Medical Research News

Researchers from Boston University’s Slone Epidemiology Center have found that in a given week, over 10 million Americans are taking opioids, and more than 4 million are taking them regularly (at least five days per week, for at least four weeks). These findings appear in the August 31 issue of the journal Pain.

Opioids are commonly administered for the treatment of moderate to severe pain and are among the most widely prescribed drugs in the United States. While these drugs have an essential role in pain management, there are concerns about potential abuse. Despite these concerns, characteristics of opioid use within the non-institutionalized US population are not well known, particularly for recent years.

The researchers conducted a telephone survey of randomly selected U.S. households; there were 19,150 subjects aged 18 years or older interviewed from February 1998 through September 2007. Information was gathered on all prescription and non-prescription medications taken during the preceding seven days. For each recorded medication, information was obtained on reason for use, type of administration, number of days taken in the week before the interview, and total duration of the current use.

The researchers found opioids were used ‘regularly’ by 2 percent of those surveyed. An additional 2.9 percent used opioids less frequently. Regular opioid use increased with age, decreased with education level, and was more common in females and in non-Hispanic whites. The prevalence of regular opioid use increased over time and was highest in the South Central region of the country. Among regular users, almost half had been taking opioids for two or more years and nearly one-fifth had been taking opioids for five years or longer. There was also a much higher prevalence of other medication use among regular opioid users compared to nonusers.

According to the researchers, given the large number of individuals affected, the recent increase in public health concern for safe and effective pain management is appropriate. “From this nationally representative telephone survey, we estimate that more than 4.3 million U.S. adults are taking opioids regularly in any given week,” said lead author Judith Parsells Kelly of the Slone Epidemiology Center. “The extent and characteristics of opioid use among U.S. adults reflected in this study reinforces the need to strike a rational balance between opioid misuse and effective control of chronic pain,” she added.

http://www.bu.edu/

Medical Research News

Patients discontinuing statin medication following an acute myocardial infarction (AMI) increase their risk of dying over the next year, say researchers at McGill University and the McGill University Health Centre (MUHC). Their study was published in a recent issue of the European Heart Journal.

Using data on British patients who survived an AMI and were still alive three months later, Dr. Stella Daskalopoulou and colleagues found that those who discontinued their statin medication were 88% more likely to die during the following year compared to those who had never been on the medication.

“Statins were found to be beneficial drugs,” said Dr. Daskalopoulou, of McGill’s Faculty of Medicine and the Department of Medicine and the Division of Clinical Epidemiology at the MUHC. “Patients who used statins before an AMI and continued to take them after were 16% less likely to die over the next year than those who never used them. So even if it appears that the statins failed to prevent your AMI, it is beneficial to continue taking them and potentially quite harmful to stop.”

The large, population-based cohort study was conducted using UK data to take advantage of the medical records kept in the General Practice Research Database (GPRD), which collects information on the health of more than three million patients across the UK.

“In the general population the statin discontinuation rate within the first year of prescription is 30 percent. That’s very high,” Dr. Daskalopoulou continued. “Because statins are preventative drugs, patients may not feel the immediate benefit of taking them and sometimes stop. However, it looks like this might be quite a dangerous practice after an AMI.”

The harmful effects of statin discontinuation may be the result of many different mechanisms, including individual patient characteristics, the researchers explained. “Regardless of the mechanism or explanation, physicians should be careful when assessing each patient’s medication needs,” Dr. Daskalopoulou said. “Patients also need to take their medications exactly as prescribed after an AMI. Statins in particular should only be withdrawn after an AMI under close clinical supervision.”

http://www.mcgill.ca/

Medical Research News

Finnish scientists have identified genes that may predispose to anxiety disorders. Research conducted under the supervision of Academy Research Fellow Iiris Hovatta have focused on genes that influence human behaviour, and some of the studied genes show a statistical association with specific anxiety disorders. The work is carried out as part of the Academy of Finland Research Programme on Neuroscience (NEURO).

Previously Hovatta’s team have explored the genetic background of anxiety in experimental models. The current study follows up on these findings in humans using data collected as part of national Health 2000 Survey consisting of 321 individuals who had been diagnosed with anxiety disorder and 653 healthy controls. Hovatta says it was interesting that different genes showed evidence for association to specific types of anxiety disorders, such as panic disorder, social phobias or generalised anxiety disorder. The results will be published in Biological Psychiatry in October.

“Environmental factors, such as stressful life events, may trigger an anxiety disorder more easily in people who have a genetic predisposition to the illness,” Iiris Hovatta says. The focus in the team’s further studies will be to understand the molecular and cellular processes that link these genes to the regulation of anxiety behaviour.

Furthermore, the team’s international collaborators in Spain and the United States are trying to replicate these findings in their anxiety disorder datasets to see whether the genes identified by Finnish scientists predispose to anxiety disorders in other populations as well. Only by replicating the results firm conclusions can be drawn about the role of these genes in the predisposition to anxiety in more general.

A closer understanding of the genetics and neurobiology of anxiety disorders is expected to help improve treatment of the illness using both drugs and therapy-based approaches. For the time being, no targeted drugs are available for the treatment of anxiety disorders. Some patients with anxiety disorders do benefit from the currently used medication, but about half of the patients do not.

http://www.aka.fi/eng

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Alternative medicine is in the news again with scientists in the U.S. saying they have found high levels of toxic metals in popular herbal medicines sold online.

The scientists at Boston University School of Medicine (BUSM) ordered Ayurvedic medicines from 25 web sites and tested them for metallic poisons.

The Ayurvedic medicines were manufactured in both the U.S. and India and the researchers found that one fifth of them contained lead, mercury or arsenic.

Ayurveda is an ancient form of medicine that originated in India more than 2,000 years ago and includes herbal medicines, meditation, exercise and dietary guidelines.

It is practiced by millions on the Indian subcontinent by an estimated 80 percent of the population and increasingly in the West.

Ayurvedic remedies are available from South Asian markets, health food stores, and on the Internet and are divided into two major types: herbal only and Rasa Shastra.

Rasa shastra is an ancient practice of deliberately combining herbs with metals, minerals and gems and Ayurvedic experts believe that if Rasa Shastra medicines made with metals such as lead and mercury are properly prepared and administered, they are safe and therapeutic.

An Internet search found 673 Ayurvedic medicines, and 193 products made by 37 different manufacturers, were randomly selected and purchased.

The researchers found that overall, more than 20% of Ayurvedic medicines contained detectable lead, mercury and/or arsenic and American and Indian manufactured products were equally likely to contain toxic metals.

Rasa shastra compared with non-rasa shastra medicines were more than twice as likely to contain metals and had higher concentrations of lead and mercury.

Among products containing metals, 95 percent were sold by U.S. web sites and 75 percent claimed Good Manufacturing Practices or testing for heavy metals but all the products containing metal, exceeded one or more standards for acceptable daily intake of toxic metals.

Lead author Dr. Robert Saper, says the study highlights the need for the way dietary supplements are regulated in the U.S.to be re-examined.

Research by Dr. Saper first revealed that some Ayurvedic medicines produced in South Asia contained potentially harmful levels of toxins in 2004 and he says that herbs and supplements with high levels of lead, mercury, and arsenic should not be available for sale on the Internet or elsewhere.

The researchers say all dietary supplements should undergo mandatory testing for daily dose limits for toxic metals and all manufacturers should demonstrate their compliance through independent third-party testing.

The researchers say medicines which are supposed to cure sickness should not promote another illness due to the presence of toxic materials such as lead.

The research appears in the August 27th issue of the Journal of the American Medical Association.

Medical Research News

Most people would agree that stress increases your risk for illness and this is particularly true for severe long-term stresses, such as caring for a family member with a chronic medical illness. However, we still have a relatively limited understanding of exactly how stress contributes to the risk for illness. In the August 15th issue of Biological Psychiatry, researchers shed new light on one link between stress and illness by describing a mechanism through which stress alters immune function.

In a very promising preliminary study, Miller and colleagues found that the pattern of gene expression differed between caregivers of family members with cancer relative to a matched group of individuals who did not have this type of life stress. They found that among the caregivers, even though they had normal cortisol levels in their blood, the pattern of gene expression in the monocytes, a type of white blood cell involved in the body’s immune response, was altered so that they were relatively less responsive to the anti-inflammatory actions of cortisol, but relatively more responsive to pro-inflammatory actions of a transcription factor called nuclear factor-kappa B, or NF-? Gregory Miller, Ph.D., corresponding author, explains more simply that, although “caregivers have similar cortisol levels as controls, their cells seem to be ‘hearing’ less of this signal. In other words, something goes awry in caregivers’ white blood cells so they are not able to ‘receive’ the signal from cortisol that tells them to shut down inflammation.”

Thus, the current findings might help to explain why the caregivers would seem to be in a chronic pro-inflammatory state, a condition of immunologic activation. This activated state could contribute to the risk for a number of medical illnesses, such as depression, heart disease, and diabetes. Dr. Miller remarks that part of the importance of these findings is “because people have traditionally thought that higher cortisol is the reason that stress contributes to disease, but this work shows that, at least in caregivers, it’s actually the opposite - there’s too little cortisol signal being heard by the cells, rather than too much.”

However, many important related questions still remain unanswered, as noted by John H. Krystal, M.D., Editor of Biological Psychiatry and affiliated with both Yale University School of Medicine and the VA Connecticut Healthcare System. He comments that in addition to not knowing how stress produces these altered patterns of gene expression in the immune system, “we don’t know how to account for the resilience of some stressed people exposed to severe sustained stress or the vulnerability of some people to relatively mild stress.” He adds that “the better that we understand the underlying molecular mechanisms that link stress to illness, the more likely we are to make progress in answering these important questions,” and this article is certainly a vital step in that direction. adequately to our available treatments.”

http://www.elsevier.com/locate/biopsychiat

Medical Research News

The news about antidepressant medications over the past several years has been mixed. The bad news from large multicenter studies such as STAR*D is that current antidepressant medications are effective, but not as effective as one might hope. Thus, there is a significant need for new treatment mechanisms for depression. On that front, there has been mixed news as well.

One of the most exciting new drugs to reach human clinical trials, one that blocks the corticotrophin releasing factor-1 (CRF1) receptor, did not work in a large clinical trial sponsored by Pfizer Pharmaceuticals. Is it time to abandon CRF1 antagonists as antidepressants or should we revisit these agents from a new perspective? It is in this context that a new paper by Alexandre Surget and colleagues, scheduled for publication in the August 15th issue of Biological Psychiatry, is particularly interesting.

Through prior work, it has been shown that the ability to reverse the stress-related disruption of hippocampal neurogenesis, the ability of the brain to make new nerve cells in adulthood, was important to the actions of our available antidepressant medications. In this new study, the researchers affirm the prior findings, but suggest that two experimental approaches to the treatment of depression, blockade of the CRF1 receptor or the vasopressin-1B (V1B) receptor, retain their efficacy in reversing the impact of stress on behavior even when neurogenesis is disrupted. Catherine Belzung, Ph.D., corresponding author on this article, further explains that “we now report evidence that restoration of the functioning of the stress axis may be the key to how these new antidepressant approaches might work.”

How can one reconcile these interesting research findings in animals with the lack of antidepressant efficacy of a CRF1 receptor antagonist in the Pfizer study? Is this approach simply ineffective in humans or might there be subgroups of patients who might be more likely to respond to a CRF1 antagonist? The Surget et al. data raise the possibility that CRF1 receptor antagonists might be effective in treating stress-related behavioral disturbances even in a context where other antidepressants do not work, perhaps due to disruption of neurogenesis. John H. Krystal, M.D., Editor of Biological Psychiatry and affiliated with both Yale University School of Medicine and the VA Connecticut Healthcare System, comments: “These findings lend weight to the hope that CRF1 antagonists might play a role in the treatment of antidepressant-resistant symptoms of depression or posttraumatic stress disorder. If so, CRF1 antagonists could fulfill an important unmet need.” He adds that “we do not need another Prozac, but we urgently need to find ways to help the large number of patients who fail to respond adequately to our available treatments.”

http://www.elsevier.com/locate/biopsychiat

Medical Research News

A large international survey for the International Union Against Cancer (UICC) has revealed that many people have misconceptions about what causes cancer.

The survey involving 29,925 people from 29 countries, has found that many people have in their minds an exaggerated idea of the threat from environmental factors that have relatively little impact and minimize the hazards of behaviours which are well established as cancer risk factors.

The survey has identified important areas where misconceptions can be addressed and lives saved, and is the first study to provide internationally comparable data on perceptions about cancer risk factors between high, middle and low income countries.

The survey found that people in high-income countries were the least likely to believe that drinking alcohol was a greater risk factor for cancer than not eating enough fruits and vegetables, even though the scientific evidence for the protective effect of fruit and vegetables is weaker than the evidence that alcohol intake is harmful.

Those in rich countries also rated stress and air pollution as higher perceived risk factors for cancer than alcohol intake, even though stress is not recognized as a cause of cancer and air pollution is a minor contributor compared with alcohol consumption.

In low and middle-income countries it appears people have more pessimistic beliefs about cancer treatment than those in high-income countries and many believe cancer to be incurable.

This is a concern say the researchers because it could deter people from participating in cancer screening programmes which save lives.

Most people it seems, accept more readily that things outside of their control might cause cancer such as air pollution, than things that are within their own control such as overweight, which is a well-established cancer risk factor.

In low income countries a surprising number prefer their doctor to make all the treatment decisions, very few in fact favoured joint decisions being made between doctor and patient and even fewer thought the patient should decide.

In richer countries a more equitable decision-making style is favoured where the decision is made together with the doctor or rests with the patient alone.

Dr. David Hill, President-Elect of UICC and director of the Cancer Council Victoria in Melbourne, Australia, whose team analyzed the survey data, says the survey reveals there are some unheard messages.

Dr. Hill says governments around the world now have sound information to support the development of education campaigns to address these beliefs and change them to save lives and the data will help to quantify the differences between countries and also highlight where additional efforts are needed.

He says people need to be given a reason why they should change, shown how to change and be given the resources and support to make that change.

Dr. Hill says the UICC will use the data to promote a worldwide agenda to ensure people have more accurate knowledge of cancer as a basis for making cancer control programmes as effective as they can be.

High-income countries in the survey included Australia, Austria, Canada, Czech Republic, Greece, Israel, New Zealand, Spain, UK, and the USA.

Middle income countries included Bolivia, China, Dominican Republic, Georgia, Guatemala, Indonesia, Lebanon, Mexico, Panama, Peru, Philippines, Romania, Serbia, Turkey, Ukraine, Venezuela, Uruguay and low-income countries included Kenya and Nigeria.

The UICC is the only global non-governmental organization devoted exclusively to cancer prevention, treatment and care, with members in 100 countries.

The survey was conducted for the UICC by Roy Morgan Research and Gallup International.

Medical Research News

Scientists at the Stanford University School of Medicine are shedding light on how type-1 diabetes begins.

Doctors have known the disease is caused by an autoimmune attack on the pancreas, but the exact trigger of the attack has been unclear. Now, a new study in mice implicates the immune signal interferon-alpha as an early culprit in a chain of events that upend sugar metabolism and make patients dependent on lifelong insulin injections.

“We never considered that interferon-alpha could be a major player in early type-1 diabetes,” said Qing Li, MD, PhD, a postdoctoral scholar in microbiology and immunology who was the primary author of a paper describing the new result. The study is published in today’s issue of Proceedings of the National Academy of Sciences. “This was a pretty surprising finding.”

Interferon-alpha normally helps the body fight viruses. Synthetic interferon-alpha is injected as a drug for treating hepatitis C and some forms of cancer, Li noted.

“Everybody’s been wondering what process initiates type-1 diabetes,” said Hugh McDevitt, MD, professor of microbiology and immunology and the study’s senior author.

Type-1 diabetes is caused by complete deficiency of insulin, a hormone that helps the body store and burn sugar. About 1 million Americans have the disease, also known as juvenile diabetes because it tends to be diagnosed in children and young adults, for which there is no effective prevention or cure. Diabetes is a leading cause of heart disease, blindness, limb amputations and kidney failure.

The early pathology of type-1 diabetes is hard to study in humans, McDevitt said, because it’s almost impossible to predict who will get the disease and when it will develop. Scientists have relied on animal models, such as diabetic mice, because they predictably develop high blood sugar and other features of the human disease.

To pinpoint interferon-alpha, Li and McDevitt worked backwards from what they knew about how type-1 diabetes starts. Prior studies in diabetic mice showed a pathogenic role for immune cells called CD4+ T cells. These cells are an early player in the immune attack on the body’s insulin factories, pancreatic beta cells. The scientists used silicon gene-chip technology to measure which genes are revved up in the CD4+ T cells just before they assault the pancreas. The measurements fell into a pattern: many of the upregulated genes were known to be controlled by interferon-alpha.

To confirm the signal’s nefarious role, the researchers gave mice an antibody that blocks interferon-alpha activity several weeks before the animals were expected to develop diabetes. Thwarting interferon-alpha delayed the start of the disease by an average of four weeks, and, in 60 percent of treated mice, it prevented diabetes entirely.

The finding confirmed the importance of interferon-alpha and helped the scientists connect the dots between normal mouse physiology and early diabetes. Mice are born with more pancreatic beta cells than they need, Li noted. The extras soon undergo programmed cell death, leaving plenty of working beta cells to pump out insulin. However, in mice that develop diabetes, debris left behind by the dying cells triggers an inappropriate immune response, with lots of interferon-alpha. The interferon-alpha cues immune destruction of more and more beta cells, causing insulin deficiency and diabetes.

The mechanism may be more complex in humans, the scientists cautioned, explaining that while their new finding goes a long way toward explaining the beginnings of diabetes in the mice, additional genetic and environmental factors influence the human disease. But the basic principle of disease is likely the same in diabetic mice and humans, they said.

“A normal process - programmed cell death - causes a normal response,” McDevitt said. “But it does this in such a way that, in a small subset of the population, it starts them on the road to type-1 diabetes.”

Li and McDevitt collaborated with Stanford colleagues Baohui Xu, PhD, senior research scientist in pathology; Sara Michie, MD, professor of pathology; and Kathleen Rubins, PhD, a former postdoctoral scholar at Stanford who is now a research fellow at the Massachusetts Institute of Technology; and with Robert Schreiber, a professor at the Washington University School of Medicine in St. Louis.

The research was funded by grants from the Juvenile Diabetes Research Foundation, the American Diabetes Association Mentor-Based Postdoctoral Fellowship and the National Institutes of Health.

http://med.stanford.edu

Medical Research News

Vitamin D is the key to preventing rickets and osteoporosis, but Rockefeller University scientists suspect it may also play a role in heading off atherosclerosis in people with chronic kidney disease.

In a new clinical study, investigators at The Rockefeller University Hospital are examining patients with moderately reduced kidney function to investigate the effect of vitamin D therapy on endotoxemia, a condition that is common among those with renal disease and is widely viewed as a contributor to heart disease. The study, led by Instructor in Clinical Investigation Manish Ponda, is partially funded by a $25,000 grant from the Center for Clinical and Translational Science.

The high rate of atherosclerosis among patients with kidney disease is well documented but little understood by medical experts. Endotoxins, products of the natural breakdown process of bacteria, are a hot topic of clinical investigation with regard to both heart and kidney disease. “The number one killer among people with kidney disease is heart disease, just like in the rest of the population, except that in people with kidney disease, the heart disease exhibits an accelerated course,” says Ponda, a member of Jan Breslow’s Laboratory of Biochemical Genetics and Metabolism at Rockefeller. The research is an extension of earlier clinical work by Ponda that showed a high incidence of vitamin D deficiency among early-stage kidney disease patients.

Study participants - males and postmenopausal females between ages 50 and 80 with stage three chronic kidney disease and vitamin D deficiency - will be provided with thrice-weekly doses of vitamin D3, also known as cholecalciferol, the form of vitamin D produced by the body in response to sunlight. Participants will make three outpatient visits at intervals of four weeks each to The Rockefeller University Hospital, where investigators test for levels of endotoxins in response to vitamin D repletion.

The dose of vitamin D prescribed for the study - 30,000 international units per week - equals more than 20 times the intake recommended by the United States Department of Agriculture and approximately 10 times the amount in an average multivitamin supplement. The dosage is designated to safely reverse vitamin D deficiency.

If Ponda’s hypothesis - that vitamin D repletion will be accompanied by decreases in blood endotoxin levels - holds true, a larger, more-extensive, ‘progression’ study will follow, to chart the connection over longer periods of treatment and in later stages of renal disease. “Kidney disease puts a person at significantly higher risk for cardiovascular disease, but it is often asymptomatic even as late as stage three,” says Ponda. “The more definitively we can characterize renal disease, the closer we are to effectively treating both it and its comorbid conditions.”

http://www.rucares.org/ and http://www.rockefeller.edu

Medical Research News

Asian-American/Pacific Islanders with early-stage stomach cancers have an overall median survival rate that is higher than those of other races or ethnicities, according to new research, Reuters Health reports.

For the study, Barry Feig of the University of Texas M.D. Anderson Cancer Center and colleagues examined more than 81,000 cases of gastric cancers from the National Cancer Database between 1995 and 2002. The researchers’ sample was made up of 71.5% whites, 13.7% blacks, 7% Hispanics, 5.8% Asian-American/Pacific Islanders and 2% from other groups. The five-year relative survival rates for stage I and stage II stomach cancers in Asian-American/Pacific Islanders were about 77% and 48%, respectively, compared with 61% and 39% for Hispanics, 59% and 33% for whites, and 56% and 38% for blacks.

Researchers concluded that while there were “significant differences” in survival rates that favored Asian-American/Pacific Islanders, “Further studies should target underlying biologic and socioeconomic factors to explain these differences” (Reuters Health, 8/22).

This article is republished with kind permission from our friends at The Kaiser Family Foundation. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery of in-depth coverage of health policy developments, debates and discussions. The Kaiser Daily Health Policy Report is published for Kaisernetwork.org, a free service of The Henry J. Kaiser Family Foundation. Copyright 2008 Advisory Board Company and Kaiser Family Foundation. All rights reserved.