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Sunday, April 21, 2019

In breast cancer, reducing this amino acid could make drugs more effective

Leucine, an amino acid that the body needs for making protein, appears to have a surprising role in the development of resistance to tamoxifen in breast cancer that tests positive for the estrogen receptor.
Scientists from Harvard Medical School, in Boston, MA, recently made this “unexpected” discovery about estrogen receptor-positive (ER-positive) breast cancer in a study conducted with colleagues from other research centers.
In laboratory experiments, they also found that the cell surface protein SLC7A5, which helps cells to take in leucine, influences the response of ER-positive breast cancer cells to tamoxifen.
The study authors note, in a paper published in Nature, that “SLC7A5 was necessary and sufficient to confer resistance to tamoxifen treatment” and suggest that the protein could be a potential target for “overcoming resistance” to tamoxifen in ER-positive breast cancer.
In around three-quarters of breast cancers, the hormone estrogen helps the tumors grow and spread.
This is because the cancer cells, like healthy breast cells, have estrogen receptors that allow themto receive growth signals from the hormone.
Doctors commonly treat ER-positive breast cancer with the drug tamoxifen because it blocks the action of estrogen in the cancer cells.

Tamoxifen resistance and leucine

However, while ER-positive breast cancers may respond to tamoxifen, in many cases they develop resistance to the drug, raising the risk of recurrence and metastasis, or spread.
“Patients with ER-positive breast cancer who develop endocrine-resistant and metastatic cancerhave very poor life expectancy,” says lead study author Senthil K. Muthuswamy, Ph.D., an associate professor of medicine at Harvard Medical School.
Because there are limited alternative treatment options, the average survival of these patients is “usually less than 5 years,” he adds.
Amino acids are the building blocks that the body uses to make proteins. There are 20 of them in all. Of these, nine are essential, that is, the body must source them from food because it cannot make them itself.
Leucine is an essential amino acid that is especially important for making muscle protein. In general, apart from maize, plant foods contain less leucine than foods from animal origin. Pork, fish, chicken, and beef are examples of foods that have higher levels of leucine.

Reducing leucine stopped tumor growth

The fact that cells cannot synthesize leucine gave the researchers the opportunity to explore the reaction of ER-positive breast cancer cells to different levels of the amino acid that they could control.
Laboratory experiments using cultures of ER-positive breast cancer cells from human samples showed that reducing leucine stopped tumor cell division, while increasing it promoted cell division.
Muthuswamy says that these results point to the possibility of developing dietary interventions to help those with ER-positive breast cancer.
However, he cautions that the findings do not “imply that animal proteins will enhance growth of breast cancer cells.” All they show is that reducing leucine in the diet could be of benefit to people with ER-positive breast cancer.
He and his team have already started another study to find out whether restricting dietary leucine can reduce tumor growth or boost treatment response in a mouse model of ER-positive breast cancer.

The role of SLC7A5 in tamoxifen resistance

In a final set of experiments, the team examined the effect of leucine levels on ER-positive breast cancer cells that had developed resistance to tamoxifen. These experiments revealed that resistant cells continued to grow, even when leucine levels were low.
On closer examination, the scientists found that the tamoxifen-resistant cells had higher levels of SLC7A5. Higher levels of this ferrying protein were helping the cells to take in more leucine, even when it was scarce.
In a final set of tests on mice, the researchers found that blocking SLC7A5 caused the animals’ ER-positive tumors to shrink.

Hospitals Stand to Lose Billions Under ‘Medicare for All’

For a patient’s knee replacement, Medicare will pay a hospital $17,000. The same hospital can get more than twice as much, or about $37,000, for the same surgery on a patient with private insurance.
Or take another example: One hospital would get about $4,200 from Medicare for removing someone’s gallbladder. The same hospital would get $7,400 from commercial insurers.
The yawning gap between payments to hospitals by Medicare and by private health insurers for the same medical services may prove the biggest obstacle for advocates of “Medicare for all,” a government-run system.
If Medicare for all abolished private insurance and reduced rates to Medicare levels — at least 40 percent lower, by one estimate — there would most likely be significant changes throughout the health care industry, which makes up 18 percent of the nation’s economy and is one of the nation’s largest employers.
Some hospitals, especially struggling rural centers, would close virtually overnight, according to policy experts.
Others, they say, would try to offset the steep cuts by laying off hundreds of thousands of workers and abandoning lower-paying services like mental health.
The prospect of such violent upheaval for existing institutions has begun to stiffen opposition to Medicare for all proposals and to rattle health care stocks. Some officials caution that hospitals providing care should not be penalized in an overhaul.
Dr. Adam Gaffney, the president of Physicians for a National Health Program, warned advocates of a single-payer system like Medicare for all not to seize this opportunity to extract huge savings from hospitals. “The line here can’t be and shouldn’t be soak the hospitals,” he said.
“You don’t need insurance companies for Medicare for all,” Dr. Gaffney added. “You need hospitals.”
Soaring hospital bills and disparities in care, though, have stoked consumer outrage and helped to fuel populist support for proposals that would upend the current system. Many people with insurance cannot afford a knee replacement or care for their diabetes because their insurance has high deductibles.
Proponents of overhauling the nation’s health care argue that hospitals are charging too much and could lower their prices without sacrificing the quality of their care. High drug prices, surprise hospital bills and other financial burdens from the overwhelming cost of health care have caught the attention (and drawn the ire) of many in Congress, with a variety of proposals under consideration this year.
But those in favor of the most far-reaching changes, including Senator Bernie Sanders, who unveiled his latest Medicare for all plan as part of his presidential campaign, have remained largely silent on the question of how the nation’s 5,300 hospitals would be paid for patient care. If they are paid more than Medicare rates, the final price tag for the program could balloon from the already stratospheric estimate of upward of $30 trillion over a decade. Senator Sanders has not said what he thinks his plan will cost, and some proponents of Medicare for all say these plans would cost less than the current system.
The nation’s major health insurers are sounding the alarms, and pointing to the potential impact on hospitals and doctors. David Wichmann, the chief executive of UnitedHealth Group, the giant insurer, told investors that these proposals would “destabilize the nation’s health system and limit the ability of clinicians to practice medicine at their best.”
Hospitals could lose as much as $151 billion in annual revenues, a 16 percent decline, under Medicare for all, according to Dr. Kevin Schulman, a professor of medicine at Stanford University and one of the authors of a recent article in JAMA looking at the possible effects on hospitals.
“There’s a hospital in every congressional district,” he said. Passing a Medicare for all proposal in which hospitals are paid Medicare rates “is going to be a really hard proposition.”
Richard Anderson, the chief executive of St. Luke’s University Health Network, called the proposals “naïve.” Hospitals depend on insurers’ higher payments to deliver top-quality care because government programs pay so little, he said.
“I have no time for all the politicians who use the health care system as a crash-test dummy for their election goals,” Mr. Anderson said.
The American Hospital Association, an industry trade group, is starting to lobby against the Medicare for all proposals. Unlike the doctors’ groups, hospitals are not divided. “There is total unanimity,” said Tom Nickels, an executive vice president for the association.
“We agree with their intent to expand coverage to more people,” he said. “We don’t think this is the way to do it. It would have a devastating effect on hospitals and on the system over all.”
Rural hospitals, which have been closing around the country as patient numbers dwindle, would be hit hard, he said, because they lack the financial cushion of larger systems.
Big hospital systems haggle constantly with Medicare over what they are paid, and often battle the government over charges of overbilling. On average, the government program pays hospitals about 87 cents for every dollar of their costs, compared with private insurers that pay $1.45.
Some hospitals make money on Medicare, but most rely on higher private payments to cover their overall costs.
Medicare, which accounts for about 40 percent of hospital costs compared with 33 percent for private insurers, is the biggest source of hospital reimbursements. The majority of hospitals are nonprofit or government-owned.
The profit margins on Medicare are “razor thin,” said Laura Kaiser, the chief executive of SSM Health, a Catholic health system. In some markets, her hospitals lose money providing care under the program.
She says the industry is working to bring costs down. “We’re all uber-responsible and very fixated on managing our costs and not being wasteful,” Ms. Kaiser said.
“If you’re in a consolidated market, you are a monopolist and are setting the price,” said Mark Miller, a former executive director for the group that advises Congress on Medicare payments. He describes the prices paid by private insurers as “completely unjustified and out of control.”
Many hospitals have invested heavily in amenities like single rooms for patients and sophisticated medical equipment to attract privately insured patients. They are also major employers.
“You would have to have a very different cost structure to survive,” said Melinda Buntin, the chairwoman for health policy at the Vanderbilt University School of Medicine. “Everyone being on Medicare would have a large impact on their bottom line.”
People who have Medicare, mainly those over 65 years old, can enjoy those private rooms or better care because the hospitals believed it was worth making the investments to attract private patients, said Craig Garthwaite, a health economist at the Kellogg School of Management at Northwestern University. If all hospitals were paid the same Medicare rate, the industry “should really collapse down to a similar set of hospitals,” he said.
Whether hospitals would be able to adapt to sharply lower payments is unclear.
“It would force health care systems to go on a very serious diet,” said Stuart Altman, a health policy professor at Brandeis University. “I have no idea what would happen. Nor does anyone else.”
But proponents should not expect to save as much money as they hope if they cut hospital payments. Some hospitals could replace their missing revenue by charging more for the same care or by ordering more billable tests and procedures, said Dr. Stephen Klasko, the chief executive of Jefferson Health. “You’d be amazed,’ he said.
While both the Medicare-for-all bill introduced by Representative Pramila Jayapal, Democrat of Washington, and the Sanders bill call for a government-run insurance program, the Jayapal proposal would replace existing Medicare payments with a whole new system of regional budgets.
“We need to change not just who pays the bill but how we pay the bill,” said Dr. Gaffney, who advised Ms. Jayapal on her proposal.
Hospitals would be able to achieve substantial savings by scaling back administrative costs, the byproduct of a system that deals with multiple insurance carriers, Dr. Gaffney said. Under the Jayapal bill, hospitals would no longer be paid above their costs, and the money for new equipment and other investments would come from a separate pool of money.
But the Sanders bill, which is supported by some Democratic presidential candidates including Senators Kirsten Gillibrand of New York, Cory Booker of New Jersey, Elizabeth Warren of Massachusetts and Kamala Harris of California, does not envision a whole new payment system but an expansion of the existing Medicare program. Payments would largely be based on what Medicare currently pays hospitals.
Some Democrats have also proposed more incremental plans. Some would expand Medicare to cover people over the age of 50, while others wouldn’t do away with private health insurers, including those that now offer Medicare plans.
Even under Medicare for all, lawmakers could decide to pay hospitals a new government rate that equals what they are being paid now from both private and public insurers, said Dr. David Blumenthal, a former Obama official and the president of the Commonwealth Fund.
“It would greatly reduce the opposition,” he said. “The general rule is the more you leave things alone, the easier it is.”

Oxygen survey confirms TAM, supports Inogen bull thesis, says Piper Jaffray

Piper Jaffray analyst JP McKim believes his oxygen survey debunks a lot of the bearish arguments around the Medicare Claims data and supports his long-term Inogen bull thesis. That said, the survey did not give him a ton of confidence in near-term BTB results. While the analyst does not get the sense Q1 is going to be the snap back quarter like he expects Q2 to be, he argues that with the stock at $79, a lot of that is already reflected in the share price. Finally, as investors have been solely relying on the Medicare claims data for market sizing, McKim believes this survey provides another data point to confirm the market is large, still growing, and shifting to POCs. He reiterates an Overweight rating and $185 price target on the shares.

Fewer tests, treatments for
 NICU babies reduces infections, cuts costs

About a decade ago, it wasn’t uncommon for the babies in the neonatal intensive-care unit at Intermountain Healthcare’s Dixie Regional Medical Center to receive as many as 78 tests or treatments during their stay.
Each intervention can cause the fragile baby pain and increase the likelihood of infection, ultimately lengthening hospital stays and overall costs. Research shows that preterm babies are three times more likely to get a healthcare-associated infection than full-term babies in part because invasive monitoring and procedures are tough on their weak immune systems. Babies in the NICU typically receive many blood draws and have central lines inserted.
Disturbed by this disruption, Dr. Erick Ridout, a neonatologist at Dixie’s NICU, and the unit’s nurse manager, Jeannette Cutner, changed practices.
They began in 2008 by tracking all the interventions done every 12 hours for each baby in the 40-bed unit and sharing it with clinical staff. The goal was to justify every test and procedure.
Ridout said there’s a culture in the NICU—and universally in medicine—to administer lab tests because “we check these every Monday and it’s Monday.”
It’s estimated that about $200 billion is spent every year on healthcare services in the U.S. that provide little value.
Ridout and Cutner spoke to staff about re-evaluating that mindset to focus on the babies and what their vitals show they need. “The baby doesn’t know it’s Monday,” Ridout said.
STRATEGIES
Track the number of tests, treatments and blood draws done on every baby in the NICU.
Gather the entire clinical team along with the parents every morning to determine future care.
Allow nurses, therapists and parents to speak first in the huddle to ensure their voices are heard.
Another thing that helped change the staff mindset was the implementation of morning huddles, Cutner said. The entire clinical team and parents meet every morning to go over the baby’s last 12 hours and determine future treatment. The number of interventions done up to that point are also highlighted, which Dixie calls “pokes.” Physicians speak last at the huddles, which was done intentionally, Cutner said.
“If they (the physicians) speak first, everyone becomes quiet even though they might have had a different approach,” she said. “This way everyone has a voice, including the parents.”
The unit has 52 staff members, including nurses, nurse practitioners, respiratory therapists, dietitians and neonatologists.
Before the morning huddles were started, neonatologists led decisionmaking and other clinical staff weren’t asked for their thoughts. Now, the physician only writes an order for another test or treatment if there is consensus among everyone at the meeting.
The nurses love the work environment because they feel heard, Cutner said. Turnover in the NICU is at 1%—the lowest across all of Intermountain.
The approach has also led to other new practices. For instance, blood from newborn babies is now taken from the umbilical cord instead of from the baby to reduce pokes.
The changes in practice over the last 10 years have led to drops in infection rates and cost savings for Dixie Regional. The average length of stay for preterm babies in the NICU has decreased by 21% from 72 days to 57 days. Additionally, the average number of blood draws during stays fell from about 75 to fewer than 40 and only one baby has experienced a central line-associated bloodstream infection in 11 years. Ridout said the system has saved at least $2.8 million from the changes.
Given the growing number of NICU admissions nationally, the practice could lead to big cost reductions across the industry. A 2015 study by Dartmouth researchers found that NICU admissions had grown by 23% in just five years, with most of those babies born preterm.
In an effort to further stem costs and improve quality, Dixie Regional is looking to use artificial intelligence to identify even more unnecessary treatment in the NICU because the team has “eliminated most of the low-hanging fruit,” Ridout said. A dashboard on the electronic health record tracks all treatments and tests for every patient. Predictive analytics from AI will be able to assess more potentially unnecessary treatments.
Intermountain plans to integrate this less-intrusive approach to NICU practices across the 23-hospital system. Right now three hospitals are taking “baby steps” to implement it, Ridout said.

CMS proposes $887 million boost to skilled nursing facilities

The CMS on Friday proposed increasing payments to skilled nursing facilities by $887 million, or 2.5%, in federal fiscal 2020, as the agency hopes to align their pay with value-based care.
The agency said in a notice that it will use a new case-mix model starting in October. The model will focus Medicare payments based on the patient’s condition and resulting care rather than the amount of care provided.
The SNF Value-Based Purchasing Program currently scores any SNF on measures such as hospital readmissions.
The program will reduce an SNF’s Medicare payments by 2 percentage points if an SNF doesn’t meet the requirements. The agency will redistribute 60% of the funds collected in the program as incentive payments.
The proposed rule also releases two new quality measures to assess how health information is shared at SNFs: transferring health information from the SNF to another provider and transferring health information to a patient.
Another key change is an update to the definition of group therapy under the SNF prospective payment system. Currently group therapy is defined by the CMS as being exactly four patients.
However, other payment systems such as the one for inpatient rehabilitation facilities allow groups of two to qualify for the therapy type.
“For more fair and consistent therapy definitions across care settings, we are proposing to adopt the definition of group therapy used in the IRF PPS,” the agency said in a release. “CMS believes aligning the group therapy definition serves to improve the agency’s consistency in payment policies across [post-acute care] settings, and to create opportunities for site neutral payments.”
The decision comes a few days after the CMS released a proposed boost in payments to IRFs by $195 million for federal fiscal 2020 compared to 2019.
The CMS also proposed to increase hospice payments by 2.7%, a $540 million increase in payments.
However, if a hospice fails to meet quality reporting requirements then they will get a 2 percentage point cut.
The agency also made changes to the Hospice Quality Reporting Program, which evaluates hospice facilities based on 10 measures.
The CMS will continue to collect data on the measure on hospice visits over the last seven days, but it proposes to not publicly report the measure at this time.
“This measure identifies if hospice patients received at least one hospice visit from a medical social worker, chaplain or spiritual counselor, licensed practical nurse, or aide during their final seven days of life, and is calculated using data from the Hospice Item Set,” an agency release said. “CMS has decided not to publicly report this measure at this time to allow for further testing to determine if changes to the measure specifications or how it is displayed on Hospice Compare are needed.”

Changing Medicare rules could support care innovation for dialysis

In a commentary published in the American Journal of Kidney Diseases, public health researchers suggest adjustments to recently proposed rule changes on how Medicare pays for dialysis services.
Medicare spends approximately $35 billion annually on care for beneficiaries with end-stage renal disease (), more than 7 percent of Medicare’s total paid claims. Over half a million people receive regular  to manage this condition, with treatment costs averaging about $85,000 a year, according to the study.
“A year ago, rule changes were proposed that would limit how many dialysis treatments per week Medicare would pay for,” says first author Adam S. Wilk, Ph.D. “Nephrologists, patients and other interest groups expressed concern that this would have the effect of limiting dialysis patients’ access to innovations in treatment, like ‘frequent hemodialysis,’ that have the potential to improve outcomes and quality of life in this population.” Wilk is assistant professor of health policy and management at the Emory Rollins School of Public Health.
Under the current system, Medicare covers three hemodialysis treatments weekly per patient, but it will often pay for additional treatments when the treating nephrologist provides sufficient medical justification. The recently proposed rule changes would limit such additional payments to exceptional circumstances (for example, patients with temporary, acute kidney treatment needs). Although nephrologists would not be prevented from providing any “extra” treatments they believe are needed, they would typically bear the costs of doing so.
In their article, Wilk and colleagues discussed the limitations of the current evidence on frequent dialysis treatment, which to date has yielded mixed conclusions. The researchers’ suggested changes to Medicare’s dialysis payment system were designed to account for these limitations and give Medicare the flexibility to further modify the system in the future as new evidence comes to light. Under the most provocative of their proposals, Medicare would establish a new, separate prospective payment system for frequent hemodialysis .
“If Medicare were to adopt the policy options we describe, nephrologists would have greater clarity about how they would be paid for their dialysis care, giving them greater freedom to identify better ways to treat their dialysis patients. Given the poor prognoses most  undergoing  have, such innovations are greatly needed to improve this population’s longevity and quality of life,” says Wilk.

Explore further

More information: Adam S. Wilk et al, Paying for Frequent Dialysis, American Journal of Kidney Diseases (2019). DOI: 10.1053/j.ajkd.2019.01.027

Time to give up on biosims?

The U.S. biosims market has been notoriously slow to generate meaningful savings or price reductions, and now some experts say it’s time to scrap the idea altogether. Instead of using biosims and competition to lower prices for high-cost biologics, the experts suggest creating an independent body to set prices after the meds lose exclusivity.
In fact, the U.S. could save $50 billion a year by using cost-plus or other formulas to set prices for biologics after their exclusivity wraps up, the authors figure—up to 10 times the amount biosims are estimated to shave off annual spending.
In their two-part Health Affairs article, authors Preston Atteberry, Peter Bach, Jennifer Ohn and Mark Trusheim argue that biologic drugs enjoy a “natural monopoly,” while small molecule drugs are only protected by regulations that give them exclusive access to a market.
In other words, biosims are costly to develop and tough to manufacture, and even when they hit the market, there’s no guarantee of a payoff. Biosim makers have to shell out for marketing, too, and negotiate with payers as well. On the other hand, traditional generics typically don’t require clinical trials, production is less complicated and they’re automatically substituted for branded drugs at the pharmacy counter.
Getting into the biosims business requires clearing some high hurdles and ponying up large sums of money. Not so much with small-molecule copycats; their biggest obstacles are patent rights.
As a result—and as has been well-documented—biosims haven’t had much effect on drug prices or savings in the U.S. Generic drugs, on the other hand, quickly lower prices, thanks to plenty of competition as soon as a brand loses its lock on the market.
To fix that disconnect, the authors wrote that “price regulation rather than competition may be far more effective” to drive savings in biologic drug classes. Bach serves as director of Memorial Sloan Kettering’s Center for Health Policy and Outcomes, where Ohn is a research data analyst and Atteberry is a research fellow. Trusheim is the strategic director at MIT’s NEWDIGS program.
In an email to FiercePharma, Bach said he and his fellow authors suggest an “independent body, not the government” set prices for biologics after they lose exclusivity. Prices should be “built up from cost-reporting from the biologic manufacturers and set at a level where the built-in costs … are included as is an attractive profit,” Bach added.
In the Health Affairs piece, the authors wrote that prices after the loss of exclusivity “could be determined through any of multiple formulas, from a reported cost plus a markup, a defined profit margin on revenues, return on capital, or a blend of these.”
That way, U.S. health systems would save much more money than they would by relying on biosims, the authors argue. Their approach would generate an estimated $250 billion to $300 billion in savings over five years, after one-time costs of $10 billion to $20 billion, the article argues.
Biosims, on the other hand, are projected to save $54 billion between 2017 and 2026, the authors wrote. Prices in drug classes that face biosim competition are only expected to fall 20% to 30%, while small molecule prices often tumble 70% to 90% after generics hit.
Of course, the article is just a starting point for the proposal and such a change would face fierce backlash from the pharma industry, if Congress were to take up the issue at all. But the discussion alone outlines how far short biosims have fallen compared with early expectations. Amid the conversation this week, one influential industry voice was quick to support biosims.
“It’s far too early to throw in the towel on biosimilars,” former FDA commissioner Scott Gottlieb tweeted. While “impediments to uptake remain,” he said those barriers will eventually “erode.”
For his part, Bach told FiercePharma he doesn’t “want to gauge the likelihood of this happening, but to be clear the opportunity costs of not taking this approach and instead waiting for biosimilars to work out is extremely large.” Aside from a projected $50 billion per year in savings are the “human costs of running needless trials to compare biosimilars to biologics.”