U.S. judge grants preliminary approval to Juul settlement

 Juul Labs Inc won preliminary approval of a settlement aimed at ending thousands of lawsuits alleging the company was a major cause of a youth-vaping epidemic in the United States, according to a court filing on Friday.

U.S. District Judge William Orrick in San Francisco said Juul's deal to settle almost 10,000 lawsuits filed by local governments across the country seemed to be "fair, reasonable, and adequate."

Juul did not immediately respond to a Reuters request for comment.

The court document provided no details of the terms of the settlement.

The company earlier said it had reached settlements with about 10,000 plaintiffs covering more than 5,000 cases in California.

Partly owned by Marlboro maker Altria Group Inc, Juul in September agreed to pay $438.5 million to settle claims from 34 U.S. states and territories that said the company targeted underage buyers and downplayed its products' risks.

The U.S. Food and Drug Administration in June briefly banned Juul's e-cigarettes, though it later put the order on hold following an appeal.

https://www.yahoo.com/entertainment/juul-settlement-end-youth-vaping-233010662.html

Abortion opponents call for stricter bans at first post-Roe Washington march

 Thousands of abortion opponents rallied in Washington on Friday for the 50th annual "March for Life," marking a new chapter for a movement that has organized for decades around overturning Roe v. Wade, the landmark ruling that recognized a women's right to an abortion.

With that ruling now thrown out, March for Life leaders and activists were celebrating their movement's win, pushing for stricter limits on abortion at the state and national level, and praying to change the "hearts and minds" of Americans who support abortion rights.

"We are not yet done," March for Life President Jeanne Mancini said to the crowd, which appeared thinner than the previous year but still spilled across the National Mall.

"We will march until abortion is unthinkable," she said.

Since the end of Roe on June 24, 2022, 12 states have enforced total abortion bans with limited exceptions and abortion is unavailable in two additional states, according to the Guttmacher Institute, a reproductive rights research and advocacy organization.

Rally-goers said they wanted to see abortion banned in every state, at every stage of pregnancy. Some held signs that read, "I demand protection at conception" and "abortion is genocide."

"I believe that, just like we wouldn't want to murder anybody out here, we wouldn't want to see any of these lives hurt or lost," said Rob McNutt, a pastor affiliated with a crisis pregnancy center in Maryland.

"Life begins at conception," said Kathleen Stahl, a 60-year-old nurse from Washington, D.C., who works in maternal and child health.

Stahl and others said that beyond abortion bans, they wanted to see more legislation aimed at getting resources to women struggling with unexpected pregnancies.

"We need to provide healthcare to our mothers, and a lot of our young mothers need more support," Stahl said.

https://www.yahoo.com/now/abortion-opponents-push-post-roe-110743714.html

Fed May Have to Raise Rates More Than Expected: Citi

 Citi's Chief US Economist Andrew Hollenhorst says wage growth, and service inflation may force the Federal Reserve to reassess its approach to rate hikes during an interview with Tom Keene on "Bloomberg Surveillance."

https://www.marketscreener.com/quote/stock/CITIGROUP-INC-4818/news/Fed-May-Have-to-Raise-Rates-More-Than-Expected-Citi-42778488/

'Mental health benefits of gender-affirming hormones for teens persist for two years': study

 Trans and nonbinary teenagers who receive gender-affirming hormones experience less depression and anxiety and more satisfaction with life than before the treatment, according to a new study published Wednesday in the New England Journal of Medicine.

Researchers followed over 300 adolescents across the U.S. for two years after initiating hormone treatment. The results augment a substantial body of research that shows gender-affirming care improves mental health, but most previous studies had been done with smaller, single-location cohorts and shorter follow-up windows. The new paper also focuses primarily on hormone therapy, while earlier work often included a variety of care options, including drugs to delay onset of puberty.

“It’s nice to have a structured analysis that supports what I and others experience in practice,” said Carl Streed Jr., a physician and research lead at Boston Medical Center’s Center for Transgender Medicine and Surgery, who was not involved with the new study. “This is another big contribution to saying that gender-affirming care is in fact evidence-based and has benefits and should be standard of practice at this point.”

Despite the mounting evidence, lawmakers in many states continue attempting to restrict or ban gender-affirming care, particularly for teens. Before 2020, no states had attempted these bans. But in 2021, such bills were introduced in almost two dozen state legislatures. Four states — Alabama, Arkansas, Arizona, and Tennessee — have since enacted bans, according to Movement Advancement Project, a nonprofit think tank, though in Alabama and Arkansas, those bans have been blocked temporarily by state judges. Other measures, though, such as Florida’s “Don’t Say Gay” bill, which prohibits teachers from discussing sexuality or gender identity in school, still may leave many queer adolescents feeling unsafe and unable to discuss their medical needs.

Experts say attempts to ban gender-affirming care for teens misunderstand the nature of this care. The NEJM study, led by researchers at Lurie Children’s Hospital’s Stanley Manne Children’s Research Institute in Chicago, found that almost 70% of participants who started the study with severe depression saw it reduced to the minimal or moderate range after two years of hormone therapy. On average, participants started the trial with mild depression and ended with subclinical levels. Almost 40% of participants who started the trial with clinical anxiety saw it reduced to the non-clinical range after two years.

Hormone therapy fundamentally alters one’s appearance. Among other changes, testosterone may increase body hair growth, deepen a person’s voice, and increase muscle mass; estrogen may slow the growth of body hair, increase breast growth while lowering muscle mass, and more.

The researchers met with participants, who ranged from ages 12-20, every six months to assess their psychosocial functioning. They found that as appearance congruence increased — meaning that as participants felt more comfortable with their changing physical appearance — depression and anxiety decreased, while positive moods and life satisfaction increased.

Unlike previous research, the new study focuses primarily on the effects of gender-affirming hormones — each participant received either testosterone or estradiol hormone treatment, and the vast majority had gone through puberty and never received the separate treatment known as hormone or puberty blockers. Researchers found that those who had not gone through puberty yet (either because of their younger age or because they were part of the small portion of participants who had received puberty blockers) saw even higher levels of appearance congruence, positive affect, and life satisfaction, and lower scores for depression and anxiety. The researchers believe this is likely because, even with hormone therapy, the effects of puberty cannot easily be erased, making appearance congruence harder to achieve.

This reflects previous evidence, the researchers note, that the earlier children can have access to gender-affirming care, the better.

“The adults that I see, every one of them is like, ‘Man, I wish I could have accessed this sooner,’” said Streed, who works mainly with adults in his role at BMC’s clinic. “There is nobody who is like, ‘Boy, I’m glad I waited until this point of my life.’”

Streed sees patients as young as teenagers who are transitioning out of pediatric care into adult care. But, he said, “you have to survive to see me as an adult.” Trans and nonbinary youth die by suicide at higher rates than their cisgender counterparts. In the current study, two participants died by suicide. Streed said that, while every suicide is absolutely tragic, he would have been surprised if there were none in the study, given those higher rates.

“Transgender people disproportionately experience poor mental health symptoms, largely as a result of living in a transphobic society,” Diana Tordoff, a researcher at Stanford who has done similar research on gender-affirming care and mental health, wrote in an email to STAT.

Study participants designated female at birth benefited from hormones more than those designated male at birth in regard to depression, anxiety, and life satisfaction. The authors theorize that this may be related to differences in the ways society accepts transfeminine and transmasculine people.

“We are really happy, and it’s really important,” said Annelou de Vries, a researcher at Amsterdam University Medical Center who co-authored a commentary on the study with colleague Sabine Hannema, also published Wednesday in NEJM. “Then the nuance comes. There remain some questions to be answered, and some of them, this study will not give.”

The amount of research focused on gender-affirming care has increased in recent years, in part due to increased prioritization from the National Institutes of Health. In 2016, the organization formally recognized “sexual and gender minorities” as a “health disparity population” for research. Experts hope that the increased focus will lead to more studies that follow trans and nonbinary people long-term, in order to learn more about potential benefits and effects of treatment long-term.

The study authors, who were not available for interviews, plan to continue following the same cohort to document longer-term results. They are also working on a similar study looking specifically at the effects of puberty blockers.

“Access to gender affirming care is fundamentally a human rights issue,” wrote Tordoff. “Trans people and their families deserve high quality science and research with which to make their own person medical decisions and to inform evidence-based clinical guidelines — not just for access to gender-affirming care, but also for preventive care, screening, and treatment for a wide range of health issues that impact all people.”

https://www.statnews.com/2023/01/18/mental-health-benefits-of-gender-affirming-hormones-for-teens-persist-two-years/

Upcoding: Reason Medicare Advantage pays clinicians to make home health checkups

 At the start of 2023, an estimated 2.5 million Americans age 65 and older began using Medicare Advantage programs. Some made this choice in response to aggressive marketing campaigns. This brings the total enrollment of Medicare Advantage plans to nearly 31 million.

One unexpected “benefit” of these plans is an offer by the insurance company sponsoring the plan to send a nurse or physician’s assistant, often from a startup company, to an individual’s home. There is no charge for the visit, and the insurance company may even pay the beneficiary for agreeing to do this. Some companies call relentlessly to get the offer accepted.

Before explaining whose interests these visits serve, it helps to tease out the roles of the players. Health insurance companies do not deliver health care. That’s what medical providers and groups do. The primary role of insurance companies is to pay the bills; they profit by taking in more money from beneficiaries than they pay for the medical care they need. To be sure, this distinction is getting murky: some health insurers have bought medical provider groups, and some health systems offer health insurance.

When an individual signs up for Medicare Advantage, which they get through a private insurance company instead of through the federal government, Medicare no longer directly pays providers for their services. Instead, it pays a fixed fee to the insurance company, which establishes its own rules for how much and when it pays providers.

Here’s the catch: the amount the insurer collects from Medicare is based on risk-score codes. The more diagnoses individuals have, the higher their risk scores, and the higher the risk score, the more the insurance company collects from Medicare.

In theory, that sounds reasonable. In reality, some Medicare Advantage insurers assign diagnoses and risk codes that generate higher premiums regardless of whether these diagnoses actually affect an individual’s health or whether they are being treated for the condition. This is where the free at-home physicals come in. Even though Medicare already offers those it covers annual comprehensive wellness visits with their primary care providers, some Medicare Advantage insurers push for at-home visits to find additional risk codes that allow them to secure higher fixed fees from Medicare. This is referred to as upcoding. Even though traditional Medicare beneficiaries are often sicker than Medicare Advantage beneficiaries, the use of custom software, specially trained professionals, and business consultants have created an entire industry dedicated to gaming the system.

The rewards for upcoding are not trivial. A company might get paid about $6,700 for an older man with uncomplicated diabetes. But adding a single code for vascular disease — which may or may not be influencing the treatment decisions by the individual’s health care provider — can increase what Medicare pays the insurance company by 45%. And because only 5% of Medicare Advantage insurers are audited annually, companies often get away with upcoding.

Medical provider groups may also use upcoding to increase profits, typically on people insured by their own Medicare Advantage plans. Richard Kronick, the former director of the federal Agency for Healthcare Research and Quality, has estimated that upcoding will increase Medicare spending by about $20 billion per year over the next decade. To put that in perspective, that overcharge could completely support current federal expenditures for biomedical research on cancer, heart disease, Alzheimer’s disease, diabetes, mental health, and childhood illnesses.

How can insurer profits be redirected from what Richard Gilfillan and Donald Berwick, former leaders of the Centers for Medicare and Medicaid Services, have labeled the “money machine,” to instead serve the health needs of Medicare beneficiaries.

First on the list is developing a scorecard that measures what truly matters to people: maintaining functional capabilities and quality of life. Many of the quality measures currently used to rate health insurers simply reflect what health care providers do, like order blood tests on a regular schedule, instead of whether the benefits of care delivered are leading to longer or better lives, fewer medical errors, or fewer preventable deaths. This is the essence of value-based care: paying health care providers on the outcomes of the patients they serve, not just what they do to their patients.

Because of Medicare Advantage upcoding abuses, new measures also need to be designed with anti-gaming provisions. Instead of rewarding insurers for adding premium-raising codes to medical records, codes should be counted only if providers are actively managing those conditions. To combat gaming schemes, Medicare will soon release a new auditing policy that will identify when insurance companies are using risk adjustment inappropriately. The audits could force companies to repay tens of millions of dollars. But the industry is prepared to fight back, as STAT reported, possibly by suing the Biden administration to block the audits.

When health insurance profits grow unchecked, less money is available for other social needs, such as food, housing, education, and clean energy, to name a few. Health care in the United States is the biggest sector in the largest economy in the history of the world. Unjustifiable upcoding inflates costs without helping patients. This beast must be tamed. Putting an end to it helps us all.

Robert M. Kaplan is a faculty member at Stanford University’s Clinical Excellence Research Center, a former associate director of the National Institutes of Health, and a former chief science officer for the Agency for Healthcare Research and Quality. Paul Tang is a primary care internist, faculty member at Stanford’s Clinical Excellence Research Center, and former medical informatics executive.

https://www.statnews.com/2023/01/19/rein-in-upcoding-medicare-advantage-companies/

Is mesothelin a key to tackling solid tumors?

 Scientists working to produce immunotherapies for solid tumor cancers have spent decades searching for biological targets that can help them distinguish between healthy cells and cancerous ones. Finding such biomarkers is critical to developing treatments that can kill the cancer without also killing the patient.

But so far, researchers have only identified a few proteins that meet that requirement. One of the most promising is mesothelin or MSLN, a protein found in certain cancers, including ovarian and pancreatic cancers and some mesotheliomas. Mesothelin is also found in some healthy membrane tissues, like the mesothelium of the pleura and peritoneum, meaning that therapies that target mesothelin would attack those tissues, as well.

But patients can survive without these membranes, and scientists believe any damage they might suffer from the therapy isn’t critical as long as the therapy also destroys or beats back the cancer.

The abundance of mesothelin on various solid tumor cancers leads some researchers to believe that the protein might be key to getting cell therapies and bispecific antibodies — which can bind to two different antigens— to work. And, as STAT’s latest report, “Targeting cancer: the new frontier of immunotherapy and precision oncology,” explains, there are now several cancer immunotherapies and precision therapies that use mesothelin to target cancer being developed by companies like Atara Biotherapeutics and Lonza.

“Every investigator has their favorite antigen they’re going after,” said Kristin Anderson, a cell therapy researcher at the Fred Hutchinson Cancer Center. “I’m excited about [mesothelin] because it’s overexpressed in 75% to 80% of high-grade ovarian cancer patients. It’s a high-priority antigen for me and my team to work on.”

The discovery

Ira Pastan, a cell biologist and immunologist at the National Institutes of Health, and his colleagues discovered mesothelin in the 1990s. Their original goal was to find out what gave a cancer cell its molecular identity. Pathologists peering down their microscopes can tell from the shape and organization of tissues not only whether they’re malignant but whether the cells are breast, lung, pancreatic or another type of cancer.

Researchers, including Pastan, believed there must be something in a cancer cell, like an embedded protein, that set it apart from other cells. “Something that says, ‘I’m a breast cancer cell. Look at me,’” Pastan said. And if there were, he added, then you should be able to create drugs and therapies that would target that protein and use it to mark cancer cells for death.

So Pastan started looking for therapeutic targets in cancers that arose in organs that are  sometimes removed as part of surgical treatment. If they did hit upon some proteins that were potential targets, the toxicity might be limited to organs that are not necessary to sustain life, like the prostate or ovaries.

To look for antigens, Pastan injected a tumor into mice, then looked for antibodies on the surface of the cancer cells that reacted. “We looked in ovary, breast, prostate, and found candidates in all three, but the only one that panned out was immunizing mice with ovarian cancer. That target turned out to be mesothelin,” Pastan said.

Pastan and his colleagues then found that mesothelin was a cell surface protein and that it was only present on certain membranes in the body. “It’s not in the liver, the brain, the stomach. It had a pretty limited distribution on normal tissue,” he said. “That’s how we discovered it. Then we showed it was present in many other cancers: almost all pancreatic cancers, most ovarian cancers, and mesothelioma.”

The biology

It’s not yet clear what mesothelin’s role is either in normal biology or in cancer. Pastan and his colleagues created mesothelin “knockout” mice,  mice without the gene allowing them to create mesothelin. Breaking a gene in an animal model is a classic experiment in biology, since it might cause physical defects in the mice that offers clues to the gene’s function. For instance, knocking out a gene important to eye formation might lead to blind mice. But in this case, the knockout mice seemed totally normal.

“They breed fine. They lived to a normal age. Their immune system is OK,” Pastan said. “We could never find any major defects.” He said he found the result both exciting and disappointing. On the one hand, it made it much more difficult to elucidate mesothelin’s role in biology, but on the other hand it meant that targeting the protein might not lead to any untoward side effects. Since then, researchers have found that mesothelin tends to be most highly expressed in the aggressively growing edges of a tumor. That study, and other experiments, suggest that mesothelin might be important in cancer growth and metastasis.

In one experiment, Christine Alewine at the NIH wanted to see what would happen to a certain type of pancreatic cancer cell that could not express mesothelin. She found that cancers that could not create mesothelin seemed to metastasize and grow more slowly than the cancers that could make the protein. Alewine also studied a specific pancreatic cancer cell line created in lab experiments that was more aggressive, and found that it had increased expression of mesothelin.

Critically, Alewine and her colleagues also saw that mesothelin only seemed to help the cancer grow and metastasize early in the course of disease. In her experiments, mesothelin expression seemed to be related to the formation of new blood vessels that can help shuttle in nutrients that the cancer needs to grow or metastasize. But once the tumor or metastasis was established, mesothelin seemed to provide no further benefit to the cancer.

“Our data show that MSLN confers this growth advantage to pancreatic tumor cells within the first 7 days of metastatic colonization by increasing microvasculature, proliferation, and invasion,” she wrote in May 2021 in the journal Molecular Cancer Research. But after that, the growth advantage is not seen. So blocking MSLN would be unlikely to shrink or cure established metastases.

 The pipeline

As a result, companies that are targeting mesothelin are for the most part not seeking to block the action of the protein. Instead, they are seeking to use mesothelin as a way to mark cells for death. One way is by using engineered immune cells like CAR-T cells that are designed to kill any cell in the body carrying mesothelin. That’s an approach that scientists at Atara Biotherapeutics and Memorial Sloan Kettering are taking.

“We’ve been working on mesothelin for 12 years now,” said Prasad Adusumilli, a cell biologist at Sloan Kettering and the lead researcher on the study.

In the past, CAR-T therapies targeting mesothelin had been shown to be safe but with limited efficacy. CAR-T therapies in general have been disappointing as treatments for solid tumors, for many reasons. These reasons include the fact that solid tumors create a microenvironment that’s hostile to immune cells, and possibly physiological barriers that prevent efficient migration of CAR-T cells and other immune cells to the tumor.

But Adusumilli is combining the CAR-T therapy with another immunotherapy called checkpoint blockade, which works by releasing a natural brake on the immune system, causing it to become more active. By following a mesothelin-targeted CAR-T therapy with one of these drugs in clinical trials, Adusumilli is hoping that might provide just the extra boost the immune system may need to more effectively fight the cancer.

It’s still too early to draw any conclusions from the results, Adusumilli said, but so far the data have been encouraging. “As a researcher, it’s a great privilege to care for the patients. When you see the response, we go through waves of emotion. Is it a fluke? Is it transient?” he said. “But the best thing in the clinical trials has been the patient’s weight. They gain weight for hundreds of days.”

https://www.statnews.com/2023/01/20/mesothelin-solid-tumors-cancer-biotech-companies/

Abbott faces U.S. criminal probe over baby formula

 Abbott Laboratories' Michigan plant, which was at the center of the U.S. baby formula shortage last year, faces a criminal investigation by the Justice Department, the Wall Street Journal reported on Friday.

Panicked parents emptied baby formula aisles at supermarkets last year as a recall of formulas by Abbott due to complaints of bacterial infections exacerbated a shortage that began due to pandemic-induced supply chain issues.

The White House intervened to address the shortage.

Attorneys with the Justice Department's consumer-protection branch are conducting the criminal investigation, the WSJ report said, citing people familiar with the matter.

"DOJ has informed us of its investigation and we're cooperating fully," an Abbott spokesman told Reuters, without commenting further on the nature of the probe. The DOJ did not immediately respond to a request for comment.

In February 2022, Abbott, the biggest U.S. supplier of baby formula, recalled Similac and other infant formula products produced at the Michigan facility after reports of bacterial infections in babies who had consumed products made there.

The U.S. Food and Drug Administration found "shocking" results during an inspection such as cracks in vital equipment, a lack of adequate hand-washing and evidence of previous bacterial contamination. The regulator and the company later reached an agreement that allowed the plant to reopen.

https://finance.yahoo.com/news/1-abbott-faces-u-criminal-001156451.html