Proposed Brain Activity Map Seeks to Crack Neuronal Code - AlzForum Alzheimer Research News

Despite decades of research, scientists still do not understand how neuronal firing encodes thought and behavior. To decipher this, a group of scientists proposes an ambitious project to map the activity of every neuron in the brain, and correlate the data with behavior and disease states. The White House has embraced the idea, with President Obama mentioning the plan in his 2013 State of the Union speech (see New York Times story). The project is expected to appear in the president's forthcoming federal budget proposal. Proponents suggest that this Brain Activity Map (BAM) Project, like the Human Genome Project, represents an investment in future technology and basic research that will pay tremendous dividends later. The findings may eventually lead to better treatments for conditions such as Parkinson's disease, epilepsy, and schizophrenia, and perhaps even Alzheimer's disease, said Rafael Yuste at Columbia University in New York City, who helped develop the proposal. BAM plans to start with animal models while developing non-invasive technology to eventually study human brains. Human studies will only come much later, despite the emphasis in popular press reports on human brain mapping.

"This is a thoughtful and provocative set of ideas that will accelerate our efforts to decipher the fantastic complexities of brains," David Van Essen at Washington University in St. Louis, Missouri, told Alzforum. He is not involved with the BAM proposal. However, he co-leads the Human Connectome Project, another large brain mapping initiative. This ongoing study maps the structural wiring of the human brain. It also gathers whole-brain activity data using functional magnetic resonance imaging (fMRI) (see ARF related news story). Van Essen noted that the proposed Brain Activity Map Project will provide an immense number of data that will be complementary to the Human Connectome Project. By measuring the activity of large ensembles of individual neurons in animal models, the BAM Project could help researchers develop computational models of how brain circuits operate. "That would give us a much better basis for interpreting and making sense of the vast numbers of fMRI data being obtained on whole-brain activity in humans," Van Essen said.

With the federal budget still in limbo, it is unclear how much funding the BAM Project will receive. Story Landis, who directs the National Institute for Neurological Disorders and Stroke (NINDS), said that the project is still in the planning stages. At the moment, Landis and Thomas Insel, who directs the National Institute of Mental Health (NIMH), manage the effort. Strategy meetings are ongoing. One possibility is that the project will be funded under the National Institute of Health's Blueprint for Neuroscience Research, which tackles large projects beyond the scope of a single institution, Landis said. Scientists involved in the project claimed that private foundations will also commit funds to the project, although no public announcements have been made. At the request of the White House, scientists stayed mum on funding details, such as how much money the project might need. For comparison, government spending on the Human Genome Project amounted to almost $4 billion over 13 years, while theNational Alzheimer's Project Act has been granted about $130 million so far (see government press release).

The BAM proposal gestated at workshops supported by the Kavli Foundation, the Gatsby Charitable Foundation, and the Allen Institute for Brain Science. Six of the scientists involved published their thoughts in a June 2012 Neuron paper (see Alivisatos et al., 2012). They pointed to a need for data to bridge the gap between traditional electrophysiology, which samples from only a handful of neurons at a time, and whole-brain imaging methods like fMRI, which lack fine resolution. The solution is to record from thousands or millions of neurons at once to reveal the detailed behavior of entire circuits, the authors suggest. They plan to start with simple organisms such as C. elegans or Drosophila, which have manageable numbers of neurons. Initial circuit mapping could use the well-established technique of calcium imaging, since calcium currents reflect neuronal activation. Ultimately, however, the researchers will need to record voltage, said senior author Yuste. "We don't yet have a good voltage indicator. Some of the most promising leads for future development come from nanotechnology."

The project may draw upon advances and new technology generated by theNational Nanotechnology Initiative. For example, some inorganic nanoparticles are sensitive to the surrounding electrical field and can emit light in response to excitation, making them promising voltage indicators. Even more useful would be nanoprobes, small silicon arrays stuffed with electrodes. Nanoprobes with dozens of electrodes are already available, and the devices could potentially hold thousands, allowing massive parallel recording from neurons in a circuit, the authors note.

These methods would be too invasive to use in people. The researchers plan to develop non-invasive methods for human studies. These might include optical imaging of electrical and chemical activity, or using engineered DNA molecules to store action potential spike data, Yuste said. In this latter approach, synthetic cells would contain the DNA and serve as local reporters of brain activity. Because the error rates of DNA polymerases depend on cation concentration, patterns of errors would correspond to spike frequencies. This method would take advantage of the vast information storage capacity of DNA. Yuste noted that these approaches are still speculative.

Despite the technical hurdles, commentators agreed that the proposal is likely to further knowledge of the brain's workings. "Many of the methods are likely to yield fruit, especially if there is a substantial investment in new technology," Van Essen said.

In fact, the initiative may well spur major advances in neuroscience techniques. "MRI methodology has improved tremendously in the last decade, but there has not yet been the same kind of revolution in the way that we record activity in neural circuits," Landis pointed out. This effort may provide those tools, she suggested. Marcus Raichle, also at WashU, said, "This represents a big-time investment in technology development. You can imagine that a lot of interesting things will come out of it that may or may not be relevant to our understanding of the human brain."

The authors of the Neuron paper draw a parallel to the Human Genome Project, which launched a revolution in sequencing methods that dramatically dropped the price of sequencing and stimulated the genomics industry. An analysis by the research firm Battelle Technology Partnership Practice, which helps forge public-private partnerships, estimated that every dollar invested in the Genome Project returned $141 to the economy. This includes job creation and tax revenue from genomics companies. Moreover, the scientific impact continues to grow, the report notes. The BAM Project has the potential to do the same thing, supporters suggest. The Human Genome Project has not translated into a treatment for AD, though it has helped researchers pinpoint genetic variants that increase risk for the disease.

Researchers involved in the BAM Project believe that the work may one day lead to a number of therapeutic applications. "The deepest motivation to do this is a clinical one," Yuste told Alzforum. For example, eventually he hopes to be able to compare brain activity in people with schizophrenia to that in healthy controls to find abnormal patterns of activity. "If we can do that, we may be able to devise strategies to alter those abnormal patterns and re-channel the activity," he said. The findings might help treat other circuit disorders like epilepsy or even autism, he suggested. Landis sees additional therapeutic possibilities. Currently, deep-brain stimulation (DBS), which involves placing electrodes in specific regions of the brain, alleviates symptoms in people with Parkinson's disease, depression, and is showing promise in other diseases (see ARF series). With a better understanding of how the circuits work, "We would be able to make much more sophisticated changes," Landis said. Such knowledge would also allow researchers to develop better brain-machine interfaces for controlling prosthetic devices, already a subject of intense investigation (see ARF related news story; ARF news story).

Direct applications for Alzheimer's disease are less clear, since the disease is neurodegenerative rather than one of faulty wiring. However, brain connections also falter in AD (see ARF related news story; ARF news story; and ARF news story), and DBS can stimulate memory in patients (see ARF related news story; ARF news story). Yuste sees another possibility. Nanoprobes could be modified to serve as chemical sensors, detecting molecules such as β amyloid or tau. This technology could allow researchers to study the distribution and concentration of these molecules in real time in animal models of AD, Yuste suggested. In this way, nanotechnology being developed for the BAM Project could advance AD research.

Raichle noted, however, that given the length of time before such methods are ready, other therapeutic approaches to AD may well provide answers first. He also stressed that the BAM Project complements, but does not replace, other methods of studying the brain. "There are very important metabolic processes that don't necessarily track with the firing of an action potential," he said. One example is brain glucose use and metabolism, which can be visualized with FDG-PET.

http://www.alzforum.org/new/detail.asp?id=3414

Surgery clinical trial results selectively reported | Reuters

Selective reporting of positive results from drug clinical trials is a well-documented problem, but a new study finds that trials of surgical treatments have an even worse track record.

Researchers who looked at hundreds of surgery clinical trials found that many set out to answer one question but ended up focusing on something else, leading to less reliable evidence being published. Others never bothered to state a goal for their study or published results while the trial was still going on.

"We know that this is a huge problem in medicine, and one that we've known about for three decades," Dr. Ben Goldacre, a UK doctor and founder of Alltrials.net told Reuters Health by email.

"It's a huge cultural blindspot for doctors, academics, industry, regulators, and policy makers, but it knocks the legs out from underneath evidence based medicine," said Goldacre, who was not involved in the study.

It's harder for doctors and patients to make informed decisions about which treatment or, in this case, surgical procedure, is best when the evidence from a study is modified or absent, he said.

"If you measure lots of different outcomes, and then allow yourself to select and report the one that flatters the treatment the most, then you're misusing this basic statistical tool," Goldacre said.

Gerjon Hannink led a team of researchers at the Radboud University Nijmegen Medical Center in Nijmegen, The Netherlands, comparing the results of 327 published surgical trials with the goals set out when the trials were registered.

Putting basic information about the aims of a trial into a clinical trial registry before recruiting participants is generally a prerequisite of publication. The International Committee of Medical Journal Editors began in 2005 requiring clinical trials to be entered into a registry before they begin, and many journals include that policy in their instructions to authors.

Despite that rule, the new study found that up to half of surgery clinical trials were still not registered correctly before their results were published, according to the report from Hannink's team in Annals of Surgery.

They found that out of 327 trials, fully a third (109 trials) had never been registered and another 48 were only registered after the study was completed. Of 152 trials that had been entered into a registry in advance with an end goal clearly defined, half changed that goal when the results were published, or left it out entirely.

That's a 50 percent rate of reporting bias in surgical trials, compared to estimates of 30 or 40 percent in general medical studies for drugs and other treatments, according to the authors.

"We expected the situation to be worse for surgical trials as compared to internal medicine," Hannink told Reuters Health by email. "However, the difference found was larger than we had expected."

Hannink acknowledged that it's harder to do the gold-standard, double-blind studies for surgeries than for pills because it's difficult to keep the surgeon or the patients from knowing whether they're involved in a new procedure or getting the usual treatment for comparison.

With drugs, pharmaceutical companies tightly control most testing of their medications and they know that regulatory agencies will scrutinize the results closely, he added, but there's no equivalent oversight for surgical procedures.

Incomplete or modified publication of results can have serious consequences, Hannink said. It can lead to the promotion of ineffective or harmful treatments or to expensive therapies seeming better than cheaper alternatives when in fact they are not, and that's "the worst possible situation for patients, health care professionals, and policy makers," he said.

"Sometimes this is about money, or reputation: people may not want to publish a trial that undermines their product, or the cherished theory that underpins their career," Goldacre said. "But equally, sometimes it's simply thoughtless, or what we might have to call incompetence."

"This problem has been well documented for three decades, and everything we have tried so far has failed, laws have been ignored, codes of conduct likewise," Goldacre said.

There's no clear solution, except to provide incentives for researchers to follow the rules and for journals and their editors to enforce those rules, experts said.

Goldacre and several partners launched a petition at Alltrials.net in January to campaign for full publication of all results of clinical trials in the future and all those going on now or already completed, mainly by urging regulators and governments to enact legislation requiring publication.

"Full publication of complete trial results is essential if clinicians, patients, policy makers and others are to make well-informed decisions about health care," Hannink said.

http://www.reuters.com/article/2013/03/14/us-surgery-clinical-trial-idUSBRE92D0Y620130314

“We Gained Hope.” The Story of Lilly Grossman’s Genome – National Geographic

One – The Twitch

It started with a slight twitch. Steve and Gay Grossman both noticed it in their daughter Lilly in 1998, when she was just one-and-a-half years old. By the time she was four, the twitches had grown into full-blown muscle tremors. They wracked her whole body at night and were painful enough to wake her up.

The family stopped sleeping properly. Lilly would wake up, shaking and crying, as often as 20 or 30 times a night. During the worst bouts, Steve and Gay took shifts to console her, one staying with her until two in the morning and the other taking over from there. "I can't describe what it's like to care for a baby, a young child, who's crying and shaking all night," says Steve.

The Grossmans have dealt with this for the last 13 years and, if anything, Lilly's tremors became more frequent and more severe. They eventually started happening during the day. She developed muscle weakness, poor coordination and balance problems. She had to use a walker until middle-school and a motorised wheelchair thereafter. She was often very tired.

Then, in the summer of 2012, the tremors stopped. For 18 days, Lilly slept soundly through the night. So did Steve and Gay. "We had dreams again," he says. "We had forgotten what that was like."

This U-turn in Lilly's fortunes was the result of a study called IDIOM, led by the father-and-daughter team of Eric and Sarah Topol at the Scripps Translational Science Institute in La Jolla, California. IDIOM stands for Idiopathic Diseases of Man—that is, "serious, rare and perplexing health conditions that defy a diagnosis or are unresponsive to standard treatments". In other words, whatever Lilly had.

The Scripps team sequenced Lilly, Steve and Gay's complete genomes. Amidst the morass of As, Gs, Cs and Ts, they identified the likely causes of Lilly's mystery condition—three mutations in two different genes. One of these pointed the way to a potential treatment—a drug called Diamox that had helped another family with a fault in one of the same genes. When Lilly tried it, she gained a few weeks of sound tremor-free sleep.

"Whole-genome sequencing can change lives and maybe save some," says Steve. "It changed ours." It was no miracle—the tremors have returned to a lesser extent than before, and the team are pursuing new leads. But Steve and Gay never expected The Answer. They didn't anticipate an easy cure. Genomics gave them something arguably more important—hope. It turned the nameless, unknowable ailment that had stolen years of sleep from their daughter into something tangible—a condition with a cause that can eventually be addressed. And it bought them time with Lilly.

Two – Not Knowing

Lilly's life has been defined by both the condition that restricts her choices, and the smarts, tools and support that allow her to escape those restrictions. Gay recalls, "Ever since Lilly was really small, she'd be up most of the night and in the morning, I'd say, "Why don't you stay with me and relax?" And she would just cry and cry to go to school. She always wanted to be doing what the other kids were doing."

Schools can make many children feel isolated or different, but they have always been great equalisers for Lilly. Her weak muscles and sensitivity to warm temperatures meant that, at home, she missed out when other kids played outside. At school, everyone sat and so did she. She got to use a brain that, tiredness aside, has stayed untouched by her physical symptoms. "She's a regular teenager—smart, sarcastic, funny—and she has a grade point average of 3.5," says Steve.

Lilly became a technophile out of necessity. Since pens and books are painful to hold, she has used laptops since kindergarten. Her voice tires easily and she hates it when people talk to her like she's deaf or infirm; when she got her first cellphone and started sending texts, her social life blossomed. She was always good at maths but since drawing figures was taxing, she gravitated towards English and reading-heavy subjects. She now fancies herself a writer, penning pieces for her school newspaper, posts on her blog, and an online book about disability called Through My Eyes.

Through all of this, Steve and Gay have worked tirelessly to support her. She designs a stationery line called Letters from Lilly and spends her day "arguing with insurance companies and school bureaucracies". He works at a software company with links to aerospace and defence and sources all the technology that allows his daughter to live as independently as possible. When it came time to tell Lilly's story, Gay wrote three pages of text. Steve prepared a PowerPoint presentation.

For the longest time, the duo were bedevilled by uncertainty about Lilly's condition and the belief that her time was slowly running out. Doctors initially diagnosed Lilly with cerebral palsy, but that wasn't it. Next came a diagnosis of glutaric aciduria, leading to a modified diet and a lot of support groups. That wasn't it either. The next guess was the heartbreaker: some kind of mitochondrial disease. These disorders affect the tiny bean-shaped batteries that power our cells. They vary a lot, but given the harsh and relentless nature of Lilly's symptoms, Steve and Gay were worried. "The life expectancy for a teenager isn't so great," he recalls.

Printed out, Lilly's medical records take up two four-inch binders. She's had MRI scans, blood draws, spinal taps, skin biopsies, nerve biopsies, and a muscle biopsy. The tests hinted at a few depleted nutrients that could be fixed by supplements, but for the most part, they said the same thing: Lilly seemed normal. "We've been from world-class people to alternative quacks," says Steve. No one could offer them the surety of a true diagnosis, much less a suitable treatment.

"Every birthday was a hard one—missed milestones and another reminder that we still didn't know what's wrong with her," says Gay. When would the sand eventually run out? This year? The next one? "When you don't know what you're dealing with, and you're up all night with your kid crying and shaking like crazy, you think: Does anyone even remember this is going on? Nobody knew what to do with us."

More ...

http://phenomena.nationalgeographic.com/2013/03/11/we-gained-hope-the-story-of-lilly-grossmans-genome/?src=longreads

The Benefits of Mobile Health, On Hold - NYTimes.com

The world now has 5 billion mobile phones – one for every person over 15. Africa has a billion people and 750 million phones, and mobile is growing so fast there that in a few years there will be more phones than people. In some countries this is already true — South Africa has 47 million people, but 52 million SIM cards.

The mobile phone is doing more than revolutionizing communication. It has the potential to improve many aspects of life in poor countries: commerce, health, agriculture, education. As we say repeatedly in Fixes, there are a lot of great new products that poor people can use to improve their lives. The problem is that it's very difficult to get those out to people who need them. The same is true with information. It's there, but people can't get it, because they lack Internet service and electricity and the electronics that require these things. Delivery is the problem. It's almost always the problem.

Until now. Now we have the mobile phone, a pipeline that can be used to bring information to everyone in the world – not just information, but any product that can be chopped up into electronic bits.

Most people, of course, use basic handsets, not smartphones. But such phones are plenty useful. Money can be chopped up into electronic bits, and with mobile banking services like Safaricom's M-PESA in Kenya, millions of people who had no access to banking services now send and receive payments through their mobile phones. (Kenya, with 10 million households, has about 15 million active users of M-PESA.) Because mobile phone banking is instant, safe and trusted, it has also opened the door to other services — for example, it is persuading small farmers to adopt crop insurance.

Since a lot of health revolves around information, public health experts had high expectations for the mobile phone. Hundreds of projects throughout Africa and South Asia are testing the various ways phones might make people healthier: by texting advice or sending voice messages to pregnant women, texting reminders to AIDS patients to take their meds, tracking the spread of diseases, allowing community health workers to keep records electronically and variations on all these themes. "We had this techno-utopian optimism," said Gustav Praekelt, a South African software developer who runs a foundation aimed at making technology to solve the problems of the poor. "The moment someone's got a mobile phone we can make all this information available and we will just magically see all the behavior change we want to see."

But roughly a decade after the start of mHealth, as the mobile health field has come to be known, these expectations are far from being met. The delivery system is there. But we don't yet know what to deliver.

In the vast majority of cases, if mHealth projects have been evaluated at all, they've been evaluated for feasibility – does this system work? will people use it? – rather than impact on health. Sometimes it turns out that people won't use it. Living Goods, which sells health products in Uganda, tried to get its franchisees to track client interactions on mobile phones. "What we saw as an enormous opportunity to improve impact and sustainability, the agents saw as more work," Living Goods president Chuck Slaughter wrote on a Skoll World Forum Web site debate on scaling up mHealth. The saleswomen had to share their phones with family members, so they didn't always have them. And most didn't know how to use their phones for anything but making and receiving calls. (Living Goods has solved these problems, but is still short of its goal of universal adoption.)

When programs have tested health outcomes, the results have usually been dismal. Several recent meta-studies combed through published literature to find studies testing whether mobile phones could improve the health caredelivery process or help patients manage their diseases better. Success was extremely rare. A third study concluded: "We found some, albeit very limited, indications that in certain cases mobile phone messaging interventions may provide benefit in supporting the self-management of long-term illnesses."

Even the successful programs, moreover, tend to be tiny islands. The pilot is successful in a small group of clinics – but the project can't grow. The reason could be that it uses an operating system that doesn't mesh with the nationwide system. Or it requires a platform that can handle a few users, but not a whole lot at once. Or it would be too costly. For example, it might rely on donated phones or worse, on smartphones. The cost of sending text messages alone may make a small project impossible to scale up.

The proliferation of pilots has gotten so chaotic that at least two countries, Uganda and South Africa, took the extraordinary step of banning further mHealth pilots, at least until each government can set its health strategy and technical specifications and make sure that the projects fit. (Here's amap of pilots in Uganda that eloquently explains why.)

Mobile phones deliver more than information, of course. Suddenly everyone has a device with a camera, computer and connectivity – and the potential to become a piece of portable, cheap health care equipment. In 2009, scientists had already made a microscope capable of diagnosing malaria and tuberculosis from a mobile phone fitted with an inexpensive eyepiece and lenses. A new version made from an iPhone 4 with an $8 lens attached with double-sided tape has just been tested in Tanzania and was not great, but pretty good, at diagnosing hookworm – a first step.

Aydogan Ozcan, who runs an electrical engineering lab at U.C.L.A., has developed small attachments to cellphones that can serve as a sophisticated microscope, diagnose common diseases, detect pathogens such as E. coli and sniff out allergens. The phone can also send reports to a Google Map server to plot the spread of disease (it's only meaningful, of course, if enough people use the system). Perhaps most intriguing, his lab has developed an online game in which players undergo a brief training, then examine slides of cells to guess if they are infected with malaria. Dr. Ozcan found that a group of nonexperts came within 1.25 percent of the accuracy of an expert, opening the possibility that a crowd of amateurs could perform remote diagnoses when experts are scarce.

This technology will no doubt sell in the rich world – the United States Army, Dr. Ozcan says, is particularly interested in portable rapid diagnostics. But these products – although far cheaper than laboratory models – are likely to still be too expensive for widespread adoption where they are most needed.

It is too early to write off mHealth, a field that is still young. Studies move slowly but the pace is picking up; Patricia Mechael, executive director of the mHealth Alliance, says that a lot of new research should be finished in the next year.

And important lessons are emerging from the evidence already in. Success should mean better health outcomes – so that is what programs need to measure. Virtually every project that has been able to grow has included lots of different partners, including the government and the private sector – mobile phone providers, for example.

One of the few projects that has been successful on a large scale is Mwana, which now covers virtually all of Zambia and Malawi. Many babies are born to H.I.V.-positive women, and testing whether these babies are H.I.V.-positive and getting the results back to their caregivers used to take weeks. The Mwana program trains health workers to send the information by text message – cutting the total time by more than half. In addition, fewer results are lost.

What makes Mwana work? "Incredible simplicity," said Erica Kochi, the co-leader of tech innovation for Unicef, which is one of the partners in the project. "It's not trying to replace the health information system. For its users, it makes things easier rather than adding more complexity to an already difficult, challenging health system."

Mwana, like the other programs that have been able to grow, was also designed from the beginning to be able to work on a large scale. The program employs community health workers' own mobile phones and an open-source SMS platform.

It was also developed with its users – Mwana's designers moved for a month to the town of Mansa, Zambia, near the border of the Democratic Republic of Congo, and built the system alongside local community health workers. This co-creation may be even more important when an mHealth project works with patients instead of health workers. "We spend tons of time under the mango tree in Ghana working on refining the messages," said Tim Wood, the director of mobile health innovation at the Grameen Foundation. One of its programs, Mobile Midwife, (see the program'slessons learned), uses text and voice messages to provide health advice to pregnant women in Ghana. "It took many, many rounds of going back – even now we're looking at how people are using messages and refining them."

The moral of this story is perhaps the single most important lesson in mHealth: the technology is the easy part. An mHealth project is just as complicated as any other health project, just with a phone attached. "The tech is only as good as the people it is connecting or system it's connected to," Mechael said. "We can get excited about the shiny new object, but the real impact comes from thinking about the cultural and professional context in which it's being implemented."

http://opinionator.blogs.nytimes.com/2013/03/13/the-benefits-of-mobile-health-on-hold/

Be cautious of mind-altering drugs for kids: doctors | Reuters

Doctors warn about the ethical and medical implications of prescribing attention-boosting and mood-altering medications to healthy kids and teens, in a new statement from the American Academy of Neurology.

Focusing on stimulants typically used to treat attention deficit hyperactivity disorder, or ADHD, researchers said the number of diagnoses and prescriptions have risen dramatically over the past two decades.

Young people with the disorder clearly benefit from treatment, lead author Dr. William Graf emphasized, but the medicines are increasingly being used by healthy youth who believe they will enhance their concentration and performance in school.

According to the National Institute on Drug Abuse, 1.7 percent of eighth graders and 7.6 percent of 12th graders have used Adderall, a stimulant, for nonmedical reasons.

Some of those misused medicines are bought on the street or from peers with prescriptions; others may be obtained legally from doctors.

"What we're saying is that because of the volume of drugs and the incredible increase… the possibility of overdiagnosis and overtreatment is clearly there," said Graf, from Yale University in New Haven, Connecticut.

In their statement, published in the journal Neurology, he and his colleagues say doctors should not give prescriptions to teens who ask for medication to enhance concentration against their parents' advice.

Prescribing attention- or mood-enhancing drugs to healthy kids and teens in general cannot be justified, for both legal and developmental reasons, Graf and his co-authors conclude.

"You're giving amphetamines to kids. I think we have to be worried about how that affects the brain, mood, rational thought… and we don't have enough data about that yet," he told Reuters Health.

Almut Winterstein, a pharmacy researcher from the University of Florida in Gainesville, agreed that not much is known about the effects of long-term stimulant use - another reason to be careful and make sure they're really necessary for a specific child. In the short term, stimulants increase heart rate and blood pressure.

"If you have a child who actually can sit still and doesn't seem to have a problem focusing on a task, a stimulant won't do a thing, and definitely won't improve school performance," said Winterstein, who didn't work on the new statement.

"I am concerned personally that many parents believe that if their child doesn't do well in school, they must have ADHD," and therefore need stimulants, she told Reuters Health.

The new statement is also endorsed by the Child Neurology Society and the American Neurological Association.

Graf noted that childhood is changing in the United States: kids are being challenged in school, but also spending more and more time in front of screens.

"The majority still has to agree that we're not going to give a pill for every problem in childhood," he said. "We're talking about healthy kids."

http://www.reuters.com/article/2013/03/13/us-medications-kids-idUSBRE92C17H20130313

Advances in surgeries with robots reduce risks and trim recovery times - Houston Chronicle

What if you could have a major surgery with only a short hospital stay, very little pain, low risk of infection, little blood loss, minimal scarring, and a fast recovery and return to normal daily activities?

Such a scenario is becoming increasingly possible thanks to the developing field of medical robotics and the increasing use of robots in surgical procedures. By using robots, surgeons can perform complex operations more easily and precisely, and in a less invasive way that improves results for patients.

"Robotics is an extension of laparoscopic surgery," said Dr. Surena Matin, an associate professor in the department of urology at the University of Texas M.D. Anderson Cancer Center. Matin also is medical director of MINTOS - the Minimally Invasive New Technology in Oncologic Surgery Collaborative Group at M.D. Anderson. "The improvement over laparoscopic techniques comes in terms of improving the surgeon's visibility and dexterity. Surgeons don't have to remove their eyes from the scene of surgery, and they have more range of motion through the wrists of the device than through scopes. (Laparoscopy) is like operating with chopsticks compared to the dexterity of the microwrists on the robotic system."

At least two of the most advanced surgical robotics systems are in use in the Houston area. Surgeons atMemorial Hermann Sugar Land Hospital recently began using the da Vinci Si Surgical System robot to perform procedures in urogynecology, gynecology, oncology and general surgery. St. Luke's Episcopal Hospital has added the same system to its suite of robotics technology to perform urological and gynecological procedures, and perhaps procedures for ear nose, throat and abdominal specialties in the future.

Dr. Nina Dereska, a surgeon at Memorial Hermann Sugar Land, has been using the da Vinci robotic systems for surgeries since 2009. The system allows for more surgical options with certain patients for whom traditional surgery presents a problem.

"With robotic surgery, small mechanical arms are inserted into the patient through tiny incisions," she explained. "Surgeons will be able to control the robotic movements, or the arms, through special hand and foot controls at a console several feet away from the operating table." The robot translates the surgeon's hand, wrist and finger movements at the control console into corresponding micro movements of the instrument's tip.

In other words, the robot can be set to scale down surgeon's movements so that a 1-inch movement on the surgeon's finger becomes a movement of only a fraction of an inch at the tip of the robotic instrument. Similar movements also control the camera to allow the surgeon to see inside the patient's body. The surgeon, sitting at the console, is able to continuously view the scene of surgery and perform highly precise surgical movements without nearly as much fatigue as in traditional surgical procedures, including "straight-stick" laparoscopy.

"Straight-stick surgery is hard on the body - my elbows are up in the air, my shoulders are hunched; it's very fatiguing," Dereska said. "Robotics surgery is much easier on the surgeon, which translates to being better for the patient."

Surgeons at the Methodist Hospital recently became the first to use the Magellan Robotic System to treat patients with peripheral vascular disease. "This new intravascular robotic system represents a fundamental step forward in the transformation of vascular intervention," said Dr. Alan Lumsden, chair of the department of cardiovascular surgery and medical director of the Methodist Debakey Heart & Vascular Center. "It allows us to offer less invasive endovascular options to a broader group of patients suffering from complex vascular disease."

The system allows a surgeon to more precisely steer a catheter inside and around blood vessels. Lumsden said it can be used for any procedure involving complex catheterization and will be especially useful in lower-extremity arterial interventions and branched endografts. In addition, the technology will help reduce both the procedure time and radiation exposure.

The chief drawback of robotics in surgery is the lack of haptic feedback - the ability surgeons have to visualize in their mind what they are feeling with their hands. "We don't have our fingerpads to feel and guide, so we have to learn with our eyes to see how the tissue reacts in order to get a 'feel' for it," Matin said. "This is more of an issue for late-stage cancers where the tactile feedback plays a heavier role in determining where to cut."

Increasingly, surgeons are being trained to use robotic systems in various specialty areas. Peter Herrera directs the Memorial Hermann Surgical Innovation and Robotics Institute in the Texas Medical Center. "The institute has trained numerous robotics surgical teams from around the country since we first opened in 2003," he said. "We are the largest training site for robotic surgery in the nation and the only one in the southwest USA."

http://www.chron.com/news/health/article/Advances-in-surgeries-with-robots-reduce-risks-4293686.php

Ovarian Cancer Study Finds Widespread Flaws in Treatment - NYTimes.com

Most women with ovarian cancer receive inadequate care and miss out on treatments that could add a year or more to their lives, a new study has found.

The results highlight what many experts say is a neglected problem: widespread, persistent flaws in the care of women with this disease, which kills 15,000 a year in the United States. About 22,000 new cases are diagnosed annually, most of them discovered at an advanced stage and needing aggressive treatment. Worldwide, there are about 200,000 new cases a year.

Cancer specialists around the country say the main reason for the poor care is that most women are treated by doctors and hospitals that see few cases of the disease and lack expertise in the complex surgery and chemotherapy that can prolong life.

"If we could just make sure that women get to the people who are trained to take care of them, the impact would be much greater than that of any new chemotherapy drug or biological agent," said Dr. Robert E. Bristow, the director of gynecologic oncology at the University of California, Irvine, and lead author of the new study presented on Monday at a meeting of the Society of Gynecologic Oncology in Los Angeles.

The study found that only a little more than a third of patients received the best possible care, confirming a troubling pattern that other studies have also documented.

Karen Mason, 61, from Pitman, N.J., had been a nurse for 28 years when she was found to have ovarian cancer in 2001. She scheduled surgery with her gynecologist, who was not a cancer surgeon.

But her sisters would not allow it. They had gone on the Internet, and became convinced — rightly, according to experts — that she should go to a major cancer center.

"They took the reins out of my hands," Ms. Mason said.

She wound up having a long, complicated and successful operation performed by a gynecologic oncologist, which she does not believe her gynecologist could have done.

Dr. Barbara A. Goff, a professor of gynecologic oncology at the University of Washington, in Seattle, who was not part of Dr. Bristow's study, said the problem with ovarian cancer care was clear: "We're not making the most use of things that we know work well."

What works best is meticulous, extensive surgery and aggressive chemotherapy. Ovarian cancer spreads inside the abdomen, and studies have shown that survival improves if women have surgery called debulking, to remove all visible traces of the disease. Taking out as much cancer as possible gives the drugs a better chance of killing whatever is left. The surgery may involve removing the spleen, parts of the intestine, stomach and other organs, as well as the reproductive system.

The operations should be done by gynecologic oncologists, said Dr. Deborah Armstrong of Johns Hopkins University, who is not a surgeon. But many women, she said, are operated on by general surgeons and gynecologists.

Some women prefer the obstetricians who delivered their children. Many are desperate to start treatment and think there is no time to find a specialist. Some do not know that gynecologic oncologists exist. Some inexperienced doctors may find the cancer unexpectedly during surgery and try to remove it, but not do a thorough job.

"If this was breast cancer, and two-thirds of women were not getting guideline care that improves survival, you know what kind of hue and cry there would be," said Dr. Armstrong, who was not involved in the study. But in ovarian cancer, she said: "There's not as big an advocacy community. The women are a little older, sicker and less prone to be activists."

One patient advocacy group, the Ovarian Cancer National Alliance, ranks the availability of a gynecologic oncologist as one of its criteria in comparing the quality of care among states.

Surgeons who lack expertise in ovarian cancer should refer women to specialists if the women are suspected to have the disease, but often do not, Dr. Goff said.

Dr. Bristow's research, which has been submitted to a medical journal but not yet published, was based on the medical records of 13,321 women with ovarian cancer diagnosed from 1999 to 2006 in California. They had the most common type, called epithelial. Only 37 percent received treatment that adhered to guidelines set by the National Comprehensive Cancer Network, an alliance of 21 major cancer centers with expert panels that analyze research and recommend treatments. The guidelines for ovarian cancer specify surgical procedures and chemotherapy, depending on the stage of the disease.

Surgeons who operated on 10 or more women a year for ovarian cancer, and hospitals that treated 20 or more a year, were more likely to stick to the guidelines, the study found. And their patients lived longer. Among women with advanced disease — the stage at which ovarian cancer is usually first found — 35 percent survived at least five years if their care met the guidelines, compared with 25 percent of those whose care fell short.

But most of the women in the study, more than 80 percent, were treated by what the researchers called "low-volume" providers — surgeons with 10 or fewer cases a year, and hospitals with 20 or fewer.

Dr. Bristow said women should ask surgeons how often they operate on women with ovarian cancer and how often they achieve complete debulking. But he also acknowledged that many patients hesitate to ask for fear of offending the doctor who may operate on them.

Ovarian cancer has unusual traits that make it more treatable than some other cancers. It is less likely to spread through the bloodstream and lymph system to distant organs like the lungs and brain. The tumors do spread, but usually within the abdomen and pelvis, where they tend to coat other organs but not eat into them and destroy them, said Dr. Matthew A. Powell, a gynecologic oncologist and associate professor at Washington University School of Medicine in St. Louis.

And most ovarian cancers are extremely sensitive to chemotherapy, experts said.

In 2006, a study was published that many doctors thought would change the field forever. It compared standard intravenous chemotherapy with a regimen that pumped the drugs directly into the abdomen. The test regimen was highly toxic, and not all patients could tolerate it. But median survival on it was 65.6 months, compared with 49.7 months on the standard treatment — a survival difference of 15.9 months.

The gain was huge, almost unheard of. New cancer drugs are often approved if they buy patients just a few months. The test treatment — called intraperitoneal, or IP therapy — did not even use new drugs. It just gave the old ones in a different way. Several previous studies had had similar findings for IP therapy, but the 2006 study, led by Dr. Armstrong, had the most definitive results.

The National Cancer Institute took a rare step, one it reserves for major advances. It issued a "clinical announcement" to encourage doctors to use the IP treatment, and to urge patients to ask about it. Cancer specialists predicted that the announcement would lead to widespread changes in treatment. Expert guidelines said it should be offered to every patient considered strong enough to endure it.

Seven years later, Dr. Armstrong and other physicians said, IP therapy still has not caught on.

Part of the reason may involve money, Dr. Armstrong said. With IP chemotherapy, patients also need a lot of intravenous fluids, which means unusually long treatment sessions. Oncologists are paid for treatments, not for time, so for those in private practice, long sessions can eat away at income.

"You don't make a lot of money with somebody in the chair getting IV fluids," Dr. Armstrong said. "Chair time is money. I'm being a cynic here, but I think that is part of the issue."

Dr. Goff said: "Where I live, in the Pacific Northwest, IP chemotherapy is pretty much only being done in the major medical centers, and by very few private-practice oncologists. Many say it's too difficult, and they don't even offer it to patients, which I think is unethical."

Ms. Mason had six hours of surgery at the Fox Chase Cancer Center in Philadelphia, with a gynecologic oncologist. The cancer had spread to lymph nodes, and was Stage 3. The surgeon removed her ovaries, fallopian tubes, various lymph nodes, uterus, cervix and omentum (part of the tissue that lines the inside of the abdomen).

"Ovarian cancer looks like Rice Krispies all over the place," Ms. Mason said. "She spent most of the time picking out each little visible Rice Krispy, and left nothing behind that she could see with her naked eye."

Then, Ms. Mason had chemotherapy (not IP, because it was not being done at the time). The disease has not recurred. Had she stuck with the first doctor, she believes, "I would be gone."

"I feel so strongly about letting women know that you need to get to a center of excellence," Ms. Mason said. "It's shocking to think it's still not happening."

http://www.nytimes.com/2013/03/12/health/ovarian-cancer-study-finds-widespread-flaws-in-treatment.html?&pagewanted=print