OREGON STATE UNIVERSITY

college of pharmacy

“Antibiogram” use in nursing facilities could help improve antibiotic use, effectiveness

PORTLAND, Ore. – Use of “antibiograms” in skilled nursing facilities could improve antibiotic effectiveness and help address problems with antibiotic resistance that are becoming a national crisis, researchers conclude in a new study.

Antibiograms are tools that aid health care practitioners in prescribing antibiotics in local populations, such as a hospital, nursing home or the community. They are based on information from microbiology laboratory tests and provide information on how likely a certain antibiotic is to effectively treat a particular infection.

The recent research, published by researchers from Oregon State University in Infection Control and Hospital Epidemiology, pointed out that 85 percent of antibiotic prescriptions in the skilled nursing facility residents who were studied were made “empirically,” or without culture data to help determine what drug, if any, would be effective.

Of those prescriptions, 65 percent were found to be inappropriate, in that they were unlikely to effectively treat the target infection.

By contrast, use of antibiograms in one facility improved appropriate prescribing by 40 percent, although due to small sample sizes the improvement was not statistically significant.

“When we’re only prescribing an appropriate antibiotic 35 percent of the time, that’s clearly a problem,” said Jon Furuno, lead author on the study and an associate professor in the Oregon State University/Oregon Health & Science University College of Pharmacy.

“Wider use of antibiograms won’t solve this problem, but in combination with other approaches, such as better dose and therapy monitoring, and limiting use of certain drugs, we should be able to be more effective,” Furuno said.

“And it’s essential we do more to address the issues of antibiotic resistance,” he said. “We’re not keeping up with this problem. Pretty soon, there won’t be anything left in the medical cabinet that works for certain infections.”

In September, President Obama called antibiotic resistant infections “a serious threat to public health and the economy,” and outlined a new national initiative to address the issue. The Centers for Disease Control and Prevention has concluded that the problem is associated with an additional 23,000 deaths and 2 million illnesses each year in the U.S., as well as up to $55 billion in direct health care costs and lost productivity.

Antibiograms may literally be pocket-sized documents that outline which antibiotics in a local setting are most likely to be effective. They are often used in hospitals but less so in other health care settings, researchers say. There are opportunities to increase their use in nursing homes but also in large medical clinics and other local health care facilities for outpatient treatment. The recent study was based on analysis of 839 resident and patient records from skilled nursing and acute care facilities.

“Antibiograms help support appropriate and prudent antibiotic use,” said Jessina McGregor, also an associate  professor in the OSU/OHSU College of Pharmacy, and lead author on another recent publication on evaluating antimicrobial programs.

“Improved antimicrobial prescriptions can help save lives, but they also benefit more than just an individual patient,” McGregor said. “The judicious use of antibiotics helps everyone in a community by slowing the spread of drug-resistant genes. It’s an issue that each person should be aware of and consider.”

Multi-drug resistant organisms, such as methicillin-resistant Staphylococcus aureus, or MRSA, and other bacterial attacks that are being called “superinfections” have become a major issue.

Improved antibiotic treatment using a range of tactics, researchers say, could ultimately reduce morbidity, save money and lives, and improve patients’ quality of life.

The research led by Furuno was supported by the U.S. Department of Health and Human Services. Collaborators include researchers from the University of Maryland School of Medicine, Denver Health and Hospital Authority, University of Colorado Health Sciences Center, and Agency for Healthcare Research and Quality in Maryland.

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Jon Furuno, 503-418-9361

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“Mild” control of systolic blood pressure in older adults is adequate: 150 is good enough

CORVALLIS, Ore. – A broad review of the use of medications to reduce blood pressure has confirmed that “mild” control of systolic pressure is adequate for adults age 65 or older - in the elderly, there’s no clear benefit to more aggressive use of medications to achieve a lower pressure.

Historically, most medical practitioners tried to achieve control of systolic pressure – the higher of the two blood pressure readings – to 140 or less. Recently changed guidelines now suggest that for adults over 60, keeping the systolic pressure at 150 or less is adequate, and this extensive analysis confirms that.

However, researchers also say in the report that more work needs to be done studying blood pressure in older populations, since most of the research, and the medical guidelines based on them, were done using predominately younger adults.

The review was just published in Drugs & Aging, a professional journal, by scientists from the College of Pharmacy at Oregon State University and Oregon Health & Science University.

“The goal of a systolic pressure at or below 140 has been around a long time, and there’s still skepticism among some practitioners about accepting a higher blood pressure,” said Leah Goeres, an OSU postdoctoral fellow and lead author on the publication.

“Keeping systolic blood pressure in older adults below 150 is important, it’s what we consider a mild level of control,” Goeres said. “But for older people that level is also good enough. After an extensive review, there was no significant evidence that more intensive management is necessary.”

The issue about how low is low enough, researchers say, is important because blood pressure medications can have unwanted side effects that increase as higher dosages of medications are used. The problem is common – in the United States, about 70 percent of adults age 65 or older have hypertension, and millions of people take medication to control it.

One of the more significant side effects is what’s called “orthostatic hypotension,” a condition in which a person’s blood pressure can suddenly fall when they rise or stand, making them feel light-headed or dizzy, and sometimes leading to dangerous falls. More than 30 percent of people over the age of 80 have this problem.

High blood pressure is a serious health concern, but also one of the most treatable with medication, if such things as diet, exercise, weight management or lifestyle change prove inadequate.  Hypertension is often called the “silent killer” because it causes few obvious symptoms, but it weakens blood vessels and has been linked to higher levels of heart attacks, kidney disease and especially stroke.

“There’s clearly a value to controlling blood pressure, enough to keep it at 150 or less,” said David Lee, an OSU assistant professor of pharmacy practice. “Keeping blood pressure within acceptable levels will lower death rates. But as people get older, there’s less clear evidence that stringent control of systolic blood pressure is as important.”

The researchers said a goal for the future should be to do more studies specifically with older adult populations and try to identify health situations and conditions that might benefit from different types of management. Such “individualized” treatments, they said, would consider a person’s entire health situation instead of treating them based on findings made with large groups.

In this study, the researchers did not find that one approach or another to lowering blood pressure stood out and was clearly better than other alternatives. A variety of medications can be used to treat the condition.

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David Lee, 503-494-2258

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Oral contraception may become renewed option for HIV-positive women

CORVALLIS, Ore. – Contrary to guidelines issued by the World Health Organization, new research has found that HIV-positive women receiving one of the most common forms of drug therapy should be able to use at least some forms of oral contraceptives for birth control.

The findings, just published in the journal Contraception, may lead to new options of birth control for women with HIV. Further research should be done to confirm that clinical outcomes are consistent with conclusions that have been based on pharmacokinetic analysis, scientists said.

Worldwide, the leading cause of death among women ages 18-45 is HIV/AIDS, and prevention of mother-to-child transmission of HIV by reducing unintended pregnancy is a United Nations millennium goal for 2010-15. This research, and broad access to oral contraception, could help reach that goal.

The research was done by scientists from the Oregon State University/Oregon Health & Science University College of Pharmacy, the Albert Einstein College of Medicine and the University of Southern California.

Although millions of women around the world routinely use oral contraception, it has been largely avoided by those with HIV infections because some of the drugs commonly used to control HIV are believed to reduce the effectiveness of birth control pills.

Because of that, both the World Health Organization and Centers for Disease Control have suggested that oral contraceptives should not be used by HIV-positive women if other methods of birth control are available – such as barrier devices, IUDs or other approaches.

The new study, however, raises doubts about such a broad guideline against oral contraception. It found that while some types of oral contraceptives may be subject to this concern, others that are highly efficacious should be even more effective when particular HIV drugs are used.

“Oral contraception is used by millions of women and is among the most popular forms of birth control,” said Ganesh Cherala, an OSU assistant professor of pharmacy practice, a corresponding author on the study. Cherala is an expert in pharmacokinetics, or how drugs behave, interact and are transformed in the body.

“It’s important for women to have access to – and the ability to choose from – as wide a range of birth control options as possible,” Cherala said. “We believe this research shows the WHO guidelines are too generic and unnecessarily cautious. There clearly appear to be oral contraceptives that should be safe and effective in women being treated with HIV medications.”

In general, there are two types of oral contraceptives: “combination” drugs that include both estrogen and progestin, and drugs that are based solely on progestin for their efficacy. The concerns raised about reduced efficacy were based primarily on studies of the combination oral contraceptives, and may be valid for that group of drugs, Cherala said.

However, the new study found that progestin-only contraceptives based on at least one progestin, norethindrone, should actually have a slightly higher level of birth control efficacy, not a reduced one, when a women is taking one of the primary therapies for HIV, called a ritonavir-boosted atazanavir antiretroviral therapy.

Other progestin-only birth control drugs may also have the same properties as the ones based on norethindrone, but that has not yet been conclusively demonstrated, Cherala said. 

The research was done with both treatment and control groups of women who were HIV-positive, ages 18-44, with no other recent use of hormonal contraception.

“These findings are interesting and exciting,” Cherala said. “They should ultimately give women more options to consider for birth control.”

Historically, some of the progestin-only oral contraceptives had unwanted side effects more than the combination contraceptives, Cherala said. However, those differences are now very small as improved forms of progestin-only contraceptives have come to market.

This research was supported by the National Institutes of Health.

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Ganesh Cherala, 503-418-0447

Report urges individualized, cholesterol-targeted approach to heart disease and stroke

PORTLAND, Ore. – A recent guideline for using statins to reduce atherosclerotic cardiovascular disease has wavered too far from the simple cholesterol goals that have saved thousands of lives in the past decade, and doesn’t adequately treat patients as individuals, experts said today in a national report.

An expert panel coordinated by the National Lipid Association has created its own outline for how to best treat people at risk for cardiovascular disease, which they say focuses on reducing cholesterol to an appropriate level, and puts less emphasis on whether or not a patient fits into a certain type of group.

“We continue to believe in cholesterol targets that are easy for patients to understand and work toward, first using changes in lifestyle and then medication if necessary,” said Matt Ito, one of two lead authors on the report, an expert in cardiovascular drug treatments and a professor in the Oregon State University/Oregon Health & Science University College of Pharmacy.

“We’re also concerned about treating people just because they fall into a group that’s supposedly at risk,” Ito said. “There are ways to more accurately treat patients as individuals and understand their complete health profile. And we have a better understanding now of what conditions pose the most risk for causing a heart attack or stroke, and how to address that in a comprehensive manner.”

A report issued last year by the American College of Cardiology and American Heart Association identified four general groups that would primarily benefit from statins, and its recommendations if followed will dramatically increase the number of people using these drugs.

By contrast, the new report from the National Lipid Association has outlined what their experts believe to be a more individualized set of recommendations that practitioners could use to treat people at risk of cardiovascular disease; more information is available online at www.lipid.org/recommendations. They are intended to complement the guidelines issued by the American College of Cardiology and the American Heart Association, Ito said.

Among the conclusions in the report:

  • A root cause of atherosclerotic cardiovascular disease is cholesterol-containing particles attaching to the walls of arteries.
  • A healthy lifestyle that incorporates diet, weight management and exercise should be the first approach to lowering cholesterol levels that are too high.
  • Control and reduction of LDL, or “bad” cholesterol is important, but an even better overall marker of risk is “non-HDL cholesterol,” which is total cholesterol minus its HDL component.
  • Patients at very high risk, such as those who have already had a cardiac event, should try to achieve non-HDL cholesterol levels below 100, while those at lower risk levels should try to achieve levels below 130.
  • Drug therapies specifically aimed at lowering triglyceride levels may not be necessary unless they are very high, over 500; and efforts to specifically raise HDL levels have been shown to be both less important and less achievable.
  • Use of more potent statin drugs, at moderate to high doses if necessary, should be the first approach to reach cholesterol goals if lifestyle changes have not been adequate.
  • Use of other medications or therapies, such as fibrates, cholesterol absorption inhibitors, niacin or omega-3 fatty acids can be considered if cholesterol and triglyceride goals are not reached with statins alone.
  • Non-lipid risk factors should also be managed, such as high blood pressure, cigarette smoking and diabetes.

“Cholesterol is still a primary factor in atherosclerotic cardiovascular disease,” Ito said. “If it’s too high, the levels should be brought down by changes in lifestyle and medication if necessary. And in general, the lower the cholesterol, the better.”

Statins have proven themselves as one of the most effective way to reduce cholesterol, Ito said, and are now comparatively inexpensive with limited side effects. Proper medication management and reducing the potential for drug interactions can address some types of side effects, and any problems should be weighed against the risk of heart attack or stroke, he said.

Factors known to raise the risk of atherosclerotic cardiovascular disease include age, family history, smoking, high blood pressure, overweight, diabetes, and high cholesterol levels, especially those caused by genetics.

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Matthew Ito, 503-494-3657

Strategies identified to improve oral contraceptive success with obese women

PORTLAND, Ore. – The findings of a new study suggest two ways to effectively address the problem that birth control pills may not work as well in obese women, compared to women of a normal body mass index.

Birth control pills are a one-size-fits-all method, researchers say, but as the population has increased in weight, concern has grown about how well the pill works for obese women. Studies have consistently found that obesity has a negative impact on drug levels in the body, which may in turn affect how well the pill prevents pregnancy. 

“Birth control pills have been shown in a large population study to fail at a higher rate in women who are obese,” said Ganesh Cherala, an assistant professor in the Oregon State University/Oregon Health & Science University College of Pharmacy.

“Our original studies were focused on why this might occur,” Cherala said, “and we found that obesity changes how a woman’s body clears contraceptive hormones.”

It takes longer for the pill to reach a steady state level in obese women, with possible impacts on efficacy of the birth control, and putting them at greater risk for a pill failure if they forget to take a pill or take it later.

In order to offset these changes, Cherala and Dr. Alison Edelman, an associate professor of obstetrics and gynecology at Oregon Health & Science University, studied two alternative strategies. They found that either a slight increase in the pill dose, from a very low dose to a low dose pill; or using the pill continuously without a “period week” off, appeared to counteract the changes that obesity causes.

This, in turn, may provide improved pregnancy prevention for women of differing weights who use the pill, the researchers said. Their work is published in Contraception, a professional journal, and was supported by the National Institutes of Health.

“Since oral contraception remains one of the most popular forms of birth control in the United States and the majority of our population is obese or overweight, it’s important to find methods of contraception that work for all women, no matter what their weight,” Edelman said.

“The strategies that we studied can be, and are currently being used by women, but now we know that they help to counteract the adverse effects of weight on contraceptive hormones,” she said.

For obese women, simply shifting to an alternative form of birth control is an option, the researchers said. But they also pointed out that oral contraceptives are the most preferred form of birth control and that a woman’s individual preference influences her adherence and continuation with any method.

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Ganesh Cherala, 503-418-0447

Antibiotic use prevalent in hospice patients despite limited evidence of its value

CORVALLIS, Ore. – New research suggests that use of antibiotics is still prevalent among terminal patients who have chosen hospice care as an end-of-life option, despite little evidence that the medications improve symptoms or quality of life, and sometimes may cause unwanted side effects.

The use of antibiotics is so engrained in contemporary medicine that 21 percent of patients being discharged from hospitals directly to a hospice program leave with a prescription for antibiotics, even though more than one fourth of them don’t have a documented infection during their hospital admission.

About 27 percent of hospice patients are still taking antibiotics in the final week of their life.

This raises serious questions about whether such broad and continued antibiotic use is appropriate in so many hospice cases, experts say, where the underlying concept is to control pain and protect the remaining quality of life without aggressively continuing medical treatment.

Additional concerns with antibiotic use, the study concluded, include medication side effects and adverse events, increased risk of subsequent opportunistic infections, prolonging the dying process and increasing the risk of developing antibiotic resistant microorganisms.

The findings were just published in Antimicrobial Agents and Chemotherapy by researchers from Oregon State University and the Oregon Health & Science University. It was supported by the National Institutes of Health.

“Hospice care is very patient centered and in terminal patients it focuses on palliative care and symptom relief, not curative therapy,” said Jon Furuno, an associate professor in the Oregon State University/Oregon Health & Science University College of Pharmacy.

“It’s not for everyone, and it’s a serious decision people usually make in consultation with their family, nurses and doctors. These are tough conversations to have.

“Having decided to use hospice, however, the frequency and prevalence of antibiotic use in this patient population is a concern,” Furuno said. “Antibiotics themselves can have serious side effects that sometimes cause new problems, a factor that often isn’t adequately considered. And in terminally-ill people they may or may not work anyway.”

Issues such as this, Furuno said, continue to crop up in the evolving issue of hospice care, which is still growing in popularity as many people choose to naturally allow their life to end with limited medical treatment and often in their own homes. Hospice is covered by Medicare for people with a life expectancy of less than six months, helps to control medical costs and reduce hospital stays, and its services are now used by more than one third of dying Americans.

Unnecessary and inappropriate antibiotic use is already a concern across all segments of society, researchers said in the report, and more efforts are clearly needed to address the issue in hospice patients. The design of the study probably leads to it underestimating the significance of the problem, the researchers wrote in their conclusion.

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Jon Furuno, 503-418-9361

Research may yield new ways to treat antibiotic-resistant TB

CORVALLIS, Ore. – Scientists in the United States and India have successfully modified the precursor to one of the drugs used to treat tuberculosis, an important first step toward new drugs that can transcend antibiotic resistance issues that experts consider a serious threat to global health.

The findings, reported in the Journal of Biological Chemistry, indicate that a new compound, 24-desmethylrifampicin, has much better antibacterial activity than rifampicin against multi-drug-resistant strains of the bacteria that cause tuberculosis.

Rifampicin and related drugs are important antibiotics, the key to an effective “drug cocktail” that already takes about six months of treatment to cure tuberculosis, even if everything goes well. But two forms of tuberculosis, referred to as “multi-drug-resistant,” or MDR, and “extensively drug-resistant,” or XDR, have become resistant to rifampicin.

In 1993, resurging levels of tuberculosis due to this antibiotic resistance led the World Health Organization to declare it a global health emergency. Today more than 1 million people around the world are dying each year from tuberculosis, and after AIDS it remains the second most common cause of death by infectious disease.

“We believe these findings are an important new avenue toward treatment of multi-drug-resistant TB,” said Taifo Mahmud, a professor in the College of Pharmacy at Oregon State University, and a corresponding author on the new publication.

“Rifampicin is the most effective drug against tuberculosis, and it’s very difficult to achieve a cure without it,” Mahmud said. “The approach we’re using should be able to create one or more analogs that could help take the place of rifampicin in TB therapy.”

A combination of genetic modification and synthetic drug development was used to create the new compound, which so far has only been developed in laboratory, not commercial quantities. Further development and testing will be necessary before it is ready for human use, researchers said.

Drug resistance in rifampicin and related antibiotics has occurred when their bacterial RNA polymerase enzymes mutate, Mahmud said, leaving them largely unaffected by antibiotics that work by inhibiting RNA synthesis. The new approach works by modifying the drug so it can effectively bind to this mutated enzyme and once again achieve its effectiveness.

“We found out how the antibiotic-producing bacteria make this compound, and then genetically modified that system to remove one part of the backbone of the molecule,” Mahmud said. “Understanding this whole process should allow us to create not just this one, but a range of different analogs that can be tested for their efficacy as new antibiotics.”

In human history and before the advent of antibiotics, tuberculosis was one of the great infectious disease killers in the world. At its peak in the 1800s in Europe, it was the cause of death of one in four people. It’s still a major concern in the developing world, where drugs are often not available to treat it, and it often causes death in tandem with HIV infection.

As the bacterial strains of this disease that are multi- or extensively-drug-resistant increase in number, so too does the difficulty of treating it. Instead of a six-month regimen, these drug-resistant strains can take 18 months to several years to treat, with antibiotics that are more toxic and less effective.

Collaborators on this research were from the University of Delhi and the Institute of Genomics and Integrative Biology in India. The research has been supported by the M.J. Murdock Charitable Trust and the Medical Research Foundation of Oregon.

The approach used in this research “holds great potential to generate more rifamycin analogs to combat the threat of MDR strains of M. tuberculosis, and/or other life-threatening pathogens,” the researchers wrote in their conclusion.

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Taifo Mahmud, 541-737-9679

Statin use associated with less physical activity

CORVALLIS, Ore. – One of the longest studies of its type has found that use of statins in older men is associated with less physical activity, a significant issue for a population that’s already sedentary.

The findings, published today in JAMA Internal Medicine, raise concerns about a decline in much-needed physical activity among men who take some of the most widely prescribed medications in the world. Almost one-third of older Americans take statins, usually to reduce their cholesterol levels.

The research did not identify why men who took statins exercised less – it just confirmed that they did. Possible causes include the muscle pain that can be a side effect of statin use, and also disruption of the mitochondrial function in cells, which could contribute to fatigue and muscle weakness.

Physical activity in older adults helps to maintain a proper weight, prevent cardiovascular disease and helps to maintain physical strength and function,” said David Lee, an assistant professor in the Oregon State University/Oregon Health & Science University College of Pharmacy, and lead author of the study.

“We’re trying to find ways to get older adults to exercise more, not less,” Lee said. “It’s a fairly serious concern if use of statins is doing something that makes people less likely to exercise.”

Muscle pain is found in 5-30 percent of people who take statins, Lee said, and some people also report feeling less energetic, weak or tired.

In an analysis of 3,071 community-living men, age 65 or older, from six geographic regions in the United States, researchers found that men who took statins averaged about 40 minutes less of moderate physical activity over a one-week period, compared to those who weren’t taking the medication.

That would equate to the loss of 150 minutes a week of slow-paced walking, Lee said.

“For an older population that’s already pretty sedentary, that’s a significant amount less exercise,” he said. “Even moderate amounts of exercise can make a big difference.”

Of some significance, the study also found that new statin users had the largest drop in physical activity. An increase in sedentary behavior, which is associated with all-cause mortality and also death from cardiovascular disease, was also observed in statin users.

Some previous studies with older adults and statins had found similar results, but those analyses were short-term. This research followed men for almost seven years after initial baseline studies were done, and compared changes in physical activity among users and non-users of statins. In parts of the experiments, men wore accelerometers for a week to track by the minute their level of activity.

“Given these results, we should be aware of a possible decrease in physical activity among people taking a statin,” Lee said.

“This could decrease the benefit of the medication,” he said. “If someone is already weak, frail, or sedentary, they may want to consider this issue, and consult with their doctor to determine if statin use is still appropriate.”

This study was done with older men, and generalization of the findings to older women may not be appropriate, the researchers noted in their study.

The research was done by scientists from OSU; the Oregon Health & Science University; the Department of Veterans Affairs Medical Center in Portland, Ore.; the California Pacific Medical Center Research Institute in San Francisco; the Stanford Prevention Research Center; and the Department of Medicine at the University of California.

The study was supported by the National Institutes of Health and the Medical Research Foundation of Oregon.

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David Lee, 503-494-2258

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Extended-release medication offers promise for alcohol, opioid dependence

The study this story is based on is available online: http://bit.ly/1i9n2tD

 

PORTLAND, Ore. – A comparatively new form of a medication for alcohol and opioid dependence that’s injected once a month instead of taken orally once a day appears to be significantly more effective than some other medications – because more patients actually continue the prescribed regimen.

The findings, published in the Journal of Substance Abuse Treatment by researchers from Oregon State University and other institutions, offer support for a wider use of medications that may help reduce or prevent substance abuse and related hospital admissions.

The cost savings could offset the cost of the medication, researchers said.

In the past, there has been fairly low use of medications to treat alcohol and opioid dependence. Several treatment options are available, with differing mechanisms of action, and they generally work to reduce the pleasurable feelings associated with drug and alcohol use, thereby discouraging the use of them.

The medication in the study that was found to be more effective than some past approaches was extended-release Naltrexone, which is administered once a month by injection in a medical setting. The research was supported by Alkermes, Inc., the manufacturer of that medication.

“Some of these medications are opioid antagonists, which reduce the euphoric effects of alcohol and some drugs,” said Dan Hartung, an associate professor in the Oregon State University/Oregon Health & Science University College of Pharmacy, and lead author on the study.

“Historically, oral medications for substance abuse have not often been prescribed or found to have a high degree of success, mostly because patients stopped taking them,” Hartung said. “But there are patients who are committed to treating their problems and data showed that they clearly appear to have success with extended-release Naltrexone, which is administered just once a month.”

The issue may be of increased importance, experts said, because of health and prescription drug coverage that is now being made available through the Affordable Care Act. It may make such medications available to many people who previously did not have access to them, and in the process achieve some goals of reducing hospital admissions.

The new meta-analysis combined findings from five other papers, comprising a total of 1,565 patients who received extended-release Naltrexone compared to other therapies for six months, among nearly 60,000 overall patients – the only comprehensive analysis of its type that has been completed.

It found that even though extended-release Naltrexone is expensive – about $1,100 a month – the total health care utilization and costs were generally lower for patients taking it, compared to those using other alcohol-dependence treatments.

They found that significant savings were produced by fewer days of detoxification facility use and inpatient utilization.

Alcohol and drug use disorders affect more than 21 million Americans, the researchers noted in their study – or about 8 percent of the nation’s population. Research in New York found that substance abuse more than doubled the number of preventable hospital re-admissions. But despite this, treatment of alcohol dependence with medications ranks the lowest among 25 health and behavioral conditions.

“There has always been some reluctance on the part of health care practitioners, as well as the patients they are treating, to use prescription medication to treat a substance abuse problem,” Hartung said.  “Medication-assisted therapy is underutilized. With more people having access to these medications, now would be a good time to do further research on the comparative efficacy and use of them.”

Although most studies of extended-release Naltrexone have been six months in duration, longer-term data suggest effectiveness is maintained for longer durations of therapy. Very limited research has been done comparing the efficacy of various drugs for these purposes.

Nationally, even at addiction treatment centers, only 24 percent used pharmacotherapy for alcohol dependence and 34 percent for opioid dependence. Barriers to use include financing, concerns about cost, medical staffing, education and attitudes.

“Given rising pressures to reduce potentially preventable hospital readmissions and other reducible cost and morbidity causes,” the researchers wrote in their conclusion, “the optimization of patient care and management of resources warrant systemic change in the delivery of addiction treatment, in the advancing era of health care reform.”

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Dan Hartung, 503-494-4720

Exact outline of melanoma could lead to new diagnostic tools, therapies

CORVALLIS, Ore. – Researchers at Oregon State University have identified a specific biochemical process that can cause normal and healthy skin cells to transform into cancerous melanoma cells, which should help predict melanoma vulnerability and could also lead to future therapies.

More than 70,000 cases of melanoma, the deadliest form of skin cancer, develop in the U.S. every year.

The work was published today in PLoS Genetics, in work supported by the National Institutes of Health.

“We believe this is a breakthrough in understanding exactly what leads to cancer formation in melanoma,” said Arup Indra, an associate professor in the Oregon State University/Oregon Health & Science University College of Pharmacy. “We’ve found that some of the mechanisms which ordinarily prevent cancer are being switched around and actually help promote it.

“In melanoma, the immune system is getting thrown into reverse,” he said. “Immune cells that previously were attracted to help deal with a problem are instead repulsed.”

The key to this process, the researchers said, is a protein called retinoid-X-receptor, or RXR. When present in an adequate amount, the RXR protein aids the proper operation of the immune response in the skin. Primary players in this are skin cells called melanocytes, which produce protective pigments, or melanin, in response to exposure to ultraviolet radiation in sunlight – in simple terms, a suntan.

Even with this protection, however, both melanocytes and other skin cells called keratinocytes routinely suffer genetic damage. Sometimes the damage can be repaired, and at other times the immune response – in the presence of adequate levels of RXR in the melanocytes – will kill the defective skin cells before they become malignant.

When expressed levels of RXR are too low in the melanocytes, however, this protective process breaks down. The chemicals that can help control mutated cells are actually suppressed, and the conditions for cancer promoted. DNA-mutated melanocytes begin to thrive at the same time other skin cells die and free up space for the growing, mutating melanocytes. The ultimate result can be the malignancy known as melanoma, which in turn can spread from the skin throughout the body.

“When there isn’t enough RXR, the melanocytes that exist to help shield against cancer ultimately become part of the problem,” Indra said. “It’s routine to have genetic damage from sunlight, because normally those cells can be repaired or killed if necessary. It’s the breakdown of these control processes that result in cancer, and that happens when RXR levels get too low.”

This process has not before been outlined in its entirety, Indra said, and the new findings open several possibilities. One would be a diagnostic test to determine when RXR levels are lower than they should be – which would set the stage for melanoma and possibly other cancers, but also with careful monitoring facilitate earlier diagnosis.

Beyond that, mechanisms may be developed to stabilize or stimulate the levels of RXR expression, and form the basis for a therapy. This might be done through diet or a “nanocarrier” drug that could deliver RXR to cells, Indra said.

“It’s quite possible that a new and effective therapy can now be developed, based on increasing levels of RXR,” Indra said.

Researchers in France and at the Knight Cancer Institute of the Oregon Health & Science University in Portland, Ore., contributed to this research.

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Arup Indra, 541-737-5775

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