Technology

Health-care providers know there’s a wealth of valuable information trapped in the hand-written notes on patients’ charts. But the challenge of collecting and interpreting the data on a large scale remains to be solved. Now researchers at Stanford have taken a step forward in mining patient-based information by using existing language-analysis methods to identify drug side effects in advance of the Food and Drug Administration issuing official alerts.

My colleague writes in a release:

Although their application is new, their information-gathering methods are based on well-established text processing techniques. It’s also simpler and faster than current strategies used in the same arena, said [engineering research associate Paea LePendu, PhD, the lead author of the paper]. Content is first grouped via “ontologies,” which are information graphs organized by associative relationships instead of a rigid linear structure. For example, melanoma is a kind of skin cancer, and so is Kaposi’s sarcoma; by knowing “skin cancer” encompasses both kinds of cancer, the search process picks up this medical knowledge. The system also de-identifies patient information in the process, so sensitive data, such as names and addresses, doesn’t get revealed. With these methods, LePendu said, the technique allows them to process 11 million clinical notes in about seven hours on hardware no different from a laptop computer — a pace that other programs can’t match.

The information is also current: It’s generated from what is observed and recorded in the hospital or doctor’s office. That’s an advantage over the FDA’s AERS reports, which rely on patients and health providers to make the additional effort to report adverse events.

The researchers developed the computerized method to sift through the contents of clinical notes in electronic medical records and used it to examine how often specific drugs and diseases were mentioned in roughly 10 million notes for about 1.8 million patients over 15 years. The goal was to organize these notes into a data-mining substrate they refer to as a patient-feature matrix. “Everyone is excited about the prospect of ‘big data’ mining on electronic health record data,” Shah said. “We demonstrate it in practice.”

Previously: Researchers mine Internet search data to identify unreported side effects of drugs
Photo by The National Guard

Earlier today I wrote about a breakthrough method called CLARITY, pioneered by Stanford psychiatrist/bioengineer Karl Deisseroth, MD, PhD, for rendering intact tissue samples transparent. Above is a video clip showing off the new method’s capabilities. First you’ll witness a “fly-through” of a complete mouse brain using fluorescent imaging. The immediately following clip – it’s spectacular! – provides a three-dimensional view of a mouse hippocampus (the brain’s brain’s memory hub), with projecting neurons depicted in green, connecting interneurons in red, and layers of support cells, or glia, in blue.

Note that in both cases, there was no need to slice the tissue into ultra-thin sections, analyze them chemically and/or optically and then laboriously “sew” them back together via computer algorithms in order to reconstruct a 3-D virtual image of the biological sample. All that was required, after performing the necessary hocus-pocus, was to ”send in the stain” (i.e., use histochemical means to paint different cell types different colors) and move the sample or camera lens or shift the latter’s focal length. Nice trick. With big implications for biomedical research.

Previously: Lightning strikes twice: Optogenetics pioneer Karl Deisseroth’s newest technique renders tissues transparent, yet structurally intact, Visualizing the brain as a Universe of synapses and A federal push to further brain research

Stanford psychiatrist and bioengineer Karl Deisseroth, MD, PhD, spent much of this century’s first decade developing a revolutionary method for studying the brain: optogenetics. In 2010, Nature Methods  heralded optogenetics as its “method of the year.”

It looks as though lightning has struck the Deisseroth lab again.

Suppose, just for a moment, that you’re conducting espionage on a heavily guarded multi-story building strongly suspected to be an advanced nuclear-weapons facility. The building quickly proves utterly inaccesible. Fortunately, you manage (through methods too covert to be revealed here) to procure a floor plan. Nice going. Now, you know a lot about the floors themselves and a bit of cross-sectional detail on the bases of whatever’s sitting on them. Better than nothing.

Now, imagine - in fantasyland, anything goes – that you can don goggles enabling you to peer right through the building’s outer walls and directly observe its three-dimensional structure, including its concealed laboratories and the instruments and manufacturing machinery inside of them. Payday!

An analogous technique developed by Deisseroth promises to revolutionize cell biology. Exploring connections among, and contents within, the billions of cells in a chunk of tissue often involves slicing the chunk into ultra-thin sections, exposing each slice’s top and bottom surfaces for microscopy or histochemical and electrical manipulation. Sophisticated computation can stitch the slices back together (virtually), roughly reconstructing the sample’s three-dimensional structure. (That’s the floor plan I mentioned earlier.)

Unfortunately, all this sawing disrupts key connections within the tissue and distorts its constitutent cells’ geography. Plus, while those sections are thin, they’re not infinitely thin. Light and chemicals can penetrate only so far. Volumes of valuable information about their innards remains concealed.

Deisseroth’s paradigm-shifting method, called CLARITY, renders tissue transparent while leaving it structurally intact, yet accessible to large “detective” molecules scientist use to gain information about cells’ surface features and genetic contents. In a study just published in Nature, a group led by Deisseroth (who discusses his work in the video above) converted an entire adult mouse brain into an optically transparent, histochemically permeable replica of itself. The position and structure of proteins embedded in the membranes of cells and their intracellular organelles remained intact.

Okay, step back with me for a minute. Essentially, all cells are liquid-filled bubbles of oil. (Nerve cells are better visualized as long, branching, liquid-filled tubes whose walls are made of fat.) These oil/fat (in science-speak, “lipid“) bubbles and walls (“membranes”) both house and compartmentalize their contents, so operations inside them can be carried out in relative isolation. Dotting membranes’ surfaces are all kinds of proteins performing innumerable activities key to the health of the cells they enclose and the tissues those cells compose.

Evolution designed lipid membranes to be mostly impermeable to large molecules, and they happen to be opaque (or else we’d all be transparent). In a feat of chemical engineering, Deisseroth’s team replaced the lipids with, for all purposes, clear plastic. With their work, you could literally read a newspaper through the mouse’s brain. Formerly membrane-bound proteins remained anchored in the membranes’ doppelgangers, retaining their structures (a big deal, as a protein’s structure determines its function). The tissue was also nanoporous: It permitted bulky “reporter”molecules such as stain-carrying antibodies and strips of DNA to flow deep into the transformed tissue sample and out again.

Obviously you wouldn’t want to try this on yourself, although Plastic Man certainly seems to have worked out the kinks.

Previously: Researchers induce social deficits associated with autism, schizophrenia in mice, Anti-anxiety circuit found in unlikely brain region and Nature Methods names optogenetics its “Method of the Year
Photo in featured entry box by kainet

New findings analyzing Internet search data for major mental illnesses shows that seasonal weather changes may have a larger impact on such health conditions than previously believed.

In the study (.pdf), researchers used Google’s public database of queries to identify and monitor users’ searches for mental-health disorders, including anxiety, eating disorders, schizophrenia, ADHD, bipolar and obsessive compulsive disorder (OCD), in the United States and Australia from 2006 through 2010. According to a release:

The research showed eating disorder searches were down 37 percent in summers versus winters in the U.S., and 42 percent in summers in Australia. Schizophrenia searches decreased 37 percent during U.S. summers and by 36 percent in Australia.

Bipolar searches were down 16 percent during U.S. summers and 17 percent during Australian summers; ADHD searches decreased by 28 percent in the U.S. and 31 percent in Australia during summertime. OCD searches were down 18 percent and 15 percent, and bipolar searches decreased by 18 percent and 16 percent, in the U.S. and Australia respectively.

Searches for suicide declined 24 and 29 percent during U.S. and Australian summers and anxiety searches had the smallest seasonal change – down 7 percent during U.S. summers and 15 percent during Australian summers.

While some conditions, such as seasonal affective disorder, are known to be associated with seasonal weather patterns, the connections between seasons and a number of major disorders were surprising. “We didn’t expect to find similar winter peaks and summer troughs for queries involving every specific mental illness or problem we studied, however, the results consistently showed seasonal effects across all conditions – even after adjusting for media trends,” said James Niels Rosenquist, MD, PhD, a psychiatrist at Massachusetts General Hospital.

The work appears in the latest issue of American Journal of Preventive Medicine.

Previously: Sweating the small stuff may harm your mental health and Ask Stanford Med: David Spiegel answers your questions on holiday stress and depression
Via The Atlantic
Photo by Tom Hilton

Adam de la Zerda, PhD, likes to tell his students that the sky’s the limit – something he most likely told himself many times over. At just 28 years old, he already has a pretty impressive laundry list of accomplishments: He’s co-founder of a Silicon Valley startup, he was recently listed in Forbes magazine’s “30 under 30″ in science and health care, and he has garnered numerous other awards, including ones from the Damon Runyon Cancer Research Foundation and the National Institutes of Health.

A story in today’s Inside Stanford Medicine profiles the young Stanford faculty member and a technology he developed called photoacoustic molecular imaging, which allows researchers to see cancerous tumors hiding under tissues. As writer Elizabeth Devitt explains, the imaging technique holds promise for cancer detection and other diseases:

The unique advantage of photoacoustic molecular imaging is that it allows scientists to see tumors hiding under other tissues and structures. It can also outline tumor boundaries during surgery, which helps surgeons see what to cut out and what to leave in — avoiding mistakes either way. “It’s like having Superman vision,” said de la Zerda.

“There may be a million different things we can do with this,” he added. “We can study basic tumor biology. We can monitor the treatment of cancer patients. We can even apply this technique to diseases other than cancer.”

Previously: Stanford structural biologist named one of Forbes Magazine’s 30 under 30 rising stars
Photo by Norbert von der Groeben

I’m not really in the dark when it comes to things that cause me stress (even my very small daughters can tell you that traffic ranks right up there), but I’m nonetheless intrigued by an app that monitors users’ stress levels and logs their daily stressors. Developer Dirk Trossen, PhD, with the University of Cambridge, describes how the app works and shares a few other thoughts in a New Scientist Q&A:

Aren’t people aware of what stresses them and how their bodies respond? We want to help people get away from preconceived ideas of what is important. Heart rate is a very good example. It is such a concrete, well-known parameter that people tend to focus on it. But increased heart rate alone actually gives you very little sense of someone’s stress level.

Why is it important to keep track of all of this? Stress can undermine our health in the long run. The fact that today’s workforce is likely to work longer than the previous generation increases the importance of stress management as an aspect of general well-being. We want users to be aware of the ways stress can negatively impact them.

…

You’ve been monitoring yourself with the app for over a year. What stresses you? Email. Insights into how it interrupts my work have caused me to change my behaviour. I now have clear intervals between checking email, and even entire blackout days where I don’t look at it. I have also changed how I travel. Yet, apart from stress management, it is sometimes just fun to look back. Though this isn’t its main purpose, the app also makes a worthwhile memory collection tool.

Previously: Stressed? There’s an app for that and No surprise here: Anger and stress are bad for your health
Via @RitaRubin
Photo by Danielle Scott

A recent report from the Pew Internet & American Life Project found that 35 percent of American adults have used the Internet to specifically diagnose a medical condition they, or someone else, might have. Similarly, a 2011 survey showed that 46 percent of physicians frequently turn to sites like Google or Yahoo to treat, diagnose or care for patients.

But as many patients with rare diseases know, using conventional Internet search engines to diagnose a condition that occurs in less than 1 in 2000 of the population can prove tricky. So a group of European researchers developed an alternative, called FindZebra, to help physicians and patients’ conduct more effective search queries. Technology Review’s Physics arXiv Blog reports:

The magic sauce in FindZebra is the index it uses to hunt for results. [Radu Dragusin, assistant lecturer at the University of Copenhagen in Denmark, and colleagues] have created this index by crawling a specially selected set of curated  databases on rare diseases. These include the Online Mendelian Inheritance in Man database, the Genetic and Rare Diseases Information Center and Orphanet.

They then use the open source information retrieval tool Indri to search this index via a website with a conventional search engine interface. The result is FindZebra.

Finally, they compared the results of searches on FindZebra against the same search on Google applied to the same limited dataset, a feature that is possible with advanced Google searches.  Dragusin and co say that the Google results are significantly worse than their own.

…

Although still a research project, [developers] have made their rare disease search engine publicly available at www.findzebra.com. This could clearly become a valuable tool for the medical community.

Previously: Report shows 35 percent of U.S. adults turn to the Internet to diagnose a medical condition, Dr. Google: Threat or menace? and Patient self-diagnosis: From the browser to the exam room

Past research has shown that telemedicine can help reduce health disparities between rural and urban areas and be as effective as in-office visits for diagnosing and treating dermatology conditions. Now findings recently published in JAMA Neurology suggest that “virtual” house calls for Parkinson’s patients provide clinical benefits comparable to seeing a physician in person.

In the small study, researchers at Johns Hopkins University and the University of Rochester Medical Center randomly selected patients with Parkinson’s disease to participate in three web-based conferencing sessions while the rest of the group visited a physician’s office over seven months. According to a university release:

At the end of the seven months, the researchers measured the patients’ perception of their quality of life and the level of care they were receiving. They found that the patients who received virtual house calls did as well as those who received in-person care.

The researchers also measure the economic value of allowing individuals to receive care in their own homes. They found that the average telemedicine visit lasted 53 minutes from beginning to end. In contrast, patients who received in-person care spent an average of 255 minutes per visit when factoring in the trip to and from the doctor’s office for a total of 100 miles and 3 hours of travel time over the seven months duration of the study.

Researchers commented on the significance of the findings saying they “demonstrate that quality specialized care can be effectively delivered to individuals in remote locations.” But, they also noted several barriers to telemedicine becoming widespread such as licensing and reimbursement requirements.

Previously: FCC allocates $400 million in funding to develop and expand telemedicine, Telemedicine takes root in the Midwest, How a Stanford dermatologist is using telemedicine to reach underserved populations in California and Can telemedicine work for dermatology patients?

Nearly 60 percent of American adults turn to the Internet in search of health information. Now investigators at Stanford and Microsoft Research have joined forces to develop a method for mining consumers’ web search history and identifying unreported side effects of drugs or drug combinations.

For the study, the Microsoft researchers developed automated tools that were used to analyze anonymized data from 82 million drug, symptom and condition searches performed by 6 million Internet users who consented to sharing their search history for research purposes. As my colleague explains in a release:

… [T]he team used the automated tools to identify searches for information on paroxetine, pravastatin or both during 2010. The tools then computed the likelihood that users in each group would also search for hyperglycemia – or almost 80 of its symptoms or descriptors, such as “high blood sugar,” “blurry vision,” “frequent urination” or “dehydration.”

…

Among people who searched for the drug paroxetine or its brand names in 2010, about 5 percent also searched for one of the hyperglycemia-related terms. For pravastatin and its brand names, the rate was below 4 percent. But for those who searched for both drugs, suggesting that they might be taking both drugs, the search rate for hyperglycemia was 10 percent.

To test the accuracy of the search engine analysis, the team looked at 31 drug-drug interactions already known to cause hyperglycemia, and 31 interactions known to be safe. Overall, the drugs with known interactions led to more search queries on hyperglycemia. But the results also suggested that around 12 percent of users searching for drug combinations known to have no interactions also had an unusually high rate of hyperglycemia searches, which would lead researchers down dead ends if they pursued them.

Stanford professor and study co-author Russ Altman, MD, PhD, commented on the findings saying, “I believe patients are telling us lots of things about drugs, and we need to figure out ways to listen… This is just one way of listening and one application.”

A New York Times story published today noted that researchers are “also now thinking about how to add new sources of information, like behavioral data and information from social media sources.”

Previously:Thousands of previously unknown drug side effects and interactions identified by Stanford study, Mining for research: How computerized records open new doors for medical researchers and Unexpected drug interactions identified by Stanford data mining
Photo by Victor

Convincing my grandparents to join me in a game of Wii bowling or try their hand at playing Mario Kart would be a long shot, to say the least. But perhaps I could change their minds by telling them about new research from North Carolina State University showing that seniors who play video games have higher levels of well-being.

In the study, researchers surveyed a group of participants aged 63 and older about their video-game playing habits. Individuals then completed a number of tests designed to evaluate emotional and social well-being. Overall, nearly half of the participants said they played a digital game in the past year and a third reported playing once a week. Researchers wrote in the discussion section:

… Much of the psychological research conducted on the impact of digital games has focused on the possible adverse effects of playing digital games. Contrary to these and other studies, the findings of the current investigation suggest that older adults who reported playing digital games score, on average, significantly better than non-digital game playing on measures assessing a number of domains of successful aging. Specifically, older adults who were classified as Regular and Occasional Gamers reported less depression and lower negative affect as well as higher well-being than their non-gaming counterparts. One possibility for these findings is that digital games serve as a source of entertainment, which may lower negative affect and depression and increase well-being. In support of this interpretation, previous studies have found that adults who engage in more leisure activities report better emotional outcomes

The findings are particularly interesting in light of the nation’s aging population and past research showing baby boomers are more depressed than other age groups.

Previously: Improving patients’ lives through video games and Elderly adults turn to social media to stay connected, stave off loneliness
Photo by North Carolina State University