The Most Promising Cancer Treatments In a Century Have ArrivedBut Not For Everyone

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.

Read more: https://www.wired.com/story/cancer-immunotherapy-has-arrived-but-not-for-everyone/

Amazon Threat Causes Shakeout in the Health-Care Industry

Amazon.com Inc. is casting a long shadow over the health-care industry.

The prospect of the giant Internet retailer entering the business is beginning to cause far-reaching reverberations for a range of companies, roiling the shares of drugstore chains, drug distributors and pharmacy-benefit managers, and potentially precipitating one of the biggest corporate merger deals this year.

On Thursday, the pressure was plain to see. A report that Amazon had received pharmacy-wholesaler licenses in a dozen states triggered a fast and steep selloff that wounded the likes of McKesson Corp., AmerisourceBergen Corp. and Cardinal Health Inc. And late in the day, shares of Aetna Inc. surged after a report that it was in talks to be taken over by CVS Health Corp.

Executives in the drug industry say that Amazon could use its expansive online reach and its logistical muscle to threaten companies that ship and sell medicines to consumers and cut pricing deals with drug makers.

“Size and scale-wise, they can disrupt anywhere they want to disrupt,” said Chip Davis, president of the Association for Accessible Medicines, a trade group for generic medication, in an interview Thursday.

Competitive Squeeze

A deal for Aetna could conceivably move CVS further away from the business of brick-and-mortar retail drugstores and deeper in health services such as pharmacy benefits, where it already has a sizable presence.

Combining Aetna and CVS would create a health-services giant and a bigger competitor for UnitedHealth Group Inc., which is the largest U.S. health insurer and has its own own clinics and a pharmacy-benefits unit.

The presence of Amazon is already being felt by retailers and companies that sell drugs over the counter. The head of of Bayer AG’s consumer-health business said on a conference call with analysts Thursday that the wider shift to online shopping by U.S. consumers was hurting its business. Erica Mann, the division’s chief, dubbed it the “Amazon effect,” saying buyers are looking for value.

At the same time, the pecking order in the health-supply chain is beginning to shift.

Earlier this month, insurance giant Anthem Inc. said it was cutting ties with Express Scripts Holding Co. after a long dispute over pricing and starting its own pharmacy-benefits manager in 2020. A bulked-up CVS and Anthem’s new venture could raise the pressure on Express Scripts, which has touted its independence.

Any tie-up of Aetna and CVS would follow a pair of failed mergers among health insurers. The deals would have reduced the ranks of big U.S. health insurers from five to three, a prospect that led the Justice Department to oppose both prospective tie-ups.

If the Aetna deal happened, “CVS would have a dominant position” in the drug-benefits business, said Michael Rea, founder of Rx Savings Solutions, which has an app that helps patients find low cost drugs.

Pharmacy Threat

Analysts have speculated that Amazon could soon enter the business of selling prescription drugs, threatening to disrupt retail drugstores, drug wholesalers, and the pharmacy-benefits management business. While Amazon has never publicly commented on what its plans may be, CNBC reported this month that the Internet giant could make a decision about selling drugs online by Thanksgiving. The network didn’t name its sources.

McKesson slid 5.2 percent at 4 p.m. in New York, while AmerisourceBergen shares fell 4.2 percent and Express Scripts sank 3.7 percent following the report on Amazon’s state licenses by the St. Louis Post-Dispatch.

Bloomberg News confirmed that Amazon had obtained wholesale-pharmacy licenses in at least 13 states, including Nevada, Idaho, Arizona, North Dakota, Oregon, Alabama, Louisiana, New Jersey, Michigan, Connecticut, New Hampshire, Utah and Iowa. An application is pending in Maine. Some of the licenses were obtained late last year and some this year.

Amazon declined to comment.

The licenses could be part of Amazon’s business-to-business sales effort, which would include sales to hospitals, doctor’s offices and dentists. Amazon on Tuesday announced “Business Prime Shipping,” which brings the quick delivery associated with Amazon household orders to workplaces. 

The Seattle company launched Amazon Business in 2015, offering tractor parts, latex gloves, file folders and millions of other products needed in factories, hospitals, schools and offices. Businesses are shifting their supply shopping online from less-efficient methods such as browsing print catalogs, faxing orders and telephoning sales representatives.

Online business-to-business sales – a broad category that includes pens and paper for the office as well as lab equipment and parts used in factories — will grow to $1.2 trillion in 2021 from $889 billion this year, according to Forrester Research Inc.

On a conference call Thursday with analysts, McKesson CEO John H. Hammergren said the wholesaler doesn’t “take the entry of any competitor lightly,” but said the company already has a large online order operation and similar to what Amazon does logistically. “To some extent, we were Amazon before it was cool to be Amazon.”

    Read more: https://www.bloomberg.com/news/articles/2017-10-26/drug-wholesalers-slump-after-amazon-com-obtains-state-licenses

    Trump Officials Dispute the Benefits of Birth Control to Justify Rules

    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.”

    Multiple studies have found that access or use of contraception reduced unintended pregnancies. 

    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.”

    Riskier Behavior

    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.”

      Read more: http://www.bloomberg.com/news/articles/2017-10-06/trump-officials-dispute-birth-control-benefits-to-justify-rules

      It was all yellow: did digitalis affect the way Van Gogh saw the world?

      Extracted from foxgloves, digitalis was once used as a treatment for epilepsy. Could a side effect have triggered the artists yellow period?

      It was recently the 127th anniversary of the tragic death of Vincent van Gogh. His short life came to an untimely end two days after he shot himself in the chest; he had experienced mental health issues through much of his life. In the absence of a definitive diagnosis, speculation as to the true nature of his illness fills volumes.

      Although he came under the care of several doctors during his life time, knowledge of diseases of the mind was in its infancy in the late nineteenth century. As a result, many of the treatments used at the time would have been ineffective if not potentially dangerous. From our point of view, however, one drug that might have been given to Van Gogh is particularly interesting.

      Towards the end of his life, under the care of Dr Gachet, it seems that Van Gogh may have been treated with digitalis for the epileptic fits he experienced. Digitalis, extracted from foxglove plants, is a powerful medicine still in use today as a treatment for certain heart conditions, but not epilepsy. In Van Goghs day, and for a long time before then, digitalis was known to be an effective treatment of dropsy, or accumulation of fluid in the body. Dropsy could have been caused by inefficient beating of the heart or because of liver disease. But with little understanding of the underlying causes of many diseases, almost anything shown to have an effect on the body even if that was simply to induce vomiting was considered a medical benefit. If the treatment for one disease was successful, it was often tried out on a host of others, just in case it proved to be a panacea. Extracts of foxglove really would have been effective in treating dropsy caused by heart failure, but would have done nothing for Van Goghs epilepsy. However, it is just possible it may have contributed to his artistic output.

      Portrait
      Portrait of Dr Gachet, by Vincent van Gogh. Gachet holds a foxglove, seen by some to suggest that he treated Van Gogh with digitalis. Photograph: DEA / G. DAGLI ORTI/De Agostini/Getty Images

      Digitalis is, in fact, a mixture of several different compounds that today are separated and used individually to treat heart conditions. One of the compounds, digoxin, is listed by the World Health Organisation as an essential medicine because of its huge benefit in the treatment of abnormal heart rhythms such as atrial fibrillation. Digoxin has two effects on the heart. Firstly, it helps to control the electrical signals that are sent across the heart to trigger the cells to beat in a coordinated way producing a heartbeat. Secondly, it makes the individual heart cells contract more slowly and strongly, improving the efficiency of the pumping action to move blood round the body.

      To achieve these effects on the heart, digoxin and related compounds interact with the enzyme Na+/K+ ATPase. Digoxin is a very potent drug, the therapeutic dose is miniscule, and it is very close to the level that can also produce digitalis intoxication. Such a narrow gap between a therapeutic and potentially harmful dose would simply not be tolerated in a new drug being brought to market. However, the undoubted benefit of digoxin and its long history of use means it is a vital part of modern medicine. Because the drug has been in use for so long over 200 years, since the physician William Withering advocated its use in 1775 we have had plenty of time to understand how the drug works and the potential side-effects. Patients taking digoxin are carefully monitored and a number of antidotes have been developed to treat overdoses.

      The problem, as with all drugs, is side-effects. To achieve its effects on the heart, digoxin and related compounds interact with the enzyme Na+/K+ ATPase.Digoxins strong interaction with the enzyme means it is very potent, but Na+/K+ ATPase is distributed throughout the body. It is therefore the interaction between the drug and the enzymes located elsewhere in the body that is the cause of side-effects. The most common problems associated with digoxin are nausea and loss of appetite, but its other effects are more intriguing.

      Particularly high concentrations of digoxins target enzyme are found in the cone cells in retina of the eye. These are the cells that give us our colour perception. It is very rare, but some people taking digoxin and related drugs can experience haziness to their vision, or a yellow tinge to everything they see, known as xanthopsia. Occasionally, points of light may appear to have coloured halos around them. Rarer still are effects on pupil size, such as dilation, constriction or even unequal-sized pupils.

      The effects of digitalis intoxication have been suggested as the cause of Van Goghs yellow period and the spectacular sky he painted in The Starry Night. More circumstantial evidence comes from the two portraits Van Gogh produced of his doctor, Paul Gachet, showing him holding a foxglove flower. One of Van Goghs self portraits also shows uneven pupils.

      All of this is very interesting but it is pure speculation. Van Gogh may not have taken digitalis, and perhaps simply liked the colour yellow and the effect of swirling colours around the stars he painted. Unequal pupil size in his self-portrait may have been the result of a simple slip of the paintbrush.

      There are also many other factors to consider. Van Gogh was known to drink large quantities of absinthe (though not enough to produce yellow colour perception) as well as turpentine (which can affect vision but not colour perception). Whatever the reason for Van Goghs particular artistic choices, we can still appreciate his remarkable output from such a tragically short life.

      Read more: https://www.theguardian.com/science/blog/2017/aug/10/it-was-all-yellow-did-digitalis-affect-the-way-van-gogh-saw-the-world

      Rule that patients must finish antibiotics course is wrong, study says

      Experts suggest patients should stop taking the drugs when they feel better rather than completing their prescription

      Telling patients to stop taking antibiotics when they feel better may be preferable to instructing them to finish the course, according to a group of experts who argue that the rule long embedded in the minds of doctors and the public is wrong and should be overturned.

      Patients have traditionally been told that they must complete courses of antibiotics, the theory being that taking too few tablets will allow the bacteria causing their disease to mutate and become resistant to the drug.

      But Martin Llewelyn, a professor in infectious diseases at Brighton and Sussex medical school, and colleagues claim that this is not the case. In an analysis in the British Medical Journal, the experts say the idea that stopping antibiotic treatment early encourages antibiotic resistance is not supported by evidence, while taking antibiotics for longer than necessary increases the risk of resistance.

      There are some diseases where the bug can become resistant if the drugs are not taken for long enough. The most obvious example is tuberculosis, they say. But most of the bacteria that cause people to become ill are found on everybodys hands in the community, causing no harm, such as E coli and Staphylococcus aureus. People fall ill only when the bug gets into the bloodstream or the gut. The longer such bacteria are exposed to antibiotics, the more likely it is that resistance will develop.

      The experts say there has been too little research into the ideal length of a course of antibiotics, which also varies from one individual to the next, depending in part on what antibiotics they have taken in the past.

      In hospital, patients can be tested to work out when to stop the drugs. Outside hospital, where repeated testing may not be feasible, patients might be best advised to stop treatment when they feel better, they say. That, they add, is in direct contravention of World Health Organisation advice.

      Other experts in infectious diseases backed the group. I have always thought it to be illogical to say that stopping antibiotic treatment early promotes the emergence of drug-resistant organisms, said Peter Openshaw, president of the British Society for Immunology.

      This brief but authoritative review supports the idea that antibiotics may be used more sparingly, pointing out that the evidence for a long duration of therapy is, at best, tenuous. Far from being irresponsible, shortening the duration of a course of antibiotics might make antibiotic resistance less likely.

      Alison Holmes, a professor of infectious diseases at Imperial College London, said a great British authority, Prof Harold Lambert, had made the same point in a Lancet article entitled Dont keep taking the tablets as early as 1999. It remains astonishing that apart from some specific infections and conditions, we still do not know more about the optimum duration of courses or indeed doses in many conditions, yet this dogma has been pervasive and persistent.

      Jodi Lindsay, a professor of microbial pathogenesis at St Georges, University of London, said it was sensible advice. The evidence for completing the course is poor, and the length of the course of antibiotics has been estimated based on a fear of under-treating rather than any studies, she said. The evidence for shorter courses of antibiotics being equal to longer courses, in terms of cure or outcome, is generally good, although more studies would help and there are a few exceptions when longer courses are better for example, TB.

      But the Royal College of GPs expressed concerns. Recommended courses of antibiotics are not random, said its chair, Prof Helen Stokes-Lampard. They are tailored to individual conditions and in many cases, courses are quite short for urinary tract infections, for example, three days is often enough to cure the infection.

      We are concerned about the concept of patients stopping taking their medication midway through a course once they feel better, because improvement in symptoms does not necessarily mean the infection has been completely eradicated. Its important that patients have clear messages and the mantra to always take the full course of antibiotics is well known. Changing this will simply confuse people.

      The UKs chief medical officer, Prof Dame Sally Davies, said: The message to the public remains the same: people should always follow the advice of healthcare professionals. To update policies, we need further research to inform them.

      [The National Institute for Health and Care Excellence] is currently developing guidance for managing common infections, which will look at all available evidence on appropriate prescribing of antibiotics.

      The Department of Health will continue to review the evidence on prescribing and drug-resistant infections, as we aim to continue the great progress we have made at home and abroad on this issue.

      Read more: https://www.theguardian.com/society/2017/jul/26/rule-patients-must-finish-antibiotics-course-wrong-study-says

      People taking heartburn drugs could have higher risk of death, study claims

      Research suggests people on proton pump inhibitors are more likely to die than those taking different antacid or none at all

      Millions of people taking common heartburn and indigestion medications could be at an increased risk of death, research suggests.

      The drugs, known as proton pump inhibitors (PPIs), neutralise the acid in the stomach and are widely prescribed, with low doses also available without prescription from pharmacies. In the UK, doctors issue more than 50m prescriptions for PPIs every year.

      Now researchers say the drugs can increase risk of death, both compared with taking a different type of acid suppressant and not taking any at all.

      We saw a small excess risk of dying that could be attributed to the PPI drug, and the risk increased the longer they took them, said Ziyad Al-Aly, an epidemiologist from the University of Washington and co-author of the study.

      The team say the study suggests those who take the drugs without needing to could be most at risk. They urged people taking PPIs to check whether this was necessary.

      Previous research has raised a range of concerns about PPIs, including links to kidney disease, pneumonia, more hip fractures and higher rates of infection with C difficile, a superbug that can cause life-threatening sepsis, particularly in elderly people in hospitals.

      But the latest study is the first to show that PPIs can increase the chance of death. Published in the journal BMJ Open, it examined the medical records of 3.5 million middle-aged Americans covered by the US veterans healthcare system.

      The researchers followed 350,000 participants for more than five years and compared those prescribed PPIs to a group receiving a different type of acid suppressant known as an H2 blocker. They also took into account factors such as the participants age, sex and conditions ranging from high blood pressure to HIV.

      The results show that those who took PPIs could face a 25% higher risk of death than those who took the H2 blocker.

      In patients on [H2 blocker] tablets, there were 3.3 deaths per 100 people over one year. In the PPI group, this figure was higher at 4.7 per 100 people per year, said Al-Aly.

      The team also reported that the risk of death for those taking PPIs was 15% higher than those taking no PPIs, and 23% higher than for those taking no acid suppressants at all.

      Similar levels of increased risk were seen among people who used PPIs but had no gastrointestinal conditions, a result which the authors speculated might be driving the higher risk seen overall.

      Gareth Corbett, a gastroenterologist from Addenbrookes hospital in Cambridge who was not involved with the study, cautioned against panic, pointing out that in most cases the benefits of PPI far outweighed any risk. What was more, he said, while the increased risk sounded high, it was still very low for each person.

      PPIs are very effective medicines, proven to save lives and reduce the need for surgery in patients with bleeding gastric and duodenal ulcers and several other conditions, he said.

      The studys authors said it was important that PPIs were used only when necessary and stopped when no longer needed.

      Corbett agreed that many people take PPIs unnecessarily. They could get rid of their heartburn by making lifestyle changes, such as losing weight and cutting back on alcohol, caffeine and spicy foods, he said.

      The authors said the study was observational, meaning it did not show that PPIs were the cause of the increased risk of death, and that it was unclear how the drugs would act to affect mortality. They said the drugs could affect components within cells, known as lysosomes, that help break down waste material, or shortening protective regions at the end of chromosomes, known as telomeres.

      Aly said people on PPIs should check with their GP whether the drugs were still needed, adding: In some cases we expect that PPIs can be safely stopped, particularly in patients who have been taking them for a long time.

      Read more: https://www.theguardian.com/science/2017/jul/04/people-taking-heartburn-drugs-could-have-higher-risk-of-death-study-claims

      In Seattle US old-timers rediscover the high life on cannabis tours

      Retirement home residents take a trip to a producer

      Forget bingo, tea dances and seaside trips. Residents from a chain of Seattle retirement homes are going on Pot for Beginners tours to learn about and buy cannabis in the city, where its now legal.

      Connie Schick said her son roared with laughter when he heard she was joining a field trip to a cannabis-growing operation, an extraction plant and shop. The 79-year-old, who smoked the odd joint in the 70s, wanted to know how legalisation has changed the way the drug is used and produced.

      Schick was one of eight women, from their late 60s to mid-80s, who descended from a minibus emblazoned with the name of their assisted living centre, El Dorado West, outside Vela cannabis store last Tuesday.

      You can only play so many games of bingo, said Schick. My son thought it was hilarious that I was coming here, but Im open-minded and want to stay informed. Cannabis has come so far from the days when you smoked a sly joint and got into trouble if they found out. We used to call it hemp then and didnt know its strength. It just used to make me sleepy, so I didnt see the point.

      Schick, who uses a wheelchair after suffering a stroke, is interested in the therapeutic effects of cannabis. Its so different now. There are so many ways you can take it, and all these different types to help with aches and pains.

      They used to say it was a gateway drug to other things, like cocaine Lots of peoples views are changing.

      Certainly, the number of people aged 65 or older taking cannabis in the US is growing. The proportion of this age group who reported cannabis use in the past year rose more than tenfold from 0.2% to 2.1% between 2002 and 2014, according to the National Survey on Drug Use and Health. A Gallup poll last year showed that 3% of those over 65 smoke cannabis.

      Much of this is attributed to the ageing of the baby-boomer generation, who dabbled with the drug when they were young and are returning to it for medical or recreational use as it becomes legal and more normalised. Cannabis is now legal for medical use in 29 states and for medical and recreational use in eight (since 2012 in Seattle and the rest of Washington state).

      Most of the women on the tour were more interested in the medical use, although Denise Roux, 67, said: I would like to buy it to get high too but Im a cheap high, it doesnt take much.

      A seminar over sandwiches was held for thegroup as they sat in front of the large windows of the cultivation room, where they could see scores of plants growing under intense lighting.

      They were told about the different strains: uplifting sativa plants and more sedating indicas. They learned about tetrahydrocannabinol (THC), which gives a high, and cannabidiol (CBD) which does not, making CBD-rich cannabis appealing for medical use. A scientist in a lab coat who worked in the processing facility spoke about terpenes fragrant oils secreted by glands in the flower that give strains their different smells and flavours. Vials were sniffed and various ways to take cannabis were also covered, including smoking, vaporising and eating it.

      Roux, a retired administrative assistant, said: Im a big Google girl, but I wanted to talk to people who know about it so I can understand it all better. I have an autoimmune disease, which stops my appetite, and Im interested in marijuana from that standpoint. She added she had used cannabis recreationally in the 80s and had returned to it to help with her illness. I use a vape. It makes me sleepy and its a pain control, and it gives me an appetite.

      After the briefing, it was time for shopping. The store looked like an upmarket jewellers, with muted lighting and art on the walls, except the glass cabinets in the store were stocked with pre-rolled joints, edibles including chocolates and sweets, vape pens and bags of different strains of cannabis rather than diamond rings and necklaces.

      Darlene Johnson, 85, a former nurse, perused their contents. On the advice of a bearded bud tender, she bought a deep tissue and joint gel and a tincture to put in drinks, which she hopes will help with her severe neck pain. I wanted a non-psychoactive option, she said. I dont want to get high. I used to work in the emergency room and saw people come in sick from taking too many drugs, though not usually marijuana.

      Her friend, Nancy Mitchell, 80, has never tried cannabis. She has MS and had read that cannabis could help with her symptoms. I wanted to know more details, she said. My kids keep telling me, Mom, try it. I dont want to smoke things, but I see there are other ways.

      Smoking is not allowed at El Dorado West. Village Concepts, which runs the chain, has a no-smoking policy and it is illegal to consume cannabis in public in the state.

      The chains director of corporate development, Tracy Willis, said: There was one man who was smoking it on his patio and he refused to stop, so he had to leave. If youre using an edible, we dont have any issue with it, thats your own business. We treat it as a recreational thing.

      The tours began in response to questions from residents.They wanted to know where it was sold, how much money was made from it, where it was grown, said Willis. Weve had a good reaction [to the tours] from nine out of 10 relatives, but some are horrified. One angry daughter said we were encouraging marijuana use. Her mother told her to butt out.

      Participants
      Participants on the tour learned about different ways to use cannabis. Photograph: Jason Redmond/Reuters

      Read more: https://www.theguardian.com/society/2017/jul/01/seattle-retirement-home-cannabis-tours

      How I Reversed Type 2 Diabetes, Hypertension, AND Lost Weight Naturally Without Drugs

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      Thanksgiving 2007 a family member tested my blood sugar. It was 417. I started reading and bout a test-meter. By the time I got to see a Dr about 3 months later I had already begun making progress (my graph: ) – and found him less knowledgeable about the basics than myself so I rejected his drugs and his certainty that I would die if I didn't do what he said (he was annoyingly deadly IMHO).

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      DSCN0719.MOV

      5. Medical Conference: Beat, Reverse, Cure Type 2 Diabetes Naturally Without Drugs

      Say Goodbye to High Blood Sugar Levels & Painful Insulin Shots!

      diabetes image 2

      The New Nutraceutical Breakthrough To Help You Manage Your Diabetes 

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      V

      1 2 3
      What Is The Chinese
      Secret To Optimum
      Blood Pressure?
      Why This Is The
      Healthiest Oil On Earth?
      Click To Learn More
      Bring Your Old
      Battery Back To Life!
      4 5 6
      How To Survive In
      Bed & Nail Women
      Like A Rockstar!
      100% of Your
      Vital Nutrition In
      Just 30 Seconds
      How A 2000-Year-Old
      Nepalese Secret To Cure
      Your Sciatica in 7
      DAYS OR LESS

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      Segment No. 5 of diabetes lecture in Pittsburgh. Topics: Cell biology/5 functions, Nutritional biomarkers, The 5 "super" foods, Q&A, Testimonial. Ex-diabetic, who almost died of diabetic coma, explains how to defeat Type 2 diabetes, based on his experience, research, and acclaimed diabetic book, Death to Diabetes (ISBN 0977360741), the Diabetes DVD (ISBN 0977360733), and the soon-to-be-released The Diabetes Handbook (ISBN 097736075X).

      Penn State graduate, Xerox engineer, Hughes Aircraft, Urban League math tutor, Eta Kappa Nu honor society, Farrell High School, Shenango Valley