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In the News, Pain, Patient Care, Research

More benefit than bite: Potential therapies from “pest” animals

More benefit than bite: Potential therapies from "pest" animals

512px-Scary_scorpionA painful spider bite can make you question why such creatures exist. Yet just because “pests” like spiders, scorpions, and snakes lack the appeal that kittens and puppies possess, it doesn’t mean they aren’t important or useful.

Yesterday, an article from Medical News Today drove this message home by highlighting some of the medical benefits we derive from six of the creatures we tend to complain the most about. As writer Honor Whiteman explains in the story, scientists are exploring ways to use toxins and substances produced by so-called pest animals, such as spiders scorpions, and reptiles, to treat chronic pain, repair nerves, and develop new ways to kill the human immunodeficiency virus.

From the piece:

In 2013, MNT [Medical News Today] reported on a study published in Antiviral Therapy, in which researchers revealed how a toxin found in bee venom – melittin – has the potential to destroy human immunodeficiency virus (HIV).

The investigators, from the Washington University School of Medicine, explained that melittin is able to make holes in the protective, double-layered membrane that surrounds the HIV virus. Delivering high levels of the toxin to the virus via nanoparticles could be an effective way to kill it.

A more recent study published in September 2014 claims bees may also be useful for creating a new class of antibiotics. Researchers from the Lund University in Sweden discovered lactic acid bacteria in fresh honey found in the stomachs of bees that has antimicrobial properties.

The story cites several other potential uses for venoms and animal-derived substances, such as my favorite example, Gila monster spit:

In 2007, a study by researchers from the University of North Carolina at Chapel Hill School of Medicine revealed how exenatide – a synthetic form of a compound found in the saliva of the Gila monster, called exendin-4 – may help people with diabetes control their condition and lose weight.

The compound works by causing the pancreas to produce more insulin when blood sugar is too high. In the study, 46% of patients who were given exenatide in combination with diabetes drug metformin had good control of their blood sugar, compared with only 13% of control participants.

As Whiteman explains in the article, many of these potential medical treatments are still in the early stages of development. Yet some therapies, such as the synthetic version of the compound found in Gila monster saliva, exenatide, are already in use, offering hope that other animal-derived medical treatments may be available in the future.

Previously: Tiny fruit flies as powerful diabetes modelFruit flies headed to the International Space Station to study the effects of weightlessness on the heartBiomedical Indiana Jones travels the world collecting venom for medical research and Tarantula venom peptide shows promise as a drug
Photo by H Dragon

Pain, Patient Care, SMS Unplugged

Comfort care: “We always have something to give”

Comfort care: "We always have something to give"

SMS (“Stanford Medical School”) Unplugged is a forum for students to chronicle their experiences in medical school. The student-penned entries appear on Scope once a week; the entire blog series can be found in the SMS Unplugged category.

15952622460_20fb32e76a_z A hospital can be full of discomfort. My patients tell me that the food is unappetizing. The beds hurt their backs. The noise echoing through the hallways at night makes it impossible to sleep. And for those patients near the end of life, the treatments being offered may no longer be of benefit, causing more pain than good.

The answer to discomfort for those who are very ill is comfort care, the use of palliation when life-advancing measures are no longer indicated or desired. These measures include things like giving morphine to dull the pain and ease the breath, applying lip balm over cracked skin, offering ice chips to revive the mouth, adjusting blankets or fans, deciding not to press on someone’s chest, to stifle their airways with tubes, if their status declines. The decision to turn to comfort care often means that a patient can receive a private room in the hospital for family to stay close, to feel sunlight through a window. The triumph of comfort over the many indignities of being away from home.

Death does not need to happen in a hospital, yet too often it happens here. In January, I saw two people die. One was old. He had lived a full life; his room was decorated with photographs from his youth, his tall form in a service uniform, or in a tuxedo on his wedding night, half-cropped face suspended in a laugh.

When I met him, he was on a morphine drip, no longer able to speak. To gauge the adequacy of his pain control, we looked at his heart rate, his blood pressure, scouring for signs of bodily agony. He was tucked into a warming blanket, yellow hospital socks on his feet. Every morning we circled around him, whispering hello into the room where he slept, taking stock of the fluorescent etches of the vital signs monitor, the coolness of his legs.

When he passed, we pronounced him after checking for a pulse and listening for a heartbeat. I felt solemn, but also grateful for his smooth passage.

The second person I saw die was young. She had been full of life and her death ripped up all those who loved her. As she became more ill, and more confused, her family made the brave decision to transition to comfort care. There was nothing gratifying about it, her loss was unspeakable. But perhaps the final moments, free from the blinking of machines, the infusion of drugs that upset her bowels and irritated her veins, carried a dim current of peace.

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Events, Pain, Stanford News

Advances in diagnosing and treating a painful and common jaw disorder

Advances in diagnosing and treating a painful and common jaw disorder

3439490784_46b2cfd9e3_zOn New Years Eve, Australian rapper Iggy Azalea shared with her Twitter followers that she was diagnosed with a temporomandibular joint dysfunction (often referred to as TMD or TMJ). The singer is among the estimated 10 million Americans who suffer from the condition, which is more common in women than men and people ages 20 to 40.

Symptoms of the disorder include a stiffness of jaw muscles, limited movement, clicking or locking of the jaw and radiating facial pain. It was previously believed that problems with how the teeth fit together or the structure of the jaw caused the condition. But in talking to Michele Jehenson, DDS, a clinical assistant professor at the Pain Management Center at Stanford, I was told, “There is still a lot we do not know about what causes [temporomandibular joint dysfunction] but one thing we do know is that they are not caused by upper and lower teeth misalignment or improper jaw position. We now believe that TMD susceptibility is, at least, partly genetic.”

Since the causes of the TMD are not clear, diagnosing the condition can be challenging. Currently, there is no standardize test for providers to use to diagnose patients, so physicians continue to rely on the clinical evaluation, including palpation, range of motion and auscultation. But imaging technologies are starting to play a more important role. Jehenson noted, “We now have more accurate imaging such as cone beam CT scans or MRIs. Some dentists use joint vibration analysis or EMG, but these electronic sensors have been shown to be unreliable and lead to over diagnosis.”

Over the past two decades, there as been a significant amount of research on the outcomes of TMD treatments. As Jehenson told me:

Evidence is very clear that aggressive and non-reversible treatments for TMD (braces, jaw surgery, crowns, full time wear of appliance, jaw repositioning) are rarely indicated. The best treatments should be conservative. Depending on the case, treatments are usually a mix of medication (oral or topical), nighttime appliance wear, injections, physical therapies, behavior modification and counseling, sleep and stress management.

To learn more about the diagnosis and treatment of TMD, join Jehenson for a Stanford Health Library talk on Thursday at 7 PM Pacific Time. During the event, she’ll l further discuss evidence based versus non-evidence based treatments. Those unable to attend in person can watch the talk online.

Photo by Eric Allix Rogers

Addiction, Pain, Public Health, Research

Medical marijuana and the risk of painkiller overdose

Medical marijuana and the risk of painkiller overdose

medical marijuanaAfter a study published this fall showed that that opioid overdoses (e.g., with painkillers such as Oxycontin) occur at lower rates in states with legalized medical marijuana, many people interpreted the results as proof that using medical marijuana lowers an individual’s risk of overdose. For example, some speculated that marijuana allows people in pain to forgo using opioids or at least use them in lower doses. Other suggested that medical marijuana reduces users’ consumption of alcohol and anti-anxiety medications, both of which make opioid use more likely to lead to overdose. Still others hypothesized that medical marijuana improves mental health, reducing the risk of intentional opioid overdose (i.e., suicide attempts),

However, all of this speculation was premature. Many things that are associated when geographic areas are compared are not associated in the lives of the individuals who reside in those areas. For example, geographic areas with higher rates of cigarette smoking and higher radon exposure have lower cancer rates, even though individuals who smoke and/or get exposed to radon have higher rather than lower risk of cancer.

The only way to understand the influence of medical marijuana on individuals’ risk of opioid overdose is to actually research individuals, and that is what an Australian team has done. In a recently published study of more than 1,500 people who were on prescribed opioids for pain, they examined experiences with medical marijuana.

Seeking pain relief from medical marijuana was common in the sample, with 1 in 6 participants doing so and 1 in 4 saying they would do so if they had ready access to it. The results did not support the idea that medical marijuana users are at relatively low risk of opioid overdose. Indeed, on every dimension they appeared to be at higher risk than those individuals who did not use medical marijuana for pain.

Specifically, relative to individuals who only used opioids for pain, the medical marijuana users were on higher doses of opioids, were more likely to take opioids in ways not recommended by their doctor, were over twice as likely to have an alcohol use disorder and four times as likely to have a heroin use disorder. Medical marijuana users were also over 50 percent more likely to be taking anti-anxiety medications (benzodiazepines), which when combined with opioids are particularly likely to cause an overdose.

Neither did the medical marijuana users have better mental health. Almost two-thirds were depressed and about 30 percent had an anxiety disorder.   These rates were half again as high as those for non-medical marijuana users.

Medical marijuana thus appears to be commonly sought for pain relief among people who are taking prescribed opioids for pain. But in this population, it’s a marker for much higher rather than lower risk for opioid overdose.

Addiction expert Keith Humphreys, PhD, is a professor of psychiatry and behavioral sciences at Stanford and a career research scientist at the Palo Alto VA. He has served in the past as a senior advisor in the Office of National Drug Control Policy in Washington, DC. He can be followed on Twitter at @KeithNHumphreys.

Previously: Assessing the opioid overdose epidemicTo reduce use, educate teens on the risks of marijuana and prescription drugs and Study shows prescribing higher doses of pain meds may increase risk of overdose
Photo by David Trawin

Health Costs, Pain, Public Health, Research

Study examines trends in headache management among physicians

Study examines trends in headache management among physicians

4175034274_63cd0d4a7c_zAn estimated 12 percent, or 36 million Americans, suffer from migraines, resulting in an economic loss of $31 billion each year due to lost productivity, medical expenses and absenteeism.

Making lifestyle changes, such as exercising regularly, getting adequate sleep, reducing stress and cutting food triggers from your diet, have been shown (.pdf) to be effective ways to manage headache symptoms. But research recently published in the Journal of General Internal Medicine shows that physicians are increasingly ordering medical tests and providing referrals to specialists instead of offering counseling to patients on how changing their behavior could relieve their pain. Medical News Today reports:

The study, which analyzed an estimated 144 million patient visits, found a persistent overuse of low-value, high-cost services such as advanced imaging, as well as prescriptions of opioids and barbiturates. In contrast, the study found clinician counseling declined from 23.5 percent to 18.5 percent between 1999 and 2010.

The use of acetaminophen and non-steroidal anti-inflammatory drugs like ibuprofen for migraine remained stable at approximately 16 percent of the medications. Meanwhile, the use of anti-migraine medications such as triptans and ergot alkaloids rose from 9.8 percent to 15.4 percent. Encouragingly, guideline-recommended preventive therapies – including anti-convulsants, anti-depressants, beta blockers and calcium channel blockers – rose from 8.5 percent to 15.9 percent.

Unlike with the treatment of back pain, researchers found no increase in the use of opioids or barbiturates, whose usage should be discouraged, although they were used in 18 percent of the cases reviewed.

Researchers also found a significant increase in advanced imaging such as CT scans and MRIs, from 6.7 percent of visits in 1999 to 13.9 percent in 2010. The use of imaging appeared to rise more rapidly among patients with acute symptoms, compared to those with chronic headache.

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Pain, Science, Stanford News, Videos

Graduate student explains pain research in two-minute video

Graduate student explains pain research in two-minute video

Earlier this year I wrote about some fascinating research from the lab of chemist Justin Du Bois, PhD, who has been working with naturally occurring toxins with the goal of developing ways of combatting pain. This class of toxins is found in a number of poisonous animals, including the newts scurrying around Stanford campus, puffer fish and mollusks in red tides.

Now, graduate student Rhiannon Thomas-Tran, who has been working with Du Bois, produced a great video describing their approach, complete with some pretty creative drawings.

Previously: Toxins in newts lead to new way of locating pain

Anesthesiology, Pain, Research, Stanford News

Miniature wireless device aids pain studies

Miniature wireless device aids pain studies

DSC_0053Here’s one thing I didn’t know: For every person who goes to the doctor to be treated for chronic pain, less than a half get their pain reduced even by half. I learned that from anesthesiologist David Clark, MD, who recently received a grant from Stanford Bio-X, which supports interdisciplinary teams working on biomedical problems, to improve those odds.

One of Clark’s collaborators is Scott Delp, PhD, who last spring developed a way of using light to activate and deactivate pain neurons in mice. To be clear, the nerves had to be genetically engineered to allow the light to work – not something that can currently be done in humans.

That work pointed to new ways of studying pain, but had a glitch. The light was delivered through fiber optic cables and the mice couldn’t behave normally in their cages. That’s where engineer Ada Poon, PhD, enters the picture. She’s been developing a variety of devices that work wirelessly in the body, and she’s now working on a wireless device to deliver the light to nerves in mice. Here’s what I wrote in an online story yesterday:

Coupling a wireless technology to optogenetics eliminates the wire and allows a mouse to move freely, use an exercise wheel and socialize. Clark said this combination will allow researchers to design experiments that more closely mirror a patient’s experience.

For example, Clark said that when he sees patients they don’t necessarily complain only about the pain. They complain about not wanting to see friends, not being able to go to work, or not being able to do activities they enjoy.

“What we will be able to look at is a more natural measure of pain relief,” Poon said. They could assess whether a treatment allows mice to return to normal activities by tallying time spent on an exercise wheel or socializing.

Clark went on to tell me the value of working in this team: “When you combine people with different skills you will come up with something with truly high impact.”

Previously: Using light to get muscles moving and Stanford researchers demonstrate feasibility of ultra-small, wirelessly powered cardiac device
Image courtesy of Ada Poon

Clinical Trials, Immunology, Pain, Research, Stanford News, Surgery, Technology

Discovery may help predict how many days it will take for individual surgery patients to bounce back

Discovery may help predict how many days it will take for individual surgery patients to bounce back

pandaPost-surgery recovery rates, even from identical procedures, vary widely from patient to patient. Some feel better in a week. Others take a month to get back on their feet. And – until now, anyway – nobody has been able to accurately predict how quickly a given surgical patient will start feeling better. Docs don’t know what to tell the patient, and the patient doesn’t know what to tell loved ones or the boss.

Worldwide, hundreds of millions of surgeries are performed every year. Of those, tens of millions are major ones that trigger massive inflammatory reactions in patients’ bodies. As far as your immune system is concerned, there isn’t any difference between a surgical incision and a saber-tooth tiger attack.

In fact, that inflammatory response is a good thing whether the cut came from a surgical scalpel or a tiger’s tooth, because post-wound inflammation is an early component of the healing process. But when that inflammation hangs on for too long, it impedes rather than speeds healing. Timing is everything.

In a study just published in Science Translational Medicine, Stanford researchers under the direction of perioperative specialist Martin Angst, MD, and immunology techno-wizard Garry Nolan, PhD, have identified an “immune signature” common to all 32 patients they monitored before and after those patients had hip-replacement surgery. This may permit reasonable predictions of individual patients’ recovery rates.

In my news release on this study, I wrote:

The Stanford team observed what Angst called “a very well-orchestrated, cell-type- and time-specific pattern of immune response to surgery.” The pattern consisted of a sequence of coordinated rises and falls in numbers of diverse immune-cell types, along with various changes in activity within each cell type.

While this post-surgical signature showed up in every single patient, the magnitude of the various increases and decreases in cell numbers and activity varied from one patient to the next. One particular factor – changes, at one hour versus 24 hours post-surgery, in the activation states of key interacting proteins inside a small set of “first-responder” immune cells – accounted for 40-60 percent of the variation in the timing of these patients’ recovery.

That robust correlation dwarfs those observed in earlier studies of the immune-system/recovery connection – probably because such previous studies have tended to look at, for example, levels of one or another substance or cell type in a blood sample. The new method lets scientists simultaneously score dozens of identifying surface features and goings-on inside cells, one cell at a time.

The Stanford group is now hoping to identify a pre-operation immune signature that predicts the rate of recovery, according to Brice Gaudilierre, MD, PhD, the study’s lead author. That would let physicians and patients know who’d benefit from boosting their immune strength beforehand (there do appear to be some ways to do that), or from pre-surgery interventions such as physical therapy.

This discovery isn’t going to remain relevant only to planned operations. A better understanding, at the cellular and molecular level, of how immune response drives recovery from wounds may also help emergency clinicians tweak a victim’s immune system after an accident or a saber-tooth tiger attack.

Previously: Targeting stimulation of specific brain cells boosts stroke recovery in mice, A closer look at Stanford study on women and pain and New device identifies immune cells at an unprecedented level of detail, inside and out
Photo by yoppy

Behavioral Science, Pain, Podcasts

Chronic pain: Getting your head around it

Chronic pain: Getting your head around it

Less Pain cover - smallerI have to admit: When it comes to pain, I’m a total wimp. The few times I’ve approached anything near chronic pain was in my neck – the result from unilateral breathing as a lap swimmer. When I had the pain, I was obsessed with it, and it was a complete drag on my psyche. My painful experience gave me deep empathy for anyone who lives with chronic pain.

Beth Darnall, PhD, is a clinical associate professor at the medical school and a clinical psychologist at Stanford’s Pain Management Center. She has practiced this unique specialty – pain psychology – for the past 10 years, working with chronic pain sufferers to find alternative means to controlling their pain rather than being stuck in a downward spiral of opioid use. And she’s written a new book, Less Pain, Fewer Pills, where she details a methodical approach that enables one to get their “head” out from their pain.

Clearly it’s not all attitude, but a significant portion of pain is how we think about it and catastrophize it and therefore unknowingly give it strength. She told me in this 1:2:1 podcast that “early life trauma can lead to changes in the central nervous system and immune systems… that could prime someone to experience chronic pain later on.” She also said:

We have just pure genetics, an underlying predisposition to acquire chronic pain… But we also know that a person’s psychological makeup, what the person brings to the table, is a big predictor in terms of whether or not their pain resolves or whether it becomes entrenched.

I asked Darnall whether her role as a clinical psychologist helps patients rethink their pain. She told me, “A key message that I bring forward to the table is that pain isn’t something that just happens to us. Once we acquire chronic pain we are constantly participating with our pain in terms of our thoughts, our beliefs, our emotions, and our choices. If we can focus on that and optimize our control there, then we can set ourselves up to have the best response to all of the treatments that our doctors are going to be trying for us.”

If you suffer from chronic pain or know someone who does, I hope you’ll find this conversation with Darnall of value.

Previously: Stanford researchers address the complexities of chronic pain, Exploring the mystery of pain, Relieving Pain in America: A new report from the Institute of Medicine, Stanford’s Sean Mackey discusses recent advances in pain research and treatment and Oh what a pain

Addiction, In the News, Pain, Public Health

Stanford addiction expert: It’s often a "subtle journey" from prescription-drug use to abuse

Stanford addiction expert: It's often a "subtle journey" from prescription-drug use to abuse

Here are some frightening facts you might not know: Drug overdose death rates in the United States have more than tripled since 1990, with the majority of drug-related deaths caused by prescription drugs. And as of 2010, about 18 women in the U.S. die every day of a prescription painkiller overdose. Prescription-drug abuse, which we’ve written about extensively here on Scope, is a very real and pressing issue – and it was the focus of a recent Forum on KQED-FM.

Among the panelists on Friday’s show was Stanford addiction psychiatrist Anna Lembke, MD, who made the important point that most people who end up addicted to prescription painkillers didn’t start out “looking for a buzz” and that most doctors who prescribe the drugs are merely trying to help their patients. As she explained to listeners:

The problem with… prescription opioids is that they actually do work for pain initially… But for most people, after you take them every day for let’s say a month or more, [you] build up tolerance where they stop working so then you need more of the same drug to get the same effect and it escalates on like that. I really think the process is insidious, both for the patients who become addicted and the doctors who prescribe them. It happens in a subtle journey – when all of the sudden [patients are] using them not just for pain but also maybe to relax themselves, to lift their mood, to be able to go out to a party if they’re feeling anxious, and the doctors continue to prescribe them because they started out working, the patients were happy [and] their function improved. The dose is escalating, but they want to keep the patient happy for all kinds of reasons.

The entire conversation is worth a listen.

Previously: Why doctors prescribe opioids to patients they know are abusing them, Patients’ genetics may play a role in determining side effects of commonly prescribed painkillers, Report shows over 60 percent of Americans don’t follow doctors’ orders in taking prescription meds and Study shows prescribing higher doses of pain meds may increase risk of overdose and Prescription drug addiction: How the epidemic is shaking up the policy world

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