Common bronchodilator linked to increased deaths

2008 Post for filing

Contact: Marla Paul Marla-Paul@northwestern.edu 312-503-8928 Northwestern University

CHICAGO — A common bronchodilator drug which has been used for more than a decade by patients with chronic obstructive pulmonary disease (COPD) has been linked to a one-third higher risk of cardiovascular-related deaths.

The drug, ipratropium, is sold under the brand names Atrovent and Combivent, the latter a combination product that contains ipratropium.

A new study from Northwestern University’s Feinberg School of Medicine found that veterans with recently diagnosed COPD using ipratropium were 34 percent more likely to die of a heart attack or of arrhythmia than COPD patients using only albuterol (another bronchodilator) or patients not using any treatment.

The study is published in the Sept. 15 issue of the Annals of Internal Medicine.

“This medication may be having some systemic cardiovascular effect that is increasing the risk of death in COPD patients,” said Todd Lee, lead author and research assistant professor in the Institute for HealthCare Studies at the Feinberg School.

COPD is an umbrella term for respiratory diseases that include chronic bronchitis and emphysema. The primary cause is smoking. An estimated 12 million people in the U.S.  have COPD. The disease is the fourth leading cause of death in the U.S. and is expected to grow to the third leading cause by 2020 due largely to an aging population with a higher historical rate of smoking.

Todd noted his study is observational and indicates the need for researchers to take a closer look at this medication, which has been considered safe for many years. The study looked at the cause of death of 145,000 veterans with newly diagnosed COPD from 1999 to 2003.

“The safety of drugs for COPD patients has flown under the radar,” Lee said. “We decided to look into the safety of respiratory medications for COPD patients because of some concerns that had been raised in asthma drugs. We were curious as to whether there were safety problems with these medications in patients with COPD.”

Todd said patients and providers should be aware of the potential risk. “When they make treatment decisions they need to weigh these potential risks against other medications that are available for COPD,” he noted

Predicting If Scientists Will Be Stars: New Formula Reveals If Young Scientists Will Have Brilliant Future

ScienceDaily (Sep. 12, 2012) — A medical school committee is weighing whether to hire a promising young neuroscientist. Will she have a brilliant future as a researcher, publish in top journals and nab abundant research funds?

If only there were a crystal ball. Wait, now there is!

A new Northwestern Medicine study published Sept. 13 in Nature offers the first formula that accurately predicts a young scientist’s success up to 10 years into the future and could be useful for hiring and funding decisions.

Currently, hiring decisions are made using the instincts and research of search committees. Universities are increasingly complementing this with a measure of the quality and quantity of papers published, called the h index.

But the new formula is more than twice as accurate as the h index for predicting future success for researchers in the life sciences. It considers other important factors that contribute to a scientist’s trajectory including the number of articles written, the current h index, the years since publishing the first article, the number of distinct journals one has published in and the number of articles in high impact journals.

The formula was developed in the lab of Konrad Kording, senior author of the Nature paper and associate professor in physical medicine and rehabilitation at Northwestern University Feinberg School of Medicine and a researcher at the Rehabilitation Institute of Chicago.

“The algorithm could be useful for hiring and tenure decisions as well as funding decisions, particularly at a time when funding agencies and hiring committees are dealing with vast number of applications,” Kording said. “You want to fund someone who will have high impact in the future.”

While the formula won’t replace evaluation by a group of peers who examine scientific contributions and research depth, it could provide a valuable complementary tool, Kording noted. The predictions are targeted to a scientist at the level of assistant professor, someone within five to 15 years of writing his or her first paper as a Ph.D. student.

Kording and colleagues based and tested the formula on data from 3,293 scientists (3,085 neuroscientists, 57 Drosphila scientists and 151 evolutionary scientists) for whom they constructed a publication, citation and funding history.

The paper shows that the number of articles written, the diversity of publication and the number of top articles over time all become increasingly influential predictors of a scientist’s success.

Perhaps publishing in many different journals leads to less overlapping populations of scientists who cite the work, Kording said, which leads to an increased number of citations for already published articles. The number of top journal publications also may give visibility to other papers of a scientist, both past and future.

The ability to predict future success also shows important discoveries are the result of ongoing hard work, not random luck.

“People think scientists sit there and all of a sudden have these strokes of genius that turn them into a superstar,” Kording said. “In reality, people who have important scientific insights usually have been incredibly successful before.”

The lead author of the paper is Daniel E. Acuna, a postdoctoral student in Kording’s lab at Northwestern’s Feinberg School of Medicine and a research affiliate in biomedical engineering at the McCormick School of Engineering and Applied Science.

Try the prediction engine: http://klab.smpp.northwestern.edu/h-index.html

Kording’s research was supported by the National Science Foundation

Scientists discover one of the ways the influenza virus disarms host cells

Contact: Megan Fellman fellman@northwestern.edu 847-491-3115 Northwestern University

Advantage flu virus

When you are hit with the flu, you know it immediately — fever, chills, sore throat, aching muscles, fatigue. This is your body mounting an immune response to the invading virus. But less is known about what is happening on the molecular level.

Now Northwestern University scientists have discovered one of the ways the influenza virus disarms our natural defense system. The virus decreases the production of key immune system-regulating proteins in human cells that help fight the invader. The virus does this by turning on the microRNAs — little snippets of RNA — that regulate these proteins.

The researchers, led by molecular biologist Curt M. Horvath, are among the first to show the influenza virus can change the expression of microRNA to control immune responses in human lung cells.

The findings reveal a new aspect of the interaction between the influenza virus and its host. Knowing how viruses disable the immune system to wreak havoc in the body will help researchers design therapeutics to preserve the immune response and keep people healthy. The knowledge also may be valuable for future diagnostics.

The study is published by the Journal of Biological Chemistry. The paper will appear in its final form in September.

“It’s a battle of supremacy between virus and host,” said Horvath, the senior author of the paper. “Our goal is to understand how the flu replicates in the host. Now we’ve discovered a new pathway in which the flu controls the immune response, by shutting down vital protein production. With better understanding of this mechanism, one day we may be able to customize therapeutics to target individual flu strains.”

Horvath is the Soretta and Henry Shapiro Research Professor in Molecular Biology and professor of molecular biosciences in the Weinberg College of Arts and Sciences. He also is professor of microbiology-immunology and medicine at the Feinberg School of Medicine.

A microRNA has only 17 to 24 nucleotides, and its function is to dampen or shut down the production of proteins in the body. (Proteins are the workhorses of the cell.) There are hundreds of different types of microRNAs in animals.

It’s been known for many years that when a virus such as influenza infects respiratory cells there is an immediate antiviral response at the cellular level — the first barrier for protecting the body from the virus. Most of the changes that occur are a result of antiviral gene expression.

About 10 years ago, scientists first learned about small RNA pathways called microRNAs, which regulate gene expression. This led Horvath to want to investigate the role of microRNAs in influenza virus infection and determine what they are contributing to the antiviral response. Exactly which genes might the microRNAs be targeting?

In their current study, Horvath and his team used human lung cells, infected them with the influenza A virus and looked to see which microRNAs were activated in response to the virus. They focused on six microRNAs that were found to increase in abundance during flu infection.

The researchers found the virus activated two microRNAs that turned on the genes IRAK1 and MAPK3. This resulted in a decrease in the amount of proteins that help turn on the immune response.

Essentially, the virus uses the cell mechanisms to its advantage, disarming parts of the natural antiviral system. The flu takes over the expression of microRNAs for its own purposes. The flu increases the expression of microRNA, which decreases the amount of protein and diminishes the immune response.

Having identified a specific set of microRNAs whose expression in host respiratory cells is changed by the influenza virus, Horvath next is interested at looking at the clinical outcomes. He is working with Pedro C. Avila, M.D., professor of medicine-allergy-immunology at the Feinberg School to see if the microRNAs are disregulated in patients with influenza.

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The title of the paper is “Influenza A Virus Infection of Human Respiratory Cells Induces Primary MicroRNA Expression.” In addition to Horvath, other authors of the paper are first author William A. Buggele and Karen E. Johnson.

Dangerous experiment in fetal engineering (MUST READ)

Public release date: 2-Aug-2012


Dangerous experiment in fetal engineering

Risky prenatal use of steroid to try to prevent intersex, tomboys and lesbians

CHICAGO — A new paper just published in the Journal of Bioethical Inquiry uses extensive Freedom of Information Act findings to detail an extremely troubling off-label medical intervention employed in the U.S. on pregnant women to intentionally engineer the development of their fetuses for sex normalization purposes.

The paper is authored by Alice Dreger, professor of clinical medical humanities and bioethics at Northwestern University Feinberg School of Medicine and is co-authored by Ellen Feder, associate professor of philosophy and religion at American University, and Anne Tamar-Mattis, executive director of Advocates for Informed Choice.

The pregnant women targeted are at risk for having a child born with the condition congenital adrenal hyperplasia (CAH), an endocrinological condition that can result in female fetuses being born with intersex or more male-typical genitals and brains. Women genetically identified as being at risk are given dexamethasone, a synthetic steroid, off-label starting as early as week five of the first trimester to try to “normalize” the development of those fetuses, which are female and CAH-affected. Because the drug must be administered before doctors can know if the fetus is female or CAH-affected, only one in eight of those exposed are the target type of fetus.

The off-label intervention does not prevent CAH; it aims only at sex normalization. Like Diethylstilbestrol (DES) — which is now known to have caused major fertility problems and fatal cancers among those exposed in utero — dexamethasone is a synthetic steroid. Dexamethasone is known — and in this case intended — to cross the placental barrier and change fetal development. Experts estimate the glucocorticoid dose reaching the fetus is 60 to 100 times what the body would normally experience.

The new report provides clear evidence that:

  • For more than 10 years, medical societies repeatedly but ultimately impotently expressed high alarm at use of this off-label intervention outside prospective clinical trials, because it is so high risk and because nearly 90 percent of those exposed cannot benefit. 
  • Mothers offered the intervention have been told it “has been found safe for mother and child” but in fact there has never been any such scientific evidence. 
  • The U.S. Food and Drug Administration has indicated it cannot stop advertising of this off-label use as “safe for mother and child” because the advertising is done by a clinician not affiliated with the drug maker. 
  • A just-out report from Sweden in the Journal of Clinical Endocrinology and Metabolism documents a nearly 20 percent “serious adverse event” rate among the children exposed in utero
  • Clinician proponents of the intervention have been interested in whether the intervention can reduce rates of tomboyism, lesbianism and bisexuality, characteristics they have termed “behavioral masculinization.” 
  • The National Institutes of Health has funded research to see if these attempts to prevent “behavioral masculinization” with prenatal dexamethasone are “successful.” 
  • The United States’ systems designed to prevent another tragedy like DES and thalidomide — involving de facto experimentation on pregnant women and their fetuses — appear to be broken and ineffectual.
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The paper is available for free download at: http://www.springerlink.com/content/m1523l7615744552/?MUD=MP

Contact: Marla Paul
Marla-Paul@northwestern.edu
312-503-8928
Northwestern University

Dangerous caregivers for elderly

Agencies place unqualified, possibly criminal caregivers in homes of vulnerable seniors

CHICAGO — If you hire a caregiver from an agency for an elderly family member, you might assume the person had undergone a thorough criminal background check and drug testing, was experienced and trained for the job.

You’d be wrong in many cases, according to new Northwestern Medicine research.

A troubling new national study finds many agencies recruit random strangers off Craigslist and place them in the homes of vulnerable elderly people with dementia, don’t do national criminal background checks or drug testing, lie about testing the qualifications of caregivers and don’t require any experience or provide real training.

“People have a false sense of security when they hire a caregiver from an agency,” said lead study author Lee Lindquist, M.D., an associate professor of medicine at Northwestern University Feinberg School of Medicine and a physician at Northwestern Memorial Hospital. “There are good agencies out there, but there are plenty of bad ones and consumers need to be aware that they may not be getting the safe, qualified caregiver they expect. It’s dangerous for the elderly patient who may be cognitively impaired.”

(See Lindquist’s “10 Questions to Ask Before Hiring a Caregiver” below.)

The study will be published in the July 13 issue of the Journal of American Geriatrics Society.

Lindquist, a geriatrician, personally has seen a number of bad caregivers accompanying patients in her clinic. “Some of the paid caregivers are so unqualified it’s scary and really puts the senior at risk,” she said.

Lindquist had a 103-year-old patient whose illiterate caregiver was mixing up her own medications and the patient’s medications. The caregiver was giving her own medicines to the elderly patient by mistake. Another patient had dropped 10 percent of her weight and developed pressure ulcers because her caregiver was not properly feeding her or getting her out of bed.

“It was easier for the caregiver to sit and watch TV and not to try to feed the patient or move her,” Lindquist said.

Several agencies surveyed in the study actually made up names of screening tests they claimed to give their job applicants.

“We had agencies say they used a ‘National Scantron Test for Inappropriate Behavior’ and an ‘Assessment of Christian Morality Test’,” Lindquist said. “To our knowledge, these tests don’t exist. If you’re not a smart consumer, you won’t recognize which agencies are being deceitful.”

Identifying the good agencies from the bad is difficult because many agencies have slick websites and marketing campaigns, she added.

“It’s a cauldron of potentially serious problems that could really hurt the senior,” Lindquist said. “These agencies are a largely unregulated industry that is growing rapidly with high need as our population ages. This is big business with potentially large profit margins and lots of people are jumping into it.”

For the study, researchers posed as consumers and surveyed 180 agencies around the country about their hiring methods, screening measures, training practices, skill competencies assessments and supervision. They found:

Only 55 percent of the agencies did a federal background check.

“A number of agencies don’t do a federal background check or look at other states besides their own,” Lindquist said. “Someone could move from Wisconsin to Illinois and could have been convicted of abusing an elder adult or theft or rape and the agency would never know.”

Only one-third of agencies interviewed said they did drug testing.

“Considering that seniors often take pain medications, including narcotics, this is risky,” Lindquist said. “Some of the paid caregivers may be illicit drug users and could easily use or steal the seniors’ drugs to support their own habits.”

Few agencies (only one-third) test for caregiver skill competency. A common method of assessing skill competencies was “client feedback,” which was explained as expecting the senior or family member to alert the agency that their caregiver was doing a skill incorrectly.

“How do you expect a senior with dementia to identify what the caregiver is doing wrong?” Lindquist asked.

Many agencies (58.5 percent) use self-reports in which they ask the caregiver to describe their own skills. “In the hunt for a job, some people may report they can do tasks that in reality they have no idea how to do,” Lindquist said. “We found agencies sending caregivers out into the seniors’ home without checking.”

Inconsistent supervision of the caregiver.

Agencies should send a supervisor to do a home visit to check on the caregivers more frequently initially and then at least once a month. But this only occurred with 30 percent of the agencies.

“Amazingly, some agencies considered supervision to be asking the caregiver how things were going over the phone or when the employee stopped in to get their paycheck,” Lindquist said.

With seniors wishing to remain in their own homes, paid caregivers fill an important role.

“The public should demand higher standards, but in the short term, seniors need to be aware what explicitly to look for when hiring a paid caregiver through an agency,” Lindquist said.

Below are Lindquist’s 10 questions to ask an agency prior to hiring a paid caregiver: