays $100M to settle overcharging allegations

 Walgreens has agreed to pay $100 million to settle a class action lawsuit accusing the pharmacy chain of inflating prescription drug prices for insured customers. 

The settlement, announced after seven years of litigation, resolves claims that Walgreens improperly inflated its "usual and customary" prices for prescription drugs by not factoring in the lower prices it charged members of its prescription savings club, according to court documents obtained by Becker's

This comes after Walgreens also agreed to pay $106.8 million in September to resolve allegations of submitting false billing claims to federal healthcare programs. 

The lawsuit, initially filed in 2017, alleged that by excluding PSC prices when determining usual and customary prices, Walgreens caused insured customers and third-party payors to overpay for prescription medications. 

Plaintiffs argued that these inflated prices were deceptive and violated consumer protection laws. As a part of the settlement, Walgreens agreed to terminate the PSC program. 

In an email shared with Becker's, a Walgreens spokesperson stated, "We admit no liability and believe these claims never had any merit. We launched the prescription savings club more than 15 years ago to provide equitable access to lower-cost medications for uninsured and underinsured. This resolution allows us to focus on our turnaround strategy that will benefit our patients, customers, team members and shareholders." 

The $100 million settlement covers individuals or entities who paid for prescriptions at Walgreens using insurance between January 2007 and present. 

https://www.beckershospitalreview.com/legal-regulatory-issues/walgreens-pays-100m-to-settle-overcharging-allegations.html