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Notebook Medicine

Christopher Loren Ewers/PBS

Roger Frisch (Christopher Loren Ewers/PBS)


A steady hand

Innovative surgery stopped a violinist’s tremor, allowing him to continue in his calling

Roger Frisch had it all. A lengthy career as violinist and associate concert master of the acclaimed Minnesota Orchestra. A supportive, talented wife, Michele, principal flutist of the Minnesota Opera. Three adult children successfully launched. A fulfilling teaching post at a local Christian college.

But in 2007, at age 56, Frisch’s right arm started involuntarily quivering on a music ministry trip to China. He recalls, “It came on quickly. It progressed quickly. Real panic set in.”

Two years of deteriorating steadiness and more than a dozen doctors later culminated in a visit to neurologist Joseph Matsumoto at the Mayo Clinic in Rochester, Minn. Within 30 minutes, Matsumoto diagnosed him with essential tremor, a benign but progressive neurological disorder that could eventually render professional performing impossible. 

When medication didn’t work, Frisch knew any hope to extend his career entailed the radical next step: brain surgery. 

Renowned Mayo neurosurgeon, Dr. Kendall Lee, told me he’d been in Asia and saw a Japanese surgeon stop a patient’s tremors by lesioning, or damaging, part of the brain. Lee wanted to stop Frisch’s shaking by implanting electrodes to interrupt the tremor-causing impulses without harming tissue, a technique called deep brain stimulation.

Frisch recounts how in December 2009 he lay strapped to the operating table, his head propped up and immobilized by a bolted-on halo. He remained awake for the entire surgery, violin and bow in hand. 

The surgical team planned to measure precisely Frisch’s tremors while he played by using an oscilloscope attached to a first-ever “accelerometer” that Mayo engineers had innovatively created from inner workings of a Wii game accessory toggled to a $75 violin from eBay.

Lee drilled a small hole in Frisch’s skull and manipulated a lead with an electrode down into the correct region of the thalamus. He directed Frisch to draw his bow across the strings. Frisch complied, trembling noticeably less, but not enough to play smoothly.

After checking with Frisch, Lee in a surgical first inserted a second electrode on the same side of his brain. Frisch again drew his bow and pulled a long, steady, beautiful note, and then another. The tremor had disappeared.

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Jerry Holt/Minneapolis Star Tribune via ZUMA Wire/Alamy

Quinn Nystrom traveled from Minnesota to purchase insulin at Shoppers Drug Mart pharmacy in Fort Frances, Ontario. (Jerry Holt/Minneapolis Star Tribune via ZUMA Wire/Alamy)


A new drug war

U.S. turns to Canada for cheaper drugs, but does Canada have enough to share?

When pharmacist Heather Christ arrived for her afternoon shift at Shoppers Drug Mart in New Brunswick, Canada, she noticed a tower of empty pharmacy trays stacked nearly 2 feet high. The reason, Christ said: shortages. Patients with high blood pressure request a 90-day supply of medicine, but the pharmacist may only give them enough for 10 days. A mom comes to pick up an anti-convulsant for her epileptic child, only to find the drug isn’t available.

When drugstores run out of drugs, “people just get panicky,” says Christ. But that’s nothing new in Canada: Christ sighed heavily and said, “It’s been part of the scenery for so long.” Christ, a 30-year veteran of Canada’s pharmaceutical industry, says the country’s drug shortage has worsened in recent years. More than 1,800 drugs are on Canada’s needed list, according to the official Drug Shortages Canada website.

Last month U.S. President Donald Trump announced plans to allow the import of cheaper prescription drugs from Canada. But Canada doesn’t have enough drugs to share with the massive U.S. market, and the Canadian Health Minister’s office said, “While we’re aware of ongoing state-led initiatives to import Canadian drugs, we weren’t consulted on specifics.”

Given Canada’s preexisting drug shortages, Christ says expanding the market is “alarming from Canada’s point of view.” If the United States drills a hole in the already leaking Canadian drug pipeline, and then tries to fill a tank 10 times the size of Canada’s, the drug supply will run dry. A 2018 study published in the journal Health Economics & Outcome Research: Open Access found that if one-fifth of U.S. prescriptions are filled in Canada, Canada’s drug supply will be exhausted in six months.

Christ says Canadian pharmacists sometimes work around drug shortages by adapting prescriptions. They work from scratch to create alternative compounds. The process takes extra time and keeps patients waiting, but shortages leave them no choice.

Christ is allergic to bees, so she carries an EpiPen. When an EpiPen shortage struck Canada last summer, she didn’t feel right getting a new one. She and many other Canadians kept their expired EpiPens. A drug’s expiration date is the time after which the drug could have lost 10 percent of its potency, so an expired EpiPen might still work. But it might not work, and a severe allergic reaction would be the consequence. Thankfully, Christ didn’t have to find out because the shortage ended.

One year later, Canada is running out of EpiPens again. Pfizer, until recently the only company authorized to provide injectors to Canadians, continued to have manufacturing problems. Ginette Petitpas Taylor, the Canadian health minister, has signed an emergency interim order to allow U.S.-based provider Kaléo to send epinephrine auto-injectors to Canada.

That may sound like an easy solution, but it was complicated. The new injectors didn’t have instructions in French for distribution in Quebec. They operated differently than EpiPens, so pharmacists had to spend extra time teaching patients how to use them. The injectors came in packages of two, so pharmacists had to open the packages to redistribute them one per patient. And Kaléo had to rebuild trust, since it suffered a product recall in 2015.

Why the recurring shortages of other drugs? Opinions abound. Manufacturing and shipping problems. Disruptions in international supply. Discontinued generics in favor of newer, brand-name drugs with greater profits. Lack of suppliers. Government price caps imposed by Canada’s nationalized healthcare system. And the future of Canada’s drug supply? Christ said, “I’m discouraged.” She sees the recurring problems as the new normal: a normal that could be worsened if the United States comes looking for a share.

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Jessica Hill/AP

(Jessica Hill/AP)


Anatomy of an epidemic

Diagnosing the causes of the opioid crisis 

Massachusetts officials are suing Purdue Pharma, maker of OxyContin, alleging that its sales tactics fueled a surge in opioid addiction. Massachusetts is also suing the Sackler family, which owns and runs Purdue Pharma. The lawsuit underscores the controversy over the pills: Did the increase in opioid prescriptions reflect doctors finally addressing untreated pain or becoming tools for sales at any cost?

Psychiatrist and addiction specialist Anna Lembke argues in the 2016 book Drug Dealer, MD that doctors believed they were finally addressing pain issues. They viewed as outdated the World Health Organization’s 1986 guidelines, which advised doctors to start with non-opioid drugs (like Tylenol and Motrin), proceed if necessary to opioids like codeine, and reserve stronger opioids like morphine for when other drugs failed.

But had medical opinion changed or was propaganda at work? New guidelines emphasized aggressive pain control, but those guidelines stemmed from Big Pharma. Lembke discovered that the Federation of State Medical Boards (FSMB) received almost $2 million in support from opioid makers. The FSMB in turn “urged state medical boards to punish doctors for undertreating pain. Doctors lived in fear of disciplinary action from the board, and the lawsuit that usually followed, if they denied a patient opioid painkillers.”

In 1999 the Department of Veterans Affairs declared pain level to be the “fifth vital sign,” which meant it had to be checked whenever a nurse or doctor checked a patient’s vitals. In 2001 the Joint Commission on Accreditation of Healthcare Organizations said appropriate (i.e., aggressive) pain control would be a factor in maintaining accreditation. 

Doctors listened: A University of Southern California study found American opioid prescribing rose 471 percent between 1996 and 2012. Purdue offered various educational and promotional materials, even via the Joint Commission’s own website. Purdue’s representatives canvassed the country, promoting OxyContin as an ideal choice with a time-release formulation that was both convenient and less likely to produce addiction.

OxyContin may have been convenient, but time proved that it certainly was addictive—especially when users realized that crushing the original version of the pills released all of the active ingredient at once. (A 2010 reformulation later addressed the problem.) A burgeoning street market for the drug showed addicts knew about this feature. Potential profits induced many people to get prescriptions and illegally resell them.

Some doctors remained skeptical of the fifth-vital-sign approach. A 2006 study found the new dispensation did not improve pain control, but the CDC took a decade to issue guidelines calling for reduced opioid use. Yet even before those restrictions, patients who had grown dependent on opioids often sought illegal sources when they could no longer get prescriptions. That’s even more dangerous now that drug gangs have learned to counterfeit popular prescriptions: When the musician Prince died of an overdose in 2016, pills found with him bore a code for generic Vicodin, but proved to contain fentanyl and two other drugs.

Both Lembke and the CDC guidelines offer practical advice: nonpharmacological and non-opioid pain management whenever possible, rational opioid prescribing to prevent further addiction, and—perhaps most important now—strategies to help those already addicted.

But why stop there? Let’s replace our society’s current addiction to rules and guidelines with a commonsense understanding that life after the Fall can’t be entirely devoid of pain, any more than corporate funding can be entirely without strings. Let’s bring back the idea of doctors and patients knowing each other, as individuals, and of doctors using that relationship to help encourage patients as they manage their pain, one day at a time.

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