Bovine Colostrum

Treatments to help people quit smoking should be paid for by insurance and offered routinely in the health care setting, according to a document issued last month by a coalition of public health officials, consumer health advocates and business leaders. Funding for quit lines also should be increased, according to the report by the National Working Group for ACTTION (Access to Cessation Treatment for Tobacco In Our Nation). The goal is the provision of comprehensive tobacco cessation services to 50% of smokers by 2015 and 100% by 2020.

"[Smokers] are making quit attempts, but they make missteps and are unaware of the resources that are out there," said Judy Monroe, MD, Indiana's state health commissioner and one of the group's members.

According to the "Call for ACTTION," only 30% of smokers who want to quit use proven treatments, and only one in 50 employers offers cessation programs. This document calls for businesses to provide access to smoking cessation, increase awareness of the availability of these services among staff and offer incentives to access them. Public health organizations should promote using evidence-based treatments for quitting and include tobacco-use treatment performance measures in "pay for performance." Health care systems should establish strategies to make it more likely that all patients are screened for tobacco use and offered treatment as appropriate.

"Ending tobacco addiction is crucial to our nation's health and its economic well-being," said John M. Clymer, president of Partnership for Prevention, the organization that coordinated this group and the writing of the report.

In a related development, the American Cancer Society and the organization's Cancer Action Network issued a statement Nov. 23 to mark the 10th anniversary of the master settlement agreement between the tobacco industry and 46 states. This group is calling for states to renew their commitment to using this money for tobacco-prevention programs, going smoke-free, increasing taxes on tobacco and expanding access to cessation tools.

The American Medical Association has copious anti-smoking policies and supports health insurance coverage for pharmacologic and behavioral treatment of nicotine dependence. It also encourages physicians to incorporate smoking-cessation efforts into medical care by asking all patients whether they use tobacco and providing counseling on quitting to those who do.

The problem of medication overuse headaches is global and in need of prevention strategies. Such pain, which is associated with the excessive use of drugs to control it, should be the focus of research to determine the best treatment course, states a collection of papers examining the incidence of the condition in eight nations. It was published in a supplement to the November Cephalalgia.

"MOH is associated with severe disability, unmet treatment need and little clinical data to support current management strategies," said David W. Dodick, MD, editor of the collection and author of the main paper. He is also a professor of neurology at Mayo Clinic Arizona in Scottsdale and president-elect of the American Headache Society.

Current strategies usually involve convincing affected patients to discontinue headache medications and helping them through the detoxification period. This process can involve other pharmaceuticals, lifestyle changes, mental health services or alternative therapies.

"It's really important that they understand that they're not likely to get better if they don't get off their daily symptomatic medicine," said Morris Maizels, MD, a family physician and director of Kaiser Permanente's Woodland Hills Headache Clinic in California. "And they need to know that the first week or two they may actually be worse."

This circumstance can be particularly hard for the many patients who have multiple pain-related conditions. For example, the paper on MOH incidence in Germany reported epidemiological data indicating those with chronic headache also often have low back pain.

Patients with chronic headaches often have low back pain.

Depression and anxiety are common in this patient population worldwide, and more than one medication frequently plays a role. Relapse is not uncommon.

"These people ... need a lot of intervention, and they're difficult to manage," said R. Allan Purdy, MD, co-author on the Canadian-focused paper. He is a professor of medicine at Dalhousie University Faculty of Medicine in Halifax, Nova Scotia. "It's worth investing the time, although even if you do everything right, some [patients] may not get better."

An emerging approach increasingly chosen by some headache experts is prescribing drugs that prevent migraine to ease patients through the difficult transition period. Others favor using steroids and analgesics, although strategies vary widely with little evidence supporting one over another. Because of this, most see an urgent need for more research to get a better handle on the difficulty.

"We don't know what the mechanism of MOH is. We don't know why some people get it, and others don't. And we need controlled trials to know the best way to help people get better," said Stephen Silberstein, MD, professor of neurology at Jefferson Medical College of Thomas Jefferson University and director of the Jefferson Headache Center in Philadelphia. He also co-wrote the main paper with Dr. Dodick.

The authors of these papers called for increased emphasis on identifying those at risk for developing this type of headache and educating them on the issue to make it less likely medication overuse will occur. Patient diaries should record symptoms as well as drugs taken. Restrictions should be placed on the use of acute meds.

"Physicians need to be vigilant about what medications they prescribe for migraine and other kinds of headaches and what over-the-counter medications patients are taking," Dr. Dodick said.

According to the other papers in the supplement, causes, prevalence and treatment of medication overuse headache are determined largely by a country's culture and accessibility to acute treatments. For example, the syndrome was less common in India, where patients tend to choose topical pain balms. Codeine and caffeine are not used in combination painkillers in Japan, meaning these products do not play a role in MOH there as they do in North America and Europe.

A study presented at a nephrologists' conference last month has provided scientific evidence to support what many physicians have long suspected. Patients who develop kidney stones are more likely to develop chronic kidney disease and end-stage renal disease.

"Kidney stones are not a traditionally recognized risk factor ... but clinicians know it," said Dr. Rajiv Saran, associate professor and director of the Kidney Epidemiology and Cost Center at the University of Michigan, Ann Arbor.

The paper presented at Renal Week 2008, the American Society of Nephrology's 41st Annual Meeting and Scientific Exposition in Philadelphia suggested that those with a history of kidney stones had a 60% increased risk of developing CKD when compared with a healthy control group. The additional chance of ESRD was 40%. Those with stones also had a 40% increased risk of having an elevated serum creatinine or a reduced estimated glomerular filtration rate.

The authors say this finding adds importance to strategies to avert kidney stones in those who tend to form them, such as prescribing certain medications or recommending dietary changes.

"This should tell us to be a little more vigilant and think about treating patients to prevent kidney stones," said John Lieske, MD, lead author and professor of medicine at the Mayo Clinic in Rochester, Minn.

Kidney stones increase the risk of developing chronic kidney disease by 60%.

But those researching this area also expressed caution in interpreting these findings. This epidemiological study showed an association, but not cause and effect. It's unclear why these two conditions would be linked.

"The issue is, 'is this real and why?' It's an intriguing observation that needs to be followed up," said Anton C. Schoolwerth, MD, a nephrologist and professor of medicine at Dartmouth-Hitchcock Medical Center in Lebanon, N.H.

Some experts theorize that the stones themselves, or treatment to destroy them, may cause damage that later progresses to CKD and ESRD. Or it may start earlier. The process of stone formation may begin the cascade, but this association also may be because the same medical conditions that increase the chance of stones also increase the possibility of these other problems.

"It could be that there are common risk factors," said Gary Curhan, MD, ScD, a nephrologist and physician investigator at Brigham and Women's Hospital in Boston. "[Kidney stones] may not be causal."

But while the link between kidney stones and kidney disease is an open question, the fact that problems with this organ are becoming more common is not. The number of people affected has grown by 30% over the past decade. Most will die of cardiovascular disease before the kidney fails, although ESRD also increased by 3.4% from 2005 to 2006. In response, the U.S. Renal Data System last month issued its first report on the subject, in conjunction with its annual paper rounding up ESRD statistics. About 27 million people have CKD. The condition accounts for 24% of Medicare costs. The ESRD population makes up about 1% of the Medicare population and 7% of the program's costs.

"The major focus on chronic kidney disease in this year's report acknowledges that this disorder is a growing public health issue deserving of wider public awareness and intensified scientific investigation," said Elias A. Zerhouni, MD. He was director of the National Institutes of Health at the time the report was issued.

CKD also is a subject of growing public health surveillance efforts and medical society attention. In June, the American Medical Association passed policy at its Annual Meeting in Chicago that called for the U.S. Preventive Services Task Force to consider developing guidelines on the screening, diagnosis and staging of the condition.

Results of a large-scale study offered significant evidence that statin drugs reduced cardiovascular disease risks for patients with normal cholesterol but high levels of an inflammatory marker. As a result, physicians now face the challenge of incorporating this promising, albeit incomplete, data into everyday preventive care.

For instance, testing for the inflammatory marker, high-sensitivity C-reactive protein, hasn't been a big part of the practice of Bob Gramling, MD, DSc, a family physician in Rochester, N.Y. But he expects that to change in the very near future.

"I will be asked to do it more," said Dr. Gramling, an assistant professor in family medicine as well as community and preventive medicine at the University of Rochester. "I'm going to be thinking about it more."

This point of view is gaining momentum because results from that heavily publicized trial -- the first to use hs-CRP to guide cardiovascular prevention rather than only assess risk -- were released Nov. 9 at the American Heart Assn.'s scientific sessions in New Orleans. They also were published in the Nov. 20 New England Journal of Medicine and attracted widespread media attention.

Researchers with the Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin, or JUPITER, tracked 17,802 participants for just short of two years. They found that patients with high levels of hs-CRP but otherwise healthy cholesterol profiles who took 20 mg of this drug daily dramatically reduced their risks of cardiovascular events and death when compared with those who were taking placebos. Another pair of papers presented at the AHA meeting reinforced hs-CRP's potential for cardiovascular disease risk stratification.

The CRP test is not a part of the Framingham Risk Score.

"These findings suggest that adding hs-CRP levels to traditional risk factors could identify millions more adults for whom treatment with statins appears to lower the risk of heart attack," said Elizabeth G. Nabel, MD, director of the National Heart, Lung, and Blood Institute.

Most physicians concur that JUPITER is a significant study. But a great deal of disagreement still exists about how widespread hs-CRP testing should become and how often a prescription for statins is needed.

"It's a very important study. It was well done. The people who did it are to be congratulated," said Mark Hlatky, MD, a cardiologist and professor at California's Stanford University School of Medicine. He wrote the accompanying NEJM editorial. "But how do we generalize the results?"

What will be JUPITER's impact?

Whether to test for hs-CRP and how to respond to the numbers has been controversial for years. Physicians increasingly are using this marker to determine strategies for those at intermediate risk for cardiovascular disease. Several studies have suggested that it is an effective strategy, and the Reynolds Risk Score includes it. This risk assessment tool was designed by Paul Ridker, MD, the principal investigator of JUPITER. He also is one of the patent holders for the hs-CRP assay.

This biomarker, however, is not a part of the more widely used Framingham Risk Score. AHA guidelines say its role in directing prevention strategies is unclear, and several papers comparing it with other risk factor measures have not found that it adds much to an overall assessment.

The response to this latest development varied widely. For some physicians, this trial gave them the evidence for which they were waiting.

"I think it's very important and very significant," said Lawrence K. Monahan, MD, an internist in Roanoke, Va., and clinical professor at the University of Virginia School of Medicine and the Virginia College of Osteopathic Medicine. He added that he would "without a doubt" be testing for hs-CRP more often.

Others are more hesitant. The relative risk reduction was significant, but questions remain about how clinically meaningful it would be to apply cholesterol-lowering treatment to those whose baseline risk may not be that high. "What we have not seen is what were the absolute levels of risk, and how far did they go down," said Dr. Hlatky.

Another necessary step is to identify the characteristics that make some patients benefit more than others from this statin use.

Concerns also stem from the potential long-term implications of more people taking statins at even younger ages for an even longer portion of their lives -- issues not answered by this project. The study, which was originally planned to follow patients for five years, was halted after an average of 1.9 years because the immediate benefits were so significant.

"We could find after 15 to 20 years of statin use higher rates of some other life-threatening condition. We have the potential to create a fair amount of harm," Dr. Gramling said.

Others worry about the cost associated with hs-CRP testing and treating patients who have high levels of this marker but normal cholesterol, especially if they are prescribed rosuvastatin. This drug is one of the more expensive in its class, although several physicians said they would likely opt for a generic. But it's not clear if JUPITER's results can be generalized in this manner.

"My own personal belief is that for the same degree of lipid lowering, it doesn't matter much which statin you're on," Dr. Hlatky said.

In addition, some physicians were skeptical about the possible role the study's funder may have played in the results. AstraZeneca Pharmaceuticals, the manufacturer of rosuvastatin, paid for the research.

"This immediately makes me suspicious," said Elizabeth Gabay, MD, an internist at Interfaith Community Health Center in Bellingham, Wash. "I would like to see a study not paid for by a maker of a statin. Then I would be more inclined to believe the results." The study authors noted in the published report, though, that AstraZeneca had no access to the data before the paper was submitted for publication and played no part in data analyses or drafting the paper.

The company now plans to file an application with the Food and Drug Administration for an expanded indication for this drug, according to an AstraZeneca statement. Rosuvastatin currently has FDA approval as an add-on to dietary efforts to lower cholesterol. It is marketed by AstraZeneca as Crestor.

The Framingham Risk Score, the crystal ball that helps physicians determine who is most and least in need of intervention to reduce the chance of a heart attack, is the subject of increasing debate over how to make it more accurate.

"We are humbled when patients at low risk have events, and we know that the sensitivity of the score is a problem," said James De Lemos, MD, a cardiologist and associate professor of medicine at the University of Texas Southwestern Medical Center at Dallas.

A version of the calculator, a product of six decades of research conducted as part of the Framingham Heart Study, was first proposed in several papers appearing in 1976 in the American Journal of Cardiology. The articles detailed how various factors could be used to profile an individual patient's risks. The goal was to identify those most in need of prevention and give peace of mind to those who may have one elevated factor but otherwise are healthy.

"The importance of risk stratification is that it helps you focus without needlessly alarming or falsely reassuring people," said William Kannel, MD, MPH, then the director and now a senior investigator with the project.

Subsequent versions have been published over the years. The most recent one was in the May 12, 1998, Circulation. That risk calculator iteration was then simplified and incorporated into a report by the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, which was published in the May 16, 2001, Journal of the American Medical Association. The current assessment incorporates age; total and HDL cholesterol; smoking status; systolic blood pressure; and whether a patient is taking an anti-hypertensive drug. Experts believe this tool is one of the reasons heart attack death rates have decreased. Still, a great deal of talk focuses on the tool's next revision.

Most people who have heart attacks and strokes were not considered high risk.

"The risk algorithm should continually be re-examined if new evidence comes along," said Christopher O'Donnell, MD, associate director of the Framingham Heart Study. "And I think there are three areas that are going to frame the next decade of risk assessment -- blood biomarkers, vascular imaging and genetic markers."

Experts also say an update is due for reasons beyond the fact that time has passed and additional data are available. The focus of risk assessment is changing, with researchers wanting to devise one tool to determine the risk of all cardiovascular conditions, not just myocardial infarction. In addition, a great deal of work is going into attempts to design more accurate assessments of those identified as having intermediate risk.

A paper published in the Feb. 14, 2007, JAMA by a group at Brigham and Women's Hospital in Boston, and another online Jan. 22 in Circulation by Framingham researchers, outlined strategies to determine the 10-year risk of any cardiovascular event. The JAMA paper, for instance, outlined the Reynolds Risk Score for women, incorporating traditional risk factors along with family history and C-reactive protein, both of which are the most likely candidates to be included in future versions of Framingham. Approximately 40% to 50% of women at intermediate risk were reclassified as having a high or low chance of a cardiovascular event. A men's version was released at the American Heart Assn. meeting in New Orleans last month.

"The bottom line of both [Framingham and Reynolds] risk scores is getting the right drug to the right patient at the right time," said Paul Ridker, MD, lead author of the JAMA paper and director of the Center for Cardiovascular Disease Prevention at Brigham and Women's Hospital. "The majority of heart attacks and strokes occur in apparently healthy men and women of intermediate risk. How can we better define high and low risk within the intermediate risk group? We did it with greatly improved accuracy by adding two simple things to do a better job of getting patients stratified."

Researchers also want to create tools that don't require blood draws or multiple patient visits. The more recent Circulation document provided two means of risk assessment. One relied on the usual Framingham risk factors, and the other substituted body mass index for cholesterol numbers.