Largest Study Ever Finds No Link Between MMR Vaccine and Autism

The rash on the skin of a measles patient. Photo credit: CDC/Dr. Heinz F. Eichenwald
The rash on the skin of a measles patient. Photo credit: CDC/Dr. Heinz F. Eichenwald
The rash on the skin of a measles patient.
Photo credit: CDC/Dr. Heinz F. Eichenwald

“A lie will go round the world while truth is pulling its boots on.”
— C. H. Spurgeon

In 1998 Andrew Wakefield, a British gastroenterologist, published a study in The Lancet reporting on 12 (remember that number) children with developmental delay, 8 of whom were diagnosed with autism within 4 weeks of receiving the MMR (measles, mumps, rubella) vaccine. The study proposed a link between the MMR vaccine and autism. Other researchers were unable to reproduce these results and find the same link. In 2004, an investigation by a journalist discovered that Wakefield had undisclosed financial conflicts of interest. The investigation found multiple fraudulent and unethical aspects of the 1998 study, leading The Lancet to retract the study in 2010, and leading the British General Medical Council to revoke Wakefield’s license to practice medicine. (I wrote a detailed post at the time of the retraction of the study. Study Linking Vaccines To Autism Not Just Wrong, Intentionally Fraudulent)

Despite the scientific rebuke and the professional disgrace, Wakefield has never recanted. Assisted by celebrities and others with more charisma than qualifications, he has continued to scare parents about vaccine risks.

In an attempt to address these concerns, many studies have attempted to find links between the MMR vaccine and autism. In 2014 a meta-analysis reviewed previous studies of MMR and autism and found no association. Two other studies in 2015 reached the same conclusions. Though most authorities found these studies definitive, critics stated that the MMR vaccine might still increase the risk of autism in children at particularly high risk of autism, even if it does not increase risk in the general population.

In response to these criticisms, a study in Denmark was undertaken that enrolled more children, counted more cases of autism, and followed children for longer than any previous study of MMR and autism. The study followed 657,461 children born in Denmark from 1999 through 2010, and followed them on average for over 7 years. To identify subgroups that might be at higher risk of autism, the study kept track of maternal and paternal age, smoking during pregnancy, the method of delivery, preterm birth, Apgar scores, low birth weight, head circumference, and siblings with autism.

During the study 6,517 children were diagnosed with autism. The risk of autism was similar among vaccinated and unvaccinated children. Importantly, in groups of children at high risk of developing autism, the risk did not change with vaccination status. The results were published this month in the Annals of Internal medicine, along with a summary written for the public. The authors concluded that “even minute increases in autism risk after MMR vaccination are unlikely”.

So now, a fraudulent study citing 12 patients has been debunked by multiple studies, most recently one following over 600,000 kids and over 6,000 kids with autism. Even a tiny effect of MMR vaccine on autism would have been disclosed by this study. But will this convince anybody?

An associated editorial expressed the concern that we now live in a world in which evidence has little persuasive value, and wonders whether the resources spent on this study might better have been spent studying something else. After all, those who care about evidence were convinced before this study; those who don’t care about evidence will not be convinced now.

Meanwhile measles outbreaks in New York, Washington, Texas and Illinois are spreading among communities with lower vaccination rates. We live in a society in which expertise carries less authority than ever before, and scientific findings are met with skepticism. Public health officials and doctors will have to find other ways of communicating with and reassuring vaccine skeptics. Perhaps our side needs our own celebrities.

Learn more:

One More Time with Big Data: Measles Vaccine Doesn’t Cause Autism (NY Times)
MMR vaccine does not cause autism, another study confirms (CNN)
Measles Outbreak Grows to 214 Cases in New York City (Wall Street Journal)
The MMR Vaccine Is Not Associated With Risk for Autism (Annals of Internal Medicine summaries for patients, free without subscription)
Measles, Mumps, Rubella Vaccination and Autism: A Nationwide Cohort Study (Annals of Internal Medicine original research, free without subscription)
Further Evidence of MMR Vaccine Safety: Scientific and Communications Considerations (Annals of Internal Medicine editorial, free without subscription)
Measles (Centers for Disease and Prevention)
Andrew Wakefield (Wikipedia)

Some of my previous posts about MMR and measles:
Study Linking Vaccines To Autism Not Just Wrong, Intentionally Fraudulent (2011)
Measles Makes A Comeback (2014)
Mickey, Minnie, Measles (on the measles outbreak in Disneyland in 2015)

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Thoughts on Board Recertification

Image credit: Alberto G/flickr

This post has a very braggy shamelessly self-promotional part. So allow me to get that out of the way first. In October 2017 I took the American Board of Internal Medicine (ABIM) recertification exam. It’s a day-long multiple-choice test that covers the entire breadth of internal medicine and is done under the watchful eyes of proctors who make sure we only had access to the information between our ears. I had studied for dozens of hours over the preceding months. I did well. How well? I’m so glad you asked. Here are my scores.

Internal medicine board certification has been clouded with controversy in the last several years, perhaps deservedly so. Critics of the process of maintaining board certification make the following reasonable charges. Studying for the test takes a lot of time for doctors who are already over-scheduled. The test covers rare diseases that any individual doctor is unlikely to encounter in practice. A multiple-choice test in a secure location is a terrible approximation for actual medical practice, in which a doctor facing a difficult case can refer to reference materials or call a colleague for advice. Since we all use textbooks (and increasingly online resources) when we see patients, shouldn’t the test allow us to refer to them too? And finally, there is no persuasive evidence that studying for the board exam makes us better doctors, or that the patients of the doctors who pass have better outcomes than the patients of those who fail.

These are all legitimate criticisms, and the ABIM has faced a lot of pressure to evolve the certification process to one that is more clinically relevant and less burdensome. It has made some strides in that direction.

Without in any way dismissing the above charges, I’d like to raise a few defenses of board certification. First of all, it’s voluntary. Unlike state licensure, which is legally required to practice, board certification is not mandatory. Critics point out that many hospitals require board certification for hospital privileges, which is true, but not all do, and one can practice medicine without hospital privileges. The second benefit is that board certification is currently the only evaluation of internists that places them above the general standard of care, that is, it’s the only current way to try to assess excellence. Disciplinary action by state boards punish doctors when care falls below the standard, so patients can use that to make sure a doctor is at least adequate, but there is no other current standard that attempts to set a bar higher than adequacy. And third, it’s objective and impartial. Unlike the recommendations of friends, online reviews, and other ways doctors are judged, board certification is a uniform yardstick by which any internist can attempt to be measured.

So while acknowledging that the current board certification system has much to improve, I think that for patients attempting to find excellent doctors, it’s still an essential tool. I found the process of studying for the exam in 2017 extremely valuable. Yes, I am unlikely to see many of the diseases I studied. But the process of studying also solidified my understanding of advances in the treatment of very common diseases, like diabetes and heart disease.

It would be wonderful if we could accurately and objectively test the essence of great doctoring. It would be so valuable if I could study and be tested on the ability to motivate the complacent patient, to comfort the panicked patient, to intuit when a patient has undisclosed concerns, to be able to know when the time is right to break the tension with some levity, and when the time is to be quiet, make eye contact, and listen. Every good doctor I know struggles with these problems daily. We would all sign up for a class to teach us to excel at that test. ABIM certification is a poor substitute for that ideal, but it’s getting better, and for now it’s the best we’ve got.

Learn more:

Stop Wasting Doctors’ Time, Board-Certification Has Gone Too Far (New York Times op-ed by Dr. Danielle Ofri 2014)
To the Barricades! The Doctors’ Revolt Against ABIM is Succeeding! (Newsweek, 2015)
Physicians Passage of MOC Exam Linked to Fewer State Disciplinary Actions (MedicalResearch.com)
American Board of Internal Medicine – Check a physician’s certification

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What Vitamin D and Fish Oil Have to do with Cancer and Heart Disease

Fish oil capsules
Photo credit: Oddman47 / Wikimedia commons

About half of U.S. adults take some sort of nutritional supplement. (My wife and I are in the other half.) Many supplements have a crucial specific function (vitamin C, for example, is the best and only treatment for scurvy) but their benefits to the general population are unproven.

Vitamin D is frequently prescribed to prevent and treat osteoporosis. It is critical in calcium metabolism and in bone health. Some observational studies have found lower rates of death from cancer and cardiovascular disease in regions with greater sun exposure than in areas with less sun exposure, leading some to speculate that vitamin D protects from cancer and heart disease.

Fish oil is frequently prescribed to decrease triglycerides. And in people with high triglycerides who are at high risk for a heart attack and are already taking a statin, there is some evidence that fish oil prevents heart attacks. As with vitamin D, some observational studies have associated fish oil with protection from cancer and heart disease.

(See this previous post for a quick explanation on what an observational study is and what a randomized study is.)

In November, the New England Journal of Medicine (NEJM) published the results of a study that attempted to find a definitive link between vitamin D use, fish oil use, and the incidence of cancer and heart disease. The study enrolled over 25,000 volunteers who were men 50 years of age or older, or women 55 or older. They were randomly assigned to four groups. One group was given vitamin D 2,000 units and omega 3 fatty acids (fish oil) 1 gm daily. The second group took vitamin D and a placebo daily. The third group took fish oil and a placebo daily. And the last group took two placebos daily. They were followed for an average of five years. They were tracked for the development of invasive cancer of any type, heart attack, stroke, and death from cardiovascular causes.

The good news is that none of the groups had any serious side effects, which reinforces our previous knowledge that vitamin D and fish oil are quite safe. The bad news is that there was no difference between groups in incidence of cancer or cardiovascular events, which means neither fish oil nor vitamin D protect the general population any better than placebo.

There are three general lessons here. The first is that many supplements may have very specific effects that benefit specific patients. That shouldn’t lead us to think that they are “good for us” in some vague general way, and that everyone should take them. For example, iron supplements are just the thing for people with iron-deficiency anemia, and maybe for people with restless leg syndrome. But that’s not a reason for everyone to take them. The second lesson is that we don’t really know anything until a randomized trial is done. Observational trial results generate hunches, not conclusions. That’s why we know very little about the effects of diet on health. Almost all dietary studies are observational. So people pontificate about foods that decrease inflammation, or foods that protect from cancer, or foods that make you taller and richer, but until someone randomizes thousands of volunteers to test it, we shouldn’t believe them.

The third lesson, and the hardest one, is another reminder that null hypothesis is usually right, and in the absence of convincing data we should always assume that any two things have no effect on each other.

Learn more:
Vitamin D And Fish Oil Supplements Mostly Disappoint In Long-Awaited Research Results (NPR Shots)
Fish Oil and Vitamin D Supplements May Not Help Prevent Heart Attacks and Cancer, Study Says (Time)
Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease (NEJM article, abstract available without subscription)
Marine n−3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer (NEJM article, abstract available without subscription)
VITAL Signs for Dietary Supplementation to Prevent Cancer and Heart Disease (NEJM editorial, by subscription only)

My prior post explaining the difference between observational and randomized studies:
Without A Randomized Study Your Results May Vary

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Symptom Relief for Your Common Cold

Air Force Airman Kia Atkins suffers from the common cold.
Photo credit: US Air Force / public domain.

Lots of my patients have been struck by a miserable cold in the last few weeks. My phone is ringing off the hook (is that a meaningful idiom anymore?) with woeful tales of coughs and runny noses and fatigue and despair. I thought it would be a perfect time to do a little teaching about the common cold, how to treat it, and other diagnoses that it can be mistaken for. But it turns out I already wrote that post a couple of years ago. I think it’s a great summary of how to tell if you have a cold or have something else, so please read it. I’ll wait here until you finish.

Some of my patients were using oxymetazoline (Afrin) for weeks at a time and wondering why their nasal congestion wasn’t improving. And some had bought phenylephrine off the shelf not knowing that it’s quite ineffective. I thought that a post summarizing the different available nasal decongestants would be very handy. I’ve already written that too. Feel free to give it a read if nasal decongestion is on your agenda.

So, I thought I would very briefly go over some commonly used cough suppressants, so you can quiet that cough and get some rest.

Dextromethorphan

Dextromethorphan is an over-the-counter cough suppressant which is an ingredient in Robitussin DM, Mucinex DM and other cold remedies. At recommended doses it’s safe and mildly effective in decreasing cough.

Codeine

Prescription cough syrups with codeine are frequently prescribed as a cough suppressant. Codeine can be sedating and cause constipation. Codeine has been proven effective in suppressing chronic cough, but trials in patients with the common cold have not found a consistent benefit compared with placebo.

Benzonatate

Prescribed under the brand Tessalon Perles, benzonatate can effectively suppress cough. It can cause dangerous overdoses, especially in children, because it is sometimes mistaken for candy. And it can cause drowsiness and confusion, especially in older patients.

Non-pharmacological treatment

Many non-medicinal cough remedies are frequently recommended, like throat lozenges, honey, and hot tea. I often suggest them to patients with mild symptoms or patients who might be sensitive to side effects of medications. There is no evidence that they suppress cough more than placebo, but when waiting for a self-limited illness to run its course, a safe placebo might be the most comforting choice.

I wish all of you a healthy 2019 free of nasty viruses. I hope that when you hear a sick colleague or loved one complaining that she can’t reach her doctor or can’t get a prompt appointment, you’ll recommend me. I’ll keep working to keep you informed and healthy.

Learn more:

My previous posts about colds:
The Common Cold
Everything You Always Wanted To Know About Nasal Decongestants But Were Afraid To Ask

Common Cold (Centers for Disease Control and Prevention)
The common cold in adults: Treatment and prevention (UpToDate, only by subscription)

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Last Year’s Flu Season Was Worst in Decades

Transmission electron micrograph of influenza virus particles from the 1918 Spanish flu epidemic.
Photo credit: Public Health Image Library #8160, CDC / Dr. Terrence Tumpey / Cynthia Goldsmith

“Oh, a storm is threat’ning
My very life today
If I don’t get some shelter
Oh yeah, I’m gonna fade away”

Gimme Shelter by The Rolling Stones

By any measure, last year’s flu season (2017-2018) was very bad. The Centers for Disease Control and Prevention released a report last month estimating that influenza killed about 80,000 people in the US last season. That’s the highest number since 1976. How much worse is that than usual? Much worse. Previous years have caused between 12,000 and 56,000 deaths. 180 of those killed were children. Most of the children who died had not been vaccinated.

The last flu season also caused 900,000 hospitalizations.

People sometimes criticize the flu shot because it’s not always effective. They’re right. Last season’s vaccine was estimated to be 40% effective. That means people who were vaccinated were 60% as likely to require medical care from the flu as unvaccinated people. It’s not great. And the effectiveness varies from year to year. (And we’ll only know this year’s vaccine effectiveness after the season is over and the data is reviewed.) But vaccinated people also frequently get a milder illness than unvaccinated people. Imagine how many of those 900,000 hospitalizations could have been prevented if more people protected themselves.

People also sometimes criticize the flu shot because the protection is temporary. They’re right. The circulating strains change from season to season, and this season’s vaccine won’t help you next year. Vaccine manufacturers try, with varying success, to predict which strains will spread through North America and make each season’s vaccine based on that prediction.

So the protection isn’t perfect, and it doesn’t last long. Still, it’s the best we can do to prevent flu, along with frequent hand washing, covering coughs, and staying home when you’re sick. We use seat belts, we use umbrellas, and we build sukkot, because imperfect temporary shelter from risk is a lot better than no protection at all.

The CDC recommends that everyone over 6 months get a flu shot before the end of October. Maximal protection takes about two weeks after the vaccination.

Those at highest risk of serious complication from the flu are pregnant women, children, older adults, and those with chronic illnesses. If you’re not in one of those categories, getting the flu shot will still help prevent you from transmitting the flu to the more vulnerable people around you. So please get your flu shot this month. Our office has them. Your pharmacy has them.

A healthier winter for you, or for your neighbor who had a liver transplant, or for your pregnant coworker, or for your nephew, it’s just a shot away.

Learn more:
Flu broke records for deaths, illnesses in 2017-2018, new CDC numbers show (Washington Post)
Flu season deaths top 80,000 last year, CDC says (CNN)

Some of my previous posts about the flu shot:
Frequently Raised Objections To The Flu Shot
Sorting Out The Different Flu Vaccines

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In Healthy Older Patients Aspirin Doesn’t Help

Aspirin tablets. Photo credit: Ragesoss / Wikimedia Commons
Aspirin tablets. Photo credit: Ragesoss / Wikimedia Commons
Aspirin tablets. Photo credit: Ragesoss / Wikimedia Commons

Before we delve into this month’s news about aspirin, let’s briefly review what we think we know. Aspirin is life-saving therapy during a heart attack. In patients who have had a stroke or a heart attack in the past, daily low dose aspirin can prevent a second stroke or heart attack. Ditto in patients who have had bypass surgery or angioplasty or those who have chronic angina (chest pain caused by narrowing of coronary arteries), daily low dose aspirin prevents heart attacks in them too.

(The term “baby aspirin” is no longer in favor because it leads some people to think that it’s aspirin for babies. Children should never take aspirin. So the 81 mg aspirin tablets in the US and the 100 mg tablets in Europe are now referred to as “low dose aspirin”.)

But because heart attack is the most common killer of men and women in the US, and because heart attack prevention is a huge healthcare priority, many people who are not in the above groups take low dose aspirin for heart attack and stroke prevention. The studies that aspirin can help prevent patients’ first stroke or heart attack show a much smaller benefit and involved mostly younger patients.

On the basis of these older studies the US Preventive Services Task Force recommends low dose aspirin to people in their 50s whose risk of stroke and heart attack over the next ten years exceeds 10%. For people in their 60s they recommend an individualized decision based on the patient’s preferences and individual risks. For patients over 70 they state that the current evidence is insufficient to assess the balance of benefits and harms of daily aspirin.

The risk of strokes and heart attacks increase with age, so one would think that if aspirin was beneficial in 55 year old patients, the benefits would be even higher in 75 year olds. Unfortunately, very few studies have focused on older patients. And while the risk of heart attacks and strokes are higher as we get older, the risk of life-threatening bleeding due to aspirin is higher too.

So in people over 70 who haven’t had a stroke or heart attack, how do the risks and benefits of low dose aspirin balance? A large study tried to answer that question. The results were published this month in three articles in the New England Journal of Medicine. The study enrolled over 19,000 people who were 70 or older. None of the enrollees had a history of stroke, heart attack, dementia, or physical disability. They were randomized to take daily low dose aspirin or placebo. They were followed for an average of 4.7 years.

Surprisingly, the two groups had similar incidence of stroke and heart attack. They also had similar incidence of physical disability and dementia. Aspirin didn’t seem to decrease the risk of any of these outcomes. Not surprisingly, the group taking aspirin had an increased risk of serious bleeding. The aspirin group also had a slightly higher death rate.

We’ve long known that daily aspirin use carries the risk of serious bleeding. But in healthy older people that risk doesn’t seem to buy any benefit. So if you’re older than 70 and haven’t had a stroke or heart attack and are taking daily aspirin, talk to your doctor about it. You might be better without it.

Learn more:
Low-Dose Aspirin Late in Life? Healthy People May Not Need It (New York Times)
Study: A Daily Baby Aspirin Has No Benefit For Healthy Older People (Shots, health news from NPR)
News For Healthy, Older Patients: Toss Your Baby Aspirin (Forbes)
Aspirin Use to Prevent Cardiovascular Disease and Colorectal Cancer (US Preventive Services Task Force recommendations)
Effect of Aspirin on Disability-free Survival in the Healthy Elderly (New England Journal of Medicine article, by subscription)
Effect of Aspirin on Cardiovascular Events and Bleeding in the Healthy Elderly (New England Journal of Medicine article, by subscription)
Effect of Aspirin on All-Cause Mortality in the Healthy Elderly (New England Journal of Medicine article, by subscription)

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What to Know Before Taking Cipro or Levaquin

Ciprofloxacin tablets. Photo credit: Wikimedia commons.
Ciprofloxacin tablets. Photo credit: Wikimedia commons.
Ciprofloxacin tablets. Photo credit: Wikimedia commons.

Fluoroquinolones are the third most commonly prescribed family of antibiotics in the U.S. for adults, and, in my opinion, the second most fun to say (right behind aminoglycosides). Fluoroquinolones include levofloxacin (Levaquin), ciprofloxacin (Cipro), moxifloxacin (Avelox), ofloxacin, and delafloxacin. Their popularity is well earned; they’re very effective at treating certain bacterial infections. But since their discovery in the late 1970s, increasing concern has been raised about their safety.

In 2008, the FDA warned about the risk of tendinitis and tendon rupture in patients taking fluoroquinolones. This happened quite rarely, but frequently enough that reports caught the FDA’s attention. In 2011 it was noted that some patients with myasthenia gravis had worsening of their symptoms on these antibiotics. In 2013 the FDA updated these warnings to add the possibility of irreversible peripheral neuropathy (nerve damage) while taking fluoroquinolones.

All medications have some side effects, and these serious side effects are relatively rare, but their severity and the fact that they persist long after the medication is stopped (and in some cases are permanent) raised concern.

There are some other risks of fluoroquinolones that we’ve known over the years. Like many other families of antibiotics, they can lead to Clostridium difficile colitis, a dangerous intestinal infection about which I’ve written many posts. Fluoroquinolones, like a few other antibiotic families, can predispose to dangerous and even fatal heart rhythm abnormalities.

In July, the FDA issued warnings about two additional adverse effects that have been reported in patients taking fluoroquinolones. The first side effect is psychiatric, causing disturbances in attention, disorientation, agitation, nervousness, memory impairment, and delirium. This has been reported after even just one dose of the medication. The second adverse effect is hypoglycemic coma, coma due to dangerously low blood sugar. This happens more frequently in elderly patients and in patients taking diabetes medications that lower blood sugar.

The FDA recommends that fluoroquinolones be avoided in patients with uncomplicated bladder infections, sinus infections, or emphysema exacerbations, unless no other antibiotic alternatives are available. They also recommend that elderly patients and patients with diabetes who are prescribed fluoroquinolones be warned about the symptoms of low blood sugar and that blood sugar be monitored in these patients. Patients should also we advised about the risk of psychiatric side effects.

Of course, one of the easiest ways to minimize the side effects of antibiotics is to avoid antibiotics altogether when they are not beneficial. Many antibiotic prescriptions are written for colds (a viral illness for which antibiotics don’t help), for acute bronchitis (also almost always caused by viruses), and for sinus infections (for which decongestants and pain relievers usually suffice).

If antibiotics are needed, fluoroquinolones should be reserved for cases in which other alternatives are absent, or for severe infections for which the broad spectrum and effectiveness of fluoroquinolones can be life-saving.

Learn more:
FDA updates warnings for fluoroquinolone antibiotics on risks of mental health and low blood sugar adverse reactions (FDA News Release)
Thinking of a Fluoroquinolone? Think Again (Medscape)
When antibiotics turn toxic (Nature, news feature)
In Brief: More Fluoroquinolone Warnings (The Medical Letter on Drugs and Therapeutics, by subscription only)

My previous posts about Clostridium difficile

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LA Magazine Recognizes Top Doctors

 

“I want to go to the best orthopedist.”

I hear this request, or a version of it, all the time. “I want my daughter to see the best cardiologist,” or breast surgeon, or neurologist.

I try to explain to patients that there’s no way to figure out who is the single best doctor in a field, or even what it would mean to be the best. Would it mean the best outcomes? The best patient satisfaction? The best reputation among colleagues?

I try to explain that there is a group in every specialty that practices excellent medicine and maintains an excellent reputation. Of that group I might personally know and trust a handful of them, and I generally try to ensure that doctors are board certified and haven’t been disciplined by the medical board. So in every specialty, I try to refer to a group of excellent doctors, but I have no way of knowing who is “the best”.

The editors of LA Magazine must think the same way. This month’s issue of LA Magazine published a list of top doctors in Los Angeles. To assemble the list, they surveyed doctors asking them which of their colleagues they considered excellent in virtually every specialty. They then screened the list against public databases of complaints and infractions. The list can be searched by name, specialty or geography. In all of LA County only 45 internal medicine doctors made the cut. I’m very proud to have been one of them.

I should spend the rest of the post congratulating myself and asking you to send me your colleagues and loved ones so that I can get my kids through college. Instead, I’ll give a shout-out to the other two internists in our office, Dr. Rubencio Quintana and Dr. Dorothy Lowe. They made the list too, and that’s no surprise. They both have excellent training, and they’re both smart doctors and nice people. So if your colleagues and loved ones are looking for a practice with a limited number of patients, after-hours access to the doctor by cell phone, and guaranteed same-day appointments, please recommend me to them. If they’re looking for a great doctor without those perks, please refer them to Dr. Quintana or Dr. Lowe (so they can get their kids through college).

I browsed the list and found lots of doctors whom I respect and admire, including some who were my professors at UCLA and others with whom I trained.

Then, I thought, what about the doctors who attract lots of patients, but who are not practicing evidence-based medicine? I searched the list for the doctor in Santa Monica who never completed a residency program, has no board certification, whose website states that he practices “regenerative” and ”anti-aging” medicine, and who has prescribed testosterone to every one of my patients who has had the misfortune to enter his office. Then I looked up the Beverly Hills doctor whose website calls her a “hormone specialist” despite having no specialty training in endocrinology and no board certification in any field. She has prescribed risky hormones of dubious effectiveness to more of my unsuspecting patients then I can count. Then I searched the list for the Santa Monica doctor whose website advertises chelation therapy, detoxification, bio-identical hormone replacement, and other phrases that are fashionable in quackery circles. None of them are on the list. Their feel-good placebos and risky hormones might be very popular with patients, but they aren’t fooling their colleagues.

I am deeply honored to be included in such an outstanding group, and I will work hard to maintain the esteem of my colleagues and my patients.

Learn more:
Los Angeles Top Doctors (LA Magazine)
American Board of Medical Specialties (where to check if a specialist is certified by their specialty board)
American Board of Internal Medicine (where to check if an internist is board certified)
Medical Board of California (where to check if a doctor has faced disciplinary action or has been the subject of large malpractice awards)

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What You Need to Know About Shingrix

This is a photo of an HPV vaccine, which has nothing to do with shingles. Photo credit: Pan American Health Organization, Creative Common license
This is a photo of an HPV vaccine, which has nothing to do with shingles.
Photo credit: Pan American Health Organization, Creative Common license

Shingrix is a new vaccine approved to prevent shingles. What’s shingles? Should you get this vaccine? What if you already had a vaccine for shingles? Good questions. Read on.

To understand shingles, we have to understand chicken pox. Chicken pox was an extremely common childhood illness before 1995, when routine vaccination for chicken pox began. Before that, an average of 4 million people got chicken pox each year in the U.S. and about 100 people died. Chicken pox is caused by the varicella zoster virus. Varicella zoster virus is never cleared from the body. After causing chicken pox it persists in the body forever. Years or decades after the initial illness the virus can become reactivated, causing a painful linear blistering rash. It is this reactivation and the painful rash that results that is called shingles. (The medical term for shingles is herpes zoster.) Shingles typically lasts about two weeks and then resolves, but sometimes the patch of skin that is affected remains permanently painful, a condition called post-herpetic neuralgia. Post-herpetic neuralgia happens most commonly in older patients and can be debilitating.

In an effort to prevent post-herpetic neuralgia, Zostavax, a vaccine to prevent shingles was developed and approved in 2006. It was recommended to everyone over 60 who previously had chicken pox. But Zostavax has some drawbacks. First, it is much less effective in older patients. It is 64% effective for patients who receive the vaccine in their 60s, but only 18% effective for patients who receive it when older than 80. Second, immunity offered by Zostavax wanes quickly. Eight years after inoculation immunity wanes to 4%. Finally, because it is a live vaccine, it can not be given to immunocompromised patients, such as patients who are taking immunosuppressive medications for rheumatologic diseases or after organ transplants.

Several months ago, Singrix, a new vaccine to prevent shingles was approved. Shingrix eliminates many of Zostavax’s flaws. It is 97% effective at preventing shingles, and is equally effective in younger and older patients. And it is not a live vaccine, so immunocompromised patients can have it. The duration of Shingrix is not yet known, but preliminary studies suggest that protection should last at least 9 years after vaccination.

Though Shingrix is an important step forward in effectiveness, it is less convenient and causes more frequent side effects. Shingrix requires two shots given 2 to 6 months apart, and is more likely to cause redness, swelling, and pain at the injection site. These side effects are not dangerous but might make patients who are ambivalent about vaccination skip the second dose, thereby missing out on the full effectiveness of the vaccine.

Shingrix is approved for everyone over 50, including those who have Zostavax. Many pharmacies are carrying it and can administer the shot, and it’s covered by some insurances. I’ll be recommending it to all my patients over 50 when their annual exams come up, and my wife and I will get it soon.

Of course, in about 30 years the first kids vaccinated against chicken pox will be turning 50, and then hopefully both chicken pox and shingles will be consigned to history books.

Learn more:
C.D.C. Panel Recommends a New Shingles Vaccine (New York Times)
CDC recommends new shingles vaccine to replace older one (CNN)
No Excuses, People: Get the New Shingles Vaccine (New York Times)
Shingles (Herpes Zoster) (Centers for Disease Control and Prevention)
What Everyone Should Know about Shingles Vaccine (Shingrix) (Centers for Disease Control and Prevention)
Shingrix – An Adjuvanted, Recombinant Herpes Zoster Vaccine (The Medical Letter, by subscription only)

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Heart Stents Don’t Decrease Chest Pain

A stent in a coronary artery. Image credit: WikiJournal of Medicine
A stent in a coronary artery. Image credit: WikiJournal of Medicine

“The first principle is that you must not fool yourself – and you are the easiest person to fool.”
— Richard Feynman

This month brought more bad news for coronary artery stents. To understand how far coronary stents have fallen, we have to understand what we’ve been using them for.

But first I should explain that coronary stents are life-saving treatments during a heart attack. That has been well established and is not changed by anything in this post. This post is about using coronary stents in patients with narrowing in the coronary arteries who are not having a heart attack.

Coronary artery stents are metal wire tubes that are inserted into narrowed arteries to keep them open. We used to think they prevented heart attacks. The reasoning was compelling and goes like this. People with narrowing in their coronary arteries caused by atherosclerosis (cholesterol build up on the inside of the arteries) sometimes have heart attacks. People without narrowing in their coronary arteries don’t have heart attacks. Heart attacks are caused by blood clots in coronary arteries that suddenly close the arteries. If we can open the narrowest parts of the arteries with stents then blood clots won’t form there and heart attacks will be averted.

Based on that reasoning coronary artery stents were widely used in patients with coronary narrowing due to atherosclerosis. Then in 2007 the COURAGE trial randomized patients with narrowed coronary arteries to receive either medications (like statins and aspirin) aimed at preventing heart attacks or a stent plus the same medications. The results showed no difference in incidence of heart attack or death between the two groups. So stents don’t prevent heart attacks and don’t save lives.

This finding actually led to fewer stents being placed nationwide. The newer understanding was that medications prevented heart attacks and saved lives, but that stents still had a role in decreasing chest pain from narrow coronary arteries. So the use of stents were recommended only for those patients with coronary artery narrowing who still had chest pain when exercising despite being on appropriate heart medications.

The belief that stents relieve chest pain is well founded physiologically. Muscles get sore when they have too little blood flow for the amount of work they do. Think about your legs when you are climbing a long hill or your biceps after lifting your child all day. A narrowed coronary artery limits the blood flow that the downstream heart muscle can receive, so when the heart is expected to do a lot of work – during exercise – the muscle gets sore and the patient feels chest pain. If the artery is kept open, chest pain should not occur. Hundreds of thousands of coronary artery stents are placed annually to relieve chest pain.

A study published online in November 2 in the British journal The Lancet turned this understanding on its head. Many previous trials comparing stents plus medications to medications alone have been randomized. But none of the studies have been blinded. That is, patients knew whether they were undergoing an invasive procedure to put a stent in their heart, or whether they were just swallowing some tablets every day. Is it possible that this knowledge biased their experiences and led to a bias in their reported symptoms? This trial attempted to answer that by actually keeping the patients from knowing which treatment they were receiving.

The study enrolled patients with severe narrowing in a coronary artery who had chest pain when they exercised. Two hundred patients were randomized to two groups. Both groups received optimum medications aimed at preventing heart attacks and decreasing chest pain. One group underwent stenting of the narrowed artery. The other group underwent a sham procedure that was nearly identical to the first group. A catheter was inserted into an artery. A wire was fed into the coronary artery, but no stent was deployed. Patients had no idea whether they were in the stent group or the sham procedure group, and neither did the physicians who followed them afterwards to measure the outcomes.

Not surprisingly, stenting led to a much more open artery than the sham procedure. That is, stenting did what it was supposed to do to the plumbing – open the artery. But the startling outcome was that both groups had equal relief of chest pain and equal improvement in ability to exercise.

That means that the stents are not relieving chest pain. The chest pain must have been relieved partially by the medications that both groups received and partially by the patient’s expectation that she received a very invasive, very dramatic, high-tech, and expensive intervention.

We’ve long known that patient expectations and physician expectations can strongly bias medical trial results. That’s not because anyone is trying to cheat, but because everyone wants to be part of good news. No one wants to tell his doctor that the surgery didn’t help. And no doctor wants to do a procedure she doesn’t think will work. Study after study confirms that our expectations strongly bias our experience. For example tasters prefer a wine in a bottle with an expensive price tag over a wine in a bottle with an inexpensive price tag even when the same wine is in both bottles.

That is why blinding is so important. The only way to isolate the effect of an experimental medication or procedure is to make sure the expectations and experience is identical in the experimental group as in the control group. With medications, that’s fairly easy. The control group can get a placebo. But in the case of an invasive procedure, that frequently means subjecting the control group to an invasive and potentially risky sham procedure. That makes it much harder to find willing patients, and makes ethical review boards less likely to approve the trial.

The study has some limitations. The number of patients randomized was relatively small, and the time that they were followed was short. It is possible that a small benefit of stents would have been found in a larger longer study. But a dramatic benefit was expected, and it was dramatically not found. The study also excluded certain patients, for example those with narrowing in multiple arteries, so the results might not apply to everyone.

Nevertheless, the lesson for doctors and patients is that medications alone decrease chest pain about as well as medications and a coronary stent. So we should save stents for patients who are having heart attacks. And the lesson for researchers is that we each carry between our ears a highly sophisticated engine for bias, error, and self-delusion. Keeping our opinion out of the data is hard work, but is the only way to learn the truth.

Learn more:

‘Unbelievable’: Heart Stents Fail to Ease Chest Pain (New York Times)
Do Heart Stents Work? What You Need to Know (Time)
Percutaneous coronary intervention instable angina (ORBITA): a double-blind, randomised controlled trial (The Lancet)
Baba Shiv: How a Wine’s Price Tag Affect Its Taste (Stanford Graduate School of Business)

My previous posts about angioplasty:

On Stinting On Stents (my post from 2013 inspired by President Bush’s angioplasty)
Is There a Patient Educator in the House? (about a 2010 study which showed angioplasty patients did not understand the benefits of the procedure)
For Most Heart Patients Medicines are as Good as Angioplasty (2008)

Tangential Miscellany

Happy Thanksgiving! I hope all of you have joyous celebrations with loved ones in which blessings are counted rather than calories.

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