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Notebook Medicine

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(iStock photo)


Physicians with prescriptions

As demand surges for drugs that could fight the coronavirus, some doctors are purchasing them—for themselves. Is that ethical?

When vital medications are scarce, should doctors and medical workers get first dibs? A recent New York Times article highlighted state efforts to conserve the supply of drugs that could prove effective against the novel coronavirus—mainly hydroxychloroquine, an anti-malarial drug I wrote about last week. Amid speculation the drug could reduce the severity of COVID-19, states have noticed a sudden increase in doctors prescribing that and other medications for themselves, presumably while they are not yet sick.

Most readers commenting on the Times article frowned on the idea of doctors prescribing themselves anything at all. Some were outraged doctors could get early access to a potentially limited stock of medicine. They cited guidance from the American Medical Association (AMA) that doctors-as-patients should normally see their own primary care physicians.

Self-prescribing is legal in most states, as is prescribing for one’s spouse and children, with certain exceptions involving commonly abused drugs. It’s a common practice and, for many drugs, uncontroversial. The AMA reluctantly agrees that self-prescribing may make sense for “short-term, minor problems.” So, doctor, heal thyself—at least thy ear infection.

Scarcity adds a twist here. It now appears there isn’t enough hydroxychloroquine to meet a recent surge in demand. As with toilet paper, the buying phenomenon mirrors the bank run from It’s a Wonderful Life: People fear a resource is running out, decide to stock up before it does, and thereby help deplete the supply. State pharmacy boards quoted in the Times stated some doctors were prescribing absurd quantities for themselves and their families. I hope those cases are few: That’s silly and selfish, and exceeds treatment guidelines, even for a person who is sick. (A normal, experimental course of hydroxychloroquine for COVID-19 ranges from 12 to 30 pills in total.)

What did we choose in our own medical household? I discussed getting a hydroxychloroquine prescription with my wife, who is a retired general surgeon. In the end we decided against it, because others might need it more. I hope we don’t regret that decision, since she is 33 weeks pregnant and I am only relatively low-risk. 

Still, I’m not on the front lines of the coronavirus fight: I practice in a surgery center that currently is taking only the most essential cases. I also have a good face mask. But if I were working in the front lines—especially in a hospital relying on improvised personal protective equipment and expecting me to return from sick leave as quickly as possible—I could well imagine keeping a course of treatment at home.

That doesn’t mean grabbing hundreds of pills. Restricting such massive purchases makes sense. I’m concerned, though, that new restrictions some states are establishing—like an Idaho rule blocking the dispensing of hydroxychloroquine except for prescriptions “consistent with the evidence for its use”—may have unintended side effects. Is it really better for infected doctors and nurses to be without medication that may help them return to service sooner, while their stressed colleagues carry a heavier workload in their absence? And will the new restrictions really affect the bad guys more than the good ones? 

Ultimately, the only real solution to hoarding is spiritual: Six thousand years of human lawmaking haven’t found a way to force the “me-first” out of people. But Jesus’ self-sacrifice shows us the way forward.

I would echo calls to invest funding in drugs that appear promising, so they’re ready to distribute if research supports their use against COVID-19. Closer to home, let’s act with others’ interests in mind: For everyone, it means stay home if you can, avoid unnecessary contact, and wash those hands! For doctors off the front lines, it means conserving protective equipment—and medicines, if possible. 

For those coming into daily contact with the virus? Personally, I’m fine with giving them everything we’ve got. They’re doing the same for us.

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Business Wire/AP

Pharmacist Gopesh Patel fills prescriptions for COVID-19 patients, supplying a formulation with hydroxychloroquine. (Business Wire/AP)


Seeking treatment

Limited research suggests anti-malarial drugs could help fight the new coronavirus

On Thursday President Donald Trump in a press conference named two anti-malarial drugs he said the government was investigating as potential treatments for COVID-19, the disease caused by the new coronavirus. Their names are chloroquine and hydroxychloroquine, and although the U.S. Food and Drug Administration has not approved the drugs specifically to treat the coronavirus, the agency has approved them to treat other ailments.

What are these drugs, and why use them on a patient with COVID-19?

Long ago—or so it seems—when we embarked on such now-rare journeys as going to a store simply to browse, my family and I loved to visit a thrift shop called Repurposed. The name described the adventures many of its items were destined for: An old picture frame might become a new home for a child’s artwork, and so on.

The shop owner’s creative mindset is analogous to what the world’s top research scientists are now doing: The drug-discovery world has essentially gone to Repurposed. It even uses the same name for its work. The Broad Institute, a collaboration between Harvard and MIT, calls one of its main projects “the Drug Repurposing Hub.” It summarizes its work thus:

The path to putting a drug on the market involves a long and exhaustive journey through basic research, discovery and optimization, preclinical development, increasingly elaborate and lengthy human clinical trials, and regulatory approval. New drugs can take more than a decade to get to market. But what if we could take thousands of drugs already approved to safely treat disease, as well as other compounds that have been studied as potential drugs, and find new uses for these old medicines?

Scientists have occasionally found those new uses by serendipity. Minoxidil, a potent treatment for high blood pressure, found new life as Rogaine after doctors noticed it often caused hair growth. That was easy to stumble upon, because high blood pressure is common in older men—who also might be bald. 

Today, advanced research tools help scientists explore less obvious connections between drugs we already know about and diseases we didn’t know they could treat.

That brings us to chloroquine, a malaria treatment that readers who have visited the developing world might have already taken. It’s nothing new: Chloroquine dates to 1934, and its cousin, hydroxychloroquine, came to market in 1955. Manufacturers already produce both in massive quantities. Neither was designed to be an anti-viral treatment, but we’ve long known chloroquine has anti-viral effects. A 2003 paper published in Lancet Infectious Diseases suggested it might be effective against SARS, another coronavirus disease.

Because of that knowledge, chloroquine was a natural choice for investigators in China to try against SARS-CoV-2, the new coronavirus that causes COVID-19. Lab experiments showed effectiveness, and since chloroquine was already a well-known drug with an established safety profile, it went straight to human trials. Preliminary results from China are encouraging, and additional research in Europe is ongoing.

Why study hydroxychloroquine? As the drug’s name suggests, it’s a close relative of chloroquine. In the developed world, its advantages usually justify its higher price: It leads to fewer side effects, and it’s less toxic if overdosed. But most importantly, developed countries have a much better supply of hydroxychloroquine than of chloroquine, and they have factories that could easily produce more. Malaria is very rare in the United States and Europe, but hydroxychloroquine is a common daily treatment for rheumatoid arthritis and lupus.

A small French trial explored hydroxychloroquine—with or without an antibiotic called azithromycin—as a treatment for the novel coronavirus. The quality of the research was not ideal: It “excluded” from the analysis patients who started treatment but then went to ICU or died—a bad approach, from a research perspective. But even if we go back through the data and assume that the treatment failed in all of those “excluded” patients, the study still appears to show it was effective: Study patients were much more likely to be virus-free after six days of treatment.

(One safety note: Please don’t combine hydroxychloroquine and azithromycin at home! Together, they can easily lead to heart rhythm disturbances.)

While the science is not fully established, treatment guidelines in Korea and Italy are starting cautiously to endorse hydroxychloroquine as—essentially—“worth a try” against COVID-19 in lieu of any other proven treatment. 

Bottom line: Limited evidence suggests the anti-malarial drugs chloroquine and hydroxychloroquine may help treat COVID-19. If so, it would be drug researchers’ best trip yet to Repurposed.

A shot in the dark?

Another drug President Trump named as a possible coronavirus treatment during his Thursday press conference is remdesivir, Gilead Sciences’ experimental anti-Ebola drug. A few patients received it for Ebola under “compassionate use” guidelines that allow doctors to prescribe unapproved medicines. It’s still at such an early stage of development that much of the research refers to it by its development name, GS-5734. 

The first known patient to be hospitalized with COVID-19 in the United States received remdesivir after developing pneumonia, and improved shortly afterward. Did the remdesivir help cure him, or was he going to improve anyway? An ongoing clinical trial, in which COVID-19 patients in China received the drug, hopes to answer this question.

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 Chicago Tribune

In this 2012 photo, a medical technician fills test tubes with serum and a reagent used to measure the levels of vitamin D in a person’s blood. ( Chicago Tribune)


The vitamin D factor

Research shows vitamin D sometimes prevents the common cold. Could it help ward off the new coronavirus?

The research world has mounted an electrifying response to the new coronavirus: Those playing a role include vaccine developers, drug researchers, gene sequencing labs, and the fields of public health and artificial intelligence. In the shadows of this effort is a less glamorous role—that of checking the archives of past research for clues to better treating and preventing COVID-19.

WORLD reader Dr. John Umhau thus calls our attention to a 2017 paper in The BMJ (formerly British Medical Journal). In it, a team performed a meta-analysis—basically, a study of other studies—investigating a common compound and its effect on immunity against respiratory infections like the common cold. The meta-analysis didn’t focus specifically on coronaviruses (a family of viruses that can also cause colds), but it may still apply to them. The drug in question? A humble compound we associate more with milk and bone health: vitamin D.

The meta-analysis combined 25 separate studies and went about it the hard way: Researchers obtained and reanalyzed individual participant data for all 25 studies, tallying up almost 11,000 study participants in what one of The BMJ’s peer reviewers called a Herculean effort. The paper is free to the public, but I’ll summarize it here: The results show that taking a moderate dose of vitamin D daily or weekly (but not more irregular, large doses) helps to protect users from respiratory infections. 

Unsurprisingly, vitamin D supplements were most helpful for study participants who started out deficient in the vitamin, but the supplements may help even those who aren’t. Equally important, people appeared to tolerate the vitamin well: The main problems linked to vitamin D supplementation were high blood calcium levels (in 1 in 200 participants) and kidney stones (in 1 in 500).

Time for a caveat. A figure called the “number needed to treat” (NNT) helps us understand how effective a treatment is. For daily or weekly vitamin D users in the meta-analysis, the overall NNT was 20, indicating a measurable but limited effect. Translating the research lingo into English, this figure means that 1 in 20 people taking vitamin D supplements could expect to avoid a cold because of it. But for study participants with “profound” vitamin D deficiency, the NNT was 4: Every fourth person taking the supplements likely dodged a cold.

So, the big question: Do I, as a doctor, advocate vitamin D supplements based on this research? In moderate doses, yes—especially for those at risk of vitamin D deficiency. (By this point in winter, that’s probably most of us.)

What’s a moderate dose? As the Mayo Clinic notes, “The recommended daily amount of vitamin D is 400 international units (IU) for children up to age 12 months, 600 IU for ages 1 to 70 years, and 800 IU for people over 70 years.” Mayo also offers useful information on potential drug interactions (that’s important to know if you’re on other medications) and cautions that over 4,000 IU per day of vitamin D increases the risk of harmful effects. For those who want to be certain they’re getting enough vitamin D, bloodwork can check whether they’ve hit the recommended level of 50 nanograms per milliliter.

None of this substitutes for the usual advice: Wash your hands frequently, don’t touch your face needlessly, and avoid being around sick people more than necessary. But given how cheap and safe vitamin D is, I’d recommend adding it as well.

In summary, while the research doesn’t yet prove vitamin D is effective against the new coronavirus strain, it does show the vitamin helps protect against common respiratory infections. With the coronavirus and other bugs going around, I plan to start taking vitamin D supplements myself, at least during the winter months.

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