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Drug prices not always aligned with value, CU Anschutz researchers say

In many countries, health care reimbursements for drugs are directly related to their value or net health benefits in treating disease.

But a new study by researchers at the University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences , in collaboration with a group of international clinical and economic experts, shows that’s not the case in the U.S.

Jon Campbell, PhD, of the Skaggs School of Pharmacy and Pharmaceutical Sciences is senior author of the study
Jon Campbell, PhD, associate professor at Skaggs School of Pharmacy and Pharmaceutical Sciences, is lead author of the study.

The study was published Monday in the August issue of the journal Health Affairs.

“In the United Kingdom, for example, cost effectiveness is a driver of decisions to pay for, or decline to pay for, health interventions,” said the study’s lead author Jon Campbell, PhD, associate professor of pharmacy. “They generally do not pay more than £30,000 to £40,000 per quality-adjusted life-year (QALY) for new medical interventions, thus signaling to manufacturers and other innovators what their country is willing to pay for additional health improvements.”

Melanie Whittington, PhD
Melanie Whittington, PhD, research faculty at the Skaggs School of Pharmacy and Pharmaceutical Sciences, is-co-author of the study.

QALY is used to measure one year of perfect health.

In the U.S., there is no formally agreed-upon cost-effectiveness threshold, due mostly to its fragmented health care system.

Using a forecasting model, they calculated the cost-effectiveness for commonly reimbursed cardiovascular drugs by estimating the cost per health outcome achieved. They wanted to see if the U.S. had an observed payment threshold, if even implicitly.

Instead they found a wide spectrum of cost-effectiveness, suggesting that drug prices are not consistently associated with what they produce in terms of health gains. Prices were, in short, not consistently aligned with value.

“When we purchase a medical treatment, we expect to get something in return, such as living a longer life or having fewer symptoms,” said study co-author Melanie Whittington, PhD, research faculty at the CU School of Pharmacy. “The results of our study show the amount insurance providers pay to get one more unit of health, such as one additional year of life in perfect health, varies considerably and can exceed what is considered good value in other parts of the world. This contributes to higher-priced medical treatments.”

She noted that the study used data from 1985-2011 and that in recent years health care leaders have been talking more about value-driven health care.

Campbell said the U.S. pays up to twice as much for branded drugs and health care services compared to other wealthy nations.

The reason, he said, may be due to the difference in price paid with little difference in the quantity of drugs or health services actually used.

“The U.S. gets very little in terms of additional health outcomes for this added price paid,” said Campbell, director of the pharmaceutical outcomes research graduate track at the Center for Pharmaceutical Outcomes Research at CU Anschutz. “In the pharmaceutical space, the U.S. has done a poor job at signaling to manufacturers what we are willing to pay for improvements in health and what improvements in health we care about.”

He and Whittington hope the study will stimulate more debate in this country about what constitutes an acceptable cost per unit of health gained for drugs and how to achieve value-driven health care delivery in the U.S.

“Solutions toward fair drug pricing include the U.S. sending more signals about what we value in health and U.S. decision makers being willing and able to walk away from unfair pricing,” Campbell said.

The study co-authors include Vasily Belozeroff, health economist at Amgen Inc., Thousand Oaks, Calif.; Robert Rubin, distinguished professor of medicine at Georgetown University in Washington D.C.; Paolo Raggi, professor of medicine at the Mazankowski Alberta Heart Institute and the University of Alberta in Edmonton; Andrew Briggs, professor of health economics at the University of Glasgow in Scotland and visiting investigator at Memorial Sloan Kettering Cancer Center, New York, N.Y.

The study can be found here: Prices for common cardiovascular drugs in the U.S. are not consistently aligned with value






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Researchers develop model on how brain reward response may impact anorexia nervosa

Researchers at the University of Colorado Anschutz Medical Campus have found that the brain’s response to taste stimuli is linked to high anxiety and a drive for thinness that could play a role in driving anorexia nervosa.

The study was published last week in the journal JAMA Psychiatry.

The researchers, led by Dr. Guido Frank, MD, associate professor of psychiatry and neuroscience at the University of Colorado School of Medicine, monitored a large group of patients with anorexia nervosa as they tasted sugar during brain imaging.

Dr. Guido Frank, associate professor of psychiatry, is an expert in eating disorders
Dr. Guido Frank, associate professor of psychiatry and neuroscience, is an expert on eating disorders

They found their brain response was higher than those in the control group, representing a biological marker for the illness. At the same time, this brain response was related to high anxiety and less weight gain for those being treated for anorexia nervosa.

Frank found that as these patients restricted their diet, a brain reward circuit associated with the neurotransmitter dopamine becomes more active but also triggers anxiety. This makes food avoidance worse and perpetuates the often deadly disease.

“When you lose weight your brain reward response goes up,” said Frank. “But instead of driving eating, we believe it elevates anxiety in anorexia nervosa, which makes them want to restrict more. This becomes then a vicious cycle.”

Using brain scans, the researchers examined 56 female adolescent and young adults with anorexia nervosa between the ages of 11 and 21 and 52 healthy control participants of the same age. They all learned to associate colored shapes with either getting or not getting a sugary solution. Sometimes when they expected sugar they got nothing, and sometimes when they didn’t expect sugar they received it.

Those with the eating disorder responded more strongly to the unexpected getting or not getting of sugar water, perhaps due to the release of dopamine.

The researchers found that the higher the brain response, the higher the harm avoidance in those with anorexia nervosa was. Harm avoidance is an anxiety measure for excessive worrying and fearfulness. In these patients, it pushes the drive for thinness and furthers body dissatisfaction.

Frank discovered that the higher the brain response, the lower the weight gain during treatment.

This brain reward response acted on the hypothalamus, which stimulates eating, in the anorexia nervosa group. The researchers hypothesized that this could make it possible to override and fend off signals to eat.

“An enhanced dopamine reward system response is an adaptation to starvation,” the study said. “Individuals vulnerable to developing anorexia nervosa could be particularly sensitive to food restriction and adaptations of reward response during the [mid-adolescence] development period.”

According to Frank, anorexia nervosa behavior could alter the brain circuits and impact its taste-reward processing mechanisms. Those who are already worried about shape and weight become even more concerned. And a strong response that says “feed me” might be overwhelming and trigger more food restriction instead of eating.

The study noted that while most people like sweet tasting things, those with eating disorders associate the taste with weight gain and try to avoid it. Frank found that the brain activation among the anorexia group was inversely connected with any pleasant experience of eating sugar.

“Our data raise the possibility that adolescents with anorexia nervosa in this study were negatively conditioned to sweet taste and may have developed an inverse association with dopamine release across the larger (brain) reward circuitry,” the study said.

Frank believes these insights could lead to new treatments for eating disorders.

“I hope we can use these findings to manipulate these biomarkers and design better treatments for this often-deadly disease,” he said.

The study’s coauthors include: Marisa C. DeGuzman, BA, BS; Megan E. Shott, BS; Mark L. Laudenslager, PhD; Brogan Rossi, BS, all from the University of Colorado Anschutz Medical Campus. And Tamara Pryor, PhD, of Eating Disorder Care, Denver, Colorado.

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Researchers find connection between viruses and inflammatory bowel disease

A study led by a University of Colorado Anschutz Medical Campus researcher reveals a key connection between viruses and inflammatory bowel diseases like ulcerative colitis and Crohn’s disease.

Breck Duerkop, PhD, assistant professor of immunology and microbiology at the University of Colorado School of Medicine, and a team of scientists focused on viruses inhabiting bacteria in the intestine known as bacteriophages or simply phages.

Breck Duerkop, PhD, assistant professor of immunology and microbiology at the University of Colorado School of Medicine
Breck Duerkop, PhD, assistant professor of immunology and microbiology at the University of Colorado School of Medicine

“Phage numbers are elevated at the intestinal mucosal surface and increase in abundance during inflammatory bowel disease (IBD), suggesting that phages play an unidentified role in IBD,” said Duerkop, lead author of the study published Monday in the journal Nature Microbiology.

IBD poses significant health burdens worldwide and has inspired intense investigation into the environmental factors causing persistent inflammation of the intestine. Microbial communities are critical in maintaining intestinal health but changes in the composition of these organisms may cause an inflammatory response by the body.

According to Duerkop, most studies looking at how these microbial communities might spark inflammation have focused chiefly on bacteria rather than the viruses residing inside them.

When inflammation occurs, Duerkop found that phage communities change randomly leading to a genetic signature indicative of the inflammatory environment.

“We hypothesize that inflammation or other host defenses alter phage abundances during colitis,” the study said. “Such stresses could produce ecological disturbances in the intestinal environment, driving alterations within the viral community.”

Those disturbances could be the result of the viruses killing off beneficial bacteria in the intestine and allowing for `bad actor’ bacteria to cause inflammation and bowel disease.

The experiments were done with mice.

“What we see in mice is consistent with what we see in humans with IBD,” Duerkop said.

While the mechanics of how these phages operate will require further study, Duerkop said this discovery could lead to new kinds of treatment for these often debilitating diseases.

Clinicians could target certain bacteria with viruses to eliminate bacteria that lead to inflammation. Bacteria could be manipulated to circumvent the development of disease.

“We could promote the growth of good bacteria – a kind of phage therapy,” Duerkop said. “We could perhaps use phages as markers to identify someone predisposed to developing these diseases. While there is clearly more research to do, the potential is very exciting.”

The co-authors include Manuel Kleiner, North Carolina State University; David Paez-Espino of the Department of Energy, Joint Genome Institute; Wenhan Zhu, University of Texas Southwestern Medical Center; Brian Bushnell, Department of Energy, Joint Genome Institute; Brian Hassell, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center; Sebastian E. Winter, University of Texas Southwestern Medical Center; Nikos C. Kyrpides, Department of Energy, Joint Genome Institute; Lora V. Hooper, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center.


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Lifestyle makeover: Wellness center study fuels transformation

With the words “morbidly obese” ringing in her ears and the thrill of crossing a 5K finish line fresh in her mind, Emily Cooley’s eyes stopped short on a Facebook post. The Anschutz Health and Wellness Center (AHWC) needed recruits for a weight-loss study. Having just been counseled by her doctor about the gravity of her weight, Cooley took it as a sign.

Emily Cooley before weight loss
A sense of accomplishment after finishing a 5K helped spur Emily Cooley’s dramatic weight loss.

That was 2-1/2 years ago. Today, the retail manager remains one of the most successful participants to take part in the 170-person study, shedding 80-plus pounds from her 5-foot-7, 240-pound frame and keeping it off, a feat that puts her in a rare group. Only one in five significant weight losers maintain the loss for more than one year, studies show.

“We can generally get individuals to lose weight, or to start exercising, but most are not successful at maintaining either of those two things long-term,” said Danielle Ostendorf, PhD, a physical activity epidemiologist on the University of Colorado Anschutz Medical Campus and recent Colorado School of Public Health graduate who worked on Cooley’s study. “Emily’s a perfect example of doing both things through lifestyle change.”

Turning points

Cooley, 39, who struggled with weight for years, had resigned herself to being a plus-size woman after her second daughter was born. But then her doctor showed her a Body Mass Index chart classifying her as morbidly obese and at risk of serious health problems.

“I want to be here for them, and not just on the sidelines.” – Emily Cooley

“Seeing morbidly obese in black and white freaked me out,” Cooley said. That, coupled with the life-long duty of parenthood, fueled her attitude reversal. “Being a mom definitely changed my perspective about it,” said the wife and mother of 4- and 6-year-old girls. “I want to be here for them, and not just on the sidelines.”

Feeling the satisfaction of finishing a 5K, which she mostly walked with the support of a runner friend, was another trigger. “I was so touched,” said Cooley, who now runs 5Ks with ease and has a BMI of 25 instead of 38. “I had finished it. I had made my goal.”

Expert guidance

The AHWC study, funded by the National Institutes of Health and led by the School of Medicine’s Victoria Catenacci, MD, helped keep her motivated through guidance, support and resources, from

Emily with family
Being around as long as possible for her family served as Emily Cooley’s “why” for losing weight.

the latest diet research to top-of-the-line fitness facilities, Cooley said. While working with a nutritionist, she learned she was absent-mindedly drinking calories, swallowing as many as 600 in a large frappe for breakfast and 300 in a large Coke for lunch.

Once her diet counseling changed things, Cooley was eating fewer calories all day than she generally consumed before noon.

Initially, Cooley was disappointed when she was placed in the “delayed-exercise” group during the study, spending the first six months on dieting only while her counterparts had exercise and diet training from the start. But now she sees the chance placement as luck. “I was focusing on only one big change at a time.”

Once exercise was added to her routine, Cooley had already dropped 50 pounds, making working out easier and less painful, she said. Participants’ exercise routines were ramped up slowly, from 20 minutes three times a week to 60 minutes five times a week, which Cooley and Ostendorf also suspect helped prevent burnout and injury, two threats that often sabotage overzealous new exercisers.

Powerful goals

Motivation, commitment and “SMART goals” set regularly along the way led to Cooley’s success, Ostendorf said, referring to Specific goals that are Measurable, Attainable, Realistic and Timely. “It could be: I want to lose 10 pounds in two months, or I want to lower my blood pressure 5 mm/Hg in six months,” she said.

Cooley largely uses a regular race plan for keeping on track, setting 5K and 10K dates with friends she’s met along the way throughout the year. “Then I tell my girls I have to go to the gym, so I can be strong for my race,” she said.

Setting an example for her daughters remains a big motivator for Cooley, who often hears: “Good job, Mommy!” and who walked a 5K with her 6-year-old this summer. Higher energy and better moods are other benefits, Cooley said, who has now set a lofty goal of completing a marathon this spring. “I just want to prove that I can.”

Curbing an epidemic: weight-loss star offers tips

With 70 percent of Americans overweight or obese, and their burgeoning waistlines costing the medical system as much as $190 billion annually, the Anschutz Health and Wellness Center’s research and promotion of weight loss helps curb an epidemic. Here are a few of study participant Emily Cooley’s tricks for success:

Be consistent.

“I will have one cheat meal once in a while, but then I get right back on track. I don’t do cheat weekends or cheat vacations anymore.”

Track exercise and calories.

“I still use MyFitnessPal. If I don’t, I underestimate what I eat.”

Have a powerful “why.”

“I can’t be morbidly obese. I have two little girls.”

Set consistent goals.

“I always have a race planned with friends; that helps keep me motivated.”

Make it fun.

“We make it a girls’ day out and do something like brunch after the race.”

Surround yourself with support.

“It just makes sense to have friends with the same goals.”


For exercise: “I lay out my workout clothes the night before. And I have two alarms: a wake-up alarm nearby, and a get-out-of-bed alarm farther away.”

For diet: “I always have things like Clif bars or trail mix with me, so I don’t get caught out with nothing.”

Make it easy.

“My gym is only 10 minutes away.”

Forget the guilt.

“I used to feel guilty about taking time away from the girls. Now I realize if I’m not a healthy mom, I can’t be the best mom.”

Just do it.

“It’s never too late to lose weight.”


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CU Anschutz awarded $8 million to refine and expand research cooperative focused on end-of-life and palliative care

The University of Colorado Anschutz Medical Campus received an $8 million, five-year continuation grant from the National Institute for Nursing Research (NINR), part of the National Institutes of Health, to refine and expand the Palliative Care Research Cooperative Group (PCRC).

Jean Kutner, MD,MSPH, professor of medicine
Jean Kutner, MD, MSPH, professor of medicine.

As the nation’s first research cooperative group focused on end-of-life and palliative care research, the PCRC was established in 2010 with initial funding from the NINR/NIH, and now includes close to 450 members and a growing network of over 150 clinical sites across the nation.

The PCRC addresses national research priorities in end-of-life and palliative care by enhancing the quality and efficiency of research. The PCRC exists to lead, catalyze, and empower a community of investigators who are developing an evidence base to ensure high quality care and optimal well-being for persons with serious illness and their caregivers. The PCRC is a vibrant, interdisciplinary research community committed to advancing rigorous palliative care science and improving care for people with serious illness.

“The PCRC has developed key resources and infrastructure that are facilitating conduct of high quality palliative care research and fostering an interdisciplinary community of investigators,” said Jean Kutner, MD, MSPH, professor of medicine at the University of Colorado School of Medicine and PCRC Co-Chair.

Christine Ritchie, MD, MSPH, professor of medicine at the University of California San Francisco, Co-Chair of PCRC, and Director of the PCRC Investigator Development Center, describes the PCRC as a community of learners. “In a field as new as palliative care with substantial research needs, it is critical for new and seasoned investigators alike to be learning cutting-edge research methods and strategies to answer complex questions faced by those with serious illness and their caregivers.”

“Palliative care research has grown by leaps and bounds. The PCRC helps ensure we conduct the most rigorous science that can inform our clinical practice to improve the lives of patients and their caregivers,” said Kathryn Pollak, PhD, professor of Population Health Sciences at Duke University, Co-Chair of PCRC, and Director of the PCRC Clinical Studies/Methodology Core.

Information about the PCRC is available on the PCRC website:

Funding for the PCRC is provided by the NINR (UC4NR012584, U24NR014637, and U2CNR014637-6).

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A RaCAS boom: Annual research showcase breaks two-decade record

Students welcome at RaCAS
Joe Pham and Diana Lee, work-study employees of the Experiential Learning Center, greet RaCAS participants in raucous fashion.

Celebrating research from the sciences to the humanities, the 21st annual Research and Creative Activities Symposium (RaCAS) primed creative minds and broke records this year, as more than 500 participants and viewers from the University of Colorado Denver and Anschutz Medical Campus joined in the event.

A record 238 student presentations infused two floors of the Student Commons Building at CU Denver with passionate inquiry on April 27, delving into topics from cancer treatments to virtual learning tools. Under the guidance of a new director, it was the largest RaCAS turnout ever in the research showcase’s two decades.

“That was one of my goals when I took this job,” said Lindsey Hamilton, director of Undergraduate Research and Creative Activities, who accepted the reins as RaCAS director on Jan. 1. “I wanted to bring more awareness to the research that’s taking place on our campuses and change the impression of RaCAS to be more inclusive of all scholarly work.”

Rather than focusing solely on outstanding completed research, Hamilton and crew advertised heavily that projects in progress and of all levels were welcome. “This is a great opportunity to practice presentation,” Hamilton said. “We told them communicating their work was a learning experience and a critical component to their education. And it worked. We had a great turnout.”

For the first time, RaCAS involved student- rather than faculty-organized mini-symposiums, with a record 15 participants. Hamilton also added an Emerging Scholar award to the honoree list, acknowledging the work of 19 students.

Student with poster
Kathleen Nguyen presents her poster project on an innovative nanoparticle therapy aimed at improving detection and treatment of bladder cancer. She won a People’s Choice award for her presentation.

Targeting bladder cancer

“This is actually my fourth poster presentation this month,” said Kathleen Nguyen, a bioengineering undergraduate in the College of Engineering and Applied Science, who won a People’s Choice award for her presentation.

“I’ve met so many people. I think this experience is invaluable,” Nguyen said, adding that, in addition to culling connections, presenting at RaCAS and other symposiums helps inspire and prepare students for graduate school.

Looking at how nanoparticles can translate into medical uses, Nguyen highlighted a collaborative research effort in the Nanosafety and Nanotoxicology Lab in the Skaggs School of Pharmacy and Pharmaceutical Sciences. By combining gold nanorods and upconversion nanoparticles, the researchers are working on a noninvasive means of detecting and eradicating bladder cancer.

“We told them communicating their work was a learning experience and a critical component to their education. And it worked. We had a great turnout.” – Lindsey Hamilton, RaCAS director

Gold nanorods contain a property called surface plasmon resonance, Nguyen said. “Basically, that means they oscillate really fast under high-frequency lasers. So, when you shine lasers at near infrared light at these gold nanorods, they vibrate really fast and create a lot of heat, which can be utilized for thermal ablation of bladder cancer.”

By attaching upconversion nanoparticles, which will brightly fluoresce under low-frequency laser light, the aim is to detect and specifically target tumors with the complexes. “The idea is to attach these two together and insert them into the bladder in some sort of solution,” Nguyen said, explaining that the gold nanorod complexes have an anti-EGFR antibody called C225.

“It turns out that bladder cancer tumors have over expression of EGFR, so these gold nanorod complexes will only attach to the tumor,” she said. After the complex solution is allowed to sit in the patient for a short period of time, doctors would insert a catheter with a laser, detecting the tumors with low-frequency light and ablating them with high-frequency light.

Nguyen’s work is focused on how the gold nanorods could be used to activate immune responses that would detect and attack the tumor. “It’s really cool,” she said. “It’s very exciting.”

Student with poster
Angelique Dueñas stands next to her poster presentation on the educational value of 3-D embryos. Dueñas won first-place recognition for another presentation on Mapping the Body: Poetry and Anatomical Art New Student Exhibit Merges Humanities and Sciences in Higher Education Collaboration.

Bolstering embryology education

Focusing on educating future students in an area she has become passionate about but that has shown signs of declining interest, Angelique Dueñas, a master’s student in Modern Human Anatomy, presented a project weighing the value of 3-D virtual embryos in learning.

“I found it fascinating to see how we develop and why things are the way they are in our bodies,” Dueñas said, explaining her passion for embryology. After seeing a number of literature reviews on the medical curricula’s decreasing emphasis on embryology, she joined colleagues in their efforts to boost interest.

“It’s super important that medical students understand embryology,” Dueñas said. But the field has unique learning challenges. “It’s a three-dimensional subject,” she said of a fetus. “Then you add in time of a developing embryo, and it can be really challenging, especially when the classic presentation is 2-dimensional,” she said of textbook visuals.

So, her team designed 3-D printed models and virtual models and assessed their value. “You can use your mouse and look at all sides of the different organs,” Dueñas said, illustrating with a brightly colored eight-week embryo model on a computer screen. “You can click, and it will tell you what structure you are looking at,” she said, adding that the application used does have virtual-reality capabilities.

After recruiting 162 first-year medical, dental and graduate students, the researchers gave each volunteer a pre-quiz. They then assigned groups to a static pamphlet representation, a 3-D printed version and a 3-D virtual version. Then volunteers completed a post-quiz and survey.

“Students who interacted with the virtual model and the 3-D printed model seemed to increase their pre-test performance statistically significantly,” she said. “The pamphlet group did not.” Nearly 90 percent of students surveyed said they would like to see these resources in other stages and that it would enhance their understanding, Dueñas said. “They said they would even buy these resources, so it was really exciting for us.”


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CU Anschutz wins $46.5 million NIH grant

The National Institutes of Health (NIH) recently awarded $46.5 million to the University of Colorado Anschutz Medical Campus and its Colorado Clinical and Translational Sciences Institute (CCTSI), a research partnership designed to speed up development of new treatments to address the greatest health needs of Coloradans.

In 2008, the CCTSI was launched with a grant of $76 million—the largest biomedical research and training award in the state’s history. This new five-year award brings the total funding from NIH to the CCTSI to more than $187 million.

Dr. Shikha Sundaram“The general public may not know the CCTSI name,” says Ronald Sokol, MD, CCTSI director and professor of pediatrics in the School of Medicine. “But they have probably benefited from the research that has come out of our institute over the past 10 years.” Examples include:

  • A cure for hepatitis C, which was made possible in part by dozens of clinical trials that were conducted by CCTSI investigators in our facilities over the past 15 years.
  • Precision medicine treatments for cystic fibrosis that target the defective protein caused by specific gene mutations and which have transformed the lives of patients.
  • Boosting the rates of health screenings that save lives in underserved Colorado communities, such as urban Latino, urban African American and rural eastern Colorado.
  • Decreased mortality rates in five Denver neighborhoods by developing community-based, culturally responsive approaches to tailor educational programs for cardiopulmonary resuscitation (CPR).

“The CCTSI is an engine that has enhanced the research enterprise on the Anschutz Medical Campus for many years,” says Dean John J. Reilly, Jr., MD, of the University of Colorado School of Medicine. “We are proud of their work and confident they will continue to provide essential support and leadership for the next generation of physicians and researchers.”

Over the next five years, the CCTSI will:

  • Develop, educate and sustain a diverse translational science workforce to ensure the highest research innovation, quality and safety.
  • Create a translational research environment in which team science and collaboration both locally and nationally are facilitated, supported and valued.
  • Engage local and national communities and stakeholders in all phases of the translational research process.
  • Create novel methodologies and resources to support and integrate research in special populations, including children, the elderly, the underserved and those with rare diseases.

“The grant will further establish the University of Colorado Anschutz Medical Campus, and all of our institutional partners, as biomedical research leaders, pioneers and innovators,” says Sokol. “We are thrilled to have the opportunity to continue to engage in the full spectrum of translational science to achieve our ultimate goal of getting more treatments to more patients more quickly.”

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Study shows prenatal cannabis use associated with low birth weights

With marijuana use during pregnancy on the rise, a new study led by the Colorado School of Public Health shows that prenatal cannabis use was associated with a 50 percent increased likelihood of low birth weight, setting the stage for serious future health problems including infection and time spent in Neonatal Intensive Care Units.

Cannabis Sativa leaf
New study shows association between prenatal cannabis use and low birth weights.

“Our findings underscore the importance of screening for cannabis use during prenatal care and the need for provider counselling about the adverse health consequences of continued use during pregnancy,” said the study’s lead author Tessa Crume, PhD, MSPH, assistant professor of epidemiology at the Colorado School of Public Health at the University of Colorado Anschutz Medical Campus.

The study was published last month in The Journal of Pediatrics.

Crume and her colleagues utilized survey data from 3,207 women who participated in the Colorado Pregnancy Risk Assessment Monitoring System in 2014 and 15. They found the prevalence of marijuana use in the state of Colorado was 5.7 percent during pregnancy and 5 percent among women who were breastfeeding.

Tessa Crume, assistant professor of epidemiology at the Colorado School of Public Health
Tessa Crume, PhD, MSPH, assistant professor of epidemiology at the Colorado School of Public Health

They also discovered that prenatal marijuana use was associated with a 50 percent increased chance of low birth weight regardless of tobacco use during pregnancy. Prenatal marijuana use was three to four times higher among women who were younger, less educated, received Medicaid or WIC, were white, unmarried and lived in poverty.

Crume said the numbers are surprising but also reflect changing attitudes toward marijuana, especially in a state like Colorado where it is legal.

“There is increased availability, increased potency and a vocal pro-cannabis advocacy movement that may be creating a perception that marijuana is safe to use during pregnancy,” Crume said.

The National Survey on Drug Use and Health suggests that cannabis use among pregnant women has increased as much as 62 percent between 2002 and 2014. At the same time, the potency of the drug has increased six or seven fold since the 1970s along with the ways it is consumed – eating, vaping, lotions etc.

“Growing evidence suggests prenatal cannabis exposure has a detrimental impact on offspring brain function starting in the toddler years, specifically issues related to attention deficit disorder,” Crume said. “But much of the research on the effects of prenatal cannabis on neonatal outcomes was based on marijuana exposures in the 1980s and 1990s which may not reflect the potency of today’s cannabis or the many ways it is used.”

The study found that 88.6 percent of women who used cannabis during pregnancy also breastfed. The risk of cannabis to the infant through breastmilk remains unknown. Various studies have found that cannabinoids are passed to the baby in this way. One of the study’s co-authors, Dr. Erica Wymore, MD, MPH, from Children’s Hospital Colorado and the CU School of Medicine, is currently conducting a study to evaluate this issue.

The researchers recommend that health care providers ask pregnant women about their cannabis use and advise them to stop during pregnancy and lactation.

“Obstetric providers should refrain from prescribing or recommending cannabis for medical purposes during preconception, pregnancy and lactation,” Crume said. “Guidance and messaging about this should be incorporated into prenatal care. And screening of pregnant women at risk for cannabis dependency should be linked to treatment options.”

The study co-authors include Ashley L. Juhl MSPH, of the Colorado Dept. of Public Health and Environment; Ashley Brooks-Russell, PhD, MPH, of the Colorado School of Public Health; Katelyn E. Hall, MPH, of the Colorado Dept. of Public Health and Environment; Erica Wymore, MD, MPH of the University of Colorado School of Medicine and Children’s Hospital Colorado and Laura M. Borgelt, PharmD, of the CU Skaggs School of Pharmacy and Pharmaceutical Sciences.

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Annual Department of Medicine Research Day 2018

Battling breast cancer, hepatitis C and the nationwide opioid-addiction crisis were just three of the research goals highlighted as part of the Department of Medicine’s sixth annual Research Day on the University of Colorado Anschutz Medical Campus.

Gathered in the Fulginiti Pavilion on April 6, the department within the CU School of Medicine recognized 22 students, faculty and staff for their outstanding research achievements as part of the event. Focused on showcasing the diverse accomplishments at CU Anschutz, the event encourages discussion and collaboration across the the Department of Medicine’s multiple disciplines.

This year, a diverse panel of faculty judges selected 22 outstanding abstracts – all submitted by Department of Medicine students, postdocs, fellows and junior faculty. The researchers were then invited to present their projects at Research Day, said Jennifer Kemp, director of the Department of Medicine Research Office.

“The Research Day poster session presents a unique opportunity for our researchers to present their latest work to a broader audience than is typically found at a more specialized conference,” Kemp said. “This broad audience brings the potential to spark new ideas and catalyze new collaborators in different fields.”

Cancer biology

Lynsey Crump shares her research in cancer biology.

Lyndsey Crump, a third-year student in the Cancer Biology

program in the Graduate School, works in Traci Lyons’s lab. Crump has been exploring how signaling proteins can affect breast cancer progression. Specifically, she has looked at SEMA7A (Semaphorin 7A) and how its presence may indicate a worse prognosis.

“I want to try to help people,” Crump said of her passion in cancer biology. “One day I want to see this lab work to translate to clinical work, to give patients another potential course of treatment.”

Hepatitis C and public health

Andy Bryant, MD, studies hepatitis C in special populations.

Andy Bryant, MD, is an internal medicine resident at CU Anschutz studying the treatment of hepatitis C in a “safety net” population, or those who are either uninsured or have Medicare or Medicaid.

“Until this study, this population was overlooked,” said Bryant as he walked onlookers through his research. “Unfortunately, these people usually come in a lot sicker than those with traditional insurance. This means that their prognosis isn’t very good.”

Recent studies have helped underscore the potential for a new drug (DAA) that can cure hepatitis C. Originally, Medicaid and Medicare did not cover this drug, but Bryant’s findings help show the long-term potential savings of administering DAA.

Opioid prescribing habits

Angela Keniston, MSPH, an instructor in the department of hospital medicine, studies the prescribing habits of health care providers across the world.

Angela Keniston researches cultural opioid prescribing habits.

“Specifically, we wondered, do doctors in the United States prescribe opioids more?” Keniston said. “The answer, one we’ve all suspected, was yes.”


In conjunction with her study, Keniston also looked into cross-cultural patients’ perceptions of pain across cultures.

In the long run, Keniston would like to help doctors understand their patients’ expectations of pain, and ultimately change prescribing habits. “Pain is a normal experience,” she said. “We need our providers to shape the conversation with patients to help curb this prescribing epidemic in our country.”


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Vascular problems associated with symptoms of menopause and quality of life measures

A new study shows that more frequent and severe menopausal symptoms such as hot flashes, sleep disturbance, loss of sexual interest, weight gain and other quality of life measures, were associated with markers of vascular aging, according to researchers at the University of Colorado Anschutz Medical Campus.

The researchers, however, found no association between these vascular markers and symptoms of depression. The study was published online today in Menopause, the Journal of the North American Menopause Society.

Kerry Hildreth, MD
Dr. Kerry Hildreth, MD, assistant professor in the Division of Geriatric Medicine, CU School of Medicine.

“The menopausal transition is a vulnerable time for women in terms of vascular health,” said the study’s lead author Kerry Hildreth, MD, assistant professor in the Division of Geriatric Medicine at the University of Colorado School of Medicine. “Many women also experience menopausal symptoms that can negatively affect their quality of life and can contribute to depression, which is an established risk factor for cardiovascular disease. We investigated whether these symptom and mood aspects of menopause were associated with markers of vascular aging.”

Hildreth and her colleagues studied 138 healthy women grouped according to the stage of menopause. They found that arteries were stiffer, and the endothelium, the layer of cells that line the blood vessels, was progressively less healthy across the stages of menopause. Menopausal symptoms and depression symptoms were greatest, and quality of life was lowest, in the late-perimenopausal and early postmenopausal stages. Importantly, more severe menopausal symptoms and lower quality of life were associated with worse vascular function.

Unique study

“To our knowledge this was the first study to examine the association of mood, menopausal symptoms, and quality of life measures with these key markers of vascular aging in a well-characterized population of women spanning the stages of menopausal transition,” the study said.

Dr. Kerrie Moreau, PhD, associate professor
Dr. Kerrie Moreau, PhD, associate professor in the Division of Geriatric Medicine, CU School of Medicine

Women entering menopause experience profound hormonal changes coinciding with adverse changes in cardiovascular disease risk factors like high blood pressure, weight gain and insulin resistance, the study said. This may help explain the acceleration of vascular aging during the menopause transition.

Although the majority of women do not experience depression during the menopause transition, the risk is two to three times higher than in premenopausal women. One hypothesis is that the brain has to adapt to the irregular fluctuations in estrogen, a potent neurosteroid, during perimenopause, and eventually to a new, lower baseline level after menopause. This may explain why depressive symptoms returned to lower levels in the late postmenopausal women.

But while the researchers did not find an association between depression and vascular dysfunction across the stages of menopause, they did find an association with common menopausal symptoms. These include vasomotor symptoms, such as hot flashes, palpitations and headaches, and general symptoms, such as sleeplessness, poor appetite, constipation, weight gain, and poor concentration.

Estrogen loss could play role

The reasons behind these changes are unclear but loss of estrogen could play a key role.

“Estrogen modulates the synthesis and uptake of serotonin which has neuromodulatory, thermoregulatory, and cardiovascular actions,” the study said. “Fluctuating and declining levels of estrogen with the menopausal transition may alter serotonin activity.”

Another culprit could be oxidative stress. Estrogen is a potent anti-oxidant and higher levels of oxidative stress are seen in estrogen-deficient, post-menopausal women compared to premenopausal women, according to the study. Hot flashes are also associated with higher oxidative stress.

Hildreth said the next step is studying the mechanisms underlying these associations between vascular aging and symptoms of menopause.

“A better understanding of these aspects of the menopausal transition will be important for developing effective lifestyle and therapeutic interventions to promote psychosocial well-being and cardiovascular health in women,” Hildreth said.

The other authors of the study include Kerrie Moreau, Ph.D.*, University of Colorado School of Medicine; Cemal Ozemek, Ph.D., University of Illinois at Chicago; Wendy Kohrt, Ph.D.*, University of Colorado School of Medicine, Associate Director of the Center for Women’s Health Research; Patrick Blatchford, Ph.D.*, Colorado School of Public Health.
*Also affiliated with the Eastern Colorado VA Geriatric Research, Education and Clinical Center

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