September 11, 2017

FDA Approves First-of-Its-Kind Cancer Treatment By Matt Smith, Brenda Goodman, MA

By Matt Smith, Brenda Goodman, MA

August 30, 2017 -- The FDA has for the first time approved a treatment that uses a patient’s own genetically modified cells to attack a type of leukemia, opening the door to what the agency calls "a new frontier" in medicine.

The approval Wednesday allows a process known as CAR T-cell therapy to be used in children or young adults fighting an often fatal recurrence of the most common childhood cancer -- B-cell acute lymphoblastic leukemia.

And it clears the way for a new approach to fighting cancer by harnessing the body’s immune system -- a long-sought goal of medical researchers. 

“This is a dream come true,” says Henry Fung, MD, director of the Fox Chase Cancer Center-Temple University Hospital Bone Marrow Transplant Program. “It’s now limited to one disease in children only, but that platform potentially can benefit a lot of different types of cancer patients, particularly blood cancer patients.”

 

'A New Frontier'

FDA Commissioner Scott Gottlieb, MD, called the approval of the therapy -- brand named Kymriah -- a "new frontier in medical innovation."

In a news conference on Wednesday, Gottlieb said the FDA had 76 active investigational new drug applications related to CAR T-cell products, and more than 500 for gene therapy products are being studied for a variety of ailments, ranging from genetic disorders to autoimmune diseases, diabetes, cancer, and HIV.

"New technologies such as gene and cell therapies hold out the potential to transform medicine and create an inflection point in our ability to treat and even cure many intractable illnesses," Gottlieb says.

Fung, who's also vice chairman of hematology/oncology at Fox Chase, says the treatment could help patients beat back an illness that has resisted conventional treatments like chemotherapy and radiation, leaving them facing death. “This is the breakthrough of the century,” he says.

And Hetty Carraway, MD, an acute leukemia doctor at the Cleveland Clinic, says the newly approved therapy represents a first step for a new way of treating cancer. “If it can bring this kind of paradigm to other types of cancers, that’s really where I think the larger implications are,” she says.

Taking the Fight to Cancer

B-cell acute lymphoblastic leukemia attacks the blood cells that make antibodies, which help your body fight off disease. Most of the time, it’s treated successfully with chemotherapy, radiation, or by transplants of bone marrow, which produces blood cells. But in some cases, treatment fails to beat back the cancer, or it comes back. When that happens, the odds of survival fall to as little as 1 in 10.

The new treatment is a one-time infusion developed by researchers at the University of Pennsylvania and the pharmaceutical company Novartis. Officially known as chimeric antigen receptor T-cell therapy, it starts with doctors extracting disease-fighting white blood cells, known as T cells, from a patient’s blood. The cells are frozen and shipped to a laboratory, where they’re genetically engineered to attack a specific protein on the cancerous B cells.

They’re then put back into the body, where they seek out and destroy cancer cells. And because they’re cells taken from the patient’s own body, there’s no need for anti-rejection drugs, which are needed after transplants.

“This is really combining everything together,” Fung says. “This is truly using patients’ own immune cells to fight cancer.”

Dangerous Side Effects Remain a Concern

The therapy can have dangerous side effects -- mainly a condition known as cytokine release syndrome (CRS). That happens when T cells release a lot of a chemical messenger into the bloodstream. This affects the vascular system, causing high fevers and sharp drops in blood pressure. More than 60% of patients in clinical trials had side effects due to cytokine release, Novartis reported, but none of those reactions were fatal. 

Emily Whitehead, the first pediatric patient to try the therapy in 2011, had such a bad reaction initially that she was in a coma for 14 days. Her doctors told the family to say their good-byes.

“They believed she had less than a 1-in-1,000 chance of surviving to the next morning,” says her father, Tom Whitehead.

As a last hope, doctors gave Emily the arthritis drug Actemra (tocilizumab), which blocks one of the main inflammatory signals driving the CRS.  On Wednesday, the FDA also approved Actemra as a treatment for CRS. In fact, under the conditions of approval, doctor's can't use CAR T therapy unless they also have Actemra on hand to manage side effects.

Within 12 hours, Emily started to recover. She has been cancer free for five years.

Because of the side effects, Kymriah won't be available everywhere. Hopsitals and clinics will have to be specially certified to administer the treatment.  Doctors and other staff will also have get additional training before they can prescribe it.

 “We know and expect that type of side effect will happen, and we know that we can successfully manage it,” she says. “But it needs to be managed by people who are familiar with this type of side effect and how best to support patients,” Carraway says.

Other side effects included anemia, nausea, diarrhea, and headaches.

In three trials involving about 150 people, the remission rates were 69%, 83%, and 95%. A total of 17 patients died after receiving the treatment; 14 of them from the disease and three from infections, according to documents the company filed with the FDA.

“We believe this treatment can change the world,” says Tom Whitehead, who frequently speaks about his daughter’s experience and testified before the FDA about the treatment. He also helps raise money for children’s cancer research through The Emily Whitehead Foundation. “But we know some children relapse and we know children who didn’t make it.”

Big Possibilities and a Big Price Tag

Another concern is the price tag associated with the therapy: The process is reported to cost as much as $475,000.

In a press release, the Center for Medicare and Medicaid Services (CMS) announced that it was exploring "innovative payment modes and arrangements" for Kymriah and other potentially life-saving treatments.

In a news release, Novartis, the company that makes Kymriah, said it was collaborating with CMS on an outcomes-based approach to pricing, which would mean that the company would only be reimbursed if a patient responds to the therapy by the end of the first month of treatment.

“Certainly, it’s far and above the expense that we typically see for drugs,” Carraway says. But current treatments can also run into the low six figures, sometimes with little success. The number of patients with relapsed acute lymphoblastic leukemia is small, “and the options for them in their young lives are pretty limited.” 

“Our hope is we’ll get better at making these medications, and hopefully, with time, the cost of this will decrease,” she adds.

Novartis spokeswoman Julie Masow says the company will do “everything we can” to help get the treatment to patients who need it.

“We are carefully considering the appropriate price for CTL019, taking into consideration the value that this treatment represents for patients, society, and the health care system, both near-term and long-term, as well as input from external health economic experts,” Masow says.

The therapy was produced “via pioneering technology and a sophisticated manufacturing process,” she says -- however, “We recognize our responsibility in bringing this innovative treatment to patients.”

'He's Started School'

One of the more recent patients to have CAR T-cell therapy is 5-year-old Liam Thistlethwaite. He has been cancer free for 4 months since starting the therapy to treat his acute lymphoblastic leukemia.

First diagnosed shortly before his second birthday, Liam had gotten 32 months of different kinds of chemotherapy drugs to poison the cancer out of his small body. The treatment is harsh but almost always successful. Doctors told Liam’s parents he had a 96% chance of a cure if he could finish it.

But 8 months later, Liam’s cancer came back, with a vengeance. Leukemia cells spread to his spinal fluid. Tumors grew on two glands in his brain.

Liam’s doctor, Ching-Hon Pui, MD, chairman of the Oncology Department at St. Jude, had recently been to a medical conference that discussed the results of the CAR T-cell therapy. He convinced Children’s Hospital of Philadelphia to put him on its waiting list, which was about 6 months long at the time. 

Because Liam was relatively healthy and had a low cancer burden when he was treated, his father thinks he avoided some of the most severe side effects of the therapy. He spiked very high fevers and spent a few days in the hospital but pulled through.

“He’s started school. He’s doing wonderfully,” says Patrick Thistlethwaite. 

Major Questions Remain Despite Optimism

One of the unanswered questions is how long CAR T cells can last in the body. In some patients, they’ve persisted for as long as 5 years. Others have their cells die in weeks or months.  Another big question is whether the cancer will come back if the CAR T cells are gone.

The Thistlethwaites say it was very hard to know whether to try CAR T on a toddler.

“Our physician truly felt that we’d have the same odds, so to speak, as going into a stem cell transplant with heavy radiation. He believed CAR T to have high side effects up front, but no high long-term side effects," Patrick Thistlethwaite says.

They knew radiation to Liam’s brain and spinal cord could cause long-term damage.

“We still have those options,” Patrick says. “We hope we never have to use them.”

“We hope CAR T is the end of it all.”

 

May 16, 2017

Modern HIV drugs can add 10 years to life expectancy, study says

By James Masters, CNN

(CNN)The latest treatments for HIV mean that young people living with the virus could live up to a decade longer, a new study says.

The paper, published Wednesday, found that 20-year-olds who started with antiretroviral therapy in 2010 are predicted to live up to 10 years longer than those who first underwent similar treatment in 1996 -- when it first became widely available.
Researchers at Bristol University in the UK said the improvements are due to fewer side effects and less toxic drugs with greater options for patients who are infected with drug-resistant HIV strains.
    "Our research illustrates a success story of how improved HIV treatments coupled with screening, prevention and treatment of health problems associated with HIV infection can extend the life span of people diagnosed with HIV," Adam Trickey, medical statistician at the University of Bristol, said in a statement.
    "Combination antiretroviral therapy has been used to treat HIV for 20 years, but newer drugs have fewer side effects, involve taking fewer pills, better prevent replication of the virus and are more difficult for the virus to become resistant to."
    However, Trickey said further efforts are needed if life expectancy is to match that of the general population.
    Greater strategies are also needed for people in developing regions of the world to get better access to treatment, said other experts in the field.
    The Bristol University team hopes the findings help reduce the stigma associated with living with HIV so those infected can keep working and have smoother access to medical insurance, where needed. In addition, the outcome should encourage people to start treatment as soon as possible, and adhere to it, the researchers said.

    Early treatment to live longer

    Antiretroviral therapy involves a combination of three or more drugs that prevents HIV from replicating in a bid to prevent damage to the body's immune system. The treatment also prevents spread of the disease, by as much as 96%, as it lowers the levels of virus inside the body significantly.
    The World Health Organization recommends treatment be given to people with HIV as soon as possible following diagnosis. Previous guidelines recommended treatment using thresholds based on a person's CD4 count -- immune cells attacked by the virus -- which became higher over time until current guidelines were set stating the need for immediate treatment.
    The Bristol team analyzed data from more than 88,500 people with HIV gathered from 18 European and North American studies. They found that fewer people who began treatment between 2008 and 2010 died during their first three years of treatment than those who started treatment between 1996 and 2007.
    Between 1996 and 2013, the life expectancy for 20-year-olds who started treatment increased by 10 years for women and nine years for men.
    The study further projected that 20-year-old men starting therapy between 2008 and 2010 who survived the first year of treatment would live to 73, with women living on average to 76.
    Life expectancy in the UK and Canada was 81 in 2014 and almost 79 in the United States, according to the World Bank.
    But for people infected with HIV through injecting drugs, life expectancy was not seen to increase as much, according to the study.
    "In drug users we must promote therapy and improve access to therapy to treat addictions as well as increasing access to hepatitis C treatment for people with both infections," Trickey said. "Although most people are likely to start treatment soon after diagnosis of HIV, this will only result in improved survival overall if the problems of late diagnosis and treatment access are addressed."
    Professor Helen Stokes-Lampard, chair of the Royal College of General Practitioners in the UK, agreed.
    "The fact that life expectancy for patients with HIV has risen so significantly is testament to the success of antiretroviral therapy since its introduction," said Stokes-Lampard, who was not involved in the research. "But continued success is dependent on people knowing they have HIV, so that they can start treatment."

    Improving life span globally

    Jimmy Whitworth, professor of international health at the London School of Hygiene and Tropical Medicine, welcomed the results but said the challenge is to translate this success to other parts of the world.
    According to UNAIDS, almost 37 million people were living with HIV in 2015. That same year, just over 17 million people were receiving antiretroviral therapy.
    Further limitations of the study were that less data was available on older age groups, meaning death rates in this group could not be accurately estimated. Changing behaviors over time were also not accounted for, such as the fact that fewer people starting treatment in more recent years became infected through drug use, according to a statement.
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    "Overall, the results of the study are very good news," Whitworth told CNN. "This was a very rigorous study, which reflects huge progress in diagnosis and management over the past 20 years.
    "But I think it's important to recognize the global aspect here. Africa has the heaviest burden of the disease where this is a challenge of early diagnosis and treatment.
    "The other issue is combating HIV in Russia and Ukraine, which is rising at frightening rate. Those are the places doing the least well."

    May 16, 2017

    Cotton swabs send dozens of children to ERs each day, study says

    By Robert Jimison, CNN

    (CNN)The advice from doctors is clear: Don't use cotton swabs to clean your ears.

    But people continue to use a soft-tipped plastic or paper stick to dig out the wax from their ear canals -- and it's a problem.
    Authors of a new study in the Journal of Pediatrics, conducted by researchers at Nationwide Children's Hospital, warn that using cotton-tip applicators to clean the ear can be dangerous, especially in the hands of little ones.
    Each year, about 12,500 children under the age of 18 are treated in US emergency departments for ear injuries related to cotton swabs, the study says. That breaks down to about 34 visits per day.
    "This is not like brushing your teeth every day. Children and adults do not need to clean out the ear canal of wax as part of a routine hygiene practice," said Dr. Kris Jatana, assistant professor of otolaryngology-head and neck surgery at the Ohio State University and the lead author of the study.
    The researchers looked at hospital visits between 1990 and 2010 and discovered that an estimated 260,000 children ended up in the emergency room with ear injuries. Of those visits, tears in the tissue that separates the ear canal from the middle ear, called the tympanic membrane or simply the eardrum, were the most common.
    Dr. Kris Jatana often sees patients with injuries and infections caused by cotton swabs.
    The largest portion of those injuries occurred when children were using the applicators themselves to clean their ears, a practice that doctors have unanimously denounced.
    Cotton swabs can cause cuts in our ear canals, perforate our eardrums and dislocate our hearing bones. And any of these things could lead to hearing loss, dizziness, ringing or other symptoms of ear injury.
    Instead of potentially pushing the wax farther into the ear, Jatana says, we should let nature do the job.
    "The ear canal is self-cleaning, and the cotton-tip applicator actually works against your ear's natural cleaning mechanism by pushing the earwax deeper toward the eardrum, where it essentially gets trapped and can't get out on its own," he said.
    Dr. Seth Schwartz of the American Academy of Otolaryngology-Head and Neck Surgery said "it's cultural" to want clear ears, but "wiping away any excess wax when it comes to the outside of the ear is enough to keep it clean."
    "It's not a bad thing to have wax in your ears. Everybody does and should. It's more of an issue when it becomes too much," he said.
    If someone is concerned about their earwax or other problems, Jatana recommends seeing a pediatrician, a primary care physician or a specialist. "People do not generally need to clean out their ear canal in the home setting, and certainly, a cotton-tip applicator should not be the product used to do so," he said.
    As for irrigators, candles and other home remedies, Jatana sticks to the medical community's basic advice: Stay out of the ear.
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    In the study, 99% of the ER patients were treated and did not suffer permanent damage. In some severe cases, however, damage sustained from injuries resulted in a permanent loss of hearing.
    The ear is sensitive, Jatana said, and the risk of harm is too high. "We need to dispel the idea of cleaning ears in the home setting and the use of any products to do so," he said.

    June 14, 2016

    Research Points to 'Smoking Gun' for PPI Risks By Brenda Goodman, MA WebMD Health News Reviewed by Michael W. Smith, MD

    June 8, 2016 -- Recent research has tied certain kinds of acid-blocking heartburn drugs called proton pump inhibitors, or PPIs, to a host of scary health problems, including higher risks for dementia, kidney disease, and heart attacks.

    What’s been less clear, though, is how these meds might be contributing to so many kinds of ills.

    Now researchers working out of Stanford University and Houston Methodist Hospital in Texas think they may have found an important piece of the puzzle: The drugs don’t just turn off acid pumps in the stomach. Instead, the researchers say, PPIs also block the production of acid in every cell in our bodies, an effect that hampers the body’s ability to rid itself of damaged proteins -- the “garbage” that builds up as we age.

    “I think we now have a smoking gun,” says John Cooke, MD, PhD, chair of Cardiovascular Disease Research at Houston Methodist Hospital.

    New Risks Tied to PPIs
    Proton pump inhibitors dramatically diminish the amount of acid made by glands that line the inside of the stomach. They can provide big relief for people who have heartburn, where stomach acid splashes into the esophagus, causing fiery pain.

    Millions of Americans take them. According to IMS Health, proton pump inhibitors were the ninth most commonly prescribed kinds of drugs in 2015, ahead of thyroid medications.

    Top sellers include Nexium, Prevacid, and Prilosec. They're available over the counter and by prescription. The maker of Nexium and Prilosec, AstraZeneca, says it stands behind the safety of its products.

    But there’s a downside to getting rid of stomach acid, too. It’s important for the absorption of some vitamins and minerals and for killing some of the harmful bacteria that we may swallow.

    The drugs already carry warnings for several known risks, including C. difficile infections, which can cause chronic diarrhea; pneumonia; low magnesium levels, which can cause muscle spasms; heart palpitations and convulsions; and fractures of the hip, wrist, or spine. Fracture risks are generally highest in people who've taken high doses of the drugs for more than one year.
    They may reduce the effectiveness of clopidogrel (Plavix), a drug that prevents blood clots.

    In addition to those risks, two recent studies have raised troubling new questions about the long-term use of these drugs.

    The first study, published in February, found that PPI use was tied to a higher risk for chronic kidney disease, while the use of a different kind of acid-blocking drug, called an H2 blocker, was not.

    The second study, published in April, found a higher risk for dementia in people who use PPIs compared to those who don’t.

    The studies linking PPIs to long-term health problems have been high-quality, but observational, experts say. At best, they can only show when two trends travel in the same direction. They can’t prove one thing causes another.


    Scott Gabbard, MD, a gastroenterologist at the Cleveland Clinic in Ohio, says so many of his patients have become frightened of PPIs that he’s had to do his homework so he can fully explain the risks.

    Take, for instance, the recent study that linked PPIs to chronic kidney disease. The study, which included more than 250,000 people, found that taking a PPI hiked a person’s risk of kidney disease by about 50%. But in absolute terms, the increased risk was still relatively small. Over 10 years, people who took a PPI had an almost 12% risk of developing chronic kidney disease, while people who weren’t taking the drugs had an 8.5% risk of getting kidney disease -- a difference of about 3%.

    The same goes for the recent study that tied PPIs to dementia. Gabbard says the absolute risk increase seen in the study was small. People who took these meds had a 13% risk of getting dementia over the 7 years of the study, while people who didn’t take them had about an 8% -- a difference of about 5%.

    Older studies have raised other health concerns. A 2015 study linked PPIs to a higher risk for heart attacks.

    Also, there’s an ongoing debate about whether taking a PPI may increase a person’s risk for cancers of the esophagus and stomach.

    People who have chronic acid reflux are at higher risk for a condition called Barrett’s esophagus, which is thought to be a precursor to full-blown esophageal cancer. Some studies have suggested that because PPIs protect damaged tissue in the esophagus from repeated exposure to stomach acid, allowing it to heal, the drugs might lower a person’s risk for cancer.

    At the same time, many doctors have noted that rates of esophageal cancers have continued to increase, even as PPI medications have become a standard treatment for Barrett’s esophagus.

    A 2014 study of 10,000 people diagnosed with Barrett’s esophagus in Denmark found that people who took PPIs were actually more likely to get cancer. The risk was highest for “high-adherence” users -- those who took their pills most faithfully. The study was observational, though, and it couldn't show cause and effect.

    “It seems to me, at the very least, we can say the drugs do not protect against cancer,” says Frederik Hvid-Jensen, MD, PhD, a surgeon and researcher at Arhus University in Aarhus, Denmark.


    A Surprise Finding Points to Unintended Effects
    Researcher Cooke doesn’t think PPIs should be available over the counter. “They should be pulled off the shelves. They should be by prescription and they should be medically monitored because of the risks,” he says.

    AstraZeneca, meanwhile, says patient safety is an important priority, and “we believe all of our PPI medicines are generally safe and effective when used in accordance with the label. This has been established through human data studies and more than a decade of real world clinical use.”

    Cooke is a cardiologist who studies the endothelium, the layer of cells that lines blood vessels.

    Healthy young endothelium, he says, is “like the Teflon coating of the blood vessels. It prevents things from sticking.”

    But as we age and our endothelium becomes damaged, it behaves more like Velcro, and things start to stick. That’s how blood clots can begin to form and cause problems like heart attacks and strokes.

    When Cooke was at Stanford, he decided to put his lab to work searching that university’s vast drug library to see if he could find any compounds that might protect the endothelium from age-related damage. Unfortunately, they didn’t find any.

    But they did find two drugs in the library that dramatically worsened how well endothelium works -- they were both proton pump inhibitors. His findings were published in 2013.

    To Cooke, the implications of what they’d found were enormous.

    He reasoned that if the drugs could truly harm blood vessel function, he should be able to find evidence of that in a large group of people. He and a colleague named Nigam Shah, PhD, used data-mining techniques to plumb a database of over 2 million patients to see if those taking proton pump inhibitors were more likely to have heart problems.

    Out of about 70,000 people diagnosed with gastroesophageal reflux disease (GERD), roughly 45% were taking a PPI, and PPI users were 16% more likely than those who weren’t to have a heart attack. The risk of a heart attack increased by 25% for people taking a PPI before the age of 55. Cooke didn't find the same risks for people taking a different kind of medication to control their heartburn called an H2 blocker (examples of those meds include Pepcid, Tagamet, and Zantac.) Those study results were published in 2015.


    Drugs’ Effects May Go Beyond the Stomach
    Just how could PPIs be causing the damage?

    In studies of mice and human cells in test tubes, PPIs have been shown to shut off acid pumps in tiny cell parts called lysosomes.

    “A lysosome is like a little bag of acid in the cell,” Cooke explains. Certain enzymes in the lysosome only work under acidic conditions. Those enzymes break down proteins that have become damaged. “It’s kind of like a little garbage disposal that requires acid to work.”

    When the lysosomes don’t work properly in cells, waste builds up and cells age more quickly than normal.

    Experts say Cooke’s research could explain why PPIs might lead to damage in many different organs at the same time.

    “In my mind, we’ve got the biologic mechanism by which the PPIs are harmful to some of these patients,” says Jonathan Lipham, MD, chief of the division of GI and general surgery at the University of Southern California’s Keck School of Medicine in Los Angeles.

    Both Lipham and Cooke are quick to say that people who really need PPIs shouldn’t be afraid to take them if that’s what their doctor advises.

    Cooke has applied for NIH funding to do a larger, longer-term clinical trial to more decisively test his theory.

    In the meantime, he says, if the benefits of the drugs outweigh the risks for someone, they should keep taking their PPI under medical supervision.

    But he points out that these drugs are often prescribed when people have no medical reason to be on them. One recent study of long-term care facilities in the Midwest found that 65% of people taking a PPI didn’t have any diagnosis that might explain why the drug was prescribed. And PPIs can be tough to quit. Stopping the meds often leads to a phenomenon called PPI rebound, which causes people to make even more stomach acid than they were before. That leads many to stay on them for years, though the drugs’ labels say patients should only take them for 4 to 8 weeks to help heal ulcers or control heartburn.

    “There are people that need PPIs long-term. But they should know what the risks are long-term, and they should be made aware of other options. There are surgical options to treat reflux,” Cooke says.


    Since his study, Hvid-Jensen says he has changed the way he treats patients with PPIs.

    “I tell my patients, if they have Barrett’s esophagus, I tell them only to use PPIs if they have symptoms and if PPIs help their symptoms,” he says.

    Gabbard takes a similar tack with his patients. He tells them if they’re able to use less of the medicines, they should.

    Some important things Gabbard tells his patients to do to relieve acid reflux:

    Lose weight. “Losing as little as 10 to 15% of your weight can reduce reflux,” he says.
    Quit smoking.
    Elevate the head of the bed.
    All, he says, are proven, drug-free ways to get relief.

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    © 2016 WebMD, LLC. All rights reserved.

     

    June 14, 2016

    Research Points to 'Smoking Gun' for PPI Risks By Brenda Goodman, MA WebMD Health News Reviewed by Michael W. Smith, MD

    June 8, 2016 -- Recent research has tied certain kinds of acid-blocking heartburn drugs called proton pump inhibitors, or PPIs, to a host of scary health problems, including higher risks for dementia, kidney disease, and heart attacks.

    What’s been less clear, though, is how these meds might be contributing to so many kinds of ills.

    Now researchers working out of Stanford University and Houston Methodist Hospital in Texas think they may have found an important piece of the puzzle: The drugs don’t just turn off acid pumps in the stomach. Instead, the researchers say, PPIs also block the production of acid in every cell in our bodies, an effect that hampers the body’s ability to rid itself of damaged proteins -- the “garbage” that builds up as we age.

    “I think we now have a smoking gun,” says John Cooke, MD, PhD, chair of Cardiovascular Disease Research at Houston Methodist Hospital.

    New Risks Tied to PPIs
    Proton pump inhibitors dramatically diminish the amount of acid made by glands that line the inside of the stomach. They can provide big relief for people who have heartburn, where stomach acid splashes into the esophagus, causing fiery pain.

    Millions of Americans take them. According to IMS Health, proton pump inhibitors were the ninth most commonly prescribed kinds of drugs in 2015, ahead of thyroid medications.

    Top sellers include Nexium, Prevacid, and Prilosec. They're available over the counter and by prescription. The maker of Nexium and Prilosec, AstraZeneca, says it stands behind the safety of its products.

    But there’s a downside to getting rid of stomach acid, too. It’s important for the absorption of some vitamins and minerals and for killing some of the harmful bacteria that we may swallow.

    The drugs already carry warnings for several known risks, including C. difficile infections, which can cause chronic diarrhea; pneumonia; low magnesium levels, which can cause muscle spasms; heart palpitations and convulsions; and fractures of the hip, wrist, or spine. Fracture risks are generally highest in people who've taken high doses of the drugs for more than one year.
    They may reduce the effectiveness of clopidogrel (Plavix), a drug that prevents blood clots.

    In addition to those risks, two recent studies have raised troubling new questions about the long-term use of these drugs.

    The first study, published in February, found that PPI use was tied to a higher risk for chronic kidney disease, while the use of a different kind of acid-blocking drug, called an H2 blocker, was not.

    The second study, published in April, found a higher risk for dementia in people who use PPIs compared to those who don’t.

    The studies linking PPIs to long-term health problems have been high-quality, but observational, experts say. At best, they can only show when two trends travel in the same direction. They can’t prove one thing causes another.


    Scott Gabbard, MD, a gastroenterologist at the Cleveland Clinic in Ohio, says so many of his patients have become frightened of PPIs that he’s had to do his homework so he can fully explain the risks.

    Take, for instance, the recent study that linked PPIs to chronic kidney disease. The study, which included more than 250,000 people, found that taking a PPI hiked a person’s risk of kidney disease by about 50%. But in absolute terms, the increased risk was still relatively small. Over 10 years, people who took a PPI had an almost 12% risk of developing chronic kidney disease, while people who weren’t taking the drugs had an 8.5% risk of getting kidney disease -- a difference of about 3%.

    The same goes for the recent study that tied PPIs to dementia. Gabbard says the absolute risk increase seen in the study was small. People who took these meds had a 13% risk of getting dementia over the 7 years of the study, while people who didn’t take them had about an 8% -- a difference of about 5%.

    Older studies have raised other health concerns. A 2015 study linked PPIs to a higher risk for heart attacks.

    Also, there’s an ongoing debate about whether taking a PPI may increase a person’s risk for cancers of the esophagus and stomach.

    People who have chronic acid reflux are at higher risk for a condition called Barrett’s esophagus, which is thought to be a precursor to full-blown esophageal cancer. Some studies have suggested that because PPIs protect damaged tissue in the esophagus from repeated exposure to stomach acid, allowing it to heal, the drugs might lower a person’s risk for cancer.

    At the same time, many doctors have noted that rates of esophageal cancers have continued to increase, even as PPI medications have become a standard treatment for Barrett’s esophagus.

    A 2014 study of 10,000 people diagnosed with Barrett’s esophagus in Denmark found that people who took PPIs were actually more likely to get cancer. The risk was highest for “high-adherence” users -- those who took their pills most faithfully. The study was observational, though, and it couldn't show cause and effect.

    “It seems to me, at the very least, we can say the drugs do not protect against cancer,” says Frederik Hvid-Jensen, MD, PhD, a surgeon and researcher at Arhus University in Aarhus, Denmark.


    A Surprise Finding Points to Unintended Effects
    Researcher Cooke doesn’t think PPIs should be available over the counter. “They should be pulled off the shelves. They should be by prescription and they should be medically monitored because of the risks,” he says.

    AstraZeneca, meanwhile, says patient safety is an important priority, and “we believe all of our PPI medicines are generally safe and effective when used in accordance with the label. This has been established through human data studies and more than a decade of real world clinical use.”

    Cooke is a cardiologist who studies the endothelium, the layer of cells that lines blood vessels.

    Healthy young endothelium, he says, is “like the Teflon coating of the blood vessels. It prevents things from sticking.”

    But as we age and our endothelium becomes damaged, it behaves more like Velcro, and things start to stick. That’s how blood clots can begin to form and cause problems like heart attacks and strokes.

    When Cooke was at Stanford, he decided to put his lab to work searching that university’s vast drug library to see if he could find any compounds that might protect the endothelium from age-related damage. Unfortunately, they didn’t find any.

    But they did find two drugs in the library that dramatically worsened how well endothelium works -- they were both proton pump inhibitors. His findings were published in 2013.

    To Cooke, the implications of what they’d found were enormous.

    He reasoned that if the drugs could truly harm blood vessel function, he should be able to find evidence of that in a large group of people. He and a colleague named Nigam Shah, PhD, used data-mining techniques to plumb a database of over 2 million patients to see if those taking proton pump inhibitors were more likely to have heart problems.

    Out of about 70,000 people diagnosed with gastroesophageal reflux disease (GERD), roughly 45% were taking a PPI, and PPI users were 16% more likely than those who weren’t to have a heart attack. The risk of a heart attack increased by 25% for people taking a PPI before the age of 55. Cooke didn't find the same risks for people taking a different kind of medication to control their heartburn called an H2 blocker (examples of those meds include Pepcid, Tagamet, and Zantac.) Those study results were published in 2015.


    Drugs’ Effects May Go Beyond the Stomach
    Just how could PPIs be causing the damage?

    In studies of mice and human cells in test tubes, PPIs have been shown to shut off acid pumps in tiny cell parts called lysosomes.

    “A lysosome is like a little bag of acid in the cell,” Cooke explains. Certain enzymes in the lysosome only work under acidic conditions. Those enzymes break down proteins that have become damaged. “It’s kind of like a little garbage disposal that requires acid to work.”

    When the lysosomes don’t work properly in cells, waste builds up and cells age more quickly than normal.

    Experts say Cooke’s research could explain why PPIs might lead to damage in many different organs at the same time.

    “In my mind, we’ve got the biologic mechanism by which the PPIs are harmful to some of these patients,” says Jonathan Lipham, MD, chief of the division of GI and general surgery at the University of Southern California’s Keck School of Medicine in Los Angeles.

    Both Lipham and Cooke are quick to say that people who really need PPIs shouldn’t be afraid to take them if that’s what their doctor advises.

    Cooke has applied for NIH funding to do a larger, longer-term clinical trial to more decisively test his theory.

    In the meantime, he says, if the benefits of the drugs outweigh the risks for someone, they should keep taking their PPI under medical supervision.

    But he points out that these drugs are often prescribed when people have no medical reason to be on them. One recent study of long-term care facilities in the Midwest found that 65% of people taking a PPI didn’t have any diagnosis that might explain why the drug was prescribed. And PPIs can be tough to quit. Stopping the meds often leads to a phenomenon called PPI rebound, which causes people to make even more stomach acid than they were before. That leads many to stay on them for years, though the drugs’ labels say patients should only take them for 4 to 8 weeks to help heal ulcers or control heartburn.

    “There are people that need PPIs long-term. But they should know what the risks are long-term, and they should be made aware of other options. There are surgical options to treat reflux,” Cooke says.


    Since his study, Hvid-Jensen says he has changed the way he treats patients with PPIs.

    “I tell my patients, if they have Barrett’s esophagus, I tell them only to use PPIs if they have symptoms and if PPIs help their symptoms,” he says.

    Gabbard takes a similar tack with his patients. He tells them if they’re able to use less of the medicines, they should.

    Some important things Gabbard tells his patients to do to relieve acid reflux:

    Lose weight. “Losing as little as 10 to 15% of your weight can reduce reflux,” he says.
    Quit smoking.
    Elevate the head of the bed.
    All, he says, are proven, drug-free ways to get relief.

    View Article Sources
    © 2016 WebMD, LLC. All rights reserved.

     

    June 14, 2016

    Why FDA is warning people about Imodium overdoses By Debra Goldschmidt, CNN Updated 3:53 PM ET, Thu June 9, 2016

    (CNN)Higher-than-recommended doses of the antidiarrheal medicine loperamide, sold under the brand name Imodium, can lead to serious heart problems and even death, the U.S. Food and Drug Administration warned this week. The warning applies to both over-the-counter and prescription strength medications, which are also sold under other generic names.

    "The majority of reported serious heart problems occurred in individuals who were intentionally misusing and abusing high doses of loperamide in attempts to self-treat opioid withdrawal symptoms or to achieve a feeling of euphoria," the FDA said in a safety announcement. "They are also combining loperamide with interacting drugs in attempts to increase these effects.".
    Individuals who have taken dangerously high doses may experience a rapid or irregular heartbeat, faint or become unresponsive. If any of these occur, 911 should be contacted immediately to get medical attention.
    Forty-eight cases of serious heart problems associated with Imodium have been reported to the FDA between 1976, when it was approved, and last year. More than half of them occurred after 2010. This includes 10 reported deaths. However, the agency believes the actual number of cases is higher because not all incidents are reported to the FDA.
    A recent study in the medical journal Annals of Emergency Medicine described two fatal cases of patients with a history of substance abuse who came into the emergency room after having taken "massive doses" of Imodium to self-medicate their withdrawal symptoms. Complications arose, not from the opioid ingredient but from the other ingredients because of what they do to the body and how they act. The authors conclude that "this is another reminder that all drugs, including those sold without a prescription, can be dangerous when not used as directed."
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    Calls to poison control centers about intentional exposure of this drug increased 71% from 2011 to 2014 nationwide, the American College of Emergency Physicians said. It also found that online postings about abuse of loperamide increased tenfold from 2010 to 2011. Most of the postings were about self-treatment for withdrawal symptoms, while taking it to get high was also commonly mentioned.

    June 14, 2016

    Is there really a five-second rule about food on the floor? By Paul Dawson, The Conversation Updated 11:53 AM ET, Fri June 10, 2016

    When you drop a piece of food on the floor, is it really OK to eat if you pick up within five seconds? This urban food myth contends that if food spends just a few seconds on the floor, dirt and germs won't have much of a chance to contaminate it. Research in my lab has focused on how food and food contact surfaces become contaminated, and we've done some work on this particular piece of wisdom.

    While the "five-second rule" might not seem like the most pressing issue for food scientists to get to the bottom of, it's still worth investigating food myths like this one because they shape our beliefs about when food is safe to eat.
      So is five seconds on the floor the critical threshold that separates an edible morsel from a case of food poisoning? It's a bit a more complicated than that. It depends on just how much bacteria can make it from floor to food in a few seconds and just how dirty the floor is.

      Where did the five-second rule come from?

      Wondering if food is still OK to eat after it's been dropped on the floor (or anywhere else) is a pretty common experience. And it's probably not a new one either.
      A well-known, but inaccurate, story about Julia Child may have contributed to this food myth. Some viewers of her cooking show, The French Chef, insist they saw Child drop lamb (or a chicken or a turkey, depending on the version of the tale) on the floor and pick it up, with the advice that if they were alone in the kitchen, their guests would never know.
      In fact it was a potato pancake, and it fell on the stovetop, not on the floor. Child put it back in the pan, saying "But you can always pick it up and if you are alone in the kitchen, who is going to see?" But the misremembered story persists.
      It's harder to pin down the origins of the oft-quoted five-second rule, but a 2003 study reported that 70% of women and 56% of men surveyed were familiar with the five-second rule and that women were more likely than men to eat food that had been dropped on the floor.
      So what does science tell us about what a few moments on the floor means for the safety of your food?

      Five seconds is all it takes

      The earliest research report on the five-second rule is attributed to Jillian Clarke, a high school student participating in a research apprenticeship at the University of Illinois. Clarke and her colleagues inoculated floor tiles with bacteria then placed food on the tiles for varying times.
      They reported bacteria were transferred from the tile to gummy bears and cookies within five seconds, but didn't report the specific amount of bacteria that made it from the tile to the food.
      But how much bacteria actually transfer in five seconds?
      In 2007, my lab at Clemson University published a study -- the only peer-reviewed journal paper on this topic -- in the Journal of Applied Microbiology. We wanted to know if the length of time food is in contact with a contaminated surface affected the rate of transfer of bacteria to the food.
      To find out, we inoculated squares of tile, carpet or wood with Salmonella. Five minutes after that, we placed either bologna or bread on the surface for five, 30 or 60 seconds, and then measured the amount of bacteria transferred to the food. We repeated this exact protocol after the bacteria had been on the surface for two, four, eight and 24 hours.
      We found that the amount of bacteria transferred to either kind of food didn't depend much on how long the food was in contact with the contaminated surface -- whether for a few seconds or for a whole minute. The overall amount of bacteria on the surface mattered more, and this decreased over time after the initial inoculation. It looks like what's at issue is less how long your food languishes on the floor and much more how infested with bacteria that patch of floor happens to be.
      We also found that the kind of surface made a difference as well. Carpets, for instance, seem to be slightly better places to drop your food than wood or tile. When carpet was inoculated with Salmonella, less than 1% of the bacteria were transferred. But when the food was in contact with tile or wood, 48%-70% of bacteria transferred.
      Last year, a study from from Aston University in the UK used nearly identical parameters to our study and found similar results testing contact times of three and 30 seconds on similar surfaces. They also reported that 87% of people asked either would eat or have eaten food dropped on the floor.

      Should you eat food that's fallen on the floor?

      From a food safety standpoint, if you have millions or more cells on a surface, 0.1% is still enough to make you sick. Also, certain types of bacteria are extremely virulent, and it takes only a small amount to make you sick. For example, 10 cells or less of an especially virulent strain of E. coli can cause severe illness and death in people with compromised immune systems. But the chance of these bacteria being on most surfaces is very low.
      And it's not just dropping food on the floor that can lead to bacterial contamination. Bacteria are carried by various "media," which can include raw food, moist surfaces where bacteria has been left, our hands or skin and from coughing or sneezing.
      Hands, foods and utensils can carry individual bacterial cells, colonies of cells or cells living in communities contained within a protective film that provide protection. These microscopic layers of deposits containing bacteria are known as biofilms and they are found on most surfaces and objects.
      Biofilm communities can harbor bacteria longer and are very difficult to clean. Bacteria in these communities also have an enhanced resistance to sanitizers and antibiotics compared to bacteria living on their own.

      So the next time you consider eating dropped food, the odds are in your favor that you can eat that morsel and not get sick. But in the rare chance that there is a microorganism that can make you sick on the exact spot where the food dropped, you can be fairly sure the bug is on the food you are about to put in your mouth.

      Research (and common sense) tell us that the best thing to do is to keep your hands, utensils and other surfaces clean.

      June 14, 2016

      Whole Foods gets warning letter from FDA by Paul R. La Monica @lamonicabuzz June 14, 2016: 2:28 PM ET

      When it rains, it pours for Whole Foods. Literally, it seems.

      The Food and Drug Administration sent a warning letter to Whole Foods co-CEOs John Mackey and Walter Robb about what the FDA called "serious violations" it found after inspecting a Whole Foods food preparation facility in Everett, MA, in February.

      The FDA said in the letter -- dated June 8 -- that it found various items, including pesto pasta, mushroom quesadillas, egg salad and couscous, were in areas where "condensate" was leaking from ceiling joints, a doorway and condenser fan.

      The FDA inspector cited many other violations, such as failure to sanitize food prep surfaces, dirty dishes near food, sinks without hot water for hand-washing and a worker who sprayed an ammonium-based sanitizer on "an open colander of salad leafy greens."

      Whole Foods was not immediately available for comment about the FDA's concerns.

      The FDA said that it did receive a response from the company on March 17 in which Whole Foods said it took the FDA's concerns seriously and will do what is necessary to correct the problems.

      But the FDA still doesn't seem convinced. It said that it still has "serious concerns" about what it found -- and the willingness of Whole Foods to really address them.

      "We do not consider your response acceptable because you failed to provide documentation for our review," the FDA added.

      You can read the full letter here.

      Investors weren't pleased either. Shares of Whole Foods (WFM) fell more than 2.5% Tuesday. The stock is now in the red for the year.

      It's been a tough few years for the company. The stock fell more than 10% in 2014 due to increased concerns about slowing sales.

      And Whole Foods plunged nearly 35% last year following accusations that it overcharged customers and other health scares.

      The company has found it difficult to shake off that Whole Paycheck reputation -- the perception that its products are way overpriced.

      Whole Foods may have helped create the organic food revolution. But it no longer has the natural market to itself.

      It faces tough competition from mass merchandise retailers Walmart (WMT), Target (TGT) andCostco (COST)as well as supermarket chain Kroger. Whole Foods also has to contend with organic rivals like Trader Joe's, Sprouts (SFM) and Fresh Marke (TFM)t.

      Whole Foods may have been in better position to deal with these competitive challenges if not for a slew of negative publicity about its prices.

      The store was accused last year of overcharging customers for prepackaged items in New York City. The company eventually apologized and settled with regulators in the Big Apple. But sales took a big hit as a result of the allegations.

      Shortly after the NYC allegations surfaced, a Whole Foods store in Southern California was found to be selling 3 sticks of asparagus in 16-ounce bottles of water -- for a whopping $5.99 a bottle. The company said it was a mistake.

      But HBO's John Oliver had a field day making fun of this. A mock ad on his show featured "two baby carrots tied together with artisanal twine" and a pomegranate that listened to NPR. (CNN and HBO are corporate cousins.)

      Whole Foods also had to deal with a listeria scare last year. The company recalled blue cheese and various salad bar items in two separate incidents last October.

      As if that wasn't enough, Whole Foods decided last September to stop selling products from a supplier that used inmate workers after an activist pointed out how poorly the prisoners were being paid.

      Same-store sales, a key measure of success at retailers, have fallen recently as a result of all these problems.

      And Whole Foods is dealing with all these issues as it tries to expand as well. The company just opened its first 365 by Whole Foods Market store in California. The 365 stores are aimed at urban Millennials and feature cheaper grocery products.

      August 31, 2015

      Lack of sleep can lead to the common cold

      By Nadia Kounang, CNN

           So, it turns out your mother was right again: The less sleep you get, the more likely you are to catch a cold.

      A new study published in this week's journal SLEEP, finds that people who sleep less than six hours are more likely to catch a cold. Researchers tracked 164 healthy men and women for a week at a time, monitoring how much they slept and exposing them to the rhinovirus, also known as, the common cold.

       

      Sleep at least six hours a night

       

      Aric Prather, lead author of the study, and his colleagues found that those who slept less than five hours were 4.5 times more likely to have a cold than those who slept seven hours.

      Only 18% of those who slept six or more hours got a cold, while 39% of those slept less than six hours got the virus.

      According to the Centers for Disease Control and Prevention, most adults average two to three colds a year and kids have even more.

        Prather pointed out that when we don't sleep enough, it may impact our immune systems in a variety of ways -- from how the cells act to enabling our inflammation pathways.

        "We don't know conclusively what happens, but there are a variety of pathways and they all work together and ultimately put people at risk," Prather said.

        Related: Do you have allergies or just a cold?

        Shalini Paruthi, director of the Pediatric Sleep and Research Center at Saint Louis University, put it simply: "It looks like an adequate amount of sleep allows our body to mount a better immune response."

         

        Americans sleep less and less

         

        We spend a third of our lives asleep -- that's about 25 years. But, sleeping is becoming a challenge in the United States. Americans are simply sleeping less and less. In 1985, the average amount of sleep was close to 7.5 hours, and according to the American Academy of Sleep Medicine has dropped to 7.18.

        Aside from catching more colds, lack of sleep has also been associated with mental alertness and driving ability, as well as increased risk of heart attack, stroke, diabetes and obesity.

        "I think this study provides further evidence the important for adequate sleep," Nathan Watson, president of the American Academy of Sleep Medicine said. "People need to consider sleep an important tool to healthy life, as opposed as an impediment to staying awake."

        Before you turn off your alarm off -- keep in mind that there have been studies that have found that those who sleep nine or more hours could increase their risk of death. But, according to James Gangwisch, a sleep researcher at Columbia University, said those studies didn't explore whether those people had underlying illnesses.

         

        How to sleep better

         

        So what can you do to get a better night's sleep? In addition to setting an alarm in the morning, try setting one at night to remind you that it's bedtime. Keep your bedroom as dark as possible. And when you wake in the morning, get out and get some sun. The light wakes up your brain and tells it to be alert, and later on, that helps you ease into sleeping better at night.

        Prather said we need to raise the profile of sleep.

        "Sleep usually takes a back seat to everything else we're doing, and it's a disservice," Prather said. "There's a real health cost to doing that."

        August 27, 2015

        Head Lice Resistant to Common Meds in 25 States

        By Alan Mozes

        HealthDay Reporter

        TUESDAY, Aug. 18, 2015 (HealthDay News) -- Drug-resistant head lice are very likely coming to a school near you, U.S. investigators warn.

        At least 25 states host lice populations that don't respond to common over-the-counter treatments, a new analysis reveals.


        Permethrin, part of the pyrethroid class of insecticides, has long been the go-to weapon against head lice, mosquitoes, bedbugs and other insects.

        But continued exposure to permethrin has caused a huge swath of the dreaded insects to develop genetic mutations that render such drugs useless.

        "It's a very classic resistance story," said study lead author Kyong Yoon, an assistant professor in the biological sciences and environmental sciences program at Southern Illinois University in Edwardsville.

        "Permethrin products were introduced to U.S. consumers in the early '90s," Yoon said. "But the first registered problem was reported from Israel in 1995, probably because they had it in use even earlier. Then in 2000 we found genetic mutations causing resistance in head lice here."

        Head lice, which can't jump or fly, transmit by direct physical contact. They quickly infest the neck and head, feeding on blood and attaching their eggs to the base of hair shafts.

        "They itch, but they do not transmit disease," said Yoon. "So it's not at all life-threatening, even if it's very frustrating and uncomfortable."

        Six million to 12 million U.S. children are infested with head lice every year, "with parents spending about $350 million dollars annually on permethrin-laced over-the-counter and prescription treatments," Yoon said. Lice infestations occur in rich neighborhoods as well as poor ones.

        For this study, Yoon and his fellow researchers developed molecular diagnostic tools to track American lice. Results are still coming in from several states evaluated so far.

        "We have found 100 percent resistance among 104 lice populations out of 109 we tested," Yoon said. "It's really alarming."

        In 25 states -- including Arizona, California, the Carolinas, Connecticut, Florida, Georgia, Illinois, Maine, Massachusetts, Texas and Virginia -- lice have what Yoon calls "knock-down resistant mutations" -- a triple whammy of genetic alterations that render them immune to over-the-counter permethrin treatments.

        Lice in four states -- New Jersey, New Mexico, New York and Oregon -- have developed partial resistance, the researchers found.

        Michigan's lice have no resistance as yet. Why remains unclear.

        Yoon is scheduled to present his team's findings Tuesday in Boston at a meeting of the American Chemical Society. Data and conclusions presented at meetings are usually considered preliminary until published in a peer-reviewed medical journal.

        The good news is that prescription medications that don't contain permethrin remain effective against lice. These contain powerful agents such as benzyl alcohol, ivermectin, malathion and spinosad. Lindane shampoo is another alternative for difficult-to-treat cases.

        "Prescription drugs will be pricier. But if you try and save time and money and treat it on your own it will probably get worse rather than better," Yoon said.


        Philip Tierno, professor of microbiology and pathology at the New York University School of Medicine in New York City, expressed little surprise with the findings.

        Over the years powerful pesticides have been taken off the market, Tierno explained. DDT was withdrawn in the 1970s because of environmental concerns, he said, and organophosphates, which were neuro-toxic, were restricted after 9/11 because the government feared its use by terrorists. "Only pest control experts had access," he said.

        "That meant that lice and other things like bedbugs were constantly exposed to what we had left: permethrin. So they became resistant," Tierno said.

        No one should panic, however. "There is recourse by means of prescription drugs," he said. "Just go to your doctor before you go to your drug store."

        Habibi's Home Medical Inc