Long Nights in a Sleep Lab
How two research subjects pass the time—and work to stay awake—during a Penn study on sleep deprivation
ENLARGE At the University of Pennsylvania, sleep-study subjects Amanda Burton, left, and Daniel Dougherty, right, overseen by a monitor, perform a series of tests soon after waking up from only four hours of sleep. Photo: Scott Lewis for The Wall Street Journal
By
Oct. 19, 2015 12:38 p.m. ET Andrea Petersen
Philadelphia
At 8:30 a.m., a bleary-eyed young woman wearing a bright orange bandanna and fuzzy, gray slippers is staring at a computer screen. When a number appears in a small box, she hits the space bar. She does it again and again, sometimes quickly and other times much more slowly.
"She's very sleepy. She has a lot of lapses," whispers Namni Goel, a sleep researcher at the University of Pennsylvania Perelman School of Medicine.
The young woman, Amanda Burton, is taking a test of her attention and reaction speed. As a participant in a scientific study at the Sleep and Chronobiology Laboratory here, she has had just four hours of sleep each night for the past five nights. The Penn lab is one of the busiest human sleep research labs in the world. It has deprived more than 1,500 people of sleep over the decades with the goal of figuring out what happens in the bodies and brains of people when they skimp on shut-eye.
ENLARGE Ms. Burton, left, has just completed her fifth night of sleeping only four hours. She says she normally gets a solid eight hours a night. Mr. Doughtery, right has passed the time between tests by reading, watching TV and playing Monopoly. Photo: Scott Lewis for The Wall Street Journal
It is an urgent question. Experts generally recommend that healthy adults sleep between seven and nine hours a night. But about 35% of adults say they typically get less than seven hours, according to a survey of 75,000 people conducted by the Centers for Disease Control and Prevention in 2008. Chronic insufficient sleep has been linked to everything from diabetes and obesity to high blood pressure and an increased risk of death.
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"We have to add sleep to this crazy world," says David F. Dinges, a professor in the department of psychiatry and the 66-year-old director of the Penn lab. "And if we can't stop short sleeping, the question is: How do we optimize the ability to tolerate [sleep loss], what are the effects of this and how do we reverse it, stop it and alter it?"
ENLARGE Research technician Alexis Taylor prepares blood samples from the study participants. This study is searching for biomarkers that could predict which people are more vulnerable to the effects of sleep loss. Photo: Scott Lewis for The Wall Street Journal
On a recent Monday, Ms. Burton was one of three subjects living in the Penn sleep lab, a small, windowless space with linoleum floors and dim fluorescent lighting. The participants—who are paid about $2,000—won't leave at all during the 14-day study. They can't exercise, use their phones or access the Internet. (Light and physical activity can affect sleep, mood and test performance. So can an argument with a significant other.)
The study subjects are hooked up to wires that monitor their brain activity. They sleep—the few hours they're allowed to—in hospital beds in double rooms. Meals come from the hospital cafeteria. There's no caffeine, chocolate, nicotine or alcohol allowed. But there are unlimited snacks—like Kind granola bars and spicy sweet chili Doritos—available in the small kitchen.
They are watched by technicians and "minders" (usually undergraduate employees) at all times—except for bathroom breaks and showers. The monitors make sure study subjects are completing the various study tasks and staying awake when they're supposed to.
ENLARGE David F. Dinges is the director of the University of Pennsylvania Perelman School of Medicine lab that has deprived more than 1,500 healthy adults of sleep to try to understand what happens to the body and brain when people skimp on sleep. Photo: Scott Lewis for The Wall Street Journal
"Between 2 and 4 [a.m.] I was dozing off the entire time," says Ms. Burton, a 33-year-old administrative assistant from Plainfield, N.J., who is taking time off to participate in her third sleep study at Penn. The monitors "had to constantly yell my name. 'Amanda, Amanda, hey, are you awake?' " she says.
This particular study of about 100 subjects, which Dr. Goel is leading, aims to see if people respond equally to two different types of sleep deprivation. It compares acute, total sleep loss (going 36 hours without sleep) with chronic sleep deprivation (in this case, just four hours of sleep between 4 a.m. and 8 a.m. for five nights). Preliminary results indicate that the answer is yes, Dr. Goel says.
"There are huge individual differences. [But] if you are resilient to total sleep loss, you are resilient to being chronically sleep-deprived or if you're vulnerable to one, you are vulnerable to the other," she says.
ENLARGE Mr. Dougherty eats breakfast while research technician Laura Dennis fills out paperwork. Sleep-deprived participants in Penn studies tend to eat an extra 500 calories a day and gain about 2 pounds within a week. Photo: Scott Lewis for The Wall Street Journal
The study is also looking for genes and other so-called biomarkers—substances in the blood—that can predict which people are more vulnerable to the effects of sleep loss. Dr. Goel says the researchers expect to finish the study later this year.
About every two hours, the study subjects complete a battery of tests that measure things like attention and reaction time, working memory and how quickly they can process information. They complete questionnaires that ask about mood and how sleepy they feel. Researchers calculate the number of calories they eat.
In earlier studies, the Penn lab and others have found that attention, reaction time and cognitive speed tend to be particularly affected by sleep loss. This is a big problem for driving. Higher cognitive functions, like reasoning, tend to be less affected. Mood plummets: People interpret even neutral facial expressions as more negative. Sleep-deprived subjects also eat more and gain weight: In Penn studies, they eat about 500 extra calories a day, veer toward fat-laden foods and gain about 2 pounds in a week.
ENLARGE Ms. Burton works on a puzzle between testing bouts. She plans to use the about $2,000 she's earning as a participant in the study to pay off some credit card bills. Photo: Scott Lewis for The Wall Street Journal
Most Penn sleep-deprivation studies include a control group that lives in the same environment and does the same testing protocol, but doesn't lose any sleep.
But not everyone tolerates sleep loss the same: In general about one-third of people are resistant to the effects of sleep loss, one-third are vulnerable and one-third are somewhere in the middle, Dr. Dinges says.
Ms. Burton seems to fall into the vulnerable group, Dr. Goel says. On the test where she had to hit the space bar when the number appeared, dubbed the psychomotor vigilance test or PVT, it took Ms. Burton sometimes as long as 2 seconds to react accurately. By contrast, another subject, Daniel Dougherty, usually took less than 300 milliseconds to respond. A typical, well-rested person would need about 250 milliseconds.
Other studies have shown that most people aren't good judges of how sleepy—and how impaired—they are.
"I was like, that will be a breeze," says Mr. Dougherty, a 32-year-old from Goldsboro, Md., of what he expected the study to be like. "But it is actually kind of hard. Just feeling tired and wanting to go to sleep but you can't." Mr. Doughtery is changing careers and plans to use the sleep study money to repair his 15 year-old car.
ENLARGE Namni Goel, associate professor in psychiatry, center, is leading the current Penn study. She chats with Ms. Burton and Mr. Dougherty after they complete a round of computer-based tests to measure their attention, reaction time and cognitive speed. Photo: Scott Lewis for The Wall Street Journal
Between tests the study subjects read, watch TV and play board games. There's an entire bookcase filled with games like Monopoly, Sorry and Pictionary. They binge-watch shows on Netflix. Ms. Burton got through five seasons of "Portlandia." Mr. Dougherty was plowing through "Narcos" episodes. Researchers decided that TV-watching would be acceptable because the subjects sit far enough from the televisions that the light emitted wouldn't interfere with the results.
The study is being funded by the Office of Naval Research. Dr. Dinges has also just completed a study looking at how long it takes to recover from sleep deprivation. In earlier studies, it seemed to only take a few days of regular shut-eye for people to recover from sleep loss and perform like they were well-rested.
But this new study seems to refute that. People might seem fine, but if they lose sleep again, their performance plummets more than expected. "There's a memory in this biology," Dr. Dinges says. "They are carrying a vulnerability."
If the results hold up and are replicated, he says, the days of human sleep-deprivation studies might be numbered. "If I can't reverse what I've induced, then these experiments are no longer ethical," he says. "I've got to stop doing this."
Write to Andrea Petersen at andrea.petersen@wsj.com
Debate Over Early-Stage Cancer: To Treat or Not to Treat?
More researchers suggest 'active surveillance' for certain patients instead of surgery
ENLARGEFor certain early-stage, slow-growing cancers, researchers suggest 'active surveillance' may be an acceptable alternative to surgery or radiation. Photo: no credit available By Lucette Lagnad Oct. 19, 2015 1:43 p.m. ET
To treat or not to treat is becoming a hot question.
After years of aggressive treatment of even the smallest thyroid cancers, prominent researchers in the U.S. and Japan are urging a rethinking of old practices and saying simply to watch and wait may be effective for many patients with early-stage disease.
"Active surveillance," as some call it, where doctors carefully monitor patients with small thyroid malignancies via tests and checkups, could be an acceptable alternative to surgery to remove a cancer that isn't likely to grow or spread, according to two recent articles that are set for publication in the American Thyroid Association journal Thyroid and available online now.
"We have always been taught to fear cancer, that all cancer is bad, and all cancer should be operated on," says Otis Brawley, chief medical officer of the American Cancer Society. But now as never before, he says, treatment regimens for several early forms of cancer, including prostate, breast and now thyroid, are being challenged.
R. Michael Tuttle, an endocrinologist at Memorial Sloan Kettering Cancer Center, says numbers of Americans diagnosed with thyroid cancer "are going through the roof."
ENLARGE Dr. R. Michael Tuttle, an endocrinologist at Memorial Sloan Kettering Cancer Center, says it is time to re-evaluate the traditional management approach to early-stage thyroid cancer, which routinely recommends immediate surgery. Photo: Memorial Sloan-Kettering
With more than 60,000 new cases annually, Dr. Tuttle, the principal author of one of the articles, says it is "critical that we re-evaluate our traditional management approach, which routinely recommends immediate thyroid surgery" for all early-stage thyroid cancers. A study from Japan, now online, found similarly good outcomes in patients who chose watchful waiting versus those who had surgery.
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Most thyroid cancers are "incidental findings"—asymptomatic and detected through unrelated testing. Typically the cancer shows up as a small nodule in the thyroid gland at the bottom of the neck, and often a biopsy and surgery follow.
Yet in some cases the operation was unwarranted, some would argue. Removing the thyroid can have side-effects including fatigue and weight gain— hence the need to do it more sparingly, Dr. Tuttle contends. "We are starting to understand our technology got ahead of us," he says. "We find thyroid cancers we would never have found 20 years ago."
The program he set up a couple of years ago at Sloan Kettering gives patients the option of surveillance, including a rigorous regimen of ultrasounds along with regular doctors' visits. After some "significant" early resistance from doctors and patients, he says, it has caught on and 250 patients have signed up.
ThyCa, the Thyroid Cancer Survivors' Association, a patient organization, says it is "supportive" of surveillance as an option. But some patients don't want to watch and wait. "There are definitely patients who are, 'Do not pass go, get it out of my neck,' " Dr. Tuttle said.
Watchful waiting for thyroid cancer points to a larger debate over whether Americans are being overtreated for early-stage malignancies or precancerous lesions that could possibly have been left alone with little risk of negative effects.
"We go too far and end up creating more problems than we solve," when medicine treats small harmless lesions, said H. Gilbert Welch, a professor of medicine at Dartmouth's Geisel School of Medicine in Hanover, N.H., and the author of the 2015 book "Less Medicine, More Health."
ENLARGE Donald Hawken with his son, Max. After a 2012 diagnosis of a slow-growing form of thyroid cancer, Mr. Hawken chose watchful waiting even though, he says, 'when someone says "malignant" you are terrified.' He worries less now than he used to. Photo: Hawken Family
With prostate cancer, men with early-stage disease used to be treated aggressively, with surgery or radiation. Some suffered significant side-effects, including sexual dysfunction and incontinence. In recent years, more hospitals have begun adopting surveillance programs, and the past couple of years have seen a major increase in men choosing the less-invasive course, according to Peter Carroll, chairman of the urology department at University of California, San Francisco, who oversees a surveillance program with some 1,500 men enrolled.
When he is planning a biopsy, Dr. Carroll says he tells the patient, "The goal of this biopsy isn't whether or not you have cancer, but whether you have a cancer that needs to be treated."
Next on the radar screen: Breast cancer. A form of early breast cancer, known as ductal carcinoma in situ, found in about 60,000 women a year, has spurred debate about whether to treat it. Some doctors are starting to question whether the word "carcinoma" should be removed from the name of the disease. Some researchers vehemently disagree.
Many women diagnosed with DCIS have received surgery and radiation. While DCIS isn't invasive and is classified as Stage Zero, some women opt for aggressive treatments including double mastectomy. Some doctors contend that DCIS can be a marker for invasive cancer and requires rigorous treatment, at least until there is data showing which lesions are dangerous and which can be left alone and handled with surveillance.
Ann Partridge, an oncologist at Dana-Farber Cancer Institute in Boston, says the challenge is figuring out which cases of DCIS are low-risk, which are intermediate, and which are at high risk of leading to invasive cancer.
ENLARGE Jessica Ulibarri opted for surgery after a diagnosis of early-stage thyroid cancer and says she would do it again, even though recovery from surgery was difficult. Photo: Jessica Ulibarri
"There are breast cancers that are dangerous and lethal and you have to hit them with all you have," says Dr. Partridge. But DCIS often doesn't pose such a threat, she says. The science to tell the difference with certainty isn't there yet, she acknowledges, "but we are getting better at teasing out the wolves from the sheep."
Some doctors, including those who support surveillance, are raising red flags about going too far to counter overtreatment. "Some have said, 'Let us remove the word cancer from these diagnoses.' I think that is a bit dangerous," says Dr. Carroll, the UCSF prostate expert. He worries patients with early-stage disease won't be vigilant if the word cancer is absent.
Dr. Brawley of the American Cancer Society says with DCIS, he wants to see formal clinical trials on surveillance because of the lack of data on when it can lead to dangerous invasive breast cancer. Dr. Partridge of Dana-Farber agrees and is preparing to undertake a trial with colleagues from other institutions.
Peter Angelos, chief of endocrine surgery and a medical ethicist at the University of Chicago Medicine, has similar concerns about thyroid cancer. "I worry that we lack the data to say, here are two alternative therapies and both are effective," says Dr. Angelos.
Donald Hawken a molecular biologist in Danbury, Conn., chose watchful waiting after his 2012 diagnosis of papillary microcarcinoma, a small, slow-growing and common form of thyroid cancer. "When someone says 'malignant' you are terrified," he says. He consulted with Dr. Tuttle, who outlined the pros and cons of the observational approach, including the chance of metastasis.
Mr. Hawken agreed to watchful waiting and says he felt nervous at every checkup. Two years later, though, he says, "I am much less worried."
Jessica Ulibarri, a 29-year-old social worker in Denver, was offered the option of surveillance for what appeared to be a small, early-stage thyroid cancer. She says she found the idea of waiting a year before surgery "stressful." "I am a rational person but I feared that it was going to go to my brain or my lungs," she says. "I said, 'Do it. Don't mess around with cancer.'"
The aftermath has been difficult. Ms. Ulibarri says she has suffered side-effects from the surgery, in addition to learning the cancer had spread to some lymph nodes. She often feels very tired and wants to sleep. She says she would probably make the same decision over again, but adds, "I don't know that I would recommend [surgery] to someone else" unless it was really necessary.
Write to Lucette Lagnado at lucette.lagnado@wsj.com
Can Mint Make Migraines Less Miserable?
Peppermint oil eases tension headaches, research shows
ENLARGEStopain Migraine is a gel made from menthol derived from peppermint plants. Photo: Allison Scott/The Wall Street Journal By
Oct. 19, 2015 12:13 p.m. ET Laura Johannes
The Ache: About 14% of Americans reported experiencing a migraine or severe headache in the previous three months, according to a 2012 government survey.
The Claim: Products made from peppermint—including mint oil dabbed on the forehead and a new menthol gel applied to the back of the neck—can help ease severe headaches, say companies that sell the products.
The Verdict: One rigorously designed study found peppermint oil applied to the forehead and temples was effective for tension headaches. A study published earlier this year found a menthol gel helped ease migraines, but the work is preliminary and some scientists warn that migraine patients may be highly sensitive to smell during an attack, making a minty aroma potentially unpleasant.
The research on menthol for migraines, including a 2015 Thomas Jefferson University study on a new menthol gel called Stopain Migraine, "isn't knock-your-socks off convincing," but "it's a benign treatment and some people may benefit," says Joel Saper, director of the Michigan Headache & Neurological Institute in Ann Arbor. The product sells for a suggested retail price of $14.99 from Troy HealthCare LLC of Hazleton, Pa.
Headache sufferers have long tried home remedies, such as peppermint oil or Tiger Balm on the forehead or back of the neck, scientists and clinicians say. A potential advantage, they add, is that mint doesn't appear to cause "rebound" headaches, which can result from too-frequent use of aspirin or acetaminophen, sold under such brand names as Tylenol.
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How mint works on headaches, if it does, isn't known. One theory is that mint applied to the skin relaxes muscles around the skull, says Robert G. Kaniecki, chief of the Headache Center at the University of Pittsburgh, who is currently studying whether applying oil-of-cornmint, another type of mint, in the nostrils can head off migraines. Another possibility, he says, is that the aroma relaxes the nervous system. Either way, he says, if you try mint, use it when the pain starts. "Late in the headache, forget about it. You'd better reach for something stronger."
ENLARGEOils and gels derived from peppermint have been shown to be effective against headaches. Photo: Troy Healthcare
Some of the best evidence for mint is a 1996 German government-funded study that looked at 164 tension headaches in 41 patients. Peppermint oil applied to the forehead and temples at the beginning of the headache was as effective as 1,000 milligrams of acetaminophen, the same dose as two extra strength Tylenols, and more effective than a placebo oil that contained only trace amounts of peppermint, according to the paper, published in the journal Nervenarzt.
The oil tested, which is 10% peppermint oil and the rest ethanol, is available in Germany under the brand name Euminz by Germany's Klosterfrau Healthcare Group. If people in other countries want to try peppermint oil for headaches, they should dilute it with alcohol because pure peppermint oil won't penetrate the skin sufficiently to be effective, says study co-author Hartmut Göbel, director of the Kiel Headache and Pain Center, which is affiliated with the University of Kiel.
In unpublished work, Dr. Göbel says that compared with placebo, he found peppermint oil ineffective for migraines, which are severe debilitating headaches that often come with a raft of other symptoms such as dizziness and nausea. However, two recent reports show promise for menthol, an ingredient derived from peppermint oil, in migraines. In a 2010 report by Iranian scientists, a menthol oil applied to the temples and forehead of 35 migraine patients was effective at relieving pain, compared with a placebo solution containing only trace amounts of menthol.
In a 25-patient study of Stopain Migraine, two hours after the product was applied to the back of the neck and behind the ears of patients suffering from migraines, 56% of patients had no pain or mild pain, 25% had moderate pain and 20% had severe pain, according to the report, published in Frontiers in Neurology earlier this year.
A potential issue in using mint as a migraine remedy is that some sufferers are extremely sensitive to any odors during the headache, physicians say; this was not found to be an issue in the Thomas Jefferson clinical trial, says Nick Pokoluk, director of research and quality at Troy.
The study, funded by Troy, didn't have a placebo control. However, "you would not expect to see this good a result in untreated migraines," which typically last four to 72 hours, says co-author Stephen D. Silberstein, a director of the Jefferson Headache Center at Thomas Jefferson University in Philadelphia.
Corrections & Amplifications
Nick Pokoluk is director of research and quality at Troy HealthCare. An earlier version of this article incorrectly said he was chief executive officer.
Write to Laura Johannes at laura.johannes@wsj.com
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