Spiral CT Scans Save Lives from Lung Cancer

In November I wrote about preliminary data from the National Lung Screening Trial, a large study funded by the National Cancer Institute that attempted to find out if catching lung cancer early with spiral CT scans made a difference. (See link 1 below for my November post.) Last week, the New England Journal of Medicine published the trial results (2) and an accompanying editorial (3).

The study randomized over 50,000 people who were

  • aged 55 to 74,
  • were either current smokers or had quit in the last 15 years,
  • had not been diagnosed with lung cancer, and
  • had a lifetime history of smoking at least 10,000 packs of cigarettes (the equivalent of smoking one pack per day for 30 years).

The study subjects were randomized to two groups. One group received annual chest X rays for three years. Chest X rays have already been proven not to save lives as a test for early lung cancer. The second group received annual spiral CT scans of their chest for three years. Both groups were followed for another three and a half years after the tests to assess for the development of lung cancer and death due to lung cancer.

The results were remarkably positive. The group receiving the CTs had a 20% lower rate of death from lung cancer. For every 320 patients screened by CT, one life was saved. That’s a number that compares favorably with other cancer screening tests, like mammography.

This is a very important discovery. Though lung cancer incidence has been declining with the decreasing number of smokers, it remains the number one cause of cancer death in the US. Use of CT screening in the appropriate groups of patients promises to significantly decrease lung cancer mortality.

So if you meet every point in the above list, talk to your doctor about a spiral CT of your chest. More importantly, if you smoke, stop. If you want to stop smoking and can’t, ask your doctor for help.

[Medical news posting resumes in two weeks.]

Learn more:

(1) My previous post about the National Lung Screening Trial: A Screening Test for Lung Cancer

(2) New England Journal of Medicine article: Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic Screening

(3) New England Journal of Medicine perspective article: Better Evidence about Screening for Lung Cancer

LA Times article: Study bolsters evidence that screening reduces lung cancer deaths

Wall Street Journal Health Blog: Lung-Cancer Screening Unknowns: Who Should Get it, How Much it Will Cost

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Rescuing Primary Care

For almost any category of product or service you can think of, a huge variety of price and quality is available. From clothes to food to transportation we can all think of lousy but inexpensive choices that we wouldn’t like and incredibly luxurious choices that we can’t afford. For almost all of us somewhere in the middle there are choices that are both pleasing and affordable. That doesn’t mean that my choice is the same as yours. You may not be happy with anything less than a BMW, while I’m thrilled with my Mazda. But we both found something that meets our needs and doesn’t bankrupt us.

The peculiar thing about healthcare is that for many it’s simultaneously becoming increasingly mediocre and increasingly unaffordable. It’s hard to think of another good or service for which that’s true. In fact, most everything else is getting simultaneously better and cheaper. This crisis is most acute in primary care. Articles have been warning for years about the worsening shortage of primary care doctors as two worrisome trends intersect – fewer medical students are choosing careers in primary care just as the baby boomers age and will need more of it.

This week an article in the LA Times (link 1 below) asks “What happened to the family doctor?” and accurately reviews the dissatisfaction among both patients and physicians. Primary care physicians complain about flat or declining reimbursement, increasing demands on their time, and increasing insurance regulation. Not surprisingly, when most people in a profession are cranky, that doesn’t attract newcomers. The number of medical school graduates choosing primary care training dropped by almost half between 1999 and 2009. At the same time patients complain about increased waiting times, poor access to their physicians, very short visits, and inability to have questions answered by phone or email. And, of course, both physicians and patients are right.

Before we can understand how we got here, we have to understand how other marketplaces avoid this. Why is there no accountant shortage or shoe shortage? The answer is freedom of prices. If accountants became very scarce they would become very expensive. This would draw more people to accounting, alleviating the shortage and bringing their fees back down. Since in most marketplaces producers are free to set whatever price they wish, the result is multiple providers that compete on both quality and price, yielding a great number of options for the customer.

This doesn’t work in the current healthcare system because insurance fixes the price. In the insurance model all physicians contracted with a certain insurance company receive the same fee for the same service, regardless of whether the patient is irritated or delighted, or whether the care was outstanding or marginal. This has two destructive effects. First, it prevents doctors from competing on price. Second, it means that the only way to make more money is to see more patients. Since doctors can’t charge more per visit, the incentive is to maximize the number of visits.

How about that? A system that rewards visits and not patient satisfaction has resulted in many short unsatisfying visits. Why are we surprised?

There have been myriad attempts to fix this failed system without addressing the fundamental flaw. Countless acronyms like HMOs and IPAs have been vaunted as the solution for delivering affordable excellent care. None have. Now of course, new solutions are being proposed – group visits, virtual visits, medical homes – which will all add complexity and bureaucracy without improving care.

There is no way to fix the insurance model. The insurance model is the problem.

How can we attract more students to primary care? By demonstrating to them a primary care model in which doctors are reasonably paid, love what they do, and can practice as they were trained, not as insurance companies dictate. Escaping the insurance model by charging patients directly lets doctors do just that.

But in the very same LA Times issue Steve Dudley, a Seattle physician, writes a very critical and snarky article about concierge medicine (2). Some of his criticisms of concierge medicine are reasonable. For example he criticizes some concierge doctors for both accepting insurance money and charging an additional annual fee, a practice I also find distasteful. He also notes that many physicians set up concierge practices with the help of large impersonal corporate franchises.

But his main criticism is completely hollow. He worries that not all patients would be able to afford it. First of all, some physicians have escaped the insurance model and decided to work for their patients even in blue-collar towns. So working directly for patients need not be unaffordable. Second, having physicians work at different prices is part of what is desperately missing in this marketplace. Not everyone can afford a new car either, but we don’t blame BMW dealers.

Three years ago I wrote an op-ed for the LA Times (3) describing how I came to my current practice model. I think it answers Dr. Dudley’s criticisms. I encourage you to read it. Physicians choosing to work directly for their patients are part of the solution, not part of the problem.

Learn more:

(1) Los Angeles Times article: What happened to the family doctor?

(2) Los Angeles Times article: Concierge medicine has a cost for all patients

(3) My op-ed in the LA Times in 2008: Dollars to doughnuts diagnosis

My previous posts on rescuing primary care:

Torpedoing Primary Care

On Being Doc and Being Happy

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When the Stool Hits the Sprouts

… or Technology Phobia Can Be Fatal

[This post is perfectly safe for work, but may not be safe for lunch, as it mentions poop more frequently than you may find appetizing.]

This post is an update about the E. coli food poisoning outbreak in Germany that I posted about two weeks ago (link 1 below). If you didn’t read that post, please do, as it explains some important terms like hemolytic uremic syndrome (HUS) and shiga toxin-producing E. coli (STEC). Using these phrases at your next party will make you very popular. Trust me.

This week, the New England Journal of Medicine published a review of the data collected thus far on the STEC epidemic in Germany (2). A typical case consists of an incubation period of 8 days after eating contaminated food until symptoms occur. The typical symptoms have been bloody diarrhea and abdominal pain without fever. About 25% of patients have developed HUS several days later. More cases of bloody diarrhea and HUS are still being reported, so the outbreak is not yet over, though the incidence is declining. The incidence peaked on about May 22. As of June 18 a total of 3,222 cases have been identified, including 810 cases of HUS and 39 fatalities. About two thirds of the patients have been women.

This bacterial strain and this outbreak are unusual in that the fraction of cases that proceed to HUS is much higher than previous outbreaks. Also 89% of the cases have been in adults. Prior outbreaks have more predominantly affected children. This STEC strain is also resistant to antibiotics in the penicillin and cephalosporin families.

The New England Journal of Medicine article stated that “raw produce or salad condiments are suspected” and that the investigation was still ongoing, but a Wall Street Journal article (3) and the CDC investigation (4) state that the source of the outbreak has been traced to raw bean sprouts from one organic farm in Germany. How the E. coli contaminated the sprouts is still unclear, but E. coli contamination typically happens through contact with human or animal feces.

This is tragic, but doubly so because it was likely preventable. It’s also an important indictment of our society’s two most popular technology phobias.

The first phobia is our fear of radiation. I’ve written previously about the potential benefits of irradiating our food. It would eliminate much of bacterial food contamination. Even the LA Times is writing about this issue (5).

The second phobia is our fear of synthetic pesticides and fertilizers, manifested in our current infatuation with organic food. The fact that the contaminated bean sprouts were grown in an organic farm is relevant. Sprouts are among the most likely produce to be contaminated because they grow close to the ground in warm humid environments, perfect for contact with waste and for bacterial growth. And organic food that avoids synthetic fertilizer has to use natural fertilizer – animal waste.

Organic food has no health benefits over food grown with modern methods. Indeed it has health risks. It also uses more space and more resources (hence is more expensive) than food grown through modern farming. While I don’t begrudge those who wish to pay more because they believe that organic food tastes better, it is a solution that simply can never feed most of the world.

So carefully wash all your raw fruits and vegetables, support proposals for food irradiation, and reconsider your commitment to organic food. Because it turns out that the alternative to modern technology is stool in your salad.

Learn more:

(1) My post two weeks ago: Germany Struck by Major Food Poisoning Outbreak

(2) New England Journal of Medicine article: Epidemic Profile of Shiga-Toxin–Producing Escherichia coli O104:H4 Outbreak in Germany — Preliminary Report

(3) Wall Street Journal article: EU Confirms Bean Sprouts as E. Coli Source

(4) CDC Investigation Update: Outbreak of Shiga toxin-producing E. coli O104 (STEC O104:H4) Infections Associated with Travel to Germany

(5) LA Times article: Should food irradiation return to the table?

LA Times article: German E. coli strain combines deadly properties of two pathogens

For a very informative description of the benefits of modern farming, as well as other technical revolutions that make modern life possible, I highly recommend “The Rational Optimist: How Prosperity Evolves” by Matt Ridley.

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FDA Warns of Risk of Highest Zocor Dose

What’s the difference between a medication’s intended effect and its side effects? Is there some physiologic difference between the beneficial effects of a medicine and the annoying or even toxic things that it does? Not really. All medications have lots of different effects on the body. The intended effect is simply the one that the patient (or doctor) hopes to achieve. The rest of the effects are by definition side effects. The difference lies purely in the intention of the patient and physician, not in any chemical or biological differences between the processes that result in the intended effect and the side effects. Similarly, software developers acknowledge an ambiguity between the intended and unintended effects of their applications when they joke “That’s not a bug. That’s a feature.”

About twenty years ago a new medication was being investigated as a possible treatment for heart attacks. It dilated blood vessels. So the hope was that during a heart attack dilated blood vessels would deliver more blood to oxygen-starved heart muscle and save lives. Unfortunately, the same fraction of heart attack patients died when taking this new medicine as when taking placebo. And many of the patients taking this new medicine had a side effect that was somewhat embarrassing in the cardiac care unit; they had erections. The new medication, sildenafil, marketed as Viagra, is a very effective medication, but not as a treatment for heart attacks, as a treatment for erectile dysfunction. The initial embarrassing side effect was simply switched to the intended effect. That’s not a bug. That’s a feature.

My regular readers know that statins, a family of cholesterol-lowering medicines, have been proven to prevent strokes and heart attacks. They do this in a dose-dependent manner, meaning that higher doses prevent strokes and heart attacks more than lower doses. Then why don’t we all take a bucketful of a statin daily? Because of side effects. Statins have side effects that are also dose-dependent. They occur more commonly at high doses than at low doses. Muscle injury has long been known to be an occasional statin side effect. It can range from mild injury without symptoms that is noticed only on a blood test, to more severe injury in which muscle pain and weakness is noticed. Very rarely kidney failure and death can result from very severe muscle damage.

Last week the FDA reviewed the existing studies about statin-related muscle injury and concluded that

  • muscle injury, though very rare, occurs more frequently on simvastatin (Zocor) than on the other statins,
  • muscle injury occurs more frequently on the highest dose of simvastatin, 80 mg, than on lower doses, and
  • muscle injury occurs more frequently in the first year of therapy than later.

It’s important to understand that serious muscle injury is very rare even at this highest dose, and this highest dose has greater benefits in terms of stroke and heart attack prevention than lower doses. So the FDA recommended that no new patients be started on 80 mg of simvastatin. Patients who have been taking that dose for over a year can continue it. If you’ve been taking simvastatin 80 mg for less than a year, a visit to your doctor for instructions is in order.

(By the way, with our electronic medical records we will identify all the relevant patients and reach out to them. With paper charts, doctors can only hope that the relevant patients hear the news and schedule appointments.)

Now if we can only figure out how to sell rare but serious muscle injury as a feature…

Learn more:

FDA Consumer Update: Limit Use of 80 mg Simvastatin

NY Times Prescriptions: F.D.A. Issues Safety Alert on Zocor

LA Times Booster Shots: FDA suggests new limits on cholesterol-lowering drug Zocor

Wall Street Journal article: FDA Urges Limits on Dosages of Zocor

New England Journal of Medicine perspective article: Weighing the Benefits of High-Dose Simvastatin against the Risk of Myopathy

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Germany Struck by Major Food Poisoning Outbreak

Since May Germany has been plagued with a particularly nasty outbreak of food poisoning. There have been almost 3,000 people who have become sick so far and 27 deaths, with a small number of cases in other countries.

The bacterium causing the outbreak has been identified, but the name of the bacterium is so convoluted that it needs explaining. The outbreak is caused by shiga toxin-producing Escherichia coli O104:H4 (or STEC O104:H4). Got that?

Please let me ‘splain. Escherichia coli (E. coli) is a very common bacterium. Most strains live harmlessly in human and animal colons (hence the name) and do not cause disease. Occasionally they cause bladder or kidney infections. The O104:H4 just identifies the specific strain of E. coli.

Shiga toxin is a particle produced by some strains of E. coli and other bacteria. It was named after Kiyoshi Shiga, the bacteriologist who first isolated the bacterium that causes dysentery – Shigella, which was also named after him. Shiga toxin is responsible for the particularly severe clinical features of STEC infection.

So now that we understand the name of the germ, what’s going on in Germany? Well, the source of the food contaminated with STEC is almost certainly some kind of fresh produce, but the specific food, farm or distributor has not yet been found. Cucumbers from Spain were initially blamed, and then sprouts from Northern Germany, but both of these turned out to be false alarms. Investigators are still working to track down the source.

What are the symptoms of STEC infection? That’s where our story’s antagonist, shiga toxin, comes in. Shiga toxin causes severe abdominal cramping, vomiting and acute (frequently bloody) diarrhea. That’s bad enough, but a week later, a minority of patients develop hemolytic uremic syndrome (HUS). HUS involves injury to the kidneys and destruction of the body’s blood cells. Symptoms include severe fatigue, decreased urine output, and pallor. In this outbreak over 600 people have required intensive care unit admission, likely because of HUS.

The only cases in the US have been just a handful of people who have recently travelled to Germany. No contaminated food has been imported from Europe to the US. If you’re planning a trip to Germany, review the Centers for Disease Control recommendations at the link below.

The loss of life and the thousands of people sickened is obviously tragic. The financial impact of the lost tourism and the losses to farmers and restaurants come at a particularly bad time given Europe’s financial crisis. What compounds the tragedy is that food-borne infections could be prevented if food was irradiated before it got to supermarkets or restaurants. I’ve written about food irradiation before (link below). To achieve improved safety, we wouldn’t even have to irradiate all food. If labeling was clear, consumers would have a choice. Those wishing to avoid STEC, Salmonella and Shigella would choose irradiated produce, and those with prejudices about gamma rays could still avoid irradiated produce and take their chances. Unfortunately, radiation is not an area in which we have devoted much effort in educating the public. In the wake of Japan’s Fukushima nuclear reactor disaster, Germany has recently decided to abandon nuclear power, even though Germany obtains a quarter of its electricity from nuclear power and has never had a serious reactor accident.

So this is probably not a good time to remind them about the potential benefits of food irradiation. But I hope that after this outbreak is over some influential Germans will realize that more Germans have just died from shiga toxin than have ever died from radiation.

Learn more:

New York Times article (June 6): Deadly E. Coli Outbreak Linked to German Sprouts

Wall Street Journal article (June 7): E. coli’s Trigger Remains a Mystery

Wall Street Journal article (June 8): EU Seeks to Combat E. coli’s Hit to Farms

CDC Travel Notice: Shiga toxin-producing E. coli O104:H4 infections in Germany

CDC Investigation Update: Outbreak of Shiga toxin-producing E. coli O104 (STEC O104:H4) Infections Associated with Travel to Germany

My previous posts about food-borne illness:

Your Food Is Pretty Safe, But it’s Not Getting Safer

Would You Like Some Salmonella With That?

Gamma Rays are Good for Your Veggies

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Cellphone Users Have a Higher Risk of Getting Annoyed at the World Health Organization

This week all the buzz is about cellphones and brain tumors. Who would possibly link cellphones and brain tumors? The World Health Organization, that’s WHO.

This week, an agency in WHO announced that it was declaring cellphone use to be “possibly carcinogenic”, adding it to a group of substances which include lead, engine exhaust, chloroform, coffee and pickled vegetables.

First, let’s make sure we understand what this does not mean. This does not mean that cellphone use is known to cause cancer. The WHO classifies tobacco and ultraviolet light as known carcinogens, which is not the group in which it classified cellphone use. It also doesn’t mean that cellphone use is a probable carcinogen, like some industrial chemicals and exhaust from wood combustion. Probable carcinogens have another group in the WHO classification.

This means that cellphone use might cause cancer, or not. The WHO clearly announced that adverse health effects of cellphone use have not yet been established.

So what’s the hubbub? Well, so many people use cellphones that even if a cancer link is possible, the WHO wants to keep an eye on it. Naturally, media outlets were all over this story with various levels of alarm and skepticism (links below). There are two specific concerns that some studies have suggested: gliomas and acoustic neuromas. Gliomas are malignant brain tumors. Acoustic neuromas are benign tumors of the nerve that connects the ear to the brain.

But the studies have not been consistent. Dr. David Savitz, professor of epidemiology at Brown, says that most studies looking at cellphone use and cancer failed to show a link. (The quotes are in the articles linked below.) He also cites data from Scandinavian countries which were early in cellphone adoption and yet have not seen any increased incidence in brain tumors.

So there may be no increased risk at all, and this is all very vague and preliminary. But my regular readers know I like to dive into the numbers. If we believe the scariest of the studies, how risky would cellphone use be? Well, one study suggested that the risk of glioma doubles with every decade of cell phone use. Good grief! That sounds terrible. But before resigning yourself to sending messages by carrier pigeon from now on, let’s figure out the magnitude of that risk. There are 10,000 to 12,000 new cases of glioma per year in the US. Taking the upper figure, in the US population of 300 million that yields a risk of 1 in 25,000 of developing a glioma every year. That means that the risk over a decade is 1 in 2,500. If cellphone use over that decade doubles the risk, that means that for every 2,500 people using a cellphone for ten years one additional glioma results and the other 2,499 people go on blabbering on their cellphone.

Numerically, that’s a pretty small risk. That’s much smaller, for example, than the risk that untreated high blood pressure will lead to stroke. And that’s if there’s any risk at all which has not yet been proven.

So does it make sense to use Bluetooth or wired headphones during a call to keep our cellphones a few inches from our heads? I don’t know. There’s certainly no harm in that precaution, but there may also be no benefit. Compared to cellphones distracting drivers and causing traffic collisions, and people’s phones ringing in lectures and at movies, the possible cancer connection strikes me as tentative and minor.

But perhaps the WHO actually helped by giving us another excuse to end an unwanted conversation. “I gotta go. You’re giving me a brain tumor.”

Learn more:

LA Times article (including KTLA news video clip): Study links cellphones to possible cancer risk

CNN article (including video clip): WHO: Cell phone use can increase possible cancer risk

Wall Street Journal article: Cellphone Cancer Warning

CNN Health article: Coffee, pickled veggies also ‘possibly’ cause cancer

Tangential Miscellany

Yet again the nice folks at US Airways Magazine reprinted one of my posts – This Isn’t Your Father’s Heart Disease. If you missed it when I first wrote it, give it a read. And if you fly US Airways in June, please grab a copy.

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Niacin Does Not Prevent Strokes or Heart Attacks

In the last decades we’ve made major strides in heart attack prevention through the use of blood pressure medications, smoking cessation, and statins – a family of cholesterol-lowering medications that have been proven to prevent heart attacks and strokes. Despite these advances, heart attacks remain the leading cause of death in the US. New medications to further decrease heart attack risk are being eagerly sought.

Allow me a brief digression to explain three important fat molecules in your blood. LDL is called “bad cholesterol” because it best predicts heart attack and stroke risk, meaning people with an elevated LDL have a higher risk of stroke and heart attack than people with normal LDL. Statins lower LDL. HDL is called “good cholesterol” because people with elevated levels have lower risk of stroke and heart attack. So low HDL is a risk factor for heart attacks. Finally, triglycerides are another fat molecule elevated levels of which predict increased risk of heart attack.

Given the enormous success of statins in lowering LDL and preventing strokes and heart attacks, hopes were high that a medication that raised HDL would have similar benefits. Niacin is known to raise HDL and lower triglycerides and has been used for many years in many patients to do just that. So the NIH decided to perform a study to measure its ability to prevent heart attacks.

The AIM-HIGH trial (All large clinical trials now have contrived, long, overly clever acronym names. You don’t want to know what AIM-HIGH stands for.) enrolled over 3,400 patients with a history of cardiovascular disease, low HDL and high triglycerides. That means they were at high risk of a future stroke or heart attack. Importantly, they all received simvastatin (Zocor) and had excellent LDL control. Half of the patients were randomized to also take extended release niacin (Niaspan) and the other half took placebo.

The patients were followed for an average of 32 months to see if the niacin group would have fewer strokes and heart attacks. As expected, the niacin group had higher HDL and lower triglycerides than the placebo group. But there was no difference in the numbers of strokes and heart attacks between the two groups. In fact, the niacin group had a tiny (but statistically significant) increase in strokes. This lack of benefit and small increase in harm led to the trial being stopped 18 months earlier than expected.

There was much wailing and lamentation, particularly at Abbott Laboratories which makes Niaspan and sold over $900 million of it last year. (Let that number roll around in your head for a minute while contemplating that the drug has no proven benefit. We skeptical evidence-based physicians who never prescribed it last year will be rewarded with an internal sense of accomplishment, a reward somewhat less tangible than $900 million.) Abbott is now in full damage-control spin mode suggesting that Niaspan may still have benefits in patients other than those enrolled in the trial. Sure. The trial was specifically designed to find a benefit by testing niacin on patients most likely to benefit – those at highest risk for heart attack and with high HDL and low triglycerides. Niacin didn’t help them, but it might help, who exactly? People with nasal allergies? People who need the Niaspan tablets to wedge under the short leg of a wobbly table?

Sadly, this isn’t the first bit of bad news in our attempts to help people by raising their HDL. A group of medicines called fenofibrates, which includes TriCor and Trilipix, also raise HDL and lower triglycerides and in recent trials have also failed to prevent heart attacks.

So what are we to make from these negative results? If low HDL is a risk factor for heart attacks, why doesn’t raising HDL decrease heart attacks? The answer is that risk factors are not causes; correlation is not causation. The fact that people who have low HDL have more frequent heart attacks than those with normal HDL doesn’t mean that the low HDL is causing the heart attacks. Some other unknown factor may cause both the HDL decline and the heart attacks, which would make HDL simply a marker of risk but with no effect on the heart attacks themselves. For example, ice cream sales in rural towns might be correlated with livestock deaths. So ice cream sales might be useful for predicting how many livestock die on a given day, but will banning ice cream lead to improved livestock longevity? No. Both the ice cream sales and the livestock deaths are caused by another factor – very hot days.

The many news articles covering this story (links below) seem not to understand this point. They state things like “lowering LDL prevents heart attacks” or “statins prevent heart attacks by lowering LDL” but we don’t know that. We have no idea how statins prevent heart attacks. We only know that they do prevent heart attacks and that they do lower LDL. There is no way to know if statins prevent heart attacks through lowering LDL or through some other mechanism. In fact, since estrogen lowers LDL and doesn’t prevent heart attacks, that suggests that LDL (like HDL) may be a marker of risk, not the cause.

So we can focus on risk factors to identify patients at risk, but for an effective treatment we must insist on a therapy that affects clinical outcomes (like strokes or heart attacks) not just risk factors. Niacin just failed that important test.

Learn more:

New York Times article: Study Questions Treatment Used in Heart Disease

NPR health blog: Study: Boosting Good Cholesterol With Niacin Did Not Cut Heart Risks

Wall Street Journal article: UPDATE: NIH Stops Clinical Study Involving Abbott’s Niaspan

NIH press release: NIH stops clinical trial on combination cholesterol treatment

For an explanation of the important difference between modifying risk factors and changing clinical outcomes, see my post Merck Knows More about Zetia than They’re Telling Us

Correction on December 2, 2011: In the 1960s the Coronary Drug Project (CDP) showed that niacin was superior to placebo in the prevention of stroke and heart attacks. The statement in this post that niacin has never been proven to prevent strokes and heart attacks is incorrect and has been crossed out. I regret the error. More details about the CDP and niacin are in this post. The title of this post might have been somewhat more accurate if appended with “in patients taking statins”.

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Chronic Fatigue Syndrome Study Criticized by Patients

“Everyone is entitled to his own opinion, but not his own facts.”
–attributed to Daniel Patrick Moynihan, among others

Chronic fatigue syndrome (CFS) is an illness marked by chronic disabling fatigue that is not explained by another diagnosis. Other symptoms such as non-refreshing sleep, subjective memory impairment, tender lymph nodes, and joint or muscle pain may be present. The cause of CFS remains unknown, and no consistently effective treatments have been found. Some studies have suggested a viral cause for CFS, though other studies have had contradictory findings.

In February the British journal Lancet published results of a study (link below) that should have been greeted with enthusiasm. The study randomized over 600 patients with CFS into four groups. One group received only specialist medical care, in which a CFS specialist followed and managed the patient. A second group received specialist medical care plus cognitive behavioral therapy (CBT), a specific type of psychotherapy that has been proven to be effective for several kinds of psychological conditions. A third group received specialist medical care and graded exercise therapy (GET), an exercise program which starts with very low intensity and short duration exercise and slowly increases in difficulty over time. The final group received specialist medical care and adaptive pacing therapy (APT).

APT is a popular treatment for CFS based on the theory that CFS permanently limits the patient’s available energy and ability to exert. APT teaches the patient to work and complete activities of daily living within these limitations. That is, it teaches patients to adapt to their fatigue by pacing their activity. In contrast, graded exercise therapy assumes that lack of activity is part of the cause of the fatigue and so slowly increasing activity can help the patient overcome the patient’s current limitations.

The four groups were followed for a year and were measured for levels of fatigue and physical functioning. The groups receiving cognitive behavioral therapy and graded exercise therapy had modest improvements in fatigue and physical functioning over the group receiving only specialist medical care. The group receiving adaptive pacing therapy did not improve over those receiving only specialist medical care. The improvements in the CBT and GET groups were not spectacular, but they were statistically significant.

At this point I should make it clear that I’m not a CFS specialist. I’m not familiar with the rest of the CFS literature, and I have no opinion about whether this study is definitive. It did not have a huge number of patients, there was no way to blind them to the treatments they were receiving, and the outcome measures were all self-reported. So I assume that many CFS specialists find these findings intriguing, but would like to see them confirmed in a larger study.

But what I find interesting and perhaps counterproductive is the reaction of many patients. The Wall Street Journal Health Blog has been closely following this story (see the links below) and the comments from patients on their posts are quite sobering. If I had a chronic debilitating illness which has no consistently effective treatment and a study showed a modest improvement from CBT and GET, I would be knocking at the door of the nearest CBT psychologist and calling a personal trainer. And I would be pretty happy that a study finally had a positive result. Instead, patient advocacy groups and many individual patients are quite upset. They assert that CFS is caused by a virus and they reject the study findings which they think suggests that CFS is a psychological condition. This is despite the fact that the authors of the study explicitly state that “the effectiveness of behavioural treatments does not imply that the condition is psychological in nature.”

I have two reactions to this criticism from patients. The first is, why have an agenda about something under investigation? Why prefer that your disease is caused by a virus than by anything else? It either is caused by a virus or isn’t and our strongest desires can’t change the actual disease. In ten years we may find conclusive evidence that it is caused by a virus, or that it’s an auto-immune disease, or that it has genetic predispositions or that it’s a psychiatric condition. But until we know, why have a preference? This seems to me like having a strong wish about the orbit of Jupiter. I understand the patients’ desperation for an effective treatment, but the way to get there is to let the researchers seek the truth in an unbiased way, not to tell them what you expect them to find.

My second thought is, why the automatic rejection that CFS may have a psychological component? Again, if I were a patient, I would just want honest answers. If it turned out that my illness was psychological, knowing this would certainly help me focus on the right treatments more than pretending the opposite. Obviously, there is a stigma around psychiatric illness, but that stigma is wrong and should be fought against. People with bipolar disorder, for example, don’t choose their illness and can’t “snap out of it” through an act of will any more than people with pneumonia or diabetes. So I think it would be more constructive for CFS patient advocates to say something like “We don’t know what causes CFS, and whether or not it turns out to be a psychological disease, we didn’t choose it. We deserve compassion and treatment just as much as those suffering from other illnesses.” Denying that CFS could have a mental component only exacerbates the social stigma against psychiatric illness.

CFS patients deserve understanding and treatment regardless of the cause of their illness. The first step should be a willingness to investigate this mysterious condition without preconceptions.

Learn more:

Lancet study: Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial

New York Times article (in February): Psychotherapy Eases Chronic Fatigue Syndrome, Study Finds

Wall Street Journal Health Blog post (in February): This Study on Chronic-Fatigue Syndrome Has Nothing to Do With XMRV

Wall Street Journal Health Blog post (this week): Study Blowback Shows Controversy Over Chronic Fatigue Syndrome

Tangential Miscellany

The Centers for Disease Control is clearly following my lead. This week it has finally alerted the public to a threat I’ve been warning readers about for years – the inevitable zombie apocalypse.

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Sitting Won’t Kill You, Except on Train Tracks

In the last couple of weeks the media has published stories making it sound like your Ikea chair is a death trap waiting to assist your suicide through the dangerous activity of sitting down. Stories with sensational titles like “Is Sitting a Lethal Activity?” (see link below) make you think that you’re better off walking outside for a smoke. Let’s spend a few minutes sifting the solid science from the wacky conjecture. You might as well sit down for this.

The media interest in the idea that sitting might kill you started with the publication last month of a paper entitled “Sedentary Behaviors Increase Risk of Cardiovascular Disease Mortality in Men” in the journal Medicine and Science in Sports and Exercise. (The link to the paper is below, but I’ve read it so you don’t have to.) The study followed thousands of men who in the 1980s were surveyed about their activity levels. They were asked how many hours per week they spent riding in a car and watching TV. They were also asked about how physically active they were. The study then followed these men for over twenty years and counted those who died of cardiovascular disease. The men who spent the most time watching TV and riding a car were at highest risk of dying of cardiovascular disease. So the authors conclude that time spent sedentary, regardless of how much exercise is done the rest of the day, is dangerous.

My regular readers will know that this doesn’t mean that sedentary activity causes cardiovascular disease, because the study isn’t randomized. This conclusion is just as wrong as guessing that there’s something specifically about televisions or cars that cause cardiovascular disease. The only way to sort out whether sedentary time in itself causes cardiovascular disease is to force one group to spend a lot of time sitting and to force another group not to sit (which I think is an enhanced interrogation technique). We can assume that sitting is perfectly safe and still imagine lots of factors that would lead men who sit a lot to die sooner. Sick people, for example, may feel too poorly to be active. They will therefore sit a lot more and die sooner than their healthier counterparts. The authors took some precautions to avoid such confounding factors, but these factors can’t be eliminated entirely without randomization.

The NY Times article about this issue (link below) is an interesting jumble of good science and unfounded conclusions. The article cites a study by James Levine in which subjects were instructed not to exercise and were carefully fed a diet containing 1,000 more calories than needed to maintain their weight. Some subjects gained weight and others didn’t. The ones who didn’t gain weight subconsciously increased their activity level when their caloric intake increased. They fidgeted, paced, stood, stretched and generally moved enough to burn the excess calories. That’s a fascinating discovery which teaches us that even small repeated movements can burn a lot of calories. But this has nothing to do with the article’s main claim which is that being sedentary poses a hazard that is not compensated by exercise – that sitting for 8 hours is dangerous even if you’re going to jog for 30 minutes later that day. The article supports that claim only by a lot of non-randomized epidemiology and metabolic studies, nothing persuasive.

The NPR story and The Dish graphic (links below) also commit the very common error of arguing from design. Arguing from design happens whenever someone asserts what our bodies are “built for” or “meant to do”. The stories state that “we just aren’t really structured to be sitting for such long periods of time” and “a hundred years ago, when we were all out toiling in the fields and factories, obesity was basically nonexistent.” Yes, and a hundred years ago life expectancy was much shorter. We are more sedentary now and living longer than ever. The problem with arguing from what nature “meant” us to do is that for most of human history most humans lived on the edge of starvation, fleeing from predators, and dying young. All of human progress, from wearing glasses to modern medicines, has been marked by rebellion against what nature intended for us. What we were “built” to do can’t help us figure out what we should do. Only a randomized study can.

The articles do have some good common-sense suggestions. If you’re overweight, or have poorly controlled diabetes, high blood pressure or high cholesterol, then more physical activity would certainly help you. You can get that activity by spending more time exercising or less time sitting. There’s certainly no harm in getting up from your chair periodically to stretch or pace around the office, and every calorie burned is a good thing. But if your weight, blood pressure, cholesterol and blood sugar are normal and you exercise regularly, there is nothing in these articles that should convince us that sitting in a chair is bad for you. But you should probably take your feet off the desk before your boss walks in.

Learn more:

NY Times article: Is Sitting a Lethal Activity?

NPR story: Sitting All Day: Worse For You Than You Might Think

The Dish graphic: Sitting Is Deadly?

Medicine & Science in Sports & Exercise article: Sedentary Behaviors Increase Risk of Cardiovascular Disease Mortality in Men

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Surgery Might Save Lives in Early Prostate Cancer

Last week’s post, “Armadillos Transmit Leprosy to Humans”, generated much positive feedback, which I appreciated. You all clearly enjoy stories featuring cute mammals and very little serious science or health implications. I did my best to find a story like that this week, but the closest thing I found was that SEALs cause penetrating head trauma to a few particularly nasty humans.

But there was an important study this week about prostate cancer. My regular readers know that one of the controversies surrounding prostate cancer is that no one knows yet whether treatment of prostate cancer saves lives. That’s partially because prostate cancer grows so slowly and affects older men. It’s clear that many men with prostate cancer would live normal life-spans and die of some other cause if their cancer was ignored.

This week’s issue of the New England Journal of Medicine published a European study in which nearly 700 men with early prostate cancer were randomized to two groups. One group had surgical removal of their prostate. Another group underwent “watchful waiting” – no immediate treatment, with close surveillance for tumor growth or spread, and treatment at that later point.

Both groups were followed for an average of almost 13 years. The group that received surgery had significantly fewer deaths. There was one fewer death for every 15 patients randomized to surgery. The bulk of the benefit was in men younger than 65 at the start of the study. There was one fewer death for only 8 of these younger men who underwent surgery – an impressive demonstration of the benefit of surgery.

The conclusion of this study has important caveats which are detailed in the accompanying editorial and in the media coverage (links below). Most importantly, the patients in this European trial are very dissimilar to US prostate cancer patients. The patients in the study mostly had prostate cancer that was causing symptoms which led the patients to seek medical attention. In contrast, US patients are usually diagnosed through a PSA, a screening blood test. That means that the European patients had prostate cancer that had developed for many years longer than a typical American patient at diagnosis. So whether surgery would still be beneficial in even earlier cancer diagnosed by PSA is unknown. Also, this study did not assess other important treatment options for prostate cancer: radiation and hormonal therapy.

The breakthrough from this study is that we are now fairly certain that in some men with some types of prostate cancer treatment is lifesaving. Further defining which men with which tumors will benefit is the subject of ongoing research.

Next week, I’ll try to find something about syphilitic badgers.

Learn more:

Los Angeles Times Booster Shots: Prostate cancer surgery improves survival in younger men, Swedish study finds, but there are caveats

US News article: Aggressive Treatment May Be Beneficial for Early Prostate Cancer

New England Journal of Medicine article: Radical Prostatectomy versus Watchful Waiting in Early Prostate Cancer

New England Journal of Medicine editorial: Effective Treatment for Early-Stage Prostate Cancer — Possible, Necessary, or Both?

My most recent posts about the controversies of prostate cancer:

New Evidence Supports Prostate Cancer Screening

American Cancer Society Revises its Guidelines for Prostate Cancer Screening

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