Nearing a Cure for Hepatitis C

The Hepatitis C virus is what scientists call very small. Here is an electron micrograph of one. The scale bar is 50 nanometers. Photo credit: Wikimedia/Rockefeller University
The Hepatitis C virus is what scientists call very small. Here is an electron micrograph of one.
The scale bar is 50 nanometers. Photo credit: Wikimedia/Rockefeller University

In the contest to get a creative name, few pathogens have done worse than hepatitis C. In the 1970s there were two known viruses that caused hepatitis – liver inflammation. You might have already guessed that these two viruses were called hepatitis A and hepatitis B. It was known at that time that people sometimes developed hepatitis after blood transfusions and that the majority of those patients tested negative for hepatitis A and B. A new pathogen was hypothesized and called non-A-non-B hepatitis. It wasn’t until 1989 until the virus was isolated and named [drum-roll please] hepatitis C.

Hepatitis C is transmissible through contact with blood. Before the advent of routine testing of the blood supply it was transmitted through transfusions. It is still transmitted through the sharing of drug and tattoo needles and, in less developed countries, through the reuse of unsterilized medical equipment. Hepatitis C can cause liver failure and liver cancer. There are over 3 million people in the US who are infected with hepatitis C. It is the leading cause of liver transplantation and liver cancer in the US.

There are vaccines against hepatitis A and B, but none yet for hepatitis C.

For decades the standard therapy for hepatitis C has been a regimen including interferon and ribavirin. Interferon has to be given by injection and can have debilitating side effects. A course of treatment lasts 6 to 12 months, and many who begin a course are unable to tolerate it. Fewer than 50% of patients who are treated with this regimen have a meaningful benefit. Because of the length and difficulty of the treatment many hepatitis C patients are thought to be poor candidates and never are offered treatment.

Most of my posts are about a new interesting study, but this post is about a whole crop of studies published in the last two months in the New England Journal of Medicine (NEJM) about the safety and efficacy of novel treatments for hepatitis C. (For links to the individual studies, see the right sidebar of this related NEJM editorial.) Eight recent studies have examined several new medication regimens with truly remarkable results.

The new regimens involve oral medications, so injections are unnecessary. Rather than lasting 6 to 12 months they last 8 to 12 weeks. They are very well tolerated with fairly mild side effects. Best of all, over 90% of the patients appear to have complete clearance of the virus. These results suggest that these medications are no longer in the realm of treating hepatitis C. Instead, for most patients, these medications are a cure for hepatitis C.

Of course, there’s a catch. The medications are astronomically expensive. One of the medications (sofosbuvir) costs $84,000 for a 12 week course. This has caused much consternation and bloviating about pharmaceutical corporate greed. (I’m fascinated by articles that rhapsodically praise the extraordinary medical and scientific breakthrough that these medications represent and a few sentences later vilify the companies that made those breakthroughs possible.)

If we keep our cool and do absolutely nothing, the prices will eventually drop. Competition from newer medications, expiration of patents, and negotiations with insurers will all drive prices down over the next several years. Remember, cell phones and cars were wildly unaffordable when they were new. If we all get angry and insist on making these medicines “affordable” by legislating that insurers cover them, we could make sure that their prices stay astronomic forever.

The exciting news is that within a decade or two we might be able to eradicate hepatitis C. Then maybe we can concentrate our resources on viruses with cooler names, like MERS and Ebola.

Learn more:

New Drug Combination Highly Effective For Hepatitis C (Forbes)
Eradication of hepatitis C on the horizon (The Washington Post)
A Costly Cure for Hepatitis C (The Medical Letter blog)
Therapy for Hepatitis C — The Costs of Success (NEJM editorial, by subscription only)
Therapy of Hepatitis C — Back to the Future (NEJM editorial, free without subscription. The right sidebar has links to all the recent studies of drug trials for hepatitis C.)

More

Return of the Spirochete

Treponema pallidum spirochetes
Electron micrograph of Treponema pallidum bacteria
CDC / Dr. David Cox / Public Health Image Library #1977

“Example is the school of mankind, and they will learn at no other.”
– Edmund Burke

Syphilis has been around at least since Europeans arrived in the Western Hemisphere. It’s a sexually transmitted disease caused by Treponema pallidum, a member of a group of corkscrew-shaped bacteria called spirochetes. Sometimes it causes no symptoms at all, but typically it initially causes a painless sore on the mouth or genitals. Later it can cause a rash. Untreated it may lead to blindness, spinal cord and brain damage, and death.

After the discovery of penicillin in the 1940s syphilis was for the first time easily curable and the prevalence of syphilis in the US dropped precipitously.

I trained in the bad-old-days of the mid-90s when HIV was killing tens of thousands of people in the US every year. On every inpatient ward rotation I met patients hospitalized with an opportunistic AIDS-related infection. On every ICU rotation I met patients dying of AIDS. Back then medications to treat HIV were few, new, and only modestly effective. HIV was usually a rapidly fatal disease. It was scary. Counseling patients about condom use and monogamy was not moralistic or theoretical. It had all the practical urgency of yelling at someone to get off the train tracks.

I have no evidence that HIV and the response to it was responsible for the subsequent fall in syphilis infections, but in fact syphilis did decline during the 90s and in 2000 reached its lowest rate ever in the US and was on the verge of being eliminated. You would think that a disease that can be easily diagnosed with blood tests, can be cured with antibiotics, and can be prevented with condoms would be on its way to the dustbin of history. You would be wrong.

This week the Centers of Disease Control and Prevention (CDC) published a review of syphilis trends in the US from 2005 to 2013. The statistics are dismaying. The number of syphilis cases almost doubled during that interval, from 8,724 cases in 2005 to 16,663 in 2013. 91% of the 2013 cases occurred in men. The number of cases in women was about the same in 2013 as in 2005. Of the male cases in 2013, 84% occurred in men who reported having sex with men.

The report breaks down the trends geographically and by ethnicity but it’s the age breakdown that I found fascinating. From 2005 to 2009 men aged 20 to 24 had the greatest percentage increase in syphilis rates, and from 2009 to 2013 men aged 25 to 29 had the greatest increase. But of course those two age categories are actually the same group – men born in the 1980s. I couldn’t help notice that these are the men who grew up after the bad-old-days, the men who think of HIV as the treatable chronic illness it has become, not the death sentence it was 20 years ago.

The CDC report offers wise advice to physicians. We should be testing gay and bisexual men for syphilis at least annually. Men who have multiple partners should be tested more frequently. We should be counseling consistent condom use except in prolonged monogamous relationships in which both partners have been tested.

But perhaps that won’t be enough. I have zero evidence that the attitudes about HIV contributed to the decline of syphilis in 2000 or its resurgence now, but the time course certainly seems to fit. It’s a testament to scientific research and drug development that in such a short time a disease that had the mortality of stage four lung cancer is now more like diabetes. But to young men this progress must make our advice about avoiding sexually transmitted diseases sound a lot less urgent – less like getting off the train tracks and more like putting on their seat belt. That complacency is a terrific opportunity for a patient and ambitious spirochete.

Learn more:

US Syphilis Rate Up; Mostly Gay And Bisexual Men (NPR)
Syphilis Made A Big Comeback In 2013, CDC Warns (Forbes)
CDC Reports Syphilis is Increasing in Homosexual and Bisexual Men (Science World Report)
Syphilis (CDC fact sheet)
Primary and Secondary Syphilis — United States, 2005–2013 (CDC Morbidity and Mortality Weekly Report)
Syphilis—Reported Cases by Stage of Infection, United States, 1941 – 2012 (CDC)

More

There Has Never Been a Better Time to Have Diabetes

A patient’s blood glucose is measured. Credit: Biswarup Ganguly / Wikimedia Commons
A patient’s blood glucose is measured.
Credit: Biswarup Ganguly / Wikimedia Commons

The danger of diabetes is not only the immediate risk of very high blood sugar. Diabetes also has many dreaded long-term complications. (In this post I am referring to both type 1 and type 2 diabetes mellitus. For an explanation of the differences between these two very different diseases see the first half of this post.) Diabetes greatly increases the risk of stroke, heart attack, and amputation. In the US it is the leading cause of kidney failure and of blindness in adults.

A study performed by researchers at the Centers for Disease Control and Prevention and published in the current issue of the New England Journal of Medicine tracked the frequency in the US of five serious complications of diabetes over the two decades from 1990 to 2010. This was not an experiment in which a medication or diagnostic test is evaluated. This was simply counting how many people had diabetes in the US, and how many of them suffered heart attacks, strokes, kidney failure, amputations, or death due to very high blood sugar.

The results were very encouraging. The rate of heart attacks among diabetics fell by two thirds, as did the rate of death due to very high blood sugar. This parallels a similar but smaller drop in the frequency of heart attacks in the general population. Stroke and amputation rates both declined by about half. The risk of permanent kidney failure declined by about a quarter.

What accounts for these favorable trends? Part of the credit lies with earlier detection and better treatment of diabetes. Screening for early complications of diabetes by checking for early signs of kidney injury and for the first signs of skin sores helps prevent amputations and kidney failure.

But much of the credit for these positive trends has nothing to do with diabetes, but with general improvements in preventing cardiovascular disease. Fewer people are smoking. Statins have revolutionized treatment for high cholesterol and have drastically reduced the incidence of strokes and heart attacks in the general populations. Improved use of blood pressure medications have also contributed to stroke and heart attack prevention and have prevented kidney failure. And all of these measures have helped reduce the frequency of amputations.

So as cardiovascular risks have declined in the general population, people with diabetes who are at very high risk have benefited most. That’s great news.

The one bit of data in the study that is terrible news is that from 1990 to 2010 the number of people with diabetes in the US grew from 6.5 million to 20.7 million. So the frequency of terrible complications from diabetes is declining, but the number of people subject to these complications has more than tripled. This is terrific news for the individual with diabetes. Diabetes has never been less scary or more manageable. But for the society as a whole, the news is mixed.

To make further progress in decreasing complications from diabetes we must figure out how to stem the tide of the diabetes epidemic. For type 2 diabetes this may mean earlier detection of risk factors and expanded use of weight loss surgery for appropriate patients. It may also mean working to reverse the epidemic of obesity – a quixotic task. For type 1 diabetes this may mean further work on an artificial pancreas and on immunotherapy that might arrest the disease in its very early stages when some pancreatic function remains.

We’ve come a long way. We’ve got a long way to go.

This post is dedicated to my nephew Elliott who has type 1 diabetes. His parents, Matt and Violet, have become very active with the Juvenile Diabetes Research Foundation (JDRF), an organization that funds research seeking a cure for type 1 diabetes. They are being honored for their indefatigable support of JDRF at a gala next month. Please consider supporting JDRF’s important work with your involvement or a donation. Thank you.

Learn more:

For Diabetics, Health Risks Fall Sharply (New York Times)
Study: Diabetic heart attacks and strokes falling (Washington Post)
Diabetes complications show significant decline in past two decades (Reuters)
Changes in Diabetes-Related Complications in the United States, 1990–2010 (New England Journal of Medicine article, abstract available without subscription)

More

Ebola Outbreak in West Africa Worries Health Officials

Electron micrograph of Ebola virus particle Credit: CDC Public Health Image Library #1832 / Cynthia Goldsmith
Electron micrograph of Ebola virus particle
Credit: CDC Public Health Image Library #1832 / Cynthia Goldsmith

In 1976 a new virus entered the pantheon of lethal human pathogens – Ebola virus. That year outbreaks in Zaire and Sudan sickened 284 people and killed about half of them. Ebola virus causes an illness that initially resembles a typical intestinal virus, with fever, headache, joint and muscle aches, vomiting and diarrhea. Most patients quickly worsen and develop a rash, easy bleeding, and liver and kidney failure. About two thirds of the people who are infected die. Ebola is transmitted from person to person through infected bodily fluids, but since patients are frequently vomiting and suffering from diarrhea, and since outbreaks happen frequently in places with poor sanitation, infection can spread quickly. Without medical protective equipment, like gloves and masks, healthcare workers are often infected. The incubation period is two to four weeks. Ebola is also carried by wild animals, and bats are thought to be a reservoir of the disease.

Because Ebola is so rapidly fatal, previous outbreaks have been geographically very limited. It may infect everyone in a small remote village, but at least until now, infected people have been too ill to get on a plane or take a long car ride. The worst outbreaks have killed almost 300 people. New outbreaks have recurred in Central Africa every few years, presumably from contact with infected animals.

So far there is no vaccine or specific treatment for Ebola. It cannot be spread by respiratory particles (i.e. by coughing or sneezing). If it could, it would make the perfect bioterrorism weapon. The Centers of Disease Control and Prevention lists it as a Category A bioterrorism agent.

About ten days ago an Ebola outbreak was discovered in southeastern Guinea. This in itself is worrisome as it is the first Ebola outbreak in Guinea and in West Africa. But more worrisome is that this outbreak has spread geographically more than any other. Cases have been reported in Conakry, the capital of Guinea, a city of a million and a half people. Conakry is over 400 miles away from the region of the initial cases. And cases are also suspected in Liberia and Sierra Leone. In all (as of April 1) there have been over 130 confirmed and suspected cases and 88 deaths. 14 of the infected people are healthcare workers.

International health officials are scrambling to deliver isolation equipment to hospitals and are trying to educate the public to avoid touching people who become sick. They are also identifying and trying to isolate people who were in contact with patients. The media reports (links below) suggest the mood in Conakry is understandably tense.

Time will tell how much farther this outbreak will reach and how many lives it will claim. We hope that as resources are rushed to where they are needed human-to-human transmission will be interrupted soon.

But we are reminded that in less than 40 years after making the jump from other animals to humans Ebola virus has found its way to an African capital city. How many more years will it be until someone, unaware that he is infected and still in the incubation period, boards a plane and becomes violently ill while browsing paintings at the Louvre, or riding a double-decker bus in London, or seeing a Broadway play? Will our health systems be prepared to manage the ensuing chaos?

Learn more:

Q&A: Challenges of Containing Ebola’s Spread in West Africa (National Geographic)
Ebola outbreak spreads panic in West Africa (USA Today)
Why West Africa’s Ebola Outbreak Is So Scary (Slate)
6 Things to Know About the Latest Ebola Outbreak (Time)
Outbreak of Ebola in Guinea and Liberia (Centers for Disease Control and Prevention)

More

What We Don’t Know About Eating Fat

A hamburger patty is loaded with saturated fats and is delicious. Image credit: Jeff’s Gourmet Sausage Factory, from their Facebook page
A hamburger patty is loaded with saturated fats and is delicious.
Image credit: Jeff’s Gourmet Sausage Factory, from their Facebook page

Most humans have spent most of human history nearly starving to death. So it’s no surprise that we spend a lot of time thinking about food. And it’s no surprise that food has acquired cultural, social, and religious significance in almost every society. Because food is so important, and because it’s nearly impossible for us not to ascribe powerful effects to anything important to us, every society imbues special health properties to various foods.

From believing that some foods are aphrodisiacs to believing that some foods improve sleep or fertility or athleticism, superstitions about the effects of food on health are ubiquitous. But we are modern, rational creatures that would never subscribe to such claptrap. Right? Wrong. We also cling to our own mythology about the health effects of food but we dress up our ignorance in scientific words. We (correctly) sneer at anyone who asserts that ingesting powdered rhinoceros horn improves erectile function. After all, there’s no scientific reason to even believe such a thing, and the connection between a rhinoceros horn and erectile dysfunction is purely visual. That’s like eating a giraffe because you want to be taller.

But take the assertion that eating saturated fat increases the risk of heart disease. We all believe that. After all, saturated fat is a molecule. Molecules are very scientific, which means there are men in white lab coats somewhere with blinky machines proving that saturated fats are very very bad to eat. In fact, current cardiovascular guidelines from respected groups like the American Heart Association suggest low consumption of saturated fats and high consumption of polyunsaturated fats. And the American Heart Association would never recommend rhinoceros horn.

This week’s study is an important reminder that we know much less than we believe, but before we dive into it, allow me a paragraph to make sure we know what we’re talking about.

There are three families of energy containing molecules in food – fats, carbohydrates, and proteins. Fats are further subdivided into saturated fats and unsaturated fats. Saturated fats are typically found in dairy products and fatty meats and are typically solid at room temperature (like butter, lard, and beef fat). Unsaturated fats are found in vegetable oils and fish oils and are typically liquid at room temperature (like olive oil).

For decades we have been hearing and repeating to our patients that saturated fats are unhealthy for hearts and unsaturated fats are healthy. A meta-analysis (study of studies) published in the current issue of Annals of Internal Medicine attempted to review all the studies that have ever examined the link between saturated and unsaturated fats and cardiovascular health. What they found was underwhelming. There were 45 observational studies, the kind that I routinely criticize in my posts and urge readers to ignore. There were 27 randomized studies that looked at the effects of fatty acid supplementation on heart disease. All of them tested whether supplements of unsaturated fatty acids (like fish oil) helped prevent stroke and heart attacks. None of them tested whether supplements of saturated fatty acids (lard capsules!) increased cardiovascular risks.

The results were meh. The data as a whole showed no significant increase in risk from saturated fats, nor decrease in risk from unsaturated fats. The authors conclude

“[T]his analysis did not yield clearly supportive evidence for current cardiovascular guidelines that encourage high consumption of polyunsaturated fatty acids and low consumption of saturated fats.”

Not surprisingly none of the experts quoted in the media coverage said the simple truth, which is that we have no idea if dietary fats affect health apart from the calories they contain. It would be nice to hear an expert declare “We have no clue about whether some fats are healthy or unhealthy” since that statement would be solidly supported by the evidence.

How did saturated fat’s bad reputation ever get started? I’m not sure. It’s conceivable some observational study that should have been ignored suggested that saturated fat was unhealthy. It’s also possible that saturated fat’s ignominy began because lard and butter look so much like the fat in a cholesterol plaque that blocks an artery. Olive oil is liquid. How could that block an artery? Maybe the whole idea was as simple-minded and as visual as the rhinoceros horn remedy.

Learn more:

Saturated Fat Is Back! (NPR)
Saturated fat ‘ISN’T bad for your heart’: Major study questions decades of dietary advice (Daily Mail Online)
Review questions effects of saturated fats on heart disease (Fox News)
Association of Dietary, Circulating, and Supplement Fatty Acids With Coronary Risk: A Systematic Review and Meta-analysis (Annals of Internal Medicine)
Even More Studies You Should Ignore (my last post about fish oil)

More

When Less is More

A patient undergoing a treadmill EKG stress test, hopefully for good reason. Credit: Blue0ctane / Wikipedia / public domain
A patient undergoing a treadmill EKG stress test, hopefully for good reason.
Credit: Blue0ctane / Wikipedia / public domain

When I meet a new patient, I’m frequently astounded by the healthcare he has received. I’ve met patients with absolutely no cardiac symptoms who have been receiving EKGs every six months for years. I’ve had patients brag to me about their annual executive physicals in which myriad tests including treadmill stress tests and chest X rays were routinely performed. Patients get head-to-toe CT scans under the mistaken hope that they might save their lives by finding something. I’ve seen patients with no family history of colon cancers have colonoscopies every two years, because they really want to make sure that they don’t get colon cancer. Some patients do the best they can to be tested for everything.

In the absence of appropriate indications, all these tests are not only without value, they can be harmful. Even in perfectly healthy patients they can yield abnormal results simply through error. (These results are called false positives.) These results then have to be pursued with more invasive tests that can have complications and risks. This isn’t just a theoretical risk. I’ve seen patients harmed by tests that should never have been done.

Doctors are quick (and correct) to roll their eyes when patients take various unproven alternative medicines. When they take Echinacea for their colds, pop their multivitamins, and take black cohosh for menopausal symptoms. Patients should know that what they’re doing is unproven. But it occurs to me that doctors are much less critical when unproven or ineffective interventions are pushed by our colleagues. An unindicated stress test is every bit as unlikely to help a patient as a multivitamin, but potentially riskier. After all, a false positive result from a stress test may lead to an unnecessary angiogram, a risk that the multivitamin doesn’t carry.

The incentives that perpetuate the first type of ineffective medicine – the herbs, supplements, and vitamins – are obvious. Suppliers want to sell their product. They label and advertise their product with messages that fall just below the threshold for fraud, and patients interpret these messages to mean far more than they do. Eager to find something effective for what is frequently an untreatable problem (like a cold) patients understandably flock to these ineffective remedies.

But ironically, ineffective tests and remedies prescribed by physicians have even more perverse incentives. At least the patient has to pay for her own Echinacea and her own vitamins. The pointless EKG and stress test are covered by insurance! In a system in which tests are covered and the prices are fixed by the insurance company, the incentive is to deliver as many tests as possible. The doctor doesn’t lose anything if some of those tests lead to needless anxiety and further invasive testing. The patient doesn’t think to ask questions about the proven risks and benefits because he’s not getting the bill. The incentives do not reward achieving health, or preventing disease, or maximizing patient satisfaction. They reward delivering services. And we’re surprised that the result is the delivery of lots of services with no value.

Escaping the insurance system makes it easier to see the problem more objectively. I get paid by patients to listen to them and give them advice. I don’t get paid more if I order a test, and I also don’t get paid less. And I’m not paid by anyone but the patient. So I can actually take the time to educate the patient about the risks and benefits and figure out if she really wants the test. The net result is that patients pay me more so I can make sure they get more education and less healthcare.

I’ve written before about how our current healthcare market broke and how I believe it could be fixed. I think insurance coverage of routine care is a major flaw in the current system. We are currently expending enormous resources trying to insure everyone. If, as I believe, insurance is the problem and not the solution, the results will be even worse than the broken system we started with.

More

The Scourge of Prescription Pain Medicine Abuse

generic Vicoprofen tablets
generic Vicoprofen tablets. Image credit: Wikimedia/Rotellam1. Creative Commons Licence

Opioids are a family of pain medications chemically related to opium and heroin. They include morphine, fentanyl, codeine, hydromorphone and others. Opioids have unique properties that make them both indispensable for pain management and extremely dangerous.

Unlike virtually any other family of medications, opioids have no maximum effective dose. If any dose, no matter how high, is ineffective at controlling pain, a higher dose can give more pain relief. Most other medications don’t work this way. For example, if 800 mg of ibuprofen doesn’t bring relief, it’s very unlikely that any higher dose will. This property makes opioids a mainstay for treating severe acute pain, such as from fractures or after surgery.

But the risks and side-effects are substantial. Tolerance (diminished effectiveness with repeated use) is a common problem requiring dose escalation to maintain the same pain relief. Withdrawal symptoms are miserable (but not dangerous) and addiction is very common. The most serious risk is that opioids decrease the drive to breathe. In patients who are dying and short of breath, this is a welcome benefit, not a side-effect. Opioids are essential in hospice care because of their ability to eliminate the sense of shortness of breath. But that same effect in an overdose can stop breathing entirely. Philip Seymour Hoffman is only the most recent well-known victim of this property of opioids.

When I did my residency in the mid-90s the philosophy I was taught about opioids was simple. Opioids were for acute pain. If you broke a bone or had a documented kidney stone you could have a prescription that would last a week or so. Patient requests for more prolonged treatment were met with suspicion. The exception was for dying patients. If you had chronic pain form a disease that was going to kill you, you could have all the opioids you wanted. But if you had chronic pain from arthritis, or chronic back pain, or anything else non-fatal, then opioids were simply off the table. You had to make due with other medicines.

Sometime thereafter, we went through a revolution in our attitude. I’m not a pain specialist, so I don’t know if the revolution was supported by any scientific evidence or was simply a change in philosophy. The new teaching was that pain should be treated seriously, and that doctors had been negligent in providing their patients adequate pain relief. Since pain is an entirely subjective experience, there is no test or objective measurement for pain, and the patient’s report of pain should be accepted at face value. The use of opioid analgesics for chronic conditions became acceptable when other options failed.

What followed was an explosion of opioid prescriptions, opioid addiction, and overdose deaths. In 1999 in the U.S. 4,030 people died from overdoses of opioid prescription medications. In 2010 that number had more than quadrupled to 16,651. Since 2003, more people have died from overdoses due to prescription opioids than due to heroin and cocaine combined.

This month the American College of Physicians issued a policy position paper about prescription drug abuse. It was much more of a description of the current dilemma and a recommendation for future research than a guideline for prescribing physicians. The latter is what is desperately needed.

Adding fuel to this fire is the FDA’s decision this week to approve Zohydro, a new extended release formulation of hydrocodone. This decision has received much criticism from physician groups (see links to news articles below) who warn that the potential for abuse and overdose is enormous and that the need for another opioid analgesic is nonexistent.

Has our new more lax prescribing philosophy allowed some chronic pain patients to achieve adequate relief? Is the epidemic of addiction and overdose deaths simply a terrible but acceptable price to pay for the benefit of a far greater number of people who use opiates responsibly? I honestly don’t know. I would love to hear from a pain specialist if any rigorous studies exist on the topic. The societal problem of opioid addiction may have no solutions, only trade-offs. It would be nice if those trade-offs were informed by data.

Learn more:

CDC Grand Rounds: Prescription Drug Overdoses — a U.S. Epidemic (Morbidity and Mortality Weekly Report)
QuickStats: Number of Deaths From Poisoning, Drug Poisoning, and Drug Poisoning Involving Opioid Analgesics — United States, 1999–2010 (Morbidity and Mortality Weekly Report)
Is Zohydro, The Super Potent New Opiate Painkiller, Just Too Dangerous? (Forbes)
New pain pill’s approval: ‘Genuinely frightening’ (CNN Health)
Potent New Painkiller May Prove Lethal for Addicts, Critics Warn (NBC News)
Prescription Drug Abuse: Executive Summary of a Policy Position Paper From the American College of Physicians (Annals of Internal Medicine)

More

The New Uncertainty about Mammograms

A woman has a mammogram. Photo credit: National Cancer Institute / Rhoda Baer (public domain)
A woman has a mammogram. Photo credit: National Cancer Institute / Rhoda Baer (public domain)

“I’d like to be tested for every kind of cancer.”

All primary care doctors have heard this request. Our answer is an explanation that we can’t. Understanding this explanation is important before we get to the most recent study about mammograms.

We don’t test for all kinds of cancers for an important reason. The outcome of most cancers don’t depend on when they are diagnosed. This may come as a surprise to many, since we’ve all heard the message of the importance of early diagnosis. But that message only applies to a handful of cancers. Diagnosing colon cancer early definitely saves lives, hence the value of screening colonoscopies. Early diagnosis of cervical cancer is also beneficial, hence Pap tests. But many cancers do not fit this pattern. Take leukemia for instance. Some leukemias are curable; others are not. When they’re diagnosed makes little difference. So testing everyone for leukemia wouldn’t save any lives.

This problem is compounded in cancers that are very-slow growing and occur mostly in older people. These cancers, if undetected, may never harm the patient, and the patient could live a normal lifespan and die of an entirely unrelated problem. Detecting these cancers early doesn’t help anyone. That’s called over-diagnosis – diagnosing a disease that would have never caused harm. (That’s a major problem with prostate cancer screening and is why PSA tests are no longer recommended.)

As of 2009 the best evidence we had suggested that mammograms save lives by diagnosing breast cancer early. (I reviewed the evidence in a post back then.) The U.S. Preventive Services Task Force (USPSTF) combined the data of all the randomized studies of mammograms and calculated that on average 1 life is saved from breast cancer for every 377 women in their 60s who undergo mammograms. For women in their 50s the benefit is smaller (i.e. more women must have mammograms to save one life) and for women in their 40s the benefit is smaller still. Because of the very small benefit to women in their 40s the USPSTF recommended against routine mammograms in this age range. (I disagreed in my post.) And they recommended mammograms every two years for women between the ages of 50 and 74.

This month the British Medical Journal published an important study that shines new light on the question. The study began in 1980 and randomized almost 90,000 women in Canada between the ages of 40 and 59 into two groups. One group received annual mammograms for five years, and the other (the control group) did not. If early detection by mammography saved lives, you would expect more deaths from breast cancer in the control group than in the mammogram group. The initial results, which were published long ago, showed the same number of breast cancer deaths in both groups. The objection was that since breast cancer can grow very slowly a benefit of mammography may not be noticed for many years.

The current study publishes the result of following these women for another 22 years. The results are very surprising. About 500 women died of breast cancer in both groups. The survival curves of the two groups were identical, meaning every year the same number of women died of breast cancer in both groups.

To make matters worse, the study showed definite harms of mammography. 106 more cases of breast cancer were diagnosed in the mammogram group than in the control group. But since the same number of women died in both groups those 106 caners were all cases of over-diagnosis – diagnosis of a cancer that would not have harmed the patient. For every 424 women who underwent mammography, one over-diagnosed cancer was detected, resulting in a biopsy and cancer treatment that did not help the patient.

Unfortunately, and predictably, radiologist groups immediately attacked the study. Had they argued “Please keep getting mammograms, otherwise we won’t have as much work to do,” their objections would have at least made sense. One objection was that in 1980 analog mammogram machines were used, and current digital machines are thought to be superior. But all of the studies showing that mammograms were beneficial were done in the 60s and 70s with even older equipment. So to claim that mammograms are proven life-savers and that this study should be ignored because it used old technology is purposely misleading. The current digital technology has never been proven in randomized trials to save lives. The other objection claimed some methodological flaws. These charges have been denied by the authors of the study and investigated by Canada’s National Cancer Institute which found no serious flaws. I’ll spare you the technical details. I’m no expert, but I read the study myself and the biggest methodological flaw I found is that the British Medical Journal spells randomized with an s.

So where does that leave us?

First, we have to remember that this study included women only up to the age of 59. So this study doesn’t tell us anything about the benefit of mammography in women in their 60s or 70s.

But the bigger point is not likely to be refuted – that mammograms in women in their 40s and 50s have very small or non-existent benefits and also definite harms. I might not change my current recommendations until groups like the USPSTF mull over the current findings and make new pronouncements, but I will certainly caution women that the benefit of mammograms is controversial and that an abnormal finding could lead to invasive procedures that may not extend their lives.

Learn more:

Vast Study Casts Doubts on Value of Mammograms (New York Times)
Mammograms May Be Useless, Study Finds (Wall Street Journal video)
Cancer screening expert to radiologists: Stop lying about mammograms (Los Angeles Times)
Mammograms: Are they needed or not? (CNN Health)
Mammography Screening (The Medical Letter blog)
Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial (British Medical Journal article)
New Mammogram Recommendations Betray Women, Doctors and Science (my post in 2009 reviewing the evidence on mammography)

More

The Blood Type Diet Remains on the Fiction Bookshelf

Photo credit: Wikimedia commonsIn 1996 a naturopath published “Eat Right 4 Your Type”, a diet book purporting that people with different blood types would benefit from different diets. There are a lot more people who want to lose weight than who want to exercise skepticism, so the book became a multi-million dollar success.

As an aside, the proliferation of myriad different diets on the market should make us suspect that none of them are very effective. For example, there were countless ineffective but widely used remedies for pneumonia before the discovery of penicillin. Afterwards, there was only one treatment.

I wrote in 2011 that the blood type diet had two very important flaws. The first is that it makes absolutely no sense physiologically. That is, there is absolutely no reason to suppose that blood types, which are proteins on the surfaces of our red blood cells, have anything to do with the way we burn calories or use micronutrients. This is not a fatal flaw. Just because something doesn’t mesh with our current understanding doesn’t mean it’s false. The effectiveness of this diet would be easy to show in a rigorous randomized trial, and if proven effective this would trump the first objection. That is the second flaw – that this diet was completely unproven. There was absolutely no evidence that people eating their blood-type-specified diet did any better than those eating a diet for some other blood type.

Now just because something is unproven doesn’t mean it’s not true, but that should be our assumption. Most things have nothing to do with most other things. Given any pair of things – the position of the planets and your romantic fate on Valentine’s Day, the last four digits of your social security number and the winning lottery ticket, your blood type and what you should eat –a scientist would (in the absence of evidence) assume the null hypothesis, that thing A is totally unrelated to thing B.

So it’s pretty safe to assume that something unproven is ineffective. And when that unproven thing would be easy to test and is a big money maker, we should be very suspicious that the people making the money would prefer to keep it untested.

So why is “Eat Right 4 Your Type” such a big success? As I suggested in my prior post, each of the diets it recommends for each blood type is quite sensible. Any diet that results in the consumption of fewer calories will result in weight loss. You could pick one of the four diets randomly and do pretty well.

The new chapter in this story is that last month investigators at the University of Toronto published a study in PLOS ONE testing the blood-type diet. I’ll spare you the details of the study, but it showed that people who followed most of the diets lost weight independently of whether they were following the diet suggested for their blood type or for some other blood type.

The study wasn’t randomized. It just looked at the diets that people were already eating. My regular readers know that I don’t give observational studies much weight. I would never recommend a new medication or surgery based on a non-randomized study (because I would cling to the null hypothesis). But given a diet that already had a lot going against it and no evidence for it, this is another suggestion that you should choose what you eat based on your belt size not your blood type.

Learn more:

Blood type diet not based in science, new study says (Today Health)
Blood Type Diet – Disproved (Neurologica Blog)
ABO Genotype, ‘Blood-Type’ Diet and Cardiometabolic Risk Factors (PLOS ONE article)
Eat Right for Your Belt Size, Not Your Blood Type (my post from 2011)

More

Middle East Respiratory Syndrome Coronavirus: the latest lethal germ

MERS-CoV particles as seen by electron microscopy. Credit: CDC/Wikipedia
MERS-CoV particles as seen by electron microscopy. Credit: CDC/Wikipedia

In 2003 a brand new virus named severe acute respiratory syndrome coronavirus (SARS-CoV) caused an outbreak of serious illness in Asia. The outbreak sickened over 8,000 people and killed over 700. Many of the infected were healthcare workers.

In February of last year a similar but distinct virus was identified in Saudi Arabia, the Middle East respiratory syndrome coronavirus (MERS-CoV). Since that time about 200 people have been sickened by MERS, all linked to six countries in or near the Arabian Peninsula. The World Health Organization (WHO) has confirmed 180 cases (143 in Saudi Arabia) and 77 deaths (59 in Saudi Arabia). There have been no cases thus far in the U.S. No specific treatment or vaccine exists for MERS-CoV.

The current issue of Annals of Internal Medicine published a report by researchers in Saudi Arabia describing 12 patients admitted to intensive care units (ICU) with MERS-CoV. The description of the illness that emerges from details they report is scary. Eight of the patients contracted the illness in the community. Three patients were in the ICU for other reasons and were infected in the ICU, and one was a healthcare worker who presumably contracted the illness at work. The patients ranged in age from 36 to 83. The average time from the onset of symptoms to presentation to the emergency department was one day, and to ICU admission was two days.

The majority of patients presented with shortness of breath, cough, and fever. Many of the patients had chronic illnesses, such as diabetes, high blood pressure, heart disease and kidney disease. All of them required being on a ventilator (a breathing machine). Their chest x rays (which you can check out yourself in the article) looked horrible. They spent an average of 16 days on the ventilator. Seven patients had kidney failure requiring temporary dialysis. Eight patients had dangerously low blood pressure requiring medication to elevate it. Seven patients (about half) died.

MERS-CoV is definitely transmitted from person to person, but the specific mode of transmission is still uncertain. It’s not clear if the virus is transmitted in respiratory droplets, or by direct contact. Thus far MERS-CoV appears to be much more lethal but much less infectious than SARS was. That’s another way of saying that it’s a younger virus, since germs tend to get less lethal and more infectious as they evolve. (A mutation that makes a virus more infectious will spread much faster than a mutation that makes it less infectious. Similarly a mutation that makes it less lethal will give the patient longer to infect others.)

Neither the Centers for Disease Control (CDC) nor the WHO recommends that anyone change their travel plans because of MERS. For now, it seems geographically quite localized and fairly difficult to catch. But no one can say what the future holds, and whether a few mutations from now MERS will be coming to an airport near you. If that happens, the rapid development of a vaccine will be critical.

The small lesson is that MERS is an emerging pathogen that deserves our attention, and that what is simmering on the other side of the globe this year can be a global pandemic next year. The big lesson is that nature is a mixed bag. Nature brings us both rainbows and tsunamis, both my 10 year-old daughter’s amazing eyes and the norovirus that is keeping her home from school today. And every now and then Mother Nature invents brand new ways to kill some of us.

Learn more:

Middle East Respiratory Syndrome (MERS) (Centers for Disease Control and Prevention page)
A Novel Coronavirus Called “MERS-CoV” in the Arabian Peninsula (Centers for Disease Control and Prevention travel recommendations)
Middle East respiratory syndrome coronavirus (MERS-CoV) – update (World Health Organization)
New MERS death raises Saudi toll to 59 (AFP)
Clinical Course and Outcomes of Critically Ill Patients With Middle East Respiratory Syndrome Coronavirus Infection (Annals of Internal Medicine article, free without subscription)
Medusa’s Ugly Head Again: From SARS to MERS-CoV (Annals of Internal Medicine editorial, subscription required)

More