Using drugs or diet to reduce levels of asparagine may benefit patients, say researchers
Using drugs or diet to reduce levels of asparagine may benefit patients, say researchers
New studies from the National Institutes of Health — specifically the National Toxicology Program — find that cell phone radiation is potentially linked with certain forms of cancer, but they’re far from conclusive. The results are complex and the studies have yet to be peer-reviewed, but some of the findings are clearly important enough to warrant public discussion.
An early, partial version of this study teasing these effects appeared in 2016 (in fact, I wrote about it), but these are the full (draft) reports complete with data.
Both papers note that “studies published to date have not demonstrated consistently increased incidences of tumors at any site associate with exposure to cell phone RFR [radio frequency radiation] in rats or mice.” But the researchers felt that “based on the designs of the existing studies, it is difficult to definitively conclude that these negative results clearly indicate that cell phone RFR is not carcinogenic.”
In other words, no one has taken it far enough, or simulated the radio-immersion environment in which we now live, enough to draw conclusions on the cancer front. So this study takes things up a notch, with longer and stronger exposures.
The studies exposed mice and rats to both 900 MHz and 1900 Mhz wavelength radio waves (each frequency being its own experiment) for about 9 hours per day, at various strengths ranging from 1 to 10 watts per kilogram. For comparison, the general limit the FCC imposes for exposure is 0.08 W/kg; the absolute maximum allowed, for the extremities of people with occupational exposures, is 20 W/kg for no longer than 6 minutes. So they were really blasting these mice.
“The levels and duration of exposure to RFR were much greater than what people experience with even the highest level of cell phone use, and exposed the rodents’ whole bodies. So, these findings should not be directly extrapolated to human cell phone usage,” explained NTP senior scientist John Bucher in a news release accompanying the papers. “We note, however, that the tumors we saw in these studies are similar to tumors previously reported in some studies of frequent cell phone users.”
The rodents were examined for various health effects after various durations, from 28 days to 2 years.
Before I state the conclusions, a note on terminology. “Equivocal evidence” is just above “no evidence” on the official scale, meaning “showing a marginal increase of neoplasms that may be test agent related.” In other words, something statistically significant but ultimately still somewhat mysterious. “Some evidence” is above that, meaning a more measurable response, followed by the also self-explanatory “clear evidence.”
At 900 MHz:
Some evidence linking RFR with malignant schwannoma in the hearts of male rats, no evidence for same in female rats. Equivocal evidence linking exposure to malignant brain glioma in females. Other tumors of various types in both sexes “may have been related to cell phone RFR exposure,” meaning the link is unclear or numbers aren’t conclusive. Less serious “nonneoplastic lesions” were more frequent in exposed males and females.
At 1900 MHz:
Equivocal evidence of carcinogenicity in lung, liver and other organ tissues in both male and female mice.
Although I would hesitate to draw any major conclusions from these studies, it seems demonstrated that there is some link here, though the level of radiation was orders of magnitude beyond what a person would ever experience in day to day life. As the researchers point out, however, relatively short-term studies like this one do little to illuminate the potential for harm in long-term exposure, such as babies who have never not been bathed in RF radiation.
An interesting side note is that the radiation-exposed rodents of both types lived significantly longer than their control peers: 28 percent of the original control group survived the full 2 years, while about twice that amount (48-68 percent) survived in the exposed group.
Two explanations are proffered for this strange result: either the radiation somehow suppressed the “chronic progressive nephropathy” that these mice tend to suffer from as they age, or possibly reduced feed intake related to the radiation might have done it. Either way, no one is suggesting that the radiation is somehow salutary to the rodents’ constitutions.
The reports and data run to hundreds of pages, so this is only a quick look by a non-expert. You can look over the full reports and supplemental materials here, but as this is a major study you can also expect replication, analysis and criticism from all quarters soon, including a scheduled external expert review organized by the NTP in March.
An emotional moment between former Vice President Joe Biden and Meghan McCain occurred on The View on Wednesday.
Meghan’s father Senator John McCain was diagnosed with glioblastoma six months ago, an aggressive brain cancer that sadly carries a low survival rate. Despite undergoing an operation, McCain has continued to serve on the United States Senate, famously thwarting his own party’s attempt at repealing Obamacare this summer.
Biden’s son Beau passed away in 2015 from the same cancer. So, when he made an appearance on the talk show, Meghan started off by telling Biden that she was unable to finish his book, Promise Me, Dad, and that she thought about Beau every day. As Meghan became emotional, Biden immediately stepped in, switching seat to get closer and to console her.
“Look, one of the things that gave Beau courage—my word—was John. Your dad, you may remember when you were a little kid, your dad, took care of my Beau. Your dad… became friends with Beau. And Beau talked about your dad’s courage—not about illness—but about his courage,” Biden told Megan.
Biden then spoke about some of the scientific breakthroughs that have occurred recently, in an attempt at telling Meghan that there is some hope for her father’s condition.
At the exact right moment, Biden swooped in with some much needed comedy, joking about how he and McCain had very different political views, but the two could still depend on each other to be there for one another.
“The thing that I found—and Beau insisted on, your dad is going to insist on—is you’ve got to maintain hope. There’s hope. You have to have hope,” Biden said, encouraging Meghan.
“I swear, guys, we are gonna beat this damn disease,” Biden concluded as the audience applauded.
Leslie Levines searing pains started the day after Thanksgiving in 2006. They began in her toes, which turned strangely dark. Then the agony crept upward. It felt like my legs were being dipped in boiling oil 24/7, she said.
The emergency room and a series of doctors could do little but scratch their heads and offer her painkillers.
I was living on oxycodone and very grateful for it, Levine said, then Harvard Universitys chief patent attorney. But it wasnt enough. By January, I was on disability, because I was in such pain and could hardly walk.
Her internet search for answers led her to Dr. Anne Louise Oaklander, a neurologist at Massachusetts General Hospital, who was then developing a hypothesis about inexplicable pain disorders like Levines: What if they were caused by an overactive immune system?
Oaklander treated Levine as if that were the case and the painthankfullydisappeared within five days. I didnt know how I was going to live with that level of pain, Levine said, adding that it returns every time she stops treatment.
Now, Oaklander has published a series of 55 case reports including Levines, suggesting that a number of people who suffer pain or other neurologic symptomswhich may have been diagnosed as fibromyalgia, chronic fatigue syndrome, mental illness, or a host of other problems.
Oaklander thinks that some percentage of people who have small fiber neuropathywhich can be caused by diabetes, chemotherapy, or other toxinsactually have a previously undiagnosed autoimmune problem.
Although its too soon to say how many people might be affected by this autoimmune-related small-fiber polyneuropathy, nearly 50 million Americans complain of regular or chronic pain. If even a fraction of them could be effectively treated with autoimmune therapies rather than high-dose painkillers, they may get better relief without risking an opioid addiction, said Oaklander, who is also an associate professor of neurology, at Harvard Medical School.
This is not just some rare, esoteric disease that Harvard eggheads are investigating, she said. It is common. Peopleincluding kids and teensare sick, but they dont know what they have and their doctors dont know, either.
Small-fiber polyneuropathy, in which nerves misfire, is common among people with diabetes or who have been treated with chemotherapy. But in roughly half the patients who suffer the same pain, numbness, or itching, there isnt any obvious cause.
The same tiny nerves also line the gut, Oaklander said, so people with this condition can have gastrointestinal symptoms, such as nausea or vomiting when they try to eatwhich often gets misdiagnosed as an eating disorder. Even fainting when standing up or difficulty getting out of bed can be caused by damage to these small nerve cells, she said.
In Oaklanders study, 55 mostly female patients all had objective measures of damage to small-fiber peripheral nerve cells and no diabetes or other known cause of neuropathy.
All were treated with intravenous immunoglobulin or IVIg, a therapy effectively used against other autoimmune-related nerve conditions. The case review showed that 77 percent of the patients responded to IVIg, with their pain dropping on average from 6.3 to 5.2 on a 10-point scale. Their internal organ function also improved.
Its still too soon to declare that Oaklanders discovered a new condition, and certainly no one recommends starting autoimmune treatment for anyone with unexplained pains.
But Marinos Dalakas, director of the Neuromuscular Division at Thomas Jefferson University in Philadelphia, says her results are convincing enough to encourage him to test some of his pain patients for markers of autoimmune disease. If he found such signs, Dalakas said he would try them for three months on a treatment like IVIg to see if their symptoms improve.
To definitively prove that IVIg is effective for appropriately selected patients, someone would have to conduct two, large, expensive clinical trials, likely to take 5-10 years. Oaklander has already applied to the National Institutes of Health for a research grant to prepare for one such trial.
Still, to have advanced the science this far was courageous, one colleague said.
It takes great courage to persist, to believe in your data, and to press on in the face of skeptics, Stephen Hauser, chairman of the neurology department at the University of California, San Francisco School of Medicine, told The Daily Beast. I think the world is beginning to catch up to Anne Louise.
Before changing his own medical practice, Hauser said he would want to see the results of a large, blinded trial, and confirmation that IVIg or another autoimmune treatment offers pain patients a significant improvement in their quality of life.
I do think these patients represent a huge problem for the medical community for which better treatments are sorely needed, Hauser added.
IVIg, which has side effects like nausea, headaches, and flu-like symptoms, must be delivered via infusion. And its priceycosting $10,000 per monthly dosebecause each dose contains purified proteins from 5,000-8,000 blood donors who have been screened for infectious diseases, Hauser said.
The therapy works, Oaklander said, because it bamboozles the immune system, overwhelming it with harmless proteins to distract it from attacking the nerves.
If an autoimmune condition lingers untreated, continued attacks can leave permanent nerve damage, Oaklander said. Its really important that doctors recognize when neuropathy is autoimmune and dampen down the attack as soon as possible. But that hadnt previously been recommended.
She periodically dials back her patients IVIg to see if their nerves have healed enough to stop treatment. About 16 percent of the patients in the case review were able to wean off their IVIg without their symptoms returning. If you can protect the nerves for a period and let them regrow, the autoimmune attack may die down, she said.
Oaklander said she hopes her new paper, published in the journal Therapeutic Advances in Neurological Disorders, will give patients some ammunition when they ask their insurance company to pay for autoimmune therapy.
Levines insurance company refused to pay for IVIg treatments for four years, insisting she take much cheaper steroids, instead. But the steroids didnt help nearly as much and their side effects would land her in the hospital every few months, Levine said. Finally, realizing that IVIg would be cheaper, her insurer let her back on the treatments two years agoand shes been side-effect free since.
I just had my monthly treatment this morning, Levine, who now runs a support group for people with neuropathy, said. Its changed my life.
In 1891, a New York doctor named William B. Coley injected a mixture of beef broth and Streptococcus bacteria into the arm of a 40-year-old Italian man with an inoperable neck tumor. The patient got terribly sick—developing a fever, chills, and vomiting. But a month later, his cancer had shrunk drastically. Coley would go on to repeat the procedure in more than a thousand patients, with wildly varying degrees of success, before the US Food and Drug Administration shut him down.
Coley’s experiments were the first forays into a field of cancer research known today as immunotherapy. Since his first experiments, the oncology world has mostly moved on to radiation and chemo treatments. But for more than a century, immunotherapy—which encompasses a range of treatments designed to supercharge or reprogram a patient’s immune system to kill cancer cells—has persisted, mostly around the margins of medicine. In the last few years, though, an explosion of tantalizing clinical results have reinvigorated the field and plunged investors and pharma execs into a spending spree.
Though he didn’t have the molecular tools to understand why it worked, Coley’s forced infections put the body’s immune system into overdrive, allowing it to take out cancer cells along the way. While the FDA doesn’t have a formal definition for more modern immunotherapies, in the last few years it has approved at least eight drugs that fit the bill, unleashing a flood of money to finance new clinical trials. (Patients had better come with floods of money too—prices can now routinely top six figures.)
But while the drugs are dramatically improving the odds of survival for some patients, much of the basic science is still poorly understood. And a growing number of researchers worry that the sprint to the clinic offers cancer patients more hype than hope.
When immunotherapy works, it really works. But not for every kind of cancer, and not for every patient—not even, it turns out, for the majority of them. “The reality is immunotherapy is incredibly valuable for the people who can actually benefit from it, but there are far more people out there who don’t benefit at all,” says Vinay Prasad, an Oregon Health and Science University oncologist.
Prasad has come to be regarded as a professional cancer care critic, thanks to his bellicose Twitter style and John Arnold Foundation-backed crusade against medical practices he says are based on belief, not scientific evidence. Using national cancer statistics and FDA approval records, Prasad recently estimated the portion of all patients dying from all types of cancer in America this year who might actually benefit from immunotherapy. The results were disappointing: not even 10 percent.
Now, that’s probably a bit of an understatement. Prasad was only looking at the most widely used class of immunotherapy drugs in a field that is rapidly expanding. Called checkpoint inhibitors, they work by disrupting the immune system’s natural mechanism for reining in T cells, blood-borne sentinels that bind and kill diseased cells throughout the body. The immune cells are turned off most of the time, thanks to proteins that latch on to a handful of receptors on their surface. But scientists designed antibodies to bind to those same receptors, knocking out the regulatory protein and keeping the cells permanently switched to attack mode.
The first checkpoint inhibitors just turned T cells on. But some of the newer ones can work more selectively, using the same principle to jam a signal that tumors use to evade T cells. So far, checkpoint inhibitors have shown near-miraculous results for a few rare, previously incurable cancers like Hodgkin’s lymphoma, renal cell carcinoma, and non-small cell lung cancer. The drugs are only approved to treat those conditions, leaving about two-thirds of terminal cancer patients without an approved immunotherapy option.
But Prasad says that isn’t stopping physicians from prescribing the drugs anyway.
“Hype has encouraged rampant off-label use of checkpoint inhibitors as a last-ditch effort,” he says—even for patients with tumors that show no evidence they’ll respond to the drugs. The antibodies are available off the shelf, but at a list price near $150,000 per year, it’s an investment Prasad says doctors shouldn’t encourage lightly. Especially when there’s no reliable way of predicting who will respond and who won’t. “This thwarts one of the goals of cancer care," says Prasad. "When you run out of helpful responses, how do you help a patient navigate what it means to die well?”
Merck and Bristol-Myers Squibb have dominated this first wave of immunotherapy, selling almost $9 billion worth of checkpoint inhibitors since they went on sale in 2015. Roche, AstraZeneca, Novartis, Eli Lilly, Abbvie, and Regeneron have all since jumped in the game, spending billions on acquiring biotech startups and beefing up in-house pipelines. And 800 clinical trials involving a checkpoint inhibitor are currently underway in the US, compared with about 200 in 2015. “This is not sustainable,” Genentech VP of cancer immunology Ira Mellman told the audience at last year’s annual meeting of the Society for Immunotherapy of Cancer. With so many trials, he said, the industry was throwing every checkpoint inhibitor combination at the wall just to see what would stick.
After more than a decade stretching out the promise of checkpoint inhibitors, patients—and businesses—were ready for something new. And this year, they got it: CAR T cell therapy. The immunotherapy involves extracting a patient’s T cells and genetically rewiring them so they can more efficiently home in on tumors in the body—training a foot soldier as an assassin that can slip behind enemy lines.
In September, the FDA cleared the first CAR-T therapy—a treatment for children with advanced leukemia, developed by Novartis—which made history as the first-ever gene therapy approved for market. A month later the agency approved another live cell treatment, developed by Kite Pharma, for a form of adult lymphoma. In trials for the lymphoma drug, 50 percent of patients saw their cancer disappear completely, and stay gone.
Kite’s ascendance in particular is a stunning indicator of how much money CAR-T therapy has attracted, and how fast. The company staged a $128 million IPO in 2014—when it had only a single late-phase clinical trial to its name—and sold to Gilead Science in August for $11.9 billion. For some context, consider that when Pfizer bought cancer drugmaker Medivation for $14 billion last year—one of the biggest pharma deals of 2016—the company already had an FDA-approved blockbuster tumor-fighter on the market with $2 billion in annual sales, plus two late-stage candidates in the pipeline.
While Kite and Novartis were the only companies to actually launch products in 2017, more than 40 other pharma firms and startups are currently building pipelines. Chief rival Juno Therapeutics went public with a massive $265 million initial offering—the largest biotech IPO of 2014—before forming a $1 billion partnership with Celgene in 2015. In the last few years, at least half a dozen other companies have made similar up-front deals worth hundreds of millions.
These treatments will make up just a tiny slice of the $107 billion cancer drug market. Only about 600 people a year, for example, could benefit from Novartis’ flagship CAR-T therapy. But the company set the price for a full course of treatment at a whopping $475,000. So despite the small clientele, the potential payoff is huge—and the technology is attracting a lot of investor interest. “CAR-T venture financing is still a small piece of total venture funding in oncology, but given that these therapies are curative for a majority of patients that have received them in clinical trials, the investment would appear to be justified,” says Mandy Jackson, a managing editor for research firm Informa Pharma Intelligence.
CAR-T, with its combination of gene and cell therapies, may be the most radical anticancer treatment ever to arrive in clinics. But the bleeding edge of biology can be a dangerous place for patients.
Sometimes, the modified T cells go overboard, excreting huge quantities of molecules called cytokines that lead to severe fevers, low blood pressure, and difficulty breathing. In some patients it gets even worse. Sometimes the blood-brain barrier inexplicably breaks down—and the T cells and their cytokines get inside patients’ skulls. Last year, Juno pulled the plug on its lead clinical trial after five leukemia patients died from massive brain swelling. Other patients have died in CAR-T trials at the National Cancer Institute and the University of Pennsylvania.
Scientists don’t fully understand why some CAR-T patients experience cytokine storms and neurotoxicity and others come out cured. “It’s kind of like the equivalent of getting on a Wright Brother’s airplane as opposed to walking on a 747 today,” says Wendell Lim, a biophysical chemist and director of the UC San Francisco Center for Systems and Synthetic Biology. To go from bumping along at a few hundred feet to cruise control at Mach 0.85 will mean equipping T cells with cancer-sensing receptors that are more specific than the current offerings.
Take the two FDA-approved CAR-T cell therapies, he says. They both treat blood cancers in which immune responders called B cells become malignant and spread throughout the body. Doctors reprogram patients’ T cells to seek out a B cell receptor called CD-19. When they find it, they latch on and shoot it full of toxins. Thing is, the reprogrammed T cells can’t really tell the difference between cancerous B cells and normal ones. The therapy just takes them all out. Now, you can live without B cells if you receive antibody injections to compensate—so the treatment works out fine most of the time.
But solid tumors are trickier—they’re made up of a mix of cells with different genetic profiles. Scientists have to figure out which tumor cells matter to the growth of the cancer and which ones don’t. Then they have to design T cells with antigens that can target just those ones and nothing else. An ideal signature would involve two to three antigens that your assassin T cells can use to pinpoint the target with a bullet instead of a grenade.
Last year Lim launched a startup called Cell Design Labs to try to do just that, as well as creating a molecular on-off-switch to make treatments more controlled. Only if researchers can gain this type of precise command, says Lim, will CAR-T treatments become as safe and predictable as commercial airline flight.
The field has matured considerably since Coley first shot his dying patient full of a dangerous bacteria, crossed his fingers, and hoped for the best. Sure, the guy lived, even making a miraculous full recovery. But many after him didn’t. And that “fingers crossed” approach still lingers over immunotherapy today.
All these years later, the immune system remains a fickle ally in the war on cancer. Keeping the good guys from going double-agent is going to take a lot more science. But at least the revolution will be well-financed.
CRISPR is a new biomedical technique that enables powerful gene editing. WIRED challenged biologist Neville Sanjana to explain CRISPR to 5 different people; a child, a teen, a college student, a grad student, and a CRISPR expert.
For years, pharmacy benefits were largely carved out from the rest of a medical coverage plan. But increasingly the two services are being combined, a move that in theory will make it easier to verify whether expensive drugs are worth the cost. A merger of the third-biggest health insurer with the largest U.S. drugstore chain, which also operates a pharmacy-benefit management company, could speed the process.
“You are hearing the warning for the end of the road for the classic standalone” pharmacy-benefit business, said Pratap Khedkar, managing principal at consulting firm ZS Associates.
Drugmakers are producing more pricey treatments for cancer and rare diseases. Combining drug and medical benefits in the same place is “the only way” payers will figure out whether such expensive new drugs are actually making people better and saving money by keeping them out of the hospital, he said.
A merger of CVS and Aetna would create a health-care behemoth and put huge pressure on standalone players such as Express Scripts Holding Co. and Walgreens Boots Alliance Inc. Express Scripts would become the last major standalone pharmacy-benefit manager not allied with a major insurer.
CVS and Aetna have held discussions about a potential deal, according to people familiar with the matter who asked not to be identified as the details aren’t public. A newly combined company would “own the entire chain, from prescribing and filling prescriptions to the health plans that pay for them,” said Michael Rea, of Rx Savings Solutions, which has an app that helps patients find lower cost drugs.
Under a combined roof, the insurance arm of CVS-Aetna could help keep costs down by routing patients needing basic urgent care to CVS-owned walk-in clinics and keeping them out of expensive hospital emergency rooms, analyst Ann Hynes of Mizuho Securities said in a note to clients. The company would also become a formidable competitor to UnitedHealth Group Inc., the biggest health insurer and owner of its own PBM unit, OptumRx.
But even with the new clout, a merger isn’t likely to be derailed by federal antitrust authorities, said John Briggs, an antitrust attorney at Axinn Veltrop & Harkrider in Washington.
CVS and Aetna declined to comment.
Walgreens, the No. 2 drugstore operator, could also feel the pressure. A CVS-Aetna marriage could cause the drugstore chain to look for its own acquisition targets, with Express Scripts being the most likely, Charles Rhyee, an analyst at Cowen & Co., wrote in a note to clients Friday.
And then there’s Amazon.com Inc., which recently gained drug-wholesaler licenses in 14 states. The looming threat of the e-commerce behemoth entering the mail-order pharmacy business and pushing down profit margins for drug distributors, benefit managers and retail pharmacies intensifies the pressure on standalone players.
For CVS, the move is “a natural defense against the potential threat of Amazon entering the retail pharmacy market,” Rhyee said.
Another possibility is that Amazon could buy Express Scripts. That would give the internet retailer an instant and large foothold in both the PBM industry and the mail-order pharmacy business.
Health insurer Anthem Inc., Express Scripts’ biggest current client, announced earlier this month that it would leave Express Scripts when its contract ends at the end of 2019 to form its own PBM unit. And Prime Therapeutics, another major player, manages drug benefits for nonprofit Blue Cross and Blue Shield plans in numerous states.
“Our model is strong and thriving,” said Jennifer Luddy, a spokeswoman for Express Scripts. “We believe in the value that we provide to our customers as an independent PBM.”
On an earnings call this week, Express Scripts Chief Executive Officer Tim Wentworth said he was open to a deal with Amazon to help serve cash-paying patients.
Walgreens declined to comment.
In terms of the CVS-Aetna deal, antitrust authorities will look closely at the competition between the companies in selling Medicare Part D plans for the elderly, said Briggs, the attorney.
There could be fight between the Justice Department and the Federal Trade Commission, which share antitrust enforcement, over which agency will investigate the merger, according to Briggs. The Justice Department handles insurer mergers and successfully stopped the combination of Aetna and Humana Inc. this year. The FTC investigates retail pharmacy deals. In September, it cleared Walgreens’ acquisition of 1,900 Rite Aid Corp. stores after Walgreens shrank the size of the deal.
Still, a CVS-Aetna deal would likely win approval because a number of other major players will remain in the Part D market, he said.
“That’s an easy fix,” Briggs said. “The whole deal is not going to crater on account of Part D.”
There are more than 50m prescriptions for proton pump inhibitors in the UK, though they have previously been linked to side-effects and increased risk of death
A drug commonly used to treat acid reflux is linked to a more than doubled risk of developing stomach cancer, researchers have claimed.
Proton pump inhibitors (PPIs) reduce the amount of acid made by the stomach and are used to treat acid reflux and stomach ulcers.
A study published in the journal Gut identified an association between long-term use of the drug and a 2.4 times higher risk of developing stomach cancer. In the UK, there are more than 50m prescriptions for PPIs every year but they have been linked to side-effects and an increased risk of death.
A link between PPIs and a higher stomach cancer risk has previously been identified by academics but never in a study that first eliminates a bacteria suspected of fuelling the illnesss development.
Research by the University of Hong Kong and University College London found that after the Helicobacter pylori was removed, the risk of developing the disease still rose in line with the dose and duration of PPI treatment.
They compared the use of PPI against another drug which limits acid production known as H2 blockers in 63,397 adults. The participants selected had been treated with triple therapy, which combines PPI and antibiotics to kill off the H pylori bacteria over a week, between 2003 and 2012.
Scientists then monitored them until they either developed stomach cancer, died or reached the end of the study at the end of 2015.
During this period, 3,271 people took PPIs for an average of almost three years, while 21,729 participants took H2 blockers. A total of 153 people developed stomach cancer, none of whom tested positive for H plyori but all had long-standing problems with stomach inflammation, the study found.
While H2 blockers were found to have no link to a higher risk of stomach cancer, PPIs was found connected to an increased risk of more than double.
Daily use of PPIs was associated with a risk of developing the illness that was more than four times higher (4.55) than those who used it weekly. Similarly, when the drug was used for more than a year, the risk of developing stomach cancer rose five-fold, and as high as eight-fold after three or more years, the findings showed.
The study concluded no firm cause and effect could be drawn, but doctors should exercise caution when prescribing long-term PPIs even after successful eradication of H plyori.
Responding to the study, Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene and Tropical Medicine, said: Many observational studies have found adverse effects associated with PPIs.
The most plausible explanation for the totality of evidence on this is that those who are given PPIs, and especially those who continue on them long-term, tend to be sicker in a variety of ways than those for whom they are not prescribed.
More than a decade after opioid painkillers first exploded across the U.S., John Kapoor found an aggressive way to sell even more, according to prosecutors: He began bribing doctors to prescribe them.
Speakers’ fees, dinners, entertainment, cash — federal charges unsealed Thursday claim Kapoor’s striving company, Insys Therapeutics Inc., employed all of that and more to spur prescriptions of a highly addictive fentanyl-based drug intended only for cancer patients.
As President Donald Trump declared at a White House event that opioid abuse represents a public-health emergency, authorities arrested Kapoor in Arizona and painted a stark portrait of how Insys allegedly worked hand in glove with doctors to expand the market for the powerful agents.
“Selling a highly addictive opioid-cancer pain drug to patients who did not have cancer makes them no better than street-level drug dealers,” Harold Shaw, the top FBI agent in Boston, said of Kapoor and other Insys executives charged earlier in the case.
The story of the 74-year-old billionaire and the company he founded traces the arc of a crisis that claims 175 lives each day. What began with the over-prescription of painkillers in the late 1990s soon became a race by manufacturers to dispense more and more pills.
Charged with racketeering conspiracy and other felonies, Kapoor became the highest-ranking pharma executive to be accused of an opioid-related crime, and his arrest may portend charges against companies far larger than Insys, which has a modest $417 million market capitalization.
In Connecticut, prosecutors have begun a criminal probe of Purdue Pharmaceutical Inc.’s marketing of OxyContin. Scores of states, cities and counties have sued companies including Purdue, Endo International Plc, and Johnson & Johnson’s Janssen Pharmaceuticals, alleging they triggered the opioid epidemic by minimizing the addiction and overdose risks of painkillers such as Percocet.
But so far, no recent case has been so sweeping as the one against the executives including Kapoor, who made his initial court appearance late Thursday in Phoenix. A U.S. magistrate judge set bail at $1 million and ordered Kapoor to surrender his passport and submit to electronic monitoring. His lawyer, Brian Kelly, said Kapoor posted bail after the hearing.
This week, a Rhode Island doctor admitted accepting kickbacks from Insys in exchange for writing prescriptions. Earlier this year, two doctors were sentenced to more than 20 years behind bars for accepting bribes from companies including Insys to sell fentanyl-based medications.
The Kapoor indictment pinpoints the start of the alleged scheme.
It was early 2012, and Insys’s new oral spray of the opioid fentanyl wasn’t selling well. Because it was so addictive, the pain-relief drug was subject to a tightly controlled distribution system, and regulators demanded to be notified about suspicious orders by manufacturers, wholesalers and pharmacies. And the drug wasn’t cheap, so insurers set up barriers for patients seeking it.
That was when Kapoor and others at Insys went to extremes to dramatically boost sales of the painkiller, prosecutors said. Doling out speaker fees, marketing payments and food and entertainment perks, they allegedly began bribing doctors to prescribe the drug, and then tricked insurers into paying for it.
One Insys sales executive told subordinates that it didn’t matter whether doctors were entertaining, according to the indictment: “They do not need to be good speakers, they need to write a lot of” Subsys prescriptions, the official said, referring to the brand name of the painkiller.
Over a two-year period starting in 2013, Chandler, Arizona-based Insys set aside more than $12.2 million for doctors’ speaking fees, prosecutors said. One doctor received as much as $229,640 in speaker fees for appearing at what amounted to “sham events that were mere social gatherings also attended by friends and office staff,” according to the indictment.
The company encouraged doctors to write more prescriptions by hiring their friends and family members to serve as “business liaisons’’ and “business-relation managers,’’ prosecutors said. These support-staff employees worked in the doctors’ offices but were paid by Insys in what the indictment called bribes and kickbacks.
Insys even made a video featuring a sales rep dressed as a giant fentanyl spray bottle, rapping and dancing to a song that pushed the idea of getting doctors to prescribe higher doses, prosecutors said.
Others previously charged include Michael Babich, Insys’s former CEO, Alec Burlakoff, the ex-vice president of sales, and Richard Simon, once the company’s national sales director. They all deny wrongdoing.
Joe McGrath, an Insys spokesman, declined to comment on Kapoor’s indictment in Boston federal court. The company, which wasn’t charged, has reportedly been in settlement talks with the U.S. Justice Department to resolve a probe into its Subsys marketing. The company’s shares fell more than 22 percent to $5.74 in Nasdaq trading.
The first person in his family to attend college, Kapoor rose from modest means in India to become a wealthy health-care entrepreneur, after earning a doctorate in medicinal chemistry at the University of Buffalo in 1972, according to a work-history the school posted.
He was a plant manager at Invenex Laboratories in New York and later became chief executive officer of LyphoMed, a hospital-products company. He sold LyphoMed to Fujisawa Pharmaceuticals and formed a venture capital firm that invested in health-care companies.
In 2010, he merged privately held Insys with NeoPharm Inc. to get access to technology to develop pain drugs for cancer patients. Even though he has stepped down as Insys’s chairman and chief executive officer, he still holds more than 60 percent of its stock.
Kapoor and Babich are also accused of misleading insurers about patients’ diagnoses and the types of pain they suffered that were covered by the Subsys prescriptions tied to the payment scheme, prosecutors said.
The company’s agents allegedly told insurers that patients were receiving Subsys for “breakthrough pain’’ to secure coverage. They also misled insurers about what other pain drugs patients had tried before being proscribed Subsys, according to the indictment.
Some lower-level Insys employees have pleaded guilty and are cooperating with prosecutors, according to court papers. Elizabeth Gurrieri, a former manager who oversaw insurance reimbursements, pleaded guilty to one count of conspiring to commit wire fraud in June.
When the Trump administration elected to stop requiring many employers to offer birth-control coverage in their health plans, it devoted nine of its new rule’s 163 pages to questioning the links between contraception and preventing unplanned pregnancies.
In the rule released Friday, officials attacked a 2011 report that recommended mandatory birth-control coverage to help women avoid unintended pregnancies. That report, requested by the Department of Health and Human Services, was done by the National Academies of Sciences, Engineering and Medicine — then the Institute of Medicine — an expert group that serves as the nation’s scientific adviser.
“The rates of, and reasons for, unintended pregnancy are notoriously difficult to measure,” according to the Trump administration’s interim final rule. “In particular, association and causality can be hard to disentangle.”
Claims in the report that link increased contraceptive use by unmarried women and teens to decreases in unintended pregnancies “rely on association rather than causation,” according to the rule. The rule references another study that found increased access to contraception decreased teen pregnancies short-term but led to an increase in the long run.
“We know that safe contraception — and contraception is incredibly safe — leads to a reduction in pregnancies,” said Michele Bratcher Goodwin, director of the Center for Biotechnology and Global Health Policy at the University of California, Irvine, School of Law. “This has been data that we’ve had for decades.”
The rules were released as part of a broader package of protections for religious freedom that the administration announced Friday.
The government also said imposing a coverage mandate could “affect risky sexual behavior in a negative way” though it didn’t point to any particular studies to support its point. A 2014 study by the Washington University School of Medicine in St. Louis found providing no-cost contraception did not lead to riskier sexual behavior.
The rule asserts that positive health effects associated with birth control “might also be partially offset by an association with negative health effects.” The rule connects the claim of negative health effects to a call by the National Institutes of Health in 2013 for the development of new contraceptives that stated current options can have “many undesirable side effects.”
The rule also describes an Agency for Healthcare Research and Quality review that found oral contraceptives increased users’ risk of breast cancer and vascular events, making the drugs’ use in preventing ovarian cancer uncertain.
Federal officials used all of these assertions to determine the government “need not take a position on these empirical questions.”
“Our review is sufficient to lead us to conclude that significantly more uncertainty and ambiguity exists in the record than the Departments previously acknowledged.”
Cancer and heart disease are the two leading causes of death in the United States. So far, Color Genomics has been focused on testing for mutations leading to a higher risk of certain cancers. But, today the four-year-old company is introducing a new category of genetic testing for cardiovascular health.
The new Color Hereditary High Cholesterol Testwill tell you if you have a genetic mutation for something called Familial Hypercholesterolemia (FH), a hereditary condition that causes high cholesterol levels leading to coronary heart disease.
Possibly 34 million people are affected by the disease worldwide. About one in fifty people with high cholesterol have the mutation. The problem? Most people with the genetic mutation dont know they have it until they have a potentially fatal heart attack.
Like cancer testing, earlier detection of the mutation can prevent the disease, improve survival rates and reduce medical costs. And thats where Color hopes its new test can help.
We started with cancer because it was one of the leading causes of death and the science around genetics and cancer was well-established, Color chief marketing officer Katie Jacobs Stanton told TechCrunch. Similarly, there is well-established science around genetics and cardiovascular diseaseGiven that cardiovascular disease is the leading cause of death (and combined with cancer costs over $1.1trillion per year), we saw an opportunity to help more people learn their risk of developing hereditary cardiovascular conditions and proactively managing their heart health using genetic data.
Unlike at-home genetic tests like 23andMe, you order this one through your doctor. The test is $249 for new customers. However, those whove gone through Colors cancer testing can purchase the cardiovascular test for an additional $150.