With Father Time coming to visit on New Year's Eve, my thoughts turn to aging. With the life expectancy rate continually increasing while more and more people live to be 100, quality of life is an issue. A new study on genetic telomeres suggests that endurance exercise for the elderly may be of great benefit.

Aging Is Easier with Endurance Exercise

By Todd Neale, Senior Staff Writer, MedPage Today

Published: December 28, 2012

Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania

Endurance training such as that done for track competitions may protect against the effects of aging in older individuals, a study of telomeres -- the caps on chromosomes that include repetitive, noncoding DNA sequences -- suggested.

Among individuals ages 66 to 77, endurance athletes had significantly longer telomeres compared with their less active counterparts (P=0.04), a relationship that was not seen among individuals in their 20s, according to Javaid Nauman, PhD, of the Norwegian University of Science and Technology in Trondheim, and colleagues.

The results "suggest that endurance exercise training may regulate the telomeres in old age and results in slowing of [the] aging process by maintaining telomere length," the authors wrote in online in PLOS ONE.

They noted, however, that the findings, which were based on a small sample of just 20 individuals, should be considered preliminary and interpreted cautiously.

Telomeres shorten over time as cells continue to reproduce. Telomere length has been related to both cellular age and the physical aging process. Studies examining the association between telomere length and exercise training and capacity have yielded inconsistent results.

To explore the issue, the researchers recruited 20 men, half of whom were ages 22 to 27 (mean age about 24) and the other half ages 66 to 77 (mean age about 69). In each age group, half of the participants were endurance athletes who were taking part in a cross-country ski race or track competitions. The others were nonathletes who were active, but who had never competed at higher levels in any sports.

All of the participants were free from known cardiovascular disease, obesity, and a history of current or past smoking. None was taking regular medications.

After muscle biopsies, mean telomere length was assessed using the ratio of the telomere repeat copy number to the single-gene copy number (T/S ratio) as measured by quantitative real-time polymerase chain reaction. Maximal oxygen consumption (VO_2max) was measured as the participants ran on a treadmill.

In the older age group, the endurance athletes had significantly longer telomeres (T/S ratio 1.12 versus 0.92, P=0.04), a difference that might have clinical significance in terms of longevity, according to the researchers.

"However," they added, "the design of the present study being cross-sectional in nature does not allow commenting about the causality of these results."

In the younger age group, telomere length was not significantly different between the endurance athletes and the nonathletes (T/S ratio 1.47 versus 1.33, P=0.12), possibly because of the small sample size or shorter exposure to physical activity.

Exercise capacity as measured by VO_2max was higher for the endurance athletes both in the younger age group (67 versus 53.9 mL/kg/min) and the older age group (45.4 versus 39.4 mL/kg/min).

In the overall cohort, telomere length was positively associated with VO_2max (r=0.70, P=0.001). The relationship was stronger among the endurance athletes (r=0.78, P=0.02) and fell short of statistical significance among the nonathletes (r=0.58, P=0.09).

Those findings "provide further support to the hypothesis that long-term exercise, higher aerobic fitness, and longer telomeres all are part of same phenotype expressed in some older adults," the authors wrote.

Besides the small sample size, they acknowledged other study limitations, including the inclusion of males only and the possibility of residual confounding by unknown or unmeasured factors.

The study was supported by grants from the K.G. Jebsen Foundation, the Faculty of Medicine, Norwegian University of Science and Technology.
The authors reported no conflicts of interest.

Primary source: PLOS ONE
Source reference:
Østhus I, et al "Telomere length and long-term endurance exercise: Does exercise training affect biological age? A pilot study" PLOS ONE 2012; DOI: 10.1371/journal.pone.0052769.

A story in the Milwaukee Journal Sentinal, in association with MedPage Today reveals the conflicts of interests physicians have in creating guidelines for drug use: Their ties to drug companies are all about the money, money that has influenced the creation of treatment guidelines.

Guidelines: Guides to Profit?

By John Fauber, Milwaukee Journal Sentinel/Medpage Today and Ellen Gabler, Milwaukee Journal Sentinel

Published: December 19, 2012

 

 

The stated intent of treatment guidelines is to "guide" clinicians' treatment of patients with a series of recommendations based on evidence.

But that intent may not be universally reflected in published guidelines and the disconnect is all about money.

Money Talks

Doctors with financial ties to drug companies have heavily influenced treatment guidelines, an analysis by the Milwaukee Journal Sentinel and MedPage Today has found.

Critics say those financial relationships have corrupted the guideline process so that the end products, make dangerous or ineffective recommendations.

Industry and some doctors counter that those with conflicts are often top experts in their field.

The Journal Sentinel/MedPage Today examined 20 clinical practice guidelines for conditions treated by the 25 top-selling drugs in the U.S.

These drugs sit in the medicine cabinets of millions of Americans -- Nexium (esomeprazole magnesium) for acid reflux, Lipitor (atorvastatin) for high cholesterol, Cymbalta (duloxetine) for depression, and OxyContin (oxycodone) for pain. Their collective sales topped $94 billion in 2011, accounting for 30% of drug revenue in the U.S.

An analysis of the guideline panels, which involved 293 doctors, found:

• Nine guidelines were written by panels where more than 80% of doctors had financial ties to drug companies.
• Four panels did not require members to disclose any conflicts of interest.
• Of the 16 guideline committees that required disclosure, two-thirds of the panel members had ties to drug companies.

Some guidelines written by conflicted panels recommend drugs that have not been scientifically proven to safely treat conditions, leading to inappropriate or over prescribing, specifically guidelines for anemia, chronic pain, and asthma.

In this analysis, research funded by drug companies was not counted as a conflict in the Journal Sentinel/MedPage Today analysis because there is disagreement about whether research funding poses as much of a conflict as speaking, consulting and advising.

The findings offer the latest glimpse into how pharmaceutical companies, with billions in sales at stake, exert a powerful but often unrecognized influence over the practice of American medicine.

Past Journal Sentinel/MedPage Today reports have revealed articles in medical journals that were ghostwritten by drug company marketers; instructional videos for doctors that made misleading claims about drugs; payments to medical organizations that advocated for more use of drugs; and drug companies paying for continuing medical education courses that, in essence, market their products.

"At the end of the day, the drug companies own medicine," said Eric Campbell, PhD an associate professor at Harvard Medical School who has researched conflicts of interest in treatment guidelines. "We've created a system that allows this."

In March 2011, the Institute of Medicine issued a report that said fewer than 50% of members of a guideline-writing committee should have financial relationships with drug companies. No committee chairman should have a financial conflict of interest, the IOM said.

In this Journal Sentinel/MedPage Today analysis just two guideline committees met the IOM criteria. Of the 16 panels that disclosed conflicts of interest, at least 10 had chairmen with financial ties to drug companies. Payment amounts were not disclosed in the guidelines, which were issued between 2001 and 2012.

Some medical societies have agreed to adopt the IOM recommendation, but many others complain the IOM set the bar too high, making it is too difficult, costly and contentious for societies, said Sheldon Greenfield, MD, chairman of the group that issued the report titled, "Clinical Practice Guidelines We Can Trust."

"By and large, most of the societies have ignored it," said Greenfield, a professor of medicine and executive co-director of the Health Policy Research Institute at University of California, Irvine.

Extensive time, research and expertise are poured into developing most guidelines, a process that can take years. The documents are complicated, dense and extremely technical.

At their best, rigorously-developed, unbiased guidelines can help synthesize new research and improve the quality of treatment that patients receive.

Even critics who want to minimize or eliminate conflicts acknowledge that guidelines written by doctors with financial ties to drug companies can offer solid, scientifically-backed recommendations.

But protecting the integrity of clinical guidelines is essential to the practice of medicine, said Steven Nissen, MD, chairman of cardiovascular medicine at the Cleveland Clinic.

"If those guidelines are produced in a way that is not completely free of bias, then we are guiding physicians and patients toward therapies based on opinions that may have been influenced by peoples' financial relationships," Nissen said. "That is a huge problem."

Some doctors and pharmaceutical industry representatives say physicians who consult for drug companies are among the most well-informed experts in their field and should help write guidelines.

Experienced doctors are trained to evaluate and base their decisions on complicated medical and scientific information, without being influenced by their ties with drug companies, said Marjorie Powell, senior assistant general counsel for PhRMA, a trade group that represents drug and biotechnology companies doing research to develop new medicine.

Other doctors and researchers say there are countless experts to call upon who do not have relationships with drug companies.

In fact, doctors are often willing to cut ties with drug companies in order to sit on guideline writing panels, said Daniel Ouellette, MD, vice chairman of the guidelines oversight committee for the American College of Chest Physicians and a senior staff physician at Henry Ford Hospital in Detroit.

Ouellette said he looks at excluding potential bias as part of the scientific process.

"We would rather have our panel be completely nonconflicted," he said.

People with industry ties may be allowed to give insight if their expertise is so unique no one else can provide it, Ouellette said. But they can only add comments and participate in discussions, not vote on or draft guidelines.

First, Do No Harm?

In some cases, guideline panels have recommended treatments that have not been proven to make a meaningful difference -- or that could even harm patients.

Guidelines written by conflicted panels have encouraged prescribing highly addictive narcotic painkillers to treat long-term chronic pain -- an area where the safety and effectiveness of the drugs remain unproven.

OxyContin, a popular and addictive opioid, was the 19th best-selling drug in the United States last year, with $2.9 billion in sales. In 2009, the American Pain Society and the American Academy of Pain Medicine issued a guideline endorsing opioids to treat chronic pain. The guideline was written by a panel where 14 of 21 members had ties to drug companies.

Also in 2009 the American Geriatrics Society advocated for greater opioid use to treat chronic pain in seniors. That guideline recommended that over-the-counter pain relievers, such as ibuprofen and naproxen, be used rarely and that doctors instead consider opioids for all patients with moderate to severe pain.

Panel members said they relied on research and their own experience in revising the guidelines, acknowledging "existing weak scientific evidence." Half the experts on the panel had financial ties to opioid companies.

Health and regulatory officials have declared misuse of opioids a national epidemic, citing skyrocketing addiction to painkillers and a tripling of fatal overdoses in the past decade. Emergency room departments across the country are adopting policies to discourage doctors from prescribing narcotics to patients with chronic pain and advocates are asking the Food and Drug Administration to restrict companies' marketing of the drugs.

Asthma drug Advair was the nation's fifth-best selling drug in 2011, with $4.6 billion in sales. It is part of a class of drugs recommended in a 2007 guideline from the National Heart, Lung and Blood Institute.

Twelve of the 18 members of the guideline's panel had financial ties to GlaxoSmithKline, which makes Advair. Three other panel members had ties to other companies that market that same of class of drugs, known as beta-agonists. In all, 83% of the panel had conflicts. Beta-agonists have been linked to higher rates of death and severe asthma attacks.

In recent years, medical studies, independent doctors and court records have declared that Advair has been massively overused and inappropriately prescribed.

EPO= Expensive

An anemia drug, once the most expensive drug in the Medicare formulary, was recommended in guidelines issued in 2006 by the National Kidney Foundation.

The guidelines provided recommendations for treating anemia in chronic kidney disease patients and endorsed a class of drugs including Epogen. The drug helps raise levels of hemoglobin, a protein in red blood cells that carries oxygen. Epogen is marketed by Amgen and had 2011 sales of $2.8 billion.

On almost every level, the drug company was financially linked to the guideline process.

Fifteen of 18 panel members who wrote the guideline for the Kidney Foundation had financial ties to drug companies. Those relationships included advising, consulting, speaking and research or unspecified contracts. Ten of those members, including both co-chairs, had financial relationships directly with Amgen.

Amgen paid $1.7 million in 2004 and 2005 to fund the guidelines for the Kidney Foundation. All told, foundation records show the group received $8.7 million from Amgen in those years.

Ashleigh Koss, a spokeswoman for Amgen, declined to comment for this article.

Concerns about the safety of Epogen and drugs in its class have grown steadily over the past 10 years. Such drugs can increase blood clots and the risk of heart attack, stroke, heart failure and death.

The Kidney Foundation's guideline recommended higher hemoglobin targets than those approved by the FDA, said Daniel Coyne, MD, nephrologist and professor of medicine at Washington University in St. Louis.
To reach higher targets could require higher doses of Epogen and similar drugs, which could be harmful to patients, he said.

In 2007, Coyne wrote a paper in a kidney disease journal that was highly critical of the guideline and conflicts of interest.

At the time, he was an adviser, speaker and consultant for Amgen and Roche. He said he no longer does that kind of consulting work. In 2011, the FDA warned doctors to be more conservative in dosing of drugs such as Epogen because data showed higher risk of cardiovascular problems and death in kidney disease patients.

The Kidney Foundation said Coyne's claim that the guideline raised the hemoglobin target is "a fundamental misinterpretation of the guideline." Foundation spokesman Sean Roach said there were subtleties to interpreting the guideline and FDA recommendations.

The foundation said drug companies that provide funding for the guidelines do not influence them and that a separate team of physicians without conflicts gathers evidence for the group writing guidelines.

Surrogate vs. Outcome In 2006, the American Diabetes Association and the European Association for the Study of Diabetes issued recommendations for managing high blood sugar in people with type 2 diabetes.
The recommendation included use of drugs known as glitazones. At the time, the two most popular glitazones were Avandia (rosiglitazone) and Actos (pioglitazone).

Both drugs were approved by the FDA in 1999 on the basis that they improved short-term blood sugar control -- not because they reduced heart attacks and strokes.

Six of seven panel members had worked as speakers or advisors to drug companies, including three who worked for GlaxoSmithKline, maker of Avandia, and one who worked for Takeda, maker of Actos.

Less than a year after the guideline came out, Avandia was linked to substantially increased risk of heart attacks. In 2010 the drug was banned in Europe and severely restricted in the U.S.

Actos has not been shown to increase heart attacks, though the drug has been linked to increased risk of heart failure. U.S. sales for Actos have remained over $3 billion a year in recent years.

David Nathan, MD, chairman of the 2006 diabetes guideline panel, said members did not have data showing Avandia was dangerous and as soon as that information came to light, the panel changed its recommendation.

Nathan, a professor of medicine at Harvard Medical School, was the only panel member who did not work as a speaker or adviser to drug companies. (He has received research grants from drug companies, according his disclosure in the guideline.)

Nathan said if people with conflicts of interest were eliminated from guideline panels, "we wouldn't be able to put together committees with enough expertise to make them worthwhile."

In an email, Nathan acknowledged that, at the time, there was no rigorous evidence showing that either Avandia or Actos reduced the risk of cardiovascular disease, blindness or kidney damage. He said there is no compelling data that any diabetes drug reduces cardiovascular risk.

Research has shown that improving blood sugar generally lowers the risk of microvascular events such as blindness and kidney damage. It was on that basis that the panel recommended the drugs, he said.

A statement provided by the ADA said its policies on guidelines have been evolving and "were radically revised" after the 2011 report by the Institute of Medicine.

"We currently are striving to meet all of the IOM requirements, but recognize that older efforts may not have lived up to that new more rigorous standard," the statement said.

In 2011, the ADA received $15 million in funding from drug and medical device companies, including $145,325 from GlaxoSmithKline and $638,250 from Takeda, according to its revenue statement. The association would not provide drug company funding amounts from the years prior to the 2006 guideline.
The guideline panel's recommendation is an example of an ongoing problem in medicine, especially in diabetes care, said John Yudkin, MD, an emeritus professor of medicine at University College London.

Panelists may make recommendations to use certain drugs based on a "surrogate measure," such as improving blood glucose levels, and then assuming this also reduces the risk of heart disease, kidney damage or blindness.

But an improvement in a blood measure doesn't always mean a patient is facing less risk of serious health problems. Avandia and Actos never have been proven to reduce kidney damage, amputations, blindness, heart attacks or strokes, Yudkin noted.

Psychiatrists Limit Conflicts After Controversy

Increased political scrutiny of drug companies over the past few years has led to more transparency, including the Physician Payment Sunshine Act (PPSA), which will require drug, device and medical supply companies to disclose any payments made to doctors or teaching hospitals. The first reports are due next spring.

But reformers say that merely disclosing a conflict does not eliminate it.

Four guidelines examined by the Journal Sentinel/MedPage Today did not disclose members' conflicts with drug companies. Those guidelines were issued between 2001 and 2005.

The American Psychiatric Association issued one of the guidelines in 2004 for treating schizophrenia.
A few years later, the group was embroiled in controversy when it decided to disclose conflicts of interest for a different guideline on depression. That panel included six of seven panel members who had worked as consultants, advisors or speakers for drug companies.

Before the guideline was released in 2010 the association had an independent panel with no drug company ties review the recommendations. No bias was found, said Joel Yager, MD, chairman of the group's steering committee on practice guidelines and a professor of psychiatry at the University of Colorado.

Even so, the APA no longer allows any doctors with conflicts of interest to sit on its guideline writing panels. It aims to achieve "no possibility of industry bias," Yager said.

"You have to play by the rules," he said.

Growing up we were told to drink a glass of milk with each of our three meals if we wanted strong and healthy bones. Now a new study says that we should limit our 2-5 year olds to no more than two glasses of milk per day.

Kids' Diet: Two Cup Limit for Milk

By Crystal Phend, Senior Staff Writer, MedPage Today

Published: December 17, 2012

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

 

 

More than two cups of milk a day may cut into iron stores for many young kids, an observational study affirmed. 

 

Higher consumption of cow's milk was linked to higher vitamin D levels but lower serum ferritin as a measure of iron levels (both P≤.0001), Jonathon Maguire, MD, MSc, of St. Michael's Hospital in Toronto, and colleagues found.

Each cup consumed was linked to 6.5% higher vitamin D and 3.6% lower iron on average, the group reported online in Pediatrics.

Two cups a day seemed sufficient to keep vitamin D levels up with minimal effect on iron for most 2- to 5-year-olds, they found in the primary practice-based study, although children with darker skin pigmentation may require more milk during winter months.

The study findings fit with guidelines from the American Academy of Pediatrics that suggest no more than two cups (500 mL) of cow's milk a day from ages 2 to 6 to avoid iron deficiency.

Both nutrients are critical for kids. Vitamin D is necessary for bone health and likely disease prevention too; iron plays a key role in brain and psychomotor development.

The study included 1,311 healthy children, ages 2 to 5, seen at seven large Toronto primary care group practices in the TARGet Kids! research network.

Parents reported that the average daily intake of cow's milk was a little under 2 cups (460 mL).

About a third of the children had 25-hydroxyvitamin D levels under the 75 nmol/L threshold recommended as optimal in Canadian guidelines; 6% were deficient with levels under 50 nmol/L.

Serum ferritin averaged 31 μg/L, with 4% falling under 12 μg/L.

How appropriate those iron levels might be wasn't clear, as there aren't any consensus recommendations on optimal iron stores for children, the investigators noted.

Children who drank three 250-mL cups of milk a day versus two had:

• 5.5-nmol/L higher 25-hydroxyvitamin D (95% CI 3.9 to 7.1)
• 1-μg/L lower serum ferritin (95% CI 0.3 to 1.7)

Analysis by other common clinical scenarios suggested that up to two cups a day kept median 25-hydroxyvitamin D over 75 nmol/ L, except for kids with dark skin who didn't get vitamin D supplements during the winter.

That group apparently required 3 to 4 cups of cow's milk per day to maintain 25-hydroxyvitamin D at the same threshold, although as the researchers noted, the observational results couldn't determine causality.

Higher milk intake didn't appear to be as good for children still using a bottle. In these children, higher milk intake didn't correlate with higher vitamin D levels, but were associated with sharper decreases in iron levels across gender, skin pigmentation, season, and vitamin D supplementation scenarios.

Possible explanation for this findings could be that parents under-reported milk intake from bottles, or other things like juice put in them, or that bottle use by this age group replaces vitamin D- and iron-containing solid foods, Maguire's group suggested.

"Regardless, reported cow's milk consumption among children using a bottle appears to have little benefit on micronutrient stores, suggesting that bottles should not be filled with cow's milk or used at all in this age group," they wrote.

Parent reporting was a limitation of the study, as was inclusion of children in a single urban setting at a northern latitude, which may limit how generalizable the results are.

The TARGet Kids! program was supported overall by the Canadian Institutes of Health Research Institute of Human Development, Child and Youth Health and the Institute Nutrition Metabolism and Diabetes, as well as the St. Michael's Hospital Foundation.
The analysis was supported in part by the Canadian Institutes of Health Research. The Pediatric Outcomes Research Team was supported by a grant from The Hospital for Sick Children Foundation.
The researchers reported no conflicts of interest.

Primary source: Pediatrics
Source reference:
Maguire JL, et al "The relationship between cow's milk and stores of vitamin D and iron in early childhood" Pediatr 2013;131:e144–e151.

With healthcare reform focused on how to pay for that care rather than reducing the need for it, a NYT's opinion piece asks whether healthcare interventions should be mandated in an effort to do what has been proven scientifically effective in preventing a condition. The idea raises the question of what is morally and fiscally ethical.

 

 

The 2,000-Year-Old Wonder Drug

By DAVID B. AGUS

Published: December 11, 2012

THE inexorable rise in health care spending, as all of us know, is a problem. But what’s truly infuriating, as we watch America’s medical bill soar, is that our conversation has focused almost exclusively on how to pay for that care, not on reducing our need for it. In the endless debate about “health care reform,” few have zeroed in on the practical actions we should be taking now to make Americans healthier. 

An exception is Mayor Michael R. Bloomberg of New York, who is setting new standards that we would do well to adopt as a nation. In the last several years, he’s changed the city’s health code to mandate restrictions on sodas and trans fats — products that, when consumed over the long term, harm people. These new rules will undoubtedly improve New Yorkers’ health in years to come. 

Such bold moves prompt a provocative question: when does regulating a person’s habits in the name of good health become our moral and social duty? The answer, I suggest, is a two-parter: first, when the scientific data clearly and overwhelmingly demonstrate that one behavior or another can substantially reduce — or, conversely, raise — a person’s risk of disease; and second, when all of us are stuck paying for one another’s medical bills (which is what we do now, by way of Medicare, Medicaid and other taxpayer-financed health care programs). 

In such cases, encouraging a healthy behavior, or discouraging an unhealthy one, ought to be a matter of public policy — which is why, for instance, we insist on vaccinating children for the measles, mumps, rubella and polio; we know these preventive strategies save lives. 

Under that rationale, then, why not make it public policy to encourage middle-aged people to use aspirin?

Developed in 1897 by the German chemist Felix Hoffmann, aspirin, or acetylsalicylic acid, has long proved its value as an analgesic. Two millenniums before that, Hippocrates, the father of modern medicine, used its active ingredient — which he extracted from the bark and leaves of the willow tree — to help alleviate pain and fevers. 

Since then, we’ve gained insight into both the biological mechanism and the effects of this chemical compound. Many high-quality research studies have confirmed that the use of aspirin substantially reduces the risk of cardiovascular disease. Indeed, the evidence for this is so abundant and clear that, in 2009, the United States Preventive Services Task Force strongly recommended that men ages 45 to 79, and women ages 55 to 79, take a low-dose aspirin pill daily, with the exception for those who are already at higher risk for gastrointestinal bleeding or who have certain other health issues. (As an anticoagulant, aspirin can increase the risk of bleeding — a serious and potentially deadly issue for some people.) 

New reports about aspirin’s benefits in cancer prevention are just as convincing. In 2011, British researchers, analyzing data from some 25,000 patients in eight long-term studies, found that a small, 75-milligram dose of aspirin taken daily for at least five years reduced the risk of dying from common cancers by 21 percent. 

In March, The Lancet published two more papers bolstering the case for this ancient drug. The first, reviewing five long-term studies involving more than 17,000 patients, found that a daily low-dose aspirin lowered the risk of getting adenocarcinomas — common malignant cancers that develop in the lungs, colon and prostate — by an average of 46 percent. 

In the second, researchers at Oxford and other centers compared patients who took aspirin with those who didn’t in 51 different studies. Investigators found that the risk of dying from cancer was 37 percent lower among those taking aspirin for at least five years. In a subsection of the study group, three years of daily aspirin use reduced the risk of developing cancer by almost 25 percent when compared with the aspirin-free control group. 

The data are screaming out to us. Aspirin, one of the oldest remedies on the planet, helps prevent heart disease through what is likely to be a variety of mechanisms, including keeping blood clots from forming. And experts believe it helps prevent cancer, in part, by dampening an immune response called inflammation. 

So the question remains: given the evidence we have, why is it merely voluntary for physicians to inform their patients about a health care intervention that could not only help them, but also save untold billions in taxpayer dollars each year? 

For some men over the age of 45 and women over 55, the risks of taking aspirin outweigh any benefits — and patients should talk with their doctors before taking any medication, including something as familiar as aspirin. 

But with such caveats in place, it still ought to be possible to encourage aspirin’s use in those for whom the potential benefits would be obvious and the risks minimal. Just as we discourage smoking through advertising campaigns, for example, shouldn’t we suggest that middle-aged Americans speak to their doctors about aspirin? Perhaps pharmacists or even health insurance companies should be enlisted to help spread the word about this disease-prevention drug? 

The right policy will have to be hammered out, of course. But if we’re going to address the country’s sky-high medical bill, we’re going to have to address the need for Americans to be active in protecting their own health. 

Everyone may want the right to use tobacco products and engage in other behaviors that are unequivocally linked with disease — or have the right not to wear a seat belt and refrain from other actions that may protect their well-being. But, if so, should society have the obligation to cover the costs of the consequences? 

As the former Supreme Court justice Potter Stewart once said, “There is a big difference between what we have the right to do and what is right to do.” Health care reform should, at long last, focus on the latter. 

David B. Agus is a professor of medicine and engineering at the University of Southern California and the author of “The End of Illness.”

Court ruling allowing drug off-labeling as free speech may be a boon for drug companies but will it be good for patients? Will marketing ultimately trump the ethics of "first do no harm?"

Court: Off-Label Drug Marketing Is 'Free Speech'

 

By John Fauber, Reporter, Milwaukee Journal Sentinel/MedPage Today

Published: December 04, 2012

 

A decision by a federal appeals court this week could have a dramatic impact on the marketing of prescription drugs in America, potentially affecting patient care and everything from TV advertising to future government prosecutions which, in the past, had yielded billions of dollars in settlements, doctors and attorneys said Tuesday.

"This risks taking us back to an era when people could promote snake oil without restrictions – a situation I would hate to see," said Richard Deyo, MD, a professor of family medicine at Oregon Health and Science University.

Citizens United Redux

However, others say the ruling by a three-judge panel of the Court of Appeals for the Second Circuit in Manhattan is a victory for free speech, one that could become the drug industry equivalent of Citizens United, the 2010 U.S. Supreme Court decision that gave corporations and unions the right to spend unlimited sums on political ads.

Like the Citizens United case, the ruling Tuesday by the prestigious U.S. Court of Appeals for the Second Circuit in New York, involved the right of commercial free speech, applying it to the complicated world of pharmaceutical industry promotion of prescription drugs.

How wide-ranging the decision becomes likely will depend on whether it gets to the U.S. Supreme Court, attorneys said.

Once the Food and Drug Administration approves a drug, physicians are free to prescribe that drug as they wish -- but the drug makers can only market the drug for the FDA-approved marketing indication.

The case involves Alfred Caronia, a sales representative with Orphan Medical who was criminally prosecuted for making off-label promotional statements about Xyrem, a drug approved in 2002 to treat narcolepsy patients with a condition known as cataplexy. Cataplexy involves weak or paralyzed muscles.

The FDA required a black box warning on the drug stating that its safety and effectiveness had not been established in people under the age of 16. The active ingredient in Xyrem is GHB, is a powerful medication that acts on the central nervous system and also is known as the "date rape" drug.

In 2005, the federal government began investigating Orphan Medical for its alleged off-label promotion of Xyrem.

In a taped conversation Caronia had with a doctor who was cooperating with the government, he said the drug could be used for other muscle conditions such as fibromyalgia, restless leg syndrome, and Parkinson's.

He also said it could be used in patients under 16.

Caronia had claimed that his off-label promotion was constitutionally protected free speech, saying the First Amendment does not permit the government to prohibit or criminalize a drug company's truthful, nonmisleading off-label promotion to doctors.

Protected Speech

The appeals court essentially agreed, noting that Caronia never conspired to put false or deficient labeling on the drug.

"The government clearly prosecuted Caronia for his words – for his speech," the court said.
"This could be a watershed moment for the pharmaceutical industry," said Michael Buchanan, a former federal prosecutor who now works for a New York law firm that represents drug companies.

He said the decision will be good for consumers and doctors because it will allow drug companies to disseminate more information about their products, allowing for more informed decision-making.

It is likely the decision, if upheld, will make it much more difficult for the Department of Justice to bring cases against drug companies for off-label drug promotion, he said.

Over the last decade or so, the Justice Department has obtained billions of dollars from drug companies after accusing them of promoting their products for off-label uses.

In its most recent prosecution in July, the department obtained a record $3 billion settlement from GlaxoSmithKline for its marketing of several drugs, including Wellbutrin, Paxil, and Advair.

Tamara Piety, an expert on commercial speech and the First Amendment and a professor of law at the University of Tulsa, said that if the decision is upheld by the Supreme Court it could open the doors to off-label television advertising of drugs. Piety predicted that a majority of the Supreme Court Justices would be sympathetic to the ruling.

She said the pharmaceutical industry has been trying for years to overturn the off-label marketing prohibition.

"It looks like they finally succeeded," she said.

Steven Nissen, MD, a cardiologist with the Cleveland Clinic, said the decision was short-sighted and could result in patients being exposed to unnecessary risks.

"Off-label promotion is not about free speech, it is the medical equivalent of yelling fire in a crowded auditorium." he said.

Andrew Kolodny, MD, a New York psychiatrist who has been trying to reform the use of narcotic painkillers in the U.S., said the decision was terrible for public health.

"A large portion of Americans already are taking drugs with serious risks that outweigh the benefits," he said
.
"This is going to get much worse," Kolodny said. "It's a safe bet that health outcomes will decline from medication side effects, while spending on prescription drugs will continue to rise."

Ed Silverman, who operates the popular Pharmalot blog, said drug companies had been pushing off-label promotion as a free speech issue for years.

"It (the decision) is vindication for the pharmaceutical industry," he said.

PhRMA Applauds

In a statement, the Pharmaceutical and Research Manufacturers of America said it was pleased that the court found that the FDA's ability to regulate communication about medicine is circumscribed by the First Amendment.

"PhRMA believes that truthful and nonmisleading communication between biopharmaceutical companies and healthcare professionals is good for patients, because it facilitates the exchange of up-to-date and scientifically accurate information about new treatments," PhRMA spokesman Matthew Bennett said in a statement.

Sidney Wolfe, MD, with the watchdog group Public Citizen, said the decision will further weaken the FDA.
Caronia was accused of conspiring with a psychiatrist who was a hired drug company speaker.

In overturning Caronia's conviction, the appeals court cited a 2011 U.S. Supreme Court decision involving a Vermont law that said "speech in the aid of pharmaceutical marketing ..." is a form of expression protected by the First Amendment. The law had barred drug companies from obtaining and using prescriber information for marketing purposes when a range of others such as private and academic researchers could acquire the information.

The Court of Appeals said the government's view of the law essentially legalized off-label prescribing but prohibited the free flow of information about that.

Arnold Friede, a former FDA and drug company attorney, said the next step may be for the government to ask the entire appeals court to rehear the case.

Q: When is too much exercise not a good thing? A: When it concerns preserving the integrity of your knees.

Moderate Activity May Be Key to Saving Knees

By Ed Susman, Contributing Writer, MedPage Today

Published: November 26, 2012

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco

CHICAGO – Too much exercise led to early degenerative cartilage changes in the knee in healthy people and in those at risk for osteoarthritis, according to an MRI-based study.

Over a 4-year period, 205 individuals who exercised at various intensity levels underwent MR imaging that showed significant T2 progression, suggestive of accelerated cartilage matrix biochemical degeneration (P<0.05), said Wilson Lin, a research fellow at the University of California San Francisco, during a presentation at the Radiological Society of North America meeting.

"This study seems to suggest that people should do things in moderation," Lin said during an RSNA press briefing. "You want to exercise the knee, but you don't want to stress the knee in such a way that would be detrimental. If [people] wanted to run marathons and work out several times a week, I would present them with the evidence that this could be harmful."

The relationship between physical activity and the evolution of osteoarthritis is unclear, but cross-sectional studies have shown that very low and high levels of exercise may be associated with higher cartilage T2 relaxation times compared with mild levels of exercise.

Lin's group enrolled people from two cohorts -- incidence and normal -- of the Osteoarthritis Initiative Incidence. Participants' ages ranged from 45 to 60 and the body mass indices ranged from 19 kg/m² to 27 kg/m².

None of the participants had knee pain at baseline (zero score on the Western Ontario and McMaster Universities Arthritis Index), and a Kellgren-Lawrence score of less than 2 in the right knee at baseline.

Physical activity was scored using the Physical Activity Scale for the Elderly (PASE) questionnaire, which was averaged over a 4-year time period and categorized into tertiles. The rigorous activity tertile generally consisted of 1 hour of vigorous physical activity, three times or more per week.

T2 values of articular cartilage were measured at the patella, medial/lateral femur and medial/lateral tibia of the right knee in multi-echo spin-echo sequences at baseline, 2 years, and 4 years.

All compartments in the knee showed significant T2 progression over the study period, Lin said.

The authors also reported that T2 progression was higher in the highest tertile on PASE than in the midtertile at the medial tibia (2.8 versus 2.0, P=0.04) and the patella (4.1 versus 3.1, P=0.02). The average T2 of all knee compartments combined was 2.5 versus 2.0 (P=0.03) for highest PASE tertile compared with midtertile.

T2 progression was also higher in the lowest tertile than in the midtertile in all compartments, but results were not significant. "We did observe a trend to higher T2 relaxation times in the most sedentary individuals (about 2.4) but that did not reach statistical significance (P<0.10)," co-author Thomas Link, MD, PhD, told MedPage Today.

Link also told MedPage Today that according to previous studies, people who exceed 10,000 steps a day based on a pedometer appeared to be at risk of acceleration progression of cartilage damage. However, he said there was no science to determine the number of steps that would be considered sedentary.

Link noted that study did involve individuals who were at high risk for knee osteoarthritis because of family history, obesity, or a history of knee injury or replacement surgery.

He suggested that people should use correct footwear and attend classes that emphasize exercise safety.
"This shows that titrating physical activity may be important, not just being physically active," said Candice Johnstone, MD, who moderated the RSNA press briefing. "Being super-aggressive in exercise may be worse than moderate exercise such as walking."

"I was not surprised by these results. This is more like common sense," added Johnstone, who is from the Medical College of Wisconsin in Milwaukee. "This adds to information people have to use to design their own exercise program."

The Osteoarthritis Initiative Incidence is sponsored by NIH.
Lin reported no conflicts of interest. Link disclosed commercial relationships with GE Healthcare.
Johnstone reported no conflicts of interest.

Primary source: Radiological Society of North America
Source reference:
Lin W, et al "High levels of physical activity are associated with greater cartilage degeneration over a period of 4 years as assessed with T2 relaxation time measurements – 3T MRI data from the Osteoarthritis Initiative" RSNA 2012; Abstract LL-MKS-SU1B.

A new study demonstrates better treatment outcomes for those older patients who have a positive outlook on aging and are trying to rehabilitate from a disabling injury.

Positive Outlook on Aging Helps Seniors Heal

 

By Cole Petrochko, Staff Writer, MedPage Today

Published: November 20, 2012

 

Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston

 

 

Older patients with positive attitudes on aging may be more likely to fully recover from severe disability compared with those who can't see the bright side of life, researchers found

A positive stereotype about aging was associated with a 44% greater likelihood of recovery from severe disability versus negative stereotypes (95% CI 1.01 to 2.06, P=0.04), according to Becca Levy, PhD, from the Yale School of Public Health, and colleagues.

Holding positive stereotypes in older age was also significantly associated with a slower rate of decline in activities of daily living (P=0.001), they wrote in a research letter in the Journal of the American Medical Association online.

"Further research is needed to determine whether interventions to promote positive age stereotypes could extend independent living in later life," the authors noted.

The researchers sampled patients through the Precipitating Events Project study and included 598 mostly female patients (63.3%), with an average age of 79, who belonged to a Connecticut health plan. All participants lived in a community, were nondisabled, and experienced at least 1 month of disability from active daily life during the follow-up period.

The participants were interviewed monthly for up to 129 months and filled out home-based assessments every 18 months over 10 years.

The researchers established age stereotypes by asking participants for five terms or phrases they associated with older individuals and coding those descriptors on a five-point scale, with 1 being most negative (such as decrepit) and 5 being most positive (such as spry). The participants scored a mean 2.12 on this scale.

Participants' severity of disability was based on the number of activities of daily living compromised by disability, including bathing, dressing, transferring, and walking. Three or four compromised activities were considered severely disabled; mild to severe disability required assistance with one to two activities, and mild to no disability required no assistance with activities of daily life.

The researchers grouped patients on whether they held positive or negative age stereotypes and compared rates of recovery from severe or mild injury to no or mild disability. Patients between groups were well-matched for age, sex, nonwhite ethnicity, frailty, education, chronic conditions, mental status, depression, and whether or not they lived alone. The nature of the disabling events was not described.

Patients were significantly more likely to recover from any state of injury to either no or mild disability if they fit positive age stereotypes, including from severe disability to no disability, severe disability to mild disability (HR 1.23, 95% CI 1.03 to 1.46, P=0.02), and mild disability to no disability (HR 1.15, 95% CI 1.02 to 1.29, P=0.02).

The researchers also noted that the positive age-stereotyped patients "showed an advantage in the absolute risk increase percentages" in likelihood of recovery, in addition to "a significantly slower rate of [activities of daily life] decline."

Study limitations included recruitment from a single community and an undersampling of black patients.

The study was funded by grants from NIH and Yale and an investigator award from the Patrick and Catherine Weldon Donaghue Medical Research Foundation.
The authors declared no conflicts of interest.

Primary source: Journal of the American Medical Association
Source reference:
Levy BR, et al "Association between positive age stereotypes and recovery from disability in older persons" JAMA 2012; 308: 1972-1973.

HealthDay Report: The longer and more chronic your sciatic pain, the less likely steroid injections are going to help. Outside of giving your body a chance to heal itself from acute sciatica, steroid injections may not address the cause at all.

 

Steroid Shots for Sciatica: Benefits Only Brief, Analysis Finds

Patients should discuss risks with their doctor, researcher says

By Kathleen Doheny, HealthDay Reporter
 
 

MONDAY, Nov. 12 (HealthDay News) -- Spinal steroid injections -- the type involved in the current fungal meningitis outbreak in the United States -- provide only short-term relief for sciatica-related leg and back pain, according to a new analysis.

Sciatica, a common type of low back pain, is characterized by intense pain shooting down one leg, along with tingling and numbness, as a result of injury or pressure on the sciatic nerve.

Epidural steroid treatments -- injections into the joint spaces of the spine -- have been used to treat back pain for a half-century, but consistent guidelines for their use are nonexistent, according to the new study, which was published Nov. 13 in the journal Annals of Internal Medicine.

In the new analysis, researchers analyzed 23 clinical trials involving more than 3,100 patients; the trials compared steroid injections to other treatments. Researchers had followed patients for a year or longer, gauging pain relief at various points.

"The review showed that [epidural injections] offered only small, short-term improvement in pain and disability for people with sciatica and had no long-term effect," said study co-author Dr. Chris Maher, professor of physiotherapy at the School of Public Health at the University of Sydney in Australia.

At two weeks and three months after treatment, 10 trials showed leg-pain relief and 14 reported improvements in disability. But after a year or more, no differences were found in leg pain, back pain or disability for those given injections compared to those given a placebo.

"Given that the treatment effect is likely to be small and short term, patients with sciatica should discuss the potential risks involved in [steroid injections] with their doctor before agreeing to the procedure," said Maher, who also is director of the George Institute for Global Health, in Sydney.

The results echo some of the findings of another study, published earlier this year, that concluded that after six months, epidural steroid injections were no better than the anti-inflammatory drug Enbrel (etanercept) or an injection of anesthetic and saline.

Dr. Steven Cohen, professor of anesthesiology and critical care medicine at Johns Hopkins School of Medicine in Baltimore and director of pain research at Walter Reed National Military Medical Center, said the findings shouldn't rule out use of epidural steroid treatment.

"It is likely that, at least in some people, epidurals may decrease the likelihood that they will need surgery -- not because they last so long, but because they decrease pain enough for your body to heal itself and/or prevent those deleterious changes from occurring in the nervous system," Cohen said.

Cohen was a researcher on the study comparing the injections with Enbrel, which was published in April in the Annals of Internal Medicine.

Many factors play into the injections' effectiveness, he said. One is the duration of pain. The longer a patient has had the pain, the less responsive treatment tends to be, not only to injections but also to other therapies.

Risks to patients were not examined, Maher said. These remain a concern, especially since tainted steroid injections have killed 32 people and sickened 438 to date since the fungal meningitis outbreak came to light in September. The contaminated drugs were traced to a compounding pharmacy -- now shut down -- that produced drugs to meet the needs of specific patients. Such specialty pharmacies are regulated by state boards, not the U.S. Food and Drug Administration.

Despite that outbreak, epidural injections for back pain are extremely safe, Cohen said, and ''certainly safer than commonly used alternatives such as surgery or narcotics."

"When you examine alternatives for sciatica, no treatment is very reliable or effective," he said, adding that doctors should be more selective in choosing which patients could benefit from the injections.

Dr. Roger Chou, associate professor of internal medicine at Oregon Health & Science University, in Portland, agreed.

"[This new review] underscores the importance of performing epidural steroid injections judiciously, in patients who have clear indications for it, especially in light of the fungal meningitis outbreak," Chou said. There is no evidence that the injections work, for instance, in those with low back pain without sciatica.

In a story in the Baltimore Sun, conservative treatments for back pain might be first considered over invasive procedures in light of meningitis outbreak.

Meningitis outbreak brings attention to treatment of back pain

Some argue people too dependent on drugs, surgery

Dr. Alan K. Sokoloff, chiropractor, treats patient Naomi Morgan. (Amy Davis, Baltimore Sun / October 31, 2012)

By Andrea K. Walker, The Baltimore Sun

3:36 p.m. EST, November 4, 2012

Naomi Morgan reached her limit when her doctor recommended a third surgery for chronic back pain.
Tired of being cut open only to have the pain return, Morgan, a 65-year-old nursing assistant, began looking for a less invasive and hopefully more effective way to treat her ailment, which she thinks started from lifting patients or moving furniture. She turned to a chiropractor, whom Morgan credits for helping her manage her back pain for the past 21 years with stretching, realignments and other treatments.

As the country continues to reel from a fungal meningitis outbreak — linked to a tainted steroid used to treat back pain — that has sickened 386 people in 19 states and killed 28, the medical industry is debating again about how back pain is treated.

The outbreak revived old arguments about whether back pain sufferers have become too dependent on drugs and surgeries as quick cures — and whether these treatments even work in the long run.

Back pain is the second most common neurological ailment in the United States behind headaches, according to the National Institute of Neurological Disorders and Stroke. More than a quarter of adults experienced lower back pain in the last three months, according to a recent report by the National Center for Health Statistics.

"A lot of times primary care doctors, or even patients, get into certain patterns where, if it hurts, they go the extreme route first instead of trying something natural and more conservative," said Dr. Alan Sokoloff, a Glen Burnie chiropractor who treats Morgan.

The American Academy of Pain Medicine promotes a multi-disciplinary approach and agrees that drugs should be used after other, less invasive methods are given a shot. But pain doctors also say that medications shouldn't be scapegoated and that drugs can be the best treatment for some patients.

"Too often we look at problems in a dichotomous way," said Dr. Lynn Webster, a Salt Lake City anesthesiologist and president-elect of the pain medicine group. "There is not either or. There is a spectrum of back pain problems that range from minimal pain to those who are totally incapacitated and can't walk. They may all require different treatments."

Shots of the steroid preservative-free methylprednisolone acetate, which has been linked to the meningitis outbreak, has become a common way to treat the pain. Roughly 14,000 people may have received contaminated shots of the steroid, which came from the New England Compounding Center in Framingham, Mass. In Maryland, 22 people have been sickened and one died.

Pain doctors around the country have heard from patients afraid to get the steroid shots, Webster said. Many may switch to oral pain killers. While he said the fear is justified, the medical industry has to be careful of moving too far to the extreme, he said.

The chiropractic industry is using the outbreak to advocate for more conservative, less invasive approaches to treating back pain, including yoga, acupuncture and, of course, chiropractic care.

The Foundation for Chiropractic Progress in California issued a position paper after the outbreak criticizing what it calls an overuse of drugs to treat back pain. The group said the use of drugs creates addicts and masks pain rather than treating underlying conditions.

"While living in a society where we expect to live pain-free, America may now be convinced that there needs to be a safer way to address back pain, with chiropractic care becoming a preferred option," the foundation's paper read.

In a phone interview, Dr. Gerard Clum, a foundation spokesman, said the use of drugs among doctors is inconsistent.

"There is a spectrum of behavior," Clum said. "There are some physicians that will hold surgery and epidural injections as the last resort and others who jump to it very quickly."

The type of doctor a patient sees may determine what treatment is recommended for back pain. If your primary care physician sends you to an orthopedic surgeon you may be more likely to end up in surgery, for example.

Surgeons say most of their patients with back pain don't end up on the operating table.

Patients with pain limited to the back can get physical therapy and use muscle relaxers such as Bengay, said Dr. Raj Rao, a spokesman for the American Academy of Orthopaedic Surgeons. Most patients just need to have patience and give the pain time to go away.

Surgery is more common for patients who feel pain in the legs or buttocks as well as the back, Rao said. That is a sign of nerve compression. But even these patients can be treated without surgery, he said.

"Most well-trained surgeons will exhaust non-operative measures before turning to surgery," Rao said.

Some Baltimore-area chiropractors said they've noticed more referrals from primary care doctors since the meningitis outbreak. They also are fielding more questions about the safety of steroid injections.

Chiropractor Adam Fidel, president of the Maryland Chiropractors Association, said he has had more patients want to try other options before moving to steroid injections or other invasive procedures.

"I think more people are more comfortable with going to a chiropractor than ever before," Fidel said. "And more primary care physicians are recommending them."

But even chiropractors said there is room for drugs in treating back pain.

Many chiropractors work with pain management doctors. White Marsh chiropractor Timothy Gober said people shouldn't write off drugs for treating back pain. The meningitis outbreak is an anomaly, he said.

Gober said he believes in starting with conservative treatment options and using pain killers if needed.
Sometimes he'll send a patient to get a steroid injection so he can perform a realignment without discomfort for the patient.

"A lot of times doctors try to fit patients in a box," Gabor said. "We try to see what is best for patients."

Morgan, the nursing assistant from Glen Burnie, said she still feels some aches and pains despite the treatments prescribed by her chiropractor. It's just something she has to deal with as she gets older. But her condition is better than it once was, she said. And she is not opposed to other treatment options, such as cortisone shots, if her condition ever worsened.

But she's almost sure she'll never get surgery again.

"The only way I would ever have surgery again is if I wasn't able to move my legs, back or anything else," she said. "I'd have to be in pretty bad condition."

A Special Report on the writing of clinical study reports: is this a single incident (if it occurred) or is this a sign of something done commonly in the biopharma/medical device arena?

Medtronic Helped Write, Edit Positive 'Infuse' Spine Studies

By John Fauber, Reporter, Milwaukee Journal Sentinel/MedPage Today

Published: October 25, 2012

 

 

Highly positive studies published in peer-reviewed medical journals depicted Medtronic's spine fusion product as a major breakthrough in back surgery, but those studies drafted and edited with direct input from company employees, while the doctors listed as authors were paid millions, according to a U.S. Senate investigation.

The company's heavy, undisclosed manipulation of information about its bone morphogenetic protein-2 product called Infuse included removing and downplaying concerns about serious complications linked to the product and overstating its benefits.

The Money Trail

Over the course of 15 years, Medtronic paid $210 million to a group of 13 doctors who co-authored the series of now-repudiated papers about the product. The payments also included two corporate entities associated with some of the doctors.

The investigation by Senate Committee on Finance was prompted in part by Journal Sentinel/MedPage Today investigations that showed how the practice of medicine has been corrupted by conflicts of interest involving doctors, drug and device companies and medical journals.

The Senate report, to be released Thursday, details how Medtronic employees, including some working in the company's marketing department, covertly collaborated with the academic physician authors in producing 11 different papers between 2002 and 2009.

Such "ghostwriting," though not illegal, has been condemned as a breach of integrity and transparency because doctors and patients rely on information in those articles to make medical decisions, not knowing that the papers may contain biased, inaccurate or potentially harmful information.

The Senate's findings highlight problems that should have been reported as at least a decade ago, said Ray Baker, MD, a Kirkland, Wash., pain specialist who served on an advisory panel to Medicare and Medicaid on Infuse.

"I am just sad this happened," he said. "At every level when we thought, 'that wouldn't happen,' it happened. The integrity of our scientific literature is our foundation. It's what predicates our treatments."

Medtronic Denies

Medtronic disputed many of the findings in the Senate's report.

"Medtronic vigorously disagrees with any suggestion that the company improperly influenced or authored any of the peer-reviewed published manuscripts discussed in the report, or that Medtronic intended to under-report adverse events," a statement emailed by the company said.

The company said it reported the adverse events to the Food and Drug Administration and those risks also are listed the product label for Infuse. Medtronic also called the report's characterization of the payments to the doctors misleading and unfair.

"The vast majority of such payments were royalty payments made to compensate physicians for their intellectual property rights and contributions, not consulting payments," the company said.

In 2011, after the Spine Journal devoted an entire issue to repudiating Infuse research, the company, under its new CEO, Omar Ishrak, hired Yale University to oversee an independent review of the safety and effectiveness of Infuse.

"This sounds eerily familiar to many of the transgressions we've read about from the pharmaceutical industry," said Harlan Krumholz, MD, a professor of medicine at Yale University, when told of the Senate report. "It paints a picture of a company very heavily involved in the science; marketing contaminating the science; and the medical profession and researchers being complicit.

The Public Trust

"It's no wonder the public has lost confidence in the drug and device industries."

Krumholz is overseeing Yale's review of Infuse. Those results are expected in January.

Medtronic's behavior also drew sharp criticism from two key senators on the committee.

"Medtronic's actions violate the trust patients have in their medical care," Sen. Max Baucus, (D-Mont.), chairman of the committee, said in a statement. "Patients everywhere will be better served by a more open, honest system without this kind of collusion."

Senior member Chuck Grassley (R-Iowa) said the findings support the Physician Payments Sunshine Act that he and Sen. Herb Kohl (D-Wis.) authored. That legislation will require drug and device companies to disclose such payments beginning next year.

"The findings also should prompt medical journals to take a very proactive approach...," Grassley said in a statement. "...The public will benefit from more transparency and accountability on their part."

In response to the Senate investigation, Medtronic turned over more than 5,000 documents, including emails involving the doctors and Medtronic employees as well as 14 years of payments from Medtronic to the doctors.

The Infuse Story

In January 2002, Hal Mathews, MD, spoke glowingly about Infuse to a FDA advisory panel that was considering whether to recommend approval of the product.

Mathews, then a Richmond, Va. spine surgeon who had taken part in the pivotal Infuse clinical trial, told the panel he had no direct financial interest in the product and that he was not being paid to appear at the meeting.

However, a 2001 email shows that Medtronic worked with the New York-based public relations firm, Ketchum, to prepare Mathews' speech to the panel, which went on to recommend approval of the product.

In addition, though Medtronic told the committee that Mathews was not paid for any activity undertaken in January 2002, Mathews was paid under consulting arrangements with the company in 2001.

In 2007, Mathews was hired by Medtronic as its vice president of medical and clinical affairs.

From the Pen of Medtronic

An email indicated that a Medtronic marketing employee, Julie Bearcroft, was involved in editing a 2005 Journal of Bone and Joint Surgery article and recommended against publishing a complete list complications related to the structural integrity of the fused area.

Those complications -- known as implant migration, subsidence and end-plate fracture -- had been observed in a clinical trial and had been formatted in a detailed table, according to an internal Medtronic email. But, following the advice of Bearcroft, that table was not included in the published paper.

"I personally think it is appropriate to simply report the adverse events were equivalent in the two groups without the detail," Bearcroft wrote in a note on a draft of the article.

After the editing change was made, the lead author of the paper, Ken Burkus, MD, a Columbus, Ga. surgeon, sent a draft of the paper to his co-authors with the note, "this manuscript documents the superiority in clinical and radiographic outcomes with (Infuse)..."

Burkus, who got $6.4 million from Medtronic between 1998 through 2010, did not respond to an email seeking his comment.

Medtronic officials inserted into papers language that attempted to portray Infuse as a better, less painful alternative to the standard technique of using a small amount of a patient's own hip bone for fusing vertebrae, a claim that has been questioned by independent spine surgeons.

Giving Infuse the Edge

In 2001 and 2002, after viewing early drafts of a 2002 Infuse paper, Neil Beals, a Medtronic marketing official recommended that the physician authors make "a bigger deal" out of the supposed pain reduction with Infuse.

Subsequently, a sentence was inserted in the paper stating that Infuse spared patients from being exposed to problems associated using their own bone for the fusion.

In its review of Infuse last year, doctors writing in the Spine Journal said the often-cited donor site pain was less frequent and serious than Infuse proponents suggested.

In addition, in a draft of a 2003 paper the authors said that any pain at the site of the hipbone graft site had been resolved in the study subjects within a year of the surgery. But Beals questioned that and inserted language saying residual effects of the donor site should be noted.

The final article appears to have adopted his suggestions, noting that even 24 months after the surgeries "some patients continued to experience residual pain at the donor site and rated the appearance of the site as only fair."

Downplaying Safety Concerns

The company also tried, unsuccessfully, to adopt weaker patient safety rules for a clinical trial testing the effectiveness of Infuse in the cervical spine, a use that remains unapproved and which has been linked to life threatening swelling in neck.

In 2008, the FDA warned doctors against using Infuse in cervical spine fusions, citing 38 cases of swelling in the neck and throat leading to compression of the airway. Some of those cases required emergency tracheotomies.

The weaker safety rules sought by Medtronic would have allowed the company to continue the clinical trial even if patients experienced severe swelling in neck.

Infuse is a powerful biological agent that stimulates the growth of new bone, but excess bone growth can be a serious problem when the product is used in certain off-label surgeries. It was approved in 2002 for lumbar spine fusions in which the surgical approach is from the front.

The unapproved use has caused serious problems for Patricia Caplinger and hundreds of other spine surgery patients like her, according to a lawsuit filed earlier this year against Medtronic in federal court in Oklahoma.

The complication experienced by Caplinger was the subject of a 2004 paper written by doctors who have received millions of dollars from Medtronic. That paper involved a clinical trial of Infuse that had to be halted five years earlier because of excess bone growth in the spinal canals of 70% of the patients.

That clinical trial used Infuse in a surgery similar to what Caplinger underwent in 2010.

The surgeons who wrote the article said that patients weren't harmed by the excess bone growth. But that claim that was refuted by an Oklahoma surgeon who took part in the trial and told the Journal Sentinel/MedPage Today last year that he had two patients who developed painful, excess bone growth that required additional surgeries. Caplinger who lives in Missouri was not one of those patients.

A helping hand in the OR

Caplinger says that her doctor and others surgeons were persuaded by Medtronic and its "paid physician promoters" to use Infuse in dangerous, off-label surgeries, according to her lawsuit.

In Caplinger's case, a Medtronic representative actually was present during her surgery and "was actively involved," providing information about use of Infuse in Caplinger's procedure, according to the lawsuit.

Because of the excess bone growth, Caplinger suffers continuous pain in her back and legs and developed a condition known as foot drop, which, in turn, led to a ligament tear in her right knee. She also has required revision surgery on her back and will need another revision surgery because the bone growth is continuing.

In an email, Caplinger, a nurse, said she is worried that the pain eventually will prevent her from doing what she loves the most, working in the emergency department.

"I live with pain every minute of every day," she said. "I have forgotten what not being in pain feels like."
A Medtronic spokesperson said the complaint lacks and the company has the court to dismiss the case.

Medtronic had answers

The Senate report and accompanying documents also show Medtronic employees -- in addition to editing drafts of a paper -- at times covertly drafted responses to questions raised by other doctors who were examining the work as part of medical journal peer review.

Case in point: A 2004 paper was published in the Spine Journal where co-author Charles Branch Jr., MD, also served as deputy editor. Branch, chairman of neurosurgery at Wake Forest University, received $3.1 million from Medtronic from 1998 to 2010. His royalty payments have been split with the university.

That article also was subject of a 2011 Journal Sentinel/MedPage Today investigation.

The Senate documents include a 2003 email, as the article was being drafted, in which Bill Martin, the company's vice president of spinal marketing, wrote: "We may want to steer clear of calling it a flawed technique. There are still quite a few surgeons utilizing this technique..."

About a week later, Rick Treharne, another Medtronic executive, wrote to one of the paper's authors: "In looking over the data, I was impressed with how well the BMP (Infuse) patients actually did. So much so that I added a few paragraphs at the end that you may not agree with."

As peer reviewers for the journal looked over the paper, they raised concerns that it was a slanted, advertising piece.

"This manuscript is full of biased statements that are a reflection of the data evaluators -- the company that markets the product," wrote one reviewer.

"Unless the authors can discuss the results in this study in an unbiased manner, which they have been unable to do in its present form, this data should not be published," wrote another.

Treharne then sent one of the co-authors a draft of a letter to be sent to the editor of the journal addressing the concern. Another Medtronic executive also helped formulate a response to the editor.

The letter that ultimately was sent to the journal's editor sought to reassure him, claiming that three of the co-authors were independent, the Senate investigation found.

But between 1997 and 2003, two of the "independent" authors had received $8.5 million from Medtronic.

"We were falsely reassured that there were independent people looking at the data," said Eugene Carragee, MD, who took over as editor of the Spine Journal in 2009. "It's a violation of the fundamental trust of peer review."

When published, the paper described the results of halted clinical trial as "encouraging."

This story was reported as a joint project of the Journal Sentinel and MedPage Today.

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Guess momma was right when she said "eat your beans" because now a new study shows it helps to lower cholesterol and triglycerides while improving glycemic control in diabetics.

Legumes May Aid Glycemic Control, Cut Lipids

 

By Kristina Fiore, Staff Writer, MedPage Today

Published: October 22, 2012

 

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco

 

 

Eating more legumes such as beans and chickpeas helped improve glycemic control and lowered total cholesterol and triglycerieds in patients with type 2 diabetes, researchers found.

 

In a randomized controlled trial, patients who ate at least an additional cup of legumes per day had a greater reduction in HbA1c than patients who increased their insoluble fiber consumption for 3 months (-0.5% versus -0.3%, P<0.001), David Jenkins, MD, PhD, of the University of Toronto, and colleagues reported online in the Archives of Internal Medicine.

Foods with a low glycemic index (GI) have been shown to improve glycemic control in patients with type 2 diabetes, and legumes -- such as beans, chickpeas, and lentils -- were among the first foods recognized to have low GI values.

They've been recommended in many nutrition therapy guidelines for diabetes, but their effects on glycemic control and other parameters still remain controversial, researchers say.

So Jenkins and colleagues randomized 121 patients with type 2 diabetes to one of two diets for 3 months: a low-GI legume diet that required them to eat at least a cup of legumes per day, or to a diet that increased their intake of insoluble fiber via consumption of whole wheat products.

The primary outcome was change in HbA1c, with a secondary endpoint of calculated coronary heart disease risk.

The difference they found in HbA1c reduction remained significant after adjustment for body weight change, they reported (P=0.005).

In terms of cardiac parameters, they found that the legume diet significantly lowered mean total cholesterol (-8 mg/dL, P<0.001) and triglycerides (-22 mg/dL, P<0.001), without any changes in HDL cholesterol levels.

The insoluble fiber diet increased average HDL cholesterol levels (2 mg/dL, P=0.004), although the reasons for this are unclear, given that such an association hasn't been seen before in the literature, the researchers noted.

And the legume diet reduced blood pressure and heart rate relative to the high insoluble fiber diet, they added.

Thus, the legume diet overall reduced heart risk significantly more than the insoluble fiber diet (-0.8%, P=0.003), and the researchers concluded that incorporating legumes into a low-GI diet can help improve glycemic control and reduce heart risk.

In an accompanying editorial, Marion Franz, MS, RD, questioned whether the modest benefits come from the dietary components or from a reduced energy intake overall.

She warned that low-GI diet has been controversial, with some smaller studies showing a benefit in terms of improved glycemic control but larger studies showing no such benefit.

Franz conceded that legumes are part of a healthy diet for diabetics and the general population, but "whether people with diabetes can eat the amount necessary to improve glycemic control is debatable, and, if legumes do improve glycemia, is it because of their low GI or high soluble fiber content?"

She concluded that nutrition therapy for diabetes is effective but "just as there is no one medication or insulin regimen appropriate for all persons with diabetes, there is no one nutrition therapy intervention."

The study was supported by the Agricultural Bioproducts Innovation Program through the Pulse Research Network and the Saskatchewan Pulse Growers.
The researchers reported relationships with Sanitarium, Agri-Culture, Agri-Food Canada, Canadian Agriculture Policy Institute, California Strawberry Commission, Loblaw Supermarket, Herbal Life International, Nutritional Fundamental for Health, Pacific Health Laboratories, Metagenics, Bayer Consmer Care, Orafti, Dean Foods, Kellogg's, Quaker Oats, Procter & Gamble, Coca-Cola, Abbott, Canola Council of Canada, Almond Board of California, American Peanut Council, International Tree Nut Council, the Peanut Institute, Barilla, Unilever, Solae, Oldways, Haine Celestial, Pepsi, Alpro, Pulse Research Network, Advanced Food Materials, American Pistachio Growers, Danone, General Mills, Paramount Farms, Archer Daniels Midland, and Glycemic Index Laboratories.
The editorialist reported no conflicts of interest.

From the American Heart Association:

• Implementing AHA Pediatric and Adult Nutrition Guidelines

Primary source: Archives of Internal Medicine
Source reference:
Jenkins DJA, et al "Effect of legumes as part of a low glycemic index diet on glycemic control and cardiovascular risk factors in type 2 diabetes mellitus" Arch Intern Med 2012; DOI: 10.1001/2013.jamainternmed.70.
Additional source: Archives of Internal Medicine
Source reference:
Franz MJ "Beyond the glycemic index" Arch Intern Med 2012; DOI: 10.1001/2013.jamainternmed.871