Meet the Company Trying to Democratize Clinical Trials With AI

A decade ago, Pablo Graiver was working as a VP at Kayak, the online airfare aggregator, when he sat down to dinner with an old friend—a heart surgeon from his home country of Argentina. The talk turned to how tech was doing more to save folks a few bucks on a flight to Rome than to save people’s lives. The biggest problem in healthcare? “Clinical trials,” she said. “They’re a disaster.”

Right now, the US has exactly 19,816 clinical trials open and ready to recruit patients—trials of promising new therapeutics to fight everything from HIV to cancer to Alzheimer’s. About 18,000 of them will get stuck on the tarmac because they won’t get enough people enrolled. And a third of those will never get off the ground at all, for the same reason.

So where are all the patients? Well, the vast majority of them either don’t know the trials exist, or don’t know they can participate. Since 2000, the government has kept details of every clinical drug trial in a national registry, but it’s a nightmare for the average human to navigate. So most pharma companies use recruitment firms to painstakingly comb through patient medical records and find people who might be a good fit—geographically, genetically, and generationally. Each patient hunt is basically a one-off. Like, say if every time you wanted to fly somewhere you had to search on the websites of United, Delta, American, Frontier, Alaska, and Southwest one at a time. And then do the same thing for hotels. (Man, the early aughts were bleak, weren’t they?)

Graiver’s new company, Antidote, does for clinical trials what Kayak and Orbitz and Priceline did for travel. It gives that painful patient matching problem an e-commerce solution. “Fundamentally, it’s just a question of structuring information,” says Graiver. “Which is something the tech world is great at. I was shocked no one had done it already.”

The information that most needed help was something called inclusion/exclusion criteria. It’s what makes a patient eligible to enroll (or not) in a trial: things like age, sex, prior treatment regimes, and current health status. When drugmakers submit new trial details to ClinicalTrials.gov, most of it gets entered as structured data, the kind of thing you enter in a drop-down menu. But eligibility criteria gets entered in a free text field, where you can write whatever you want. That lack of structure means a machine can’t read it—unless it’s been properly trained.

That’s what Antidote does. Graiver’s company started by amassing thousands of clinical studies from ClinicalTrials.gov and the World Health Organization, and they hired clinical experts to manually standardize all that free-wheeling trial jargon into structured language a search engine could understand. Then they trained it to categorize and identify studies using that language.

If you search for adult onset diabetes, it will know to pull up trials for Type 2 diabetes, and diabetes mellitus 2, and T2DM—since they’re all ways to describe the same disease. Called TrialReach at the time, the company proceeded slowly, focusing first only on diabetes and Alzheimer’s studies.

Then in 2015, Graiver’s platform got a big boost from big pharma. For two years prior, Novartis, Pfizer, and Eli Lilly had worked together to organize their trial data to be machine-readable. But as they looked to expand the consortium, the three pharma giants realized a need for a more neutral host organization. So they gave the tech to Graiver. Today, three years and a new name later, Antidote has annotated more than 14,000 trials—about 50 percent of what’s listed on ClinicalTrials.gov—spanning 726 conditions.

The result of all this data structuring is that Antidote can take a number (say, 50) and return studies that say something like this: “Ages Eligible for Study: Child, Adult, Senior” but not studies like this: “Ages Eligible for Study: 75 years and older.” And the interface is pretty slick. You type in your condition, where you live, then choose your age and sex. For a 50-year-old woman living in St. Louis, Missouri with lung cancer, 617 trials pop up. On the next screen, Antidote asks how far you’d be willing to travel; within 20 miles the trial options narrow to 69. If you know what kind of mutation is causing your lung cancer, Antidote can winnow down the number even further. At this point, you could print out a list of the trials, take them to your oncologist, and discuss your options.

Or, you can click on any trials you’re interested in, register your email with Antidote, and they’ll send you contact information for the trial organizers, along with next steps. They’ll also keep you updated on any new trials for which you might be a match.

The service is totally free for patients, who can find it on their own or through a widget on websites for patient organizations. Through 231 of those partnerships, including with the American Kidney Fund, Muscular Dystrophy Association, and Lung Cancer Alliance, Antidote says it reaches more than 15 million people per month. On the website of JDRF—the leading Type 1 Diabetes research fund in the world—27,863 people have searched for a trial using the Antidote widget since it launched in 2016. That’s more than in the previous 10 years combined using JDRF’s existing search tool.

“It makes it less of a wild goose chase for patients,” says Esther Schorr, COO of PatientPower, an online cancer news site and Antidote partner. Surveys of their 30,000 member community have shown an uptick in trial enrollment since the widget went up about a year ago. “There’s just so much information for the common man or woman to get through. Technology can really make a patient’s journey easier.”

It’s also making things easier (and cheaper) for drugmakers. Antidote makes money chiefly by selling limited access to this user database to the world’s biggest pharma companies and clinical research institutions, helping them to fill their own trials.1 When you enter your email address, you’re consenting not just to having your personal information shared with the sponsor of a particular trial, but to having your deidentified data shared with third parties.

Antidote maintains that it still keeps up some kind of a firewall; pharma companies can’t just contact you out of the blue—they have to place a request through Antidote, that you can accept or deny. But the broad consent language in the company’s privacy policy gives Antidote a lot of latitude with how it can use your name, age, sex, location, and any other details you provide about your medical condition.

It’s a tradeoff between privacy and care that many patients are confronting these days. Like the seniors filling their homes and wardrobes with IoT-enabled sensors to keep track of their movement and heart rates. Or the record number of Americans letting companies mine their DNA, so they can know if they’re at higher risk for genetic diseases like Alzheimer’s or cancer. For Antidote’s users, the promise of a cure—however distant—is well worth the risk.

_1 Correction appended 01/30/18 5:40pm EST This story was changed to clarify how Antidote earns revenues by providing clinical trial sponsors access to eligible patients.

Read more: https://www.wired.com/story/meet-the-company-trying-to-democratize-clinical-trials-with-ai/

The Second Coming of Ultrasound

Before Pierre Curie met the chemist Marie Sklodowska; before they married and she took his name; before he abandoned his physics work and moved into her laboratory on Rue Lhomond where they would discover the radioactive elements polonium and radium, Curie discovered something called piezoelectricity. Some materials, he found—like quartz and certain kinds of salts and ceramics—build up an electric charge when you squeeze them. Sure, it’s no nuclear power. But thanks to piezoelectricity, US troops could locate enemy submarines during World War I. Thousands of expectant parents could see their baby’s face for the first time. And one day soon, it may be how doctors cure disease.

Ultrasound, as you may have figured out by now, runs on piezoelectricity. Applying voltage to a piezoelectric crystal makes it vibrate, sending out a sound wave. When the echo that bounces back is converted into electrical signals, you get an image of, say, a fetus, or a submarine. But in the last few years, the lo-fi tech has reinvented itself in some weird new ways.

Researchers are fitting people’s heads with ultrasound-emitting helmets to treat tremors and Alzheimer’s. They’re using it to remotely activate cancer-fighting immune cells. Startups are designing swallowable capsules and ultrasonically vibrating enemas to shoot drugs into the bloodstream. One company is even using the shockwaves to heal wounds—stuff Curie never could have even imagined.

So how did this 100-year-old technology learn some new tricks? With the help of modern-day medical imaging, and lots and lots of bubbles.

Bubbles are what brought Tao Sun from Nanjing, China to California as an exchange student in 2011, and eventually to the Focused Ultrasound Lab at Brigham and Women’s Hospital and Harvard Medical School. The 27-year-old electrical engineering grad student studies a particular kind of bubble—the gas-filled microbubbles that technicians use to bump up contrast in grainy ultrasound images. Passing ultrasonic waves compress the bubbles’ gas cores, resulting in a stronger echo that pops out against tissue. “We’re starting to realize they can be much more versatile,” says Sun. “We can chemically design their shells to alter their physical properties, load them with tissue-seeking markers, even attach drugs to them.”

Nearly two decades ago, scientists discovered that those microbubbles could do something else: They could shake loose the blood-brain barrier. This impassable membrane is why neurological conditions like epilepsy, Alzheimer’s, and Parkinson’s are so hard to treat: 98 percent of drugs simply can’t get to the brain. But if you station a battalion of microbubbles at the barrier and hit them with a focused beam of ultrasound, the tiny orbs begin to oscillate. They grow and grow until they reach the critical size of 8 microns, and then, like some Grey Wizard magic, the blood-brain barrier opens—and for a few hours, any drugs that happen to be in the bloodstream can also slip in. Things like chemo drugs, or anti-seizure medications.

This is both super cool and not a little bit scary. Too much pressure and those bubbles can implode violently, irreversibly damaging the barrier.

That’s where Sun comes in. Last year he developed a device that could listen in on the bubbles and tell how stable they were. If he eavesdropped while playing with the ultrasound input, he could find a sweet spot where the barrier opens and the bubbles don’t burst. In November, Sun’s team successfully tested the approach in rats and mice, publishing their results in Proceedings in the National Academy of Sciences.

“In the longer term we want to make this into something that doesn’t require a super complicated device, something idiot-proof that can be used in any doctor’s office,” says Nathan McDannold, co-author on Sun’s paper and director of the Focused Ultrasound Lab. He discovered ultrasonic blood-brain barrier disruption, along with biomedical physicist Kullervo Hynynen, who is leading the world’s first clinical trial evaluating its usefulness for Alzheimer’s patients at the Sunnybrook Research Institute in Toronto. Current technology requires patients to don special ultrasound helmets and hop in an MRI machine, to ensure the sonic beams go to the right place. For the treatment to gain any widespread traction, it’ll have to become as portable as the ultrasound carts wheeled around hospitals today.

More recently, scientists have realized that the blood-brain barrier isn’t the only tissue that could benefit from ultrasound and microbubbles. The colon, for instance, is pretty terrible at absorbing the most common drugs for treating Crohn’s disease, ulcerative colitis, and other inflammatory bowel diseases. So they’re often delivered via enemas—which, inconveniently, need to be left in for hours.

But if you send ultrasound waves waves through the colon, you could shorten that process to minutes. In 2015, pioneering MIT engineer Robert Langer and then-PhD student Carl Schoellhammer showed that mice treated with mesalamine and one second of ultrasound every day for two weeks were cured of their colitis symptoms. The method also worked to deliver insulin, a far larger molecule, into pigs.

Since then, the duo has continued to develop the technology within a start-up called Suono Bio, which is supported by MIT’s tech accelerator, The Engine. The company intends to submit its tech for FDA approval in humans sometime later this year.

Ultrasound sends pressure waves through liquid in the body, creating bubble-filled jets that can propel microscopic drug droplets like these into surrounding tissues.
Suono Bio

Instead of injecting manufactured microbubbles, Suono Bio uses ultrasound to make them in the wilds of the gut. They act like jets, propelling whatever is in the liquid into nearby tissues. In addition to its backdoor approach, Suono is also working on an ultrasound-emitting capsule that could work in the stomach for things like insulin, which is too fragile to be orally administered (hence all the needle sticks). But Schoellhammer says they have yet to find a limit on the kinds of molecules they can force into the bloodstream using ultrasound.

“We’ve done small molecules, we’ve done biologics, we’ve tried DNA, naked RNA, we’ve even tried Crispr,” he says. “As superficial as it may sound, it all just works.”

Earlier this year, Schoellhammer and his colleagues used ultrasound to deliver a scrap of RNA that was designed to silence production of a protein called tumor necrosis factor in mice with colitis. (And yes, this involved designing 20mm-long ultrasound wands to fit in their rectums). Seven days later, levels of the inflammatory protein had decreased sevenfold and symptoms had dissipated.

Now, without human data, it’s a little premature to say that ultrasound is a cure-all for the delivery problems facing gene therapies using Crispr and RNA silencing. But these early animal studies do offer some insights into how the tech might be used to treat genetic conditions in specific tissues.

Even more intriguing though, is the possibility of using ultrasound to remotely control genetically-engineered cells. That’s what new research led by Peter Yingxiao Wang, a bioengineer at UC San Diego, promises to do. The latest craze in oncology is designing the T-cells of your immune system to better target and kill cancer cells. But so far no one has found a way to go after solid tumors without having the T-cells also attack healthy tissue. Being able to turn on T-cells near a tumor but nowhere else would solve that.

Wang’s team took a big step in that direction last week, publishing a paper that showed how you could convert an ultrasonic signal into a genetic one. The secret? More microbubbles.

This time, they coupled the bubbles to proteins on the surface of a specially designed T-cell. Every time an ultrasonic wave passed by, the bubble would expand and shrink, opening and closing the protein, letting calcium ions flow into the cell. The calcium would eventually trigger the T-cell to make a set of genetically encoded receptors, directing it it to attack the tumor.

“Now we’re working on figuring out the detection piece,” says Wang. “Adding another receptor so that we’ll known when they’ve accumulated at the tumor site, then we’ll use ultrasound to turn them on.”

In his death, Pierre Curie was quickly eclipsed by Marie; she went on to win another Nobel, this time in chemistry. The discovery for which she had become so famous—radiation—would eventually take her life, though it would save the lives of so many cancer patients in the decades to follow. As ultrasound’s second act unfolds, perhaps her husband’s first great discovery will do the same.

Read more: https://www.wired.com/story/the-second-coming-of-ultrasound/

‘I dont know how they live with themselves’ artist Nan Goldin takes on the billionaire family behind OxyContin

The photographer became an addict after getting hooked on a prescription opioid. Now clean, she is waging war on the art philanthropists who have profited from the crisis

‘I dont know how they live with themselves’ artist Nan Goldin takes on the billionaire family behind OxyContin

‘I dont know how they live with themselves’ artist Nan Goldin takes on the billionaire family behind OxyContin

The photographer became an addict after getting hooked on a prescription opioid. Now clean, she is waging war on the art philanthropists who have profited from the crisis

Read more: https://www.theguardian.com/artanddesign/2018/jan/22/nan-goldin-interview-us-opioid-epidemic-heroin-addict-oxycontin-sackler-family

Vermont just legalized marijuana, but not like Colorado

Weed, dude.
Image: The Washington Post/Getty Images

 The Green Mountain State now has a totally different meaning for Vermont.

For the first time, a state legislature in the U.S. legalized adult cannabis use for adults 21 and older. The other states that allow recreational cannabis use — Colorado, Washington, Oregon, Alaska, California, Nevada, Massachusetts, and Maine, as well as Washington D.C. — got there with ballot measures. 

Vermont Gov. Phil Scott signed the bill on Monday, which will go into effect on July 31, and will allow adults to possess one ounce or less of cannabis flower. Additionally, adults may posses up to two mature marijuana plants and up to four immature plants. 

The bill does not permit the sale of recreational cannabis, meaning you can not go to your neighborhood pot shop and pick up an ounce of OG Kush. This marks an important opportunity for states that may be considering legal cannabis use in their state, but aren’t ready to take the plunge into recreational sales like Colorado, or most recently California. The Vermont legislature is expected to develop a system for sales and taxation in the future. 

Other state legislatures that could follow in Vermont’s footsteps include Connecticut, Delaware, Illinois, Maryland, New Hampshire, New Jersey, and Rhode Island.

‘I personally believe that what adults do behind closed doors and on private property is their choice.’

“I personally believe that what adults do behind closed doors and on private property is their choice, so long as it does not negatively impact the health and safety of others, especially children,” Scott said in a statement. 

“While this legislation decriminalizes, for adults 21 and older, personal possession of no more than 1 ounce, and cultivation of two mature plants on their private property, marijuana remains a controlled substance in Vermont and its sale is prohibited. Also, consumption of marijuana in public places is prohibited. Consumption of marijuana by operators and passengers in a motor vehicle is prohibited. Schools, employers, municipalities and landlords are also empowered to adopt policies and ordinances further restricting the cultivation and use,” the statement reads. 

Scott also directly said he would veto any plan that would implement the sale of commercial cannabis until there is a plan to “develop comprehensive education, prevention and highway safety strategies.”

“To be very direct: There must be comprehensive and convincing plans completed in these areas before I will begin to consider the wisdom of implementing a commercial ‘tax and regulate’ system for an adult marijuana market,” Scott said. “It is important for the General Assembly to know that — until we have a workable plan to address each of these concerns — I will veto any additional effort along these lines, which manages to reach my desk.”

Scott previously vetoed a version of the same bill, saying, “We must get this right.” 

In an October Gallup pole, 64 percent of Americans supported legalized marijuana use in the United States, which is an all-time high. 

While states continue to legalize cannabis use, marijuana remains federally illegal as a Schedule 1 drug on the DEA’s classification list, alongside heroin. Additionally, U.S. Attorney General Jeff Sessions vetoed policies put in place by the Obama administration that protects states that legalize cannabis earlier this month, striking fear into the cannabis industry that the Feds may crack down on recreational sales.  

Read more: http://mashable.com/2018/01/22/vermont-legal-marijuana-cannabis-weed/

Photographer Reveals The Addicted Side Of The Streets Of Philadelphia, And Its Terrifying

Kensington Avenue in North Philadelphia is infamous for drug abuse and prostitution. The Avenue runs 3 miles through what is now a dangerous and crime-ridden neighborhood. Kensington Blues is a photography series by Jeffrey Stockbridge, 36, that documented the struggles and the dark reality of local residents.

Between 2008 and 2014, the photographer took a series of intimate portraits of people capturing a side of Philadelphia that is rarely seen or talked about. The residents shared their stories, talking about drugs, prostitution and other struggles of their lives.

“The goal of my work is to enable people to relate to one another in a fundamentally human way, despite any commonly perceived differences”- Jeffrey shared on his website. “I rely on the trust and sincerity of those I photograph to help me in this process.”

Take a look at the powerful images below.

“We out here so we can get money so we has somewhere to rest our heads. We look out for each other. If I can’t get money, she gets it, and whatever money we get we share…We need quick money cause we need somewhere to sleep every day. I mean, trust me, we don’t want to be out here doing this. This is the last thing I want to do….

“We out here so we can get money so we has somewhere to rest our heads. We look out for each other. If I can’t get money, she gets it, and whatever money we get we share…We need quick money cause we need somewhere to sleep every day. I mean, trust me, we don’t want to be out here doing this. This is the last thing I want to do. But I do what I have to do to take care of my sister. Cause she’s all I got and I’m all she’s got.”

Al lives in a house off Kensington Avenue without electricity or running water. He sometimes rents his upstairs bedroom to prostitutes in need of a private location for engaging in sex and drug use.

“I’m 55 years old, I have a master’s degree in psychology, but after my husband, mother and father, died in a car accident two years ago, I lost my whole family, my career, one, my health, all in one go.”

She told that she often sleeps on the streets during the day to protect herself at night.

They still have children, whom they gave away to a special agency for their protection. “We gave the kids away, people say it’s a selfish act, but I think it’s the best I could do for their better future,” Rachel said.

She is 25 years old, working in the sex industry since she was 18.

“I’ve been raped, and, you know, almost killed really”

A local resident, at the time she was 41. Carol told the photographer that she had been doing heroin for 21 years and it became “the love of her life”.

The veins in Sarah’s arms were no good for injection, so she asked Dennis for the drug to be injected to her neck.

“I don’t just do this for drugs. I do this because I wanna eat, because I like to buy clothes, because I like the small things, you know. I did have a normal life once but…I really believe, like if my, if my family say like, “Mary come, come home stay with us” like, if I could I would…”

He struggled with drug addiction after being released from prison. Sepsis developed in his left leg. Because of his addiction, he failed to meet the treatment regimen and eventually the doctors had to amputate part of the leg.

Matt shoots Brian in the neck in front of the McPherson Square Library on Kensington Avenue. It’s 10 AM on Sunday morning.

Maria: “I’ve been here almost 8 years and I see a lot of bad stuff going around. They say when you go between it, you gonna do it too.” Robert: “You don’t need no cable, you don’t have to watch TV. You just gotta sit out here. You see drama, you see soap opera, you see violence and crime.” Maria: “You even see sex.”

“I don’t really ask people for a lot, I get my money, like I don’t like to, cause a lot of times to get people to take care of you, you have to lie to them. And then lead them on and make them think that you’re gonna get clean. And then, and then it ends up getting to be too much, where they’re trying to control what you do….

“I don’t really ask people for a lot, I get my money, like I don’t like to, cause a lot of times to get people to take care of you, you have to lie to them. And then lead them on and make them think that you’re gonna get clean. And then, and then it ends up getting to be too much, where they’re trying to control what you do. And I’d rather just get the money and end it at that with no strings attached cause I don’t need someone following me around, trying to track me down like, trying to drop me off at rehabs and shit.”

“I went into rehab, for, like, snorting cocaine, taking oxies, perks, and I met people that did dope and smoked crack, and, you know, like, one thing led to another, and I was just, I was, I wanted to try it, and I did.”

“I sold a lot of drugs and was involved with a lot of like, stuff that had to do with shooting guns and all. Most of it was uh selling drugs and collecting money that was owed to me and it caused me getting into a lot of trouble.”

“What I’m doing I really don’t particularly care to be doing, but I do it anyway, and I’m not ashamed of it ’cause if I was ashamed of it, I wouldn’t do it….Until I decide to change it’s what I’m gonna do. Hopefully, like, the will of God…will make me strong enough and give me the determination to stop and get some help.”

Read more: http://www.boredpanda.com/portraits-kensington-blues-jeffrey-stockbridge/

Spinal-Cord Implants to Numb Pain Emerge as Alternative to Pills

For millions of Americans suffering from debilitating nerve pain, a once-overlooked option has emerged as an alternative to high doses of opioids: implanted medical devices using electricity to counteract pain signals the same way noise-canceling headphones work against sound. 

The approach, called neuromodulation, has been a godsend for Linda Landy, who was a 42-year-old runner when a foot surgery went awry in 2008. She was diagnosed with complex regional pain syndrome, a condition dubbed the suicide disease by doctors: The pain is so unrelenting that many people take their own lives.

Linda Landy and family

Last November, Landy underwent surgery to get an Abbott Laboratories device that stimulates the dorsal root ganglion, a spot in the spine that was the pain conduit for her damaged nerves. A year after getting her implant, called DRG, she’s cut back drastically on pain pills.

“The DRG doesn’t take the pain completely away, but it changes it into something I can live with,” said Landy, a mother of three in Fort Worth, Texas. She’s now now able to walk again and travel by plane without using a wheelchair. “It sounds minor, but it’s really huge.”

Crackdown on Opioids

Recent innovations from global device makers like Abbott to smaller specialists such as Nevro Corp. made the implants more powerful and effective. Combined with a national crackdown on narcotics and wanton pain pill prescriptions, they are spurring demand for implants.

The market may double to $4 billion in 10 years, up from about $1.8 billion in the U.S. and $500 million in Europe today, according to health-care research firm Decisions Resources Group.

“There was a big stigma around this when it first came out,” said Paul Desormeaux, a Decisions Resources analyst in Toronto. “The idea of sending an electrical signal through your nervous system was a little daunting, but as clinical data has come out and physicians have been able to prove its safety, there has been a big change in the general attitude.”

Read More: Millions Face Pain, Withdrawal as Opioid Prescriptions Plummet

At least 50 million adults in the U.S. suffer from chronic pain, according to the Centers for Disease Control and Prevention. Only a fraction of them would benefit from spinal-cord stimulation — about 3.6 million, according to Decisions Resources — but those are patients who are often given the highest doses of narcotics. They include people with nerve damage stemming from conditions like diabetic neuropathy and shingles, as well as surgeries.

“There is no question we are reducing the risk of opioid dependence by implanting these devices,” said Timothy Deer, president of the Spine and Nerve Centers of the Virginias in Charleston, West Virginia, a hotbed of the opioid epidemic. “If we get someone before they are placed on opioids, 95 percent of the time we can reduce their need to ever go on them.”

Studies show spinal-cord stimulators can reduce use of powerful pain drugs by 60 percent or more, said Deer, a clinical professor of anesthesiology.

Read More: Tangled Incentives Push Drugmakers Away From an Opioid Solution

Technology breakthroughs that are just now reaching patients came from a better understanding of how pain signals are transmitted within the spinal cord, the main thoroughfare between the command center in the brain and the body.

For some chronic pain patients, the spinal cord runs too efficiently, speeding signs of distress. Stimulators send their own pulses of electrical activity to offset or interrupt the pain zinging along the nerve fibers. They have been available for more than three decades, but until recently their invasive nature, potential safety risks and cost limited demand.

Market Leader Abbott

Illinois-based Abbott, with its $29 billion acquisition of St. Jude Medical this year, took the market lead with advances that allow it to target specific nerves and tailor the treatment. Nevro, of Redwood City, California, has rolled out improvement to its Senza system, a best-in-class approach that is safe while getting an MRI and operates without the tingling that often accompanies spinal-cord stimulation.

In the latest devices, which cost $30,000 or more, codes that are running the electrical pulses are more sophisticated. The frequency, rate and amplitude can be adjusted, often by the patients, which allows personalized therapy. 

The new implants are also smaller: The surgery is generally an outpatient procedure with minimal post-operative pain and a short recovery. They have longer battery life, reducing the need for replacement. And patients can try out a non-invasive version of the equipment before getting a permanent implant.

“This is really a defining moment in what we can do to impact the lives of people who suffer from chronic pain,” said Allen Burton, Abbott’s medical director of neuromodulation. “We can dampen the chronic pain signal and give patients their lives back.”

Medtronic Plc, which pioneered the technique but ceded the lead in recent years, is now working on next-generation devices. The company recently gained approval for the smallest pain-management implant, Intellis. In development are devices that can detect pain waves and adjust automatically, said Geoff Martha, executive vice president of Medtronic’s restorative therapies group.

“A self-correcting central nervous system — that’s the panacea. That’s the ultimate goal,” Martha said. “It could take a huge bite out of the opioid problem.”

    Read more: http://www.bloomberg.com/news/articles/2017-12-26/spinal-cord-implants-to-numb-pain-emerge-as-alternative-to-pills

    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/

    Portugals radical drugs policy is working. Why hasnt the world copied it?

    The long read: Since it decriminalised all drugs in 2001, Portugal has seen dramatic drops in overdoses, HIV infection and drug-related crime

    When the drugs came, they hit all at once. It was the 80s, and by the time one in 10 people had slipped into the depths of heroin use bankers, university students, carpenters, socialites, miners Portugal was in a state of panic.

    lvaro Pereira was working as a family doctor in Olho in southern Portugal. People were injecting themselves in the street, in public squares, in gardens, he told me. At that time, not a day passed when there wasnt a robbery at a local business, or a mugging.

    The crisis began in the south. The 80s were a prosperous time in Olho, a fishing town 31 miles west of the Spanish border. Coastal waters filled fishermens nets from the Gulf of Cdiz to Morocco, tourism was growing, and currency flowed throughout the southern Algarve region. But by the end of the decade, heroin began washing up on Olhos shores. Overnight, Pereiras beloved slice of the Algarve coast became one of the drug capitals of Europe: one in every 100 Portuguese was battling a problematic heroin addiction at that time, but the number was even higher in the south. Headlines in the local press raised the alarm about overdose deaths and rising crime. The rate of HIV infection in Portugal became the highest in the European Union. Pereira recalled desperate patients and families beating a path to his door, terrified, bewildered, begging for help. I got involved, he said, only because I was ignorant.

    In truth, there was a lot of ignorance back then. Forty years of authoritarian rule under the regime established by Antnio Salazar in 1933 had suppressed education, weakened institutions and lowered the school-leaving age, in a strategy intended to keep the population docile. The country was closed to the outside world; people missed out on the experimentation and mind-expanding culture of the 1960s. When the regime ended abruptly in a military coup in 1974, Portugal was suddenly opened to new markets and influences. Under the old regime, Coca-Cola was banned and owning a cigarette lighter required a licence. When marijuana and then heroin began flooding in, the country was utterly unprepared.

    Pereira tackled the growing wave of addiction the only way he knew how: one patient at a time. A student in her 20s who still lived with her parents might have her family involved in her recovery; a middle-aged man, estranged from his wife and living on the street, faced different risks and needed a different kind of support. Pereira improvised, calling on institutions and individuals in the community to lend a hand.

    In 2001, nearly two decades into Pereiras accidental specialisation in addiction, Portugal became the first country to decriminalise the possession and consumption of all illicit substances. Rather than being arrested, those caught with a personal supply might be given a warning, a small fine, or told to appear before a local commission a doctor, a lawyer and a social worker about treatment, harm reduction, and the support services that were available to them.

    The opioid crisis soon stabilised, and the ensuing years saw dramatic drops in problematic drug use, HIV and hepatitis infection rates, overdose deaths, drug-related crime and incarceration rates. HIV infection plummeted from an all-time high in 2000 of 104.2 new cases per million to 4.2 cases per million in 2015. The data behind these changes has been studied and cited as evidence by harm-reduction movements around the globe. Its misleading, however, to credit these positive results entirely to a change in law.

    Portugals remarkable recovery, and the fact that it has held steady through several changes in government including conservative leaders who would have preferred to return to the US-style war on drugs could not have happened without an enormous cultural shift, and a change in how the country viewed drugs, addiction and itself. In many ways, the law was merely a reflection of transformations that were already happening in clinics, in pharmacies and around kitchen tables across the country. The official policy of decriminalisation made it far easier for a broad range of services (health, psychiatry, employment, housing etc) that had been struggling to pool their resources and expertise, to work together more effectively to serve their communities.

    The language began to shift, too. Those who had been referred to sneeringly as drogados (junkies) became known more broadly, more sympathetically, and more accurately, as people who use drugs or people with addiction disorders. This, too, was crucial.

    It is important to note that Portugal stabilised its opioid crisis, but it didnt make it disappear. While drug-related death, incarceration and infection rates plummeted, the country still had to deal with the health complications of long-term problematic drug use. Diseases including hepatitis C, cirrhosis and liver cancer are a burden on a health system that is still struggling to recover from recession and cutbacks. In this way, Portugals story serves as a warning of challenges yet to come.

    Despite enthusiastic international reactions to Portugals success, local harm-reduction advocates have been frustrated by what they see as stagnation and inaction since decriminalisation came into effect. They criticise the state for dragging its feet on establishing supervised injection sites and drug consumption facilities; for failing to make the anti-overdose medication naloxone more readily available; for not implementing needle-exchange programmes in prisons. Where, they ask, is the courageous spirit and bold leadership that pushed the country to decriminalise drugs in the first place?


    In the early days of Portugals panic, when Pereiras beloved Olho began falling apart in front of him, the states first instinct was to attack. Drugs were denounced as evil, drug users were demonised, and proximity to either was criminally and spiritually punishable. The Portuguese government launched a series of national anti-drug campaigns that were less Just Say No and more Drugs Are Satan.

    Informal treatment approaches and experiments were rushed into use throughout the country, as doctors, psychiatrists, and pharmacists worked independently to deal with the flood of drug-dependency disorders at their doors, sometimes risking ostracism or arrest to do what they believed was best for their patients.

    In 1977, in the north of the country, psychiatrist Eduno Lopes pioneered a methadone programme at the Centro da Boavista in Porto. Lopes was the first doctor in continental Europe to experiment with substitution therapy, flying in methadone powder from Boston, under the auspices of the Ministry of Justice, rather than the Ministry of Health. His efforts met with a vicious public backlash and the disapproval of his peers, who considered methadone therapy nothing more than state-sponsored drug addiction.

    In Lisbon, Odette Ferreira, an experienced pharmacist and pioneering HIV researcher, started an unofficial needle-exchange programme to address the growing Aids crisis. She received death threats from drug dealers, and legal threats from politicians. Ferreira who is now in her 90s, and still has enough swagger to carry off long fake eyelashes and red leather at a midday meeting started giving away clean syringes in the middle of Europes biggest open-air drug market, in the Casal Ventoso neighbourhood of Lisbon. She collected donations of clothing, soap, razors, condoms, fruit and sandwiches, and distributed them to users. When dealers reacted with hostility, she snapped back: Dont mess with me. You do your job, and Ill do mine. She then bullied the Portuguese Association of Pharmacies into running the countrys and indeed the worlds first national needle-exchange programme.

    A flurry of expensive private clinics and free, faith-based facilities emerged, promising detoxes and miracle cures, but the first public drug-treatment centre run by the Ministry of Health the Centro das Taipas in Lisbon did not begin operating until 1987. Strapped for resources in Olho, Pereira sent a few patients for treatment, although he did not agree with the abstinence-based approach used at Taipas. First you take away the drug, and then, with psychotherapy, you plug up the crack, said Pereira. There was no scientific evidence to show that this would work and it didnt.

    He also sent patients to Lopess methadone programme in Porto, and found that some responded well. But Porto was at the other end of the country. He wanted to try methadone for his patients, but the Ministry of Health hadnt yet approved it for use. To get around that, Pereira sometimes asked a nurse to sneak methadone to him in the boot of his car.

    Pereiras work treating patients for addiction eventually caught the attention of the Ministry of Health. They heard there was a crazy man in the Algarve who was working on his own, he said, with a slow smile. Now 68, he is sprightly and charming, with an athletic build, thick and wavy white hair that bounces when he walks, a gravelly drawl and a bottomless reserve of warmth. They came down to find me at the clinic and proposed that I open a treatment centre, he said. He invited a colleague from at a family practice in the next town over to join him a young local doctor named Joo Goulo.

    Goulo was a 20-year-old medical student when he was offered his first hit of heroin. He declined because he didnt know what it was. By the time he finished school, got his licence and began practising medicine at a health centre in the southern city of Faro, it was everywhere. Like Pereira, he accidentally ended up specialising in treating drug addiction.

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    A nurse hands out methadone to addicts in Lisbon. Photograph: Horacio Villalobos/Corbis via Getty Images

    The two young colleagues joined forces to open southern Portugals first CAT in 1988. (These kinds of centres have used different names and acronyms over the years, but are still commonly referred to as Centros de Atendimento a Toxicodependentes, or CATs.) Local residents were vehemently opposed, and the doctors were improvising treatments as they went along. The following month, Pereira and Goulo opened a second CAT in Olho, and other family doctors opened more in the north and central regions, forming a loose network. It had become clear to a growing number of practitioners that the most effective response to addiction had to be personal, and rooted in communities. Treatment was still small-scale, local and largely ad hoc.

    The first official call to change Portugals drug laws came from Rui Pereira, a former constitutional court judge who undertook an overhaul of the penal code in 1996. He found the practice of jailing people for taking drugs to be counterproductive and unethical. My thought right off the bat was that it wasnt legitimate for the state to punish users, he told me in his office at the University of Lisbons school of law. At that time, about half of the people in prison were there for drug-related reasons, and the epidemic, he said, was thought to be an irresolvable problem. He recommended that drug use be discouraged without imposing penalties, or further alienating users. His proposals werent immediately adopted, but they did not go unnoticed.

    In 1997, after 10 years of running the CAT in Faro, Goulo was invited to help design and lead a national drug strategy. He assembled a team of experts to study potential solutions to Portugals drug problem. The resulting recommendations, including the full decriminalisation of drug use, were presented in 1999, approved by the council of ministers in 2000, and a new national plan of action came into effect in 2001.

    Today, Goulo is Portugals drug czar. He has been the lodestar throughout eight alternating conservative and progressive administrations; through heated standoffs with lawmakers and lobbyists; through shifts in scientific understanding of addiction and in cultural tolerance for drug use; through austerity cuts, and through a global policy climate that only very recently became slightly less hostile. Goulo is also decriminalisations busiest global ambassador. He travels almost non-stop, invited again and again to present the successes of Portugals harm-reduction experiment to authorities around the world, from Norway to Brazil, which are dealing with desperate situations in their own countries.

    These social movements take time, Goulo told me. The fact that this happened across the board in a conservative society such as ours had some impact. If the heroin epidemic had affected only Portugals lower classes or racialised minorities, and not the middle or upper classes, he doubts the conversation around drugs, addiction and harm reduction would have taken shape in the same way. There was a point whenyou could not find a single Portuguese family that wasnt affected. Every family had their addict, or addicts. This was universal in a way that the society felt: We have to do something.

    Portugals policy rests on three pillars: one, that theres no such thing as a soft or hard drug, only healthy and unhealthy relationships with drugs; two, that an individuals unhealthy relationship with drugs often conceals frayed relationships with loved ones, with the world around them, and with themselves; and three, that the eradication of all drugs is an impossible goal.

    The national policy is to treat each individual differently, Goulo told me. The secret is for us to be present.


    A drop-in centre called IN-Mouraria sits unobtrusively in a lively, rapidly gentrifying neighbourhood of Lisbon, a longtime enclave of marginalised communities. From 2pm to 4pm, the centre provides services to undocumented migrants and refugees; from 5pm to 8pm, they open their doors to drug users. A staff of psychologists, doctors and peer support workers (themselves former drug users) offer clean needles, pre-cut squares of foil, crack kits, sandwiches, coffee, clean clothing, toiletries, rapid HIV testing, and consultations all free and anonymous.

    On the day I visited, young people stood around waiting for HIV test results while others played cards, complained about police harassment, tried on outfits, traded advice on living situations, watched movies and gave pep talks to one another. They varied in age, religion, ethnicity and gender identity, and came from all over the country and all over the world. When a slender, older man emerged from the bathroom, unrecognisable after having shaved his beard off, an energetic young man who had been flipping through magazines threw up his arms and cheered. He then turned to a quiet man sitting on my other side, his beard lush and dark hair curling from under his cap, and said: What about you? Why dont you go shave off that beard? You cant give up on yourself, man. Thats when its all over. The bearded man cracked a smile.

    During my visits over the course of a month, I got to know some of the peer support workers, including Joo, a compact man with blue eyes who was rigorous in going over the details and nuances of what I was learning. Joo wanted to be sure I understood their role at the drop-in centre was not to force anyone to stop using, but to help minimise the risks users were exposed to.

    Our objective is not to steer people to treatment they have to want it, he told me. But even when they do want to stop using, he continued, having support workers accompany them to appointments and treatment facilities can feel like a burden on the user and if the treatment doesnt go well, there is the risk that that person will feel too ashamed to return to the drop-in centre. Then we lose them, and thats not what we want to do, Joo said. I want them to come back when they relapse. Failure was part of the treatment process, he told me. And he would know.

    Joo is a marijuana-legalisation activist, open about being HIV-positive, and after being absent for part of his sons youth, he is delighting in his new role as a grandfather. He had stopped doing speedballs (mixtures of cocaine and opiates) after several painful, failed treatment attempts, each more destructive than the last. He long used cannabis as a form of therapy methadone did not work for him, nor did any of the inpatient treatment programmes he tried but the cruel hypocrisy of decriminalisation meant that although smoking weed was not a criminal offence, purchasing it was. His last and worst relapse came when he went to buy marijuana from his usual dealer and was told: I dont have that right now, but I do have some good cocaine. Joo said no thanks and drove away, but soon found himself heading to a cash machine, and then back to the dealer. After this relapse, he embarked on a new relationship, and started his own business. At one point he had more than 30 employees. Then the financial crisis hit. Clients werent paying, and creditors started knocking on my door, he told me. Within six months I had burned through everything I had built up over four or five years.

    Addicts
    Addicts waiting for methadone at a drug treatment project in Lisbon. Photograph: Horacio Villalobos/Corbis via Getty Images

    In the mornings, I followed the centres street teams out to the fringes of Lisbon. I met Raquel and Sareia their slim forms swimming in the large hi-vis vests they wear on their shifts who worked with Crescer na Maior, a harm-reduction NGO. Six times a week, they loaded up a large white van with drinking water, wet wipes, gloves, boxes of tinfoil and piles of state-issued drug kits: green plastic pouches with single-use servings of filtered water, citric acid, a small metal tray for cooking, gauze, filter and a clean syringe. Portugal does not yet have any supervised injection sites (although there is legislation to allow them, several attempts to open one have come to nothing), so, Raquel and Sareia told me, they go out to the open-air sites where they know people go to buy and use. Both are trained psychologists, but out in the streets they are known simply as the needle girls.

    Good afternoon! Raquel called out cheerily, as we walked across a seemingly abandoned lot in an area called Cruz Vermelha. Street team! People materialised from their hiding places like some strange version of whack-a-mole, poking their heads out from the holes in the wall where they had gone to smoke or shoot up. My needle girls, one woman cooed to them tenderly. How are you, my loves? Most made polite conversation, updating the workers on their health struggles, love lives, immigration woes or housing needs. One woman told them she would be going back to Angola to deal with her mothers estate, that she was looking forward to the change of scenery. Another man told them he had managed to get his online girlfriends visa approved for a visit. Does she know youre still using? Sareia asked. The man looked sheepish.

    I start methadone tomorrow, another man said proudly. He was accompanied by his beaming girlfriend, and waved a warm goodbye to the girls as they handed him a square of foil.

    In the foggy northern city of Porto, peer support workers from Caso an association run by and for drug users and former users, the only one of its kind in Portugal meet every week at a noisy cafe. They come here every Tuesday morning to down espressos, fresh pastries and toasted sandwiches, and to talk out the challenges, debate drug policy (which, a decade and a half after the law came into effect, was still confusing for many) and argue, with the warm rowdiness that is characteristic of people in the northern region. When I asked them what they thought of Portugals move to treat drug users as sick people in need of help, rather than as criminals, they scoffed. Sick? We dont say sick up here. Were not sick.

    I was told this again and again in the north: thinking of drug addiction simply in terms of health and disease was too reductive. Some people are able to use drugs for years without any major disruption to their personal or professional relationships. It only became a problem, they told me, when it became a problem.

    Caso was supported by Apdes, a development NGO with a focus on harm reduction and empowerment, including programmes geared toward recreational users. Their award-winning Check!n project has for years set up shop at festivals, bars and parties to test substances for dangers. I was told more than once that if drugs were legalised, not just decriminalised, then these substances would be held to the same rigorous quality and safety standards as food, drink and medication.


    In spite of Portugals tangible results, other countries have been reluctant to follow. The Portuguese began seriously considering decriminalisation in 1998, immediately following the first UN General Assembly Special Session on the Global Drug Problem (UNgass). High-level UNgass meetings are convened every 10 years to set drug policy for all member states, addressing trends in addiction, infection, money laundering, trafficking and cartel violence. At the first session for which the slogan was A drug-free world: we can do it Latin American member states pressed for a radical rethinking of the war on drugs, but every effort to examine alternative models (such as decriminalisation) was blocked. By the time of the next session, in 2008, worldwide drug use and violence related to the drug trade had vastly increased. An extraordinary session was held last year, but it was largely a disappointment the outcome document didnt mention harm reduction once.

    Despite that letdown, 2016 produced a number of promising other developments: Chile and Australia opened their first medical cannabis clubs; following the lead of several others, four more US states introduced medical cannabis, and four more legalised recreational cannabis; Denmark opened the worlds largest drug consumption facility, and France opened its first; South Africa proposed legalising medical cannabis; Canada outlined a plan to legalise recreational cannabis nationally and to open more supervised injection sites; and Ghana announced it would decriminalise all personal drug use.

    The biggest change in global attitudes and policy has been the momentum behind cannabis legalisation. Local activists have pressed Goulo to take a stance on regulating cannabis and legalising its sale in Portugal; for years, he has responded that the time wasnt right. Legalising a single substance would call into question the foundation of Portugals drug and harm-reduction philosophy. If the drugs arent the problem, if the problem is the relationship with drugs, if theres no such thing as a hard or a soft drug, and if all illicit substances are to be treated equally, he argued, then shouldnt all drugs be legalised and regulated?

    Massive international cultural shifts in thinking about drugs and addiction are needed to make way for decriminalisation and legalisation globally. In the US, the White House has remained reluctant to address what drug policy reform advocates have termed an addiction to punishment. But if conservative, isolationist, Catholic Portugal could transform into a country where same-sex marriage and abortion are legal, and where drug use is decriminalised, a broader shift in attitudes seems possible elsewhere. But, as the harm-reduction adage goes: one has to want the change in order to make it.


    When Pereira first opened the CAT in Olho, he faced vociferous opposition from residents; they worried that with more drogados would come more crime. But the opposite happened. Months later, one neighbour came to ask Pereiras forgiveness. She hadnt realised it at the time, but there had been three drug dealers on her street; when their local clientele stopped buying, they packed up and left.

    The CAT building itself is a drab, brown two-storey block, with offices upstairs and an open waiting area, bathrooms, storage and clinics down below. The doors open at 8.30am, seven days a week, 365 days a year. Patients wander in throughout the day for appointments, to chat, to kill time, to wash, or to pick up their weekly supply of methadone doses. They tried to close the CAT for Christmas Day one year, but patients asked that it stay open. For some, estranged from loved ones and adrift from any version of home, this is the closest thing theyve got to community and normality.

    Its not just about administering methadone, Pereira told me. You have to maintain a relationship.

    In a back room, rows of little canisters with banana-flavoured methadone doses were lined up, each labelled with a patients name and information. The Olho CAT regularly services about 400 people, but that number can double during the summer months, when seasonal workers and tourists come to town. Anyone receiving treatment elsewhere in the country, or even outside Portugal, can have their prescription sent over to the CAT, making the Algarve an ideal harm-reduction holiday destination.

    After lunch at a restaurant owned by a former CAT employee, the doctor took me to visit another of his projects a particular favourite. His decades of working with addiction disorders had taught him some lessons, and he poured his accumulated knowledge into designing a special treatment facility on the outskirts of Olho: the Unidade de Desabituao, or Dishabituation Centre. Several such UDs, as they are known, have opened in other regions of the country, but this centre was developed to cater to the particular circumstances and needs of the south.

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    A man receives clean syringes after being given methadone at a clinic in Lisbon. Photograph: Horacio Villalobos/Corbis via Getty Images

    Pereira stepped down as director some years ago, but his replacement asked him to stay on to help with day-to-day operations. Pereira should be retired by now indeed, he tried to but Portugal is suffering from an overall shortage of health professionals in the public system, and not enough young doctors are stepping into this specialisation. As his colleagues elsewhere in the country grow closer to their own retirements, theres a growing sense of dread that there is no one to replace them.

    Those of us from the Algarve always had a bit of a different attitude from our colleagues up north, Pereira told me. I dont treat patients. They treat themselves. My function is to help them to make the changes they need to make.

    And thank goodness there is only one change to make, he deadpanned as we pulled into the centres parking lot: You need to change almost everything. He cackled at his own joke and stepped out of his car.

    The glass doors at the entrance slid open to a facility that was bright and clean without feeling overwhelmingly institutional. Doctors and administrators offices were up a sweeping staircase ahead. Women at the front desk nodded their hellos, and Pereira greeted them warmly: Good afternoon, my darlings.

    The Olho centre was built for just under 3m (2.6m), publicly funded, and opened to its first patients nine years ago. This facility, like the others, is connected to a web of health and social rehabilitation services. It can house up to 14 people at once: treatments are free, available on referral from a doctor or therapist, and normally last between eight and 14 days. When people first arrive, they put all of their personal belongings photos, mobile phones, everything into storage, retrievable on departure.

    We believe in the old maxim: No news is good news, explained Pereira. We dont do this to punish them but to protect them. Memories can be triggering, and sometimes families, friends and toxic relationships can be enabling.

    To the left there were intake rooms and a padded isolation room, with clunky security cameras propped up in every corner. Patients each had their own suites simple, comfortable and private. To the right, there was a colour room, with a pottery wheel, recycled plastic bottles, paints, egg cartons, glitter and other craft supplies. In another room, coloured pencils and easels for drawing. A kiln, and next to it a collection of excellent handmade ashtrays. Many patients remained heavy smokers.

    Patients were always occupied, always using their hands or their bodies or their senses, doing exercise or making art, always filling their time with something. Wed often hear our patients use the expression me and my body, Pereira said. As though there was a dissociation between the me and my flesh.

    To help bring the body back, there was a small gym, exercise classes, physiotherapy and a jacuzzi. And after so much destructive behaviour messing up their bodies, their relationships, their lives and communities learning that they could create good and beautiful things was sometimes transformational.

    You know those lines on a running track? Pereira asked me. He believed that everyone however imperfect was capable of finding their own way, given the right support. Our love is like those lines.

    He was firm, he said, but never punished or judged his patients for their relapses or failures. Patients were free to leave at any time, and they were welcome to return if they needed, even if it was more than a dozen times.

    He offered no magic wand or one-size-fits-all solution, just this daily search for balance: getting up, having breakfast, making art, taking meds, doing exercise, going to work, going to school, going into the world, going forward. Being alive, he said to me more than once, can be very complicated.

    My darling, he told me, its like I always say: I may be a doctor, but nobodys perfect.

    A longer version of this piece appears on thecommononline.org. Research and travel for this piece were made possible by the Matthew Power Literary Reporting Award

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    Read more: https://www.theguardian.com/news/2017/dec/05/portugals-radical-drugs-policy-is-working-why-hasnt-the-world-copied-it

    CVS-Aetna Deal Could Mean End of Era in How Drugs Are Paid For

    If Aetna Inc. is eventually swallowed by CVS Health Corp., an important part of the health-care business will be changed — perhaps for good.

    For years, pharmacy benefits were largely carved out from the rest of a medical coverage plan. But increasingly the two services are being combined, a move that in theory will make it easier to verify whether expensive drugs are worth the cost. A merger of the third-biggest health insurer with the largest U.S. drugstore chain, which also operates a pharmacy-benefit management company, could speed the process.

    “You are hearing the warning for the end of the road for the classic standalone” pharmacy-benefit business, said Pratap Khedkar, managing principal at consulting firm ZS Associates.

    Drugmakers are producing more pricey treatments for cancer and rare diseases. Combining drug and medical benefits in the same place is “the only way” payers will figure out whether such expensive new drugs are actually making people better and saving money by keeping them out of the hospital, he said.

    A merger of CVS and Aetna would create a health-care behemoth and put huge pressure on standalone players such as Express Scripts Holding Co. and Walgreens Boots Alliance Inc. Express Scripts would become the last major standalone pharmacy-benefit manager not allied with a major insurer. 

    All Channels

    CVS and Aetna have held discussions about a potential deal, according to people familiar with the matter who asked not to be identified as the details aren’t public. A newly combined company would “own the entire chain, from prescribing and filling prescriptions to the health plans that pay for them,” said Michael Rea, of Rx Savings Solutions, which has an app that helps patients find lower cost drugs.

    Under a combined roof, the insurance arm of CVS-Aetna could help keep costs down by routing patients needing basic urgent care to CVS-owned walk-in clinics and keeping them out of expensive hospital emergency rooms, analyst Ann Hynes of Mizuho Securities said in a note to clients. The company would also become a formidable competitor to UnitedHealth Group Inc., the biggest health insurer and owner of its own PBM unit, OptumRx.

    But even with the new clout, a merger isn’t likely to be derailed by federal antitrust authorities, said John Briggs, an antitrust attorney at Axinn Veltrop & Harkrider in Washington.

    CVS and Aetna declined to comment.

    Walgreens, the No. 2 drugstore operator, could also feel the pressure. A CVS-Aetna marriage could cause the drugstore chain to look for its own acquisition targets, with Express Scripts being the most likely, Charles Rhyee, an analyst at Cowen & Co., wrote in a note to clients Friday.

    And then there’s Amazon.com Inc., which recently gained drug-wholesaler licenses in 14 states. The looming threat of the e-commerce behemoth entering the mail-order pharmacy business and pushing down profit margins for drug distributors, benefit managers and retail pharmacies intensifies the pressure on standalone players.

    For CVS, the move is “a natural defense against the potential threat of Amazon entering the retail pharmacy market,” Rhyee said.

    Another possibility is that Amazon could buy Express Scripts. That would give the internet retailer an instant and large foothold in both the PBM industry and the mail-order pharmacy business.

    ‘Strong’ Model

    Health insurer Anthem Inc., Express Scripts’ biggest current client, announced earlier this month that it would leave Express Scripts when its contract ends at the end of 2019 to form its own PBM unit. And Prime Therapeutics, another major player, manages drug benefits for nonprofit Blue Cross and Blue Shield plans in numerous states.

    “Our model is strong and thriving,” said Jennifer Luddy, a spokeswoman for Express Scripts. “We believe in the value that we provide to our customers as an independent PBM.”

    On an earnings call this week, Express Scripts Chief Executive Officer Tim Wentworth said he was open to a deal with Amazon to help serve cash-paying patients.

    Walgreens declined to comment.

    In terms of the CVS-Aetna deal, antitrust authorities will look closely at the competition between the companies in selling Medicare Part D plans for the elderly, said Briggs, the attorney.

    There could be fight between the Justice Department and the Federal Trade Commission, which share antitrust enforcement, over which agency will investigate the merger, according to Briggs. The Justice Department handles insurer mergers and successfully stopped the combination of Aetna and Humana Inc. this year. The FTC investigates retail pharmacy deals. In September, it cleared Walgreens’ acquisition of 1,900 Rite Aid Corp. stores after Walgreens shrank the size of the deal.

    Still, a CVS-Aetna deal would likely win approval because a number of other major players will remain in the Part D market, he said.

    “That’s an easy fix,” Briggs said. “The whole deal is not going to crater on account of Part D.”

      Read more: http://www.bloomberg.com/news/articles/2017-10-27/cvs-aetna-deal-could-mean-end-of-era-in-how-drugs-are-paid-for

      Acid reflux drug linked to more than doubled risk of stomach cancer study

      There are more than 50m prescriptions for proton pump inhibitors in the UK, though they have previously been linked to side-effects and increased risk of death

      A drug commonly used to treat acid reflux is linked to a more than doubled risk of developing stomach cancer, researchers have claimed.

      Proton pump inhibitors (PPIs) reduce the amount of acid made by the stomach and are used to treat acid reflux and stomach ulcers.

      A study published in the journal Gut identified an association between long-term use of the drug and a 2.4 times higher risk of developing stomach cancer. In the UK, there are more than 50m prescriptions for PPIs every year but they have been linked to side-effects and an increased risk of death.

      A link between PPIs and a higher stomach cancer risk has previously been identified by academics but never in a study that first eliminates a bacteria suspected of fuelling the illnesss development.

      Research by the University of Hong Kong and University College London found that after the Helicobacter pylori was removed, the risk of developing the disease still rose in line with the dose and duration of PPI treatment.

      They compared the use of PPI against another drug which limits acid production known as H2 blockers in 63,397 adults. The participants selected had been treated with triple therapy, which combines PPI and antibiotics to kill off the H pylori bacteria over a week, between 2003 and 2012.

      Scientists then monitored them until they either developed stomach cancer, died or reached the end of the study at the end of 2015.

      During this period, 3,271 people took PPIs for an average of almost three years, while 21,729 participants took H2 blockers. A total of 153 people developed stomach cancer, none of whom tested positive for H plyori but all had long-standing problems with stomach inflammation, the study found.

      While H2 blockers were found to have no link to a higher risk of stomach cancer, PPIs was found connected to an increased risk of more than double.

      Daily use of PPIs was associated with a risk of developing the illness that was more than four times higher (4.55) than those who used it weekly. Similarly, when the drug was used for more than a year, the risk of developing stomach cancer rose five-fold, and as high as eight-fold after three or more years, the findings showed.

      The study concluded no firm cause and effect could be drawn, but doctors should exercise caution when prescribing long-term PPIs even after successful eradication of H plyori.

      Responding to the study, Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene and Tropical Medicine, said: Many observational studies have found adverse effects associated with PPIs.

      The most plausible explanation for the totality of evidence on this is that those who are given PPIs, and especially those who continue on them long-term, tend to be sicker in a variety of ways than those for whom they are not prescribed.

      Read more: https://www.theguardian.com/science/2017/oct/31/acid-reflux-drug-linked-to-more-than-doubled-risk-of-stomach-cancer-study