Published by
Stanford Medicine


Research, Stanford News

Nesting improves mouse well-being, could aid research studies

Nesting improves mouse well-being, could aid research studies

A new study confirms what Joseph Garner, PhD, and his colleagues have long suspected – that laboratory mice are healthier, more fertile and have better welfare when they have the means to build a nest, which reduces stress and helps them naturally warm themselves.

Garner has done a series of studies in these mice not only to enhance their living conditions and well-being, but also to improve the results of research studies. Laboratory mice now are routinely housed in cold conditions, so the animals expend much of their energy trying to keep warm. This changes their physiology and may compromise the outcome of research studies, says Garner, an associate professor of comparative medicine at Stanford. But given the means to build a nest, the mice will thrive, producing more pups that are healthier and more likely to survive, he and his colleagues report in a study out this week.

In the study, the researchers gave pairs of mice from three of the most commonly used strains a few different living options. Some got a bed alone, while others got a bed, plus a choice of one of two different materials for building nests. The nest-builders proved to be healthier in many respects – good news for the mice, as well as for the research labs that maintain them. Garner told me:

This is a great example of how ‘good welfare is good business.’ The mice with nesting material produced more pups per litter, the pups reached a healthy weight faster, the mortality of the pups is reduced, and the mice used less food.

Providing mice with nesting material is very cost-effective for commercial mouse breeders, he says. For the most commonly used mouse strain, laboratories that invest 60 cents in nesting material over six months will gain an additional $273 on average in pups, he calculates. But it’s not just mice and mouse breeders that stand to benefit:

For a scientist on campus, this means that you can reduce the cost of breeding mice because you need fewer breeding pairs to produce the mice you need, and those mice will be healthier, better quality mice. So this is a great incentive for all of us to do the right thing and invest in enrichment for our mice.

The study, a collaboration with Brianna Gaskill and researchers at the Charles River laboratory, appears online in PLoS One.

Previously: Stanford researcher’s easy solution to problems of drug testing in mice and Keeping lab mice warm could save costs, benefit scientific research

Medicine and Society, Pain, Patient Care, Public Health, Stanford News

A physician’s personal odyssey with chronic pain

A physician’s personal odyssey with chronic pain

Philip Pizzo, MD, former dean of Stanford’s medical school was preparing to head to Washington, D.C. to meet with top federal health officials when he leaned down in his office and felt the sharp sting of pain. It would be the beginning of a long odyssey into the world of chronic pain – the very subject he had planned to go to Washington to discuss.

The chair of an Institute of Medicine panel on pain, Pizzo and his colleagues had issued a report in late 2011 calling for a transformation in approaches to pain, which affects more than 100 million Americans. Suddenly he would find himself among the afflicted as he sought the opinions of multiple physicians and underwent four MRI’s, turning increasingly despondent as the months dragged on with no diagnosis.

My hope is that by sharing my personal story, it will generalize the discussion and create more dialogue about the realities that 100 million people face…

“I could easily still have been one of the many tens of thousands or millions facing chronic pain without explanation, because I had been through all the standard testing,” he said in an interview. “I had four MRI scans and none showed the lesion that ultimately contributed to my finding. The reality was because I am a physician and I kept saying, ‘Gee, there is something wrong that hasn’t been found,’ people were responsive.”

In writing about the experience in today’s New England Journal of Medicine (subscription required), Pizzo says the specialists he encountered were often circumscribed in seeking answers. He told me, “While it’s not an indictment of the medical system, it’s a reality that many have faced – physicians and providers are rushed, specialization is so significant that many people think within narrow boundaries. They don’t leap beyond their own expertise. That is another thing we have to challenge ourselves with - to think beyond the usual.”

As time wore on, he said, at least one physician would suggest that his condition was largely psychological - essentially “all in your head.”

“What I experienced is what many do when you get beyond the point when conventional tests aren’t revelatory. The medical community gets frustrated – gee we can’t find anything – and begin to think maybe there are other things happening, some suggestion perhaps that it was distress or depression… It’s easy for physicians to say you are depressed and that’s why you have pain. But it’s important to recognize that patients may be depressed because they have pain.”

A marathon runner with boundless energy and a perennially upbeat attitude, Pizzo indeed had become clinically depressed as a result of his disabling condition. But once the underlying cause of the chronic pain was diagnosed and treated – albeit with a major surgical procedure – that depression immediately lifted, along with the pain. Ultimately, it was an unusual test - an imaging study that tracked the path of the sciatic nerve - that unearthed the source of his distress, a congenital condition involving compression of the nerve.

After the surgery, Pizzo learned another valuable lesson for physicians - that not all patients respond well to opioids, typically the drugs of choice for control of severe pain. He proved highly sensitive to the medications and landed in intensive care.

Today, Pizzo is back to running and working full-time in his office on the medical school campus. In writing his personal story, he says he hopes to draw more physician attention to the overwhelming problem of chronic pain in the United States.

“My hope is that by doing this, it will generalize the discussion and create more dialogue about the realities that 100 million people face, many of whom don’t have the opportunity to have their voices expressed.”

Previously: The high cost of pain: Medical school dean testifies on problem to U.S. SenateA call to fight chronic-pain epidemic, No pain, no gain. Not!, Relieving Pain in America: A new report from the Institute of Medicine and Researching ways to “heal the hurt”

Addiction, Mental Health, Research, Stanford News

Stop-smoking program aids recovery of psychiatric patients, study finds

Stop-smoking program aids recovery of psychiatric patients, study finds

While smoking has been in decline in recent years in this country, one group where it remains endemic is among psychiatric patients, who often die prematurely of tobacco-related disease. Practitioners have long thought that smoking could be a useful tool in therapy, calming patients and helping them cope with stress. They also feared that if psychiatric patients were asked to quit, it could interfere with treatment.

But those assumptions are challenged by a new study led by a Stanford researcher, which shows that quitting smoking may be beneficial for these patients. Judith Prochaska, PhD, MPH, and her colleagues at University of California, San Francisco found that a stop-smoking program in hospitalized psychiatry patients aided their recoveries and reduced the chance that they would be hospitalized again for their psychiatric problems.

“This is a very low-cost, brief intervention that helped patients quit smoking and offers evidence that it may have helped their mental health recovery,” said Prochaska, associate professor of medicine with the Stanford Prevention Research Center.

Michael Fiore, MD, MPH, director of the University of Wisconsin Center for Tobacco Research and Intervention and a leader in national policy for tobacco treatment, said:

This paper by Dr. Prochaska and colleagues provides powerful evidence that evidence-based tobacco dependence treatments can substantially increase quit rates among psychiatric inpatients. We know that psychiatric patients smoke at very high rates and are at tremendous risk from their smoking. Thus, the findings hold promise to make an important, real-world contribution to the health of these patients.

The researchers offered stop-smoking treatment to 224 patients at UCSF’s Langley-Porter Psychiatric Institute, a smoke-free, locked unit for acute care. Half participated in a stop-smoking intervention that included a meeting with a counselor, written and electronic materials and the availability of a 10-week supply of nicotine patches. The other half received usual care – a pamphlet about the hazards of smoking and information on how to quit.

At the end of 18 months, 20 percent of those in the treatment group had quit smoking, compared to just 7.7 percent in the control group. Moreover, what was unexpected and striking is that 44 percent of those in the treatment group were rehospitalized, compared to 56 percent in the control group.

“I think some of the therapeutic contact that addressed tobacco dependence and supported participants with this major health goal may have generalized to feeling better about their mental health condition,” Prochaska said.

The study is published online today in the American Journal of Public Health.

Global Health, Infectious Disease, Public Health, Stanford News

Stanford pump project makes clean water no longer a pipe dream

Stanford pump project makes clean water no longer a pipe dream

Dhaka water lake - smallBefore Amy Pickering, PhD, left Bangladesh, she stuffed a bright green, 70-pound iron water pump into her suitcase, carefully bolstering a key piece of her research project, which aims to improve the health and save the lives of children in the Dhaka slums.

Pickering and her colleagues at Stanford, including an energetic group of students, have found a way to attach a chlorine doser to the pump, which is typical of the communal pumps used in the slums, to effectively purify the water. They have spent this summer in Bangladesh laying the groundwork for a large-scale study of the new device, which they hope will help decrease rates of diarrhea and improve weight gain among slum children.

In talking to project director Steve Luby, MD, for a Stanford Medicine story about the initiative, I learned that this approach is a radical departure from what has come before, as most water purifying systems in the developing world, like household disinfecting kits, put the burden on residents to clean their own water at home. Fewer than 10 percent take advantage of this option, he says, because it requires too much of a change in behavior. This latest pump system is a passive one, so people don’t have to do anything at all to get treated water – just turn on the communal pump, he says.

The need for such a system could not be more compelling:  Tens of thousands of children in Bangladesh die every year of diarrhea, mostly caused by drinking water fouled by debris and human waste. A microbe that might have minimal impact on a child here in Palo Alto, Calif. could be devastating to a chronically exposed, undernourished child in the Dhaka slums, where some four million people live.

“If you talk to people in these communities, almost all of them will be able to tell you about somebody they know who has died of diarrhea. So mothers are very familiar with the problem,” says Luby, a professor of medicine who is also a fellow at the Stanford Woods Institute for the Environment.

Luby spent eight years in Bangladesh with the U.S. Centers for Disease Control and Prevention and found the people in the South Asian country very warm and welcoming. But the residents suffer under crushing environmental problems, including poor water quality, he says.

“Water is a very important resource that is not being well-managed, at the risk of all humanity,” he told me. While agricultural interests are depleting the ground water in the region, surface water is being used as a garbage dump for sewage and industrial waste, he says.

The Stanford project is a hopeful one, however, as it shows how a group of engineers with expertise and entrepreneurial spirit can work together to improve the environment and better the lives of people halfway across the world.

Previously: Factoring in the environment: A report from Stanford Medicine magazine, Researchers reveal promising advancement in the way water is purified, Waste not, want not, say global sanitation innovators, A story of how children from Calcutta’s poorest neighborhood became leaders in improving health and Simple, cheap measures can prevent most needless deaths worldwide
Photo, of a washing area in a Dhaka compound, by Amy Pickering

Global Health, Sexual Health, Stanford News, Women's Health

Stanford and PSI researchers test safer, more convenient post-partum IUD inserter

Stanford and PSI researchers test safer, more convenient post-partum IUD inserter

Stanford’s Paul Blumenthal, MD, MPH, and his colleagues at Population Services International have won a grant from “Saving Lives at Birth: A Grand Challenge for Development” to expand testing of a simple, safe post-partum IUD inserter for women in the developing world.

In a July 31 presentation that resembled a high-school science fair, the group presented its proposal in Washington, D.C. to a team of judges, who picked it from among some 400 submissions, said Blumenthal, a professor of ob-gyn at Stanford and PSI’s medical director. The $250,000 seed grant will enable the researchers to test the device on a much larger scale among women in India.

The device provides “one-stop-shopping” for women seeking a long-term form of birth control. A woman can deliver a baby in the hospital, then have the device inserted either immediately after giving birth or sometime over the next 24-48 hours. Blumenthal told me:

It simplifies a process which has been complicated until now. We think it will show it is safer in terms of less contamination. And it will be much easier for clinicians to learn and a LOT more convenient. You can take it out of the package, insert it and call it a day, compared to the forceps routine clinicians have been using up to now.

Currently, physicians both in the United States and the developing world use forceps to insert the IUD into the fundus of the uterus, then remove the forceps, hopefully, without accidentally extracting the IUD. This process requires a very skilled clinician, can be painful for the woman and increases the possibility of infection. For those reasons, the device has not achieved widespread use, Blumenthal said.

The latest device is “unbelievably simple” and will likely improve access to birth control for women in the developing world, he said:

This could be a way to mainstream this approach, particularly for women in rural areas or those who have difficulty accessing family planning methods once they’ve given birth. It might be hard for them to access a method, so a post-partum IUD offers them one-stop-shopping. They go home with a method that could last them for 10 to 12 years.

The device can be manufactured in India for just 75 cents, “which is a pretty good deal,” Blumenthal said.

“Saving Lives at Birth” is a partnership between the U.S. Agency for International Development, the Bill & Melinda Gates Foundation, the governments of Norway and Canada and the U.K.’s Department for International Development.

Previously: Stanford study: Women in developing world benefit from quick, effective cervical cancer testPromoting the use of IUDs in the developing worldStanford ob-gyn Paul Blumenthal discusses advancing women’s health in developing countries and Gates Foundation grants aim to improve health in developing countries

Cancer, Global Health, Research, Rural Health, Stanford News, Women's Health

Stanford study: Women in developing world benefit from quick, effective cervical cancer test

Stanford study: Women in developing world benefit from quick, effective cervical cancer test

Stanford researchers have used a quick, effective test for cervical cancer among low-income women in Thailand – the first successful use of the test, which could be broadly applied in the developing world.

Cervical cancer rates have declined by 80 percent in the United States and other developed countries as a result of the commonly used Pap smear. But in the developing world, these kinds of prevention programs have failed, and the disease is a major public health problem, says Stanford ob-gyn Paul Blumenthal, MD, MPH.

Blumenthal has pioneered techniques for simple screening and treatment programs to prevent this potentially fatal cancer. He collaborated recently with a colleague in rural Thailand, as well as University of California, Berkeley medical student Lee Trope, in a study that used a test, called careHPV, which detects cervical cancers caused by the human papilloma virus. The test is inexpensive – about $5 – and can give women results almost immediately. A positive test can be combined with the application of acetic acid – simple household vinegar – to confirm that cancer is present (if there are pre-cancerous lesions, these will show up as opaque raised white patches, easily visible to a clinician).

In the study, Blumenthal told me, “We show that real-time HPV testing is feasible in a rural setting in a developing country, and in combination with the vinegar test and treatment with cryotherapy (freezing the malignant tissue), an approach to single-visit cervical cancer prevention is a realistic possibility.”

The testing was done among 431 women in a province in northeastern Thailand. The women did a vaginal self-swab, which was analyzed in three hours. Those who were positive for cancer were offered treatment on site. This is important, Blumenthal said, because if there isn’t an immediate link between testing and treatment, women often become lost to follow-up.

“To be sure this is a small, feasibility study, but no one has even ever attempted to use this test at the community level, and we showed that in rural Thailand, it’s possible,” he said. “This has important implications for the future of cervical cancer prevention in these kinds of settings.”

The study appears in the July issue of the Journal of Lower Genital Tract Disease.

Previously: Stanford ob-gyn Paul Blumenthal discusses advancing women’s health in developing countries and Ethiopia to benefit from low-tech cervical cancer screening

Health Policy, Medicine and Society, Stanford News

Law casts “sunshine” on physician-industry relationships

In the interest of transparency, pharmaceutical and medical device manufacturers will start to gather information about any payments they make to doctors and teaching hospitals, beginning Aug. 1. The results will be available online next year in a massive, national online database being managed by the federal government.

The so-called Sunshine Act was passed by Congress as an amendment to the Affordable Care Act. The thinking is that consumers will make more informed decisions about their care if they know their doctors received certain kinds of payments, including consulting fees, gifts, stock options or reimbursements for travel and education, from a commercial enterprise.

But there is enormous room for error in the undertaking, as the law is complicated and there is a vast quantity of data involved. For instance, there is concern about how companies will report payments for research, which could be misleading. As Harry Greenberg, MD, senior associate dean for research at Stanford, told me for an Inside Stanford Medicine article:

I am hopeful that the specific purpose for the payments will be clear and accurate in the public database. For instance, the law requires companies to report payments for specific research projects, which would be totally appropriate and important. Such payments, of course, actually are made to Stanford University not the individual principal investigator. The university then uses them to fund specific research projects. It also includes reporting of payments for participation in speakers’ bureaus, which is something not permitted at the medical school. I hope the database makes the reasons for specific payments clear and that the companies will report them accurately. But there is potential, given the massive amount of complex data, that there will be errors.

There has much speculation on the potential impact of the law. For instance, will consumers change their behavior – say, choose a different physician – based on what they learn from the reports? Or will doctors modify their own behavior by changing their drug-prescribing habits or steering away from industry connections altogether, to avoid the appearance of any potential conflicts of interest? All that remains to be seen, once the public records go online in September 2014.

Previously: Many physicians unaware of gift-disclosure law, shows survey, The NIH gets tough on conflicts of interest, Stanford’s medical school expands its policy to limit industry
, Faculty consulting work: now on public view and Let the sun shine: Legislation would publicly disclose physician-industry relationships

Evolution, Research, Stanford News

Mammals can “choose” the sex of their offspring, Stanford study finds

Mammals can "choose" the sex of their offspring, Stanford study finds

monkey and mama

A Stanford researcher and his colleagues have produced a surprising new study which shows that mammals can effectively “choose” the sex of their offspring and they’re doing it for their own selfish reasons – so they can have more grandchildren.

The researchers used data on more than 2,300 animals at the San Diego Zoo to track three generations for nearly 200 mammal species. Their numbers confirm what evolutionary biologists have theorized for decades – that females are strategically evaluating their options and making decisions that will serve their own reproductive interests, said Joseph Garner, PhD, associate professor of comparative medicine at Stanford and senior author of the study. Garner told me:

You can think of this as being girl power at work in the animal kingdom. We like to think of reproduction as being all about the males competing for females, females dutifully picking the winner. But in reality females have much more invested than males, and they are making highly strategic decisions about their reproduction based on the environment, their condition, and the quality of their mate. Amazingly, the female is somehow picking the sperm that will produce the sex that will serve her interests the most: the sperm are really just pawns in a game that plays out over generations.

What the researchers found is that grandparents could strategically choose to give birth to sons, if the sons would be of high enough quality to give them more grandchildren. In fact, they found that when females did have mostly sons, those sons had 2.7 times more children per capita than those who had equal numbers of male and female offspring. The same was true for male grandparents, with the study showing that when grandfathers produced mostly sons, those sons on average had 2.4 times more children per capita. But again, it’s most likely the females controlling the process, Garner said.

How they do it remains a bit of a mystery, he said, though one theory is that females control the sperm as it moves through the reproductive tract, selectively slowing down or speeding up the sperm they want to select.

Garner noted that there have been studies showing some similar patterns among humans. For instance, one found that billionaires are more likely to have sons than daughters because sons tend to retain the family’s wealth, or so the theory goes.

To read more on this tantalizing subject, see the study, which appears online today in PLOS ONE.

Photo by EvaSwensen

Cancer, Dermatology, Men's Health, Research, Stanford News

Stanford study: Young men more likely to succumb to melanoma

Stanford study: Young men more likely to succumb to melanoma

Young white men with melanoma have a 55 percent higher risk of death from the disease than their female counterparts, suggesting biological sex differences may play a role in outcomes in this deadly cancer, a new Stanford study shows. Though other studies have found that older men tend to fare worse when it comes to melanoma – the most serious form of skin cancer – this is one of the first to compare survival between men and women in a younger population.

The study focused on adolescent and young adults between the ages of 15 and 39 years, who were diagnosed between 1989 and 2009. Among the more than 26,000 patients studied, 1,561 died of the disease. Though males accounted for fewer cases overall (40 percent), they accounted for 64 percent of the deaths. Susan Swetter, MD, a professor of dermatology and the study’s senior author, said:

Studies worldwide have demonstrated that women diagnosed with melanoma tend to fare better than men in terms of improved survival, and this has mostly been attributed to better screening practices and behaviors in women that result in thinner, more curable tumors, and/or more frequent physician visits in older individuals that result in earlier detection. Our study focused on survival differences between young men and women diagnosed with cutaneous (skin) melanoma, who constitute a generally healthy population compared to the older adults who have primarily been studied.

The researchers found that the young men were significantly more likely to die of melanoma than young women their age, even taking into account factors typically related to poor prognosis, such as the tumor’s thickness, its location, histologic subtype and whether or not it had spread to other parts of the body.

“Our results present further evidence that a biologic mechanism may contribute to the sex disparity in melanoma survival, particularly since adolescent and young adults see physicians less frequently and are less likely to have sex-related behavior differences in skin cancer screening practices than older individuals,” said Swetter, who directs the Stanford Pigmented Lesion and Melanoma Program.

The results follow a previous analysis in Europe in 2012 which found that women with melanoma have a 30 percent survival advantage compared to men, despite similar follow-up and treatment, she said. And a more recent study out of Europe showed that even women with advanced melanoma do better in terms of survival.

Christina Gamba, MD, who recently graduated from Stanford’s medical school, was the study’s first author. She told me, “We feel that our study in a largely healthy, young population adds further evidence that a biological mechanism may be at play. Several theories for the survival disparity include differences in sex hormones, vitamin D metabolism, and immune regulation, but further investigation is needed to explore these proposed mechanisms.”

The research appears online today in JAMA Dermatology.

Previously: New research shows aspirin may cut melanoma risk, New skin cancer target identified by Stanford researchers, How ultraviolet radiation changes the protective functions of human skin and Working to prevent melanoma

Health Policy, Men's Health, Orthopedics, Research

Report deals another blow to synthetic bone growth product

Report deals another blow to synthetic bone growth product

An independent group at Yale University has dealt another blow to a bioengineered protein that was once commonly used in spinal fusion surgery. The Yale University Open Data Access Project found that the human recombinant bone morphogenetic protein-2 (rhBMP-2) “provided little or no benefit compared to bone graft and may be associated with more harms, possibly including cancer.”

The findings, published in the June 18 issue of the Annals of Internal Medicine, confirm a 2011 review of the product by the editors of the Spine Journal, led by Eugene Carragee, MD, professor of orthopedics at Stanford.

What is most troubling, Carragee says, is that the Yale group found that surgeons who received millions of dollars from Medtronic Inc., the maker of the protein, misrepresented its efficacy and underreported complications. Carragee and his colleagues had previously reported in the Spine Journal that the product, marketed as Infuse, carried a range of side-effects, including male sterility, urinary problems, infection, nerve and bone injury and possible cancer risk. Carragee said in a statement released by the journal:

To put the YODA findings in perspective, one must understand the carnival-like promotion that preceded BMP-2’s fall from grace. Market boosters advised that the BMP-2 product went beyond all other medical innovations. Perhaps confusing Infuse with penicillin or the polio vaccine, one zealot proclaimed: ‘Infuse, the single most successful biologic product ever launched in orthopedics and possibly ever in medicine.’

In a triumph of understatement, the YODA group informs us that ten years after its development, ‘it is difficult to identify a clear indication for BMP-2 use in spinal fusion.’ Ten years after penicillin was developed, people were saying it had saved a quarter million lives in World War II. Ten years after the polio vaccine, braces had disappeared from grammar schools. Ten years after BMP-2’s introduction, the YODA group could not identify a single compelling indication for use – but we know it can kill you in the cervical spine and probably can promote cancer, which can then kill you.

In 2012, the U.S. Senate Finance Committee conducted an investigation into the marketing of the product, as well as into physician/industry relationships and the scientific publishing process. It named three surgeons who had particularly lucrative financial ties with Medtronic, ranging from $10 million to $35 million each. These physicians had authored some of the early studies on BMP-2 that framed it in a positive light and helped launch it into general use by orthopedic surgeons.

Carragee says it’s unfortunate that after years of this “self-congratulatory research,” physicians still have a poor understanding of the protein:

At present these ‘concerns’ regarding higher rates of cancer, sterility, wound problems and nerve injury remain poorly described. The suggested reason for this gap in our understanding, if true, is simply appalling: these complications were systemically ‘misrepresented,’ ‘underreported,’ or just “missing’ from the first decade of publications. The research to better understand those complications and risks is still before us.

To its credit, Medtronic financed the $2.5 million YODA project.

Previously: For the record: Carragee on Medtronic spine stories, Stanford-led study on Medtronic bone product dominates the headlines, Stanford orthopedist reveals problems with Medtronic spinal fusion product, and Stanford study links spine product to male infertility

Stanford Medicine Resources: