Normal Weight Obesity: Why Losing Weight Is Not Always the Answer

Weight loss is one of the most common recommendations that doctors make.  How do we know if a patient should lose weight?  We usually use the Body Mass Index (BMI) which is a way to compare a patient’s weight to her height.  (For all you math geeks, it’s the weight in kilograms divided by the height in meters squared.  For all you physicists, I know the units make no sense.)  A BMI of 18.5 to 25 is considered normal.  A BMI of 25 to 30 is considered overweight, and over 30 is considered obese.  (See the link below to calculate your BMI.)

An article in the health section of Tuesday’s Wall Street Journal reminds us that BMI may not be telling us the whole story.  The article cites a study published in the European Heart Journal last year which followed over 6,000 adults with a normal BMI.  They all had their body fat percentage measured and were followed for about 9 years.

Surprisingly, even in these adults with a “normal” weight, those with a high body fat content had a higher likelihood of high blood pressure, high cholesterol and cardiovascular disease.

This study is too small to be definitive, and it’s observational, not randomized.  So we don’t know whether lowering body fat reverses any of these risk factors.  I’m not suggesting we all run out to measure our body fat content.  Still the article suggests a few tantalizing possibilities.

First, dieting may not be enough in improving cardiovascular health.  It may decrease overall weight without decreasing percent body fat.  Exercise is critical to burn fat and build muscle, thereby decreasing percent body fat.

Second, thin people who are inactive may have a high body fat percentage and may be falsely reassured by their “normal” weight.  This is what the authors call “normal weight obesity”.

Finally, for those of you who are exercising and not losing weight, don’t despair.  You may be losing inches from your waist, burning fat and building muscle, muscle while your weight stays the same.  Going by the weight alone is a recipe for frustration when in reality your health is improving.

Learn more:

The Centers for Disease Control BMI calculator

Wall Street Journal article:  The Scales Can Lie: Hidden Fat (only by subscription)

European Heart Journal article:  Normal weight obesity: a risk factor for cardiometabolic dysregulation and cardiovascular mortality

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A New Treatment for Clostridium difficile

You may not yet have heard of the bacterium Clostridium difficile (C. dif.), but in the next few years it will likely become a household name, as well known as Staph and Strep.  C. dif. causes a severe infection of the colon leading to severe diarrhea.  It frequently results as a consequence of antibiotic use.  Antibiotics can kill the normal intestinal bacteria and allow harmful bacteria like C. dif. to proliferate.

Decades ago, C. dif. infection was a minor nuisance, but in the last decade, due perhaps to increasing use of broad-spectrum antibiotics, C. dif. has become more common and more severe.  Many patients, especially older patients, require hospitalization for C. dif. diarrhea.  Besides causing severe dehydration, C. dif. can cause systemic infection and sometimes death.

Ironically, the typical treatment for C. dif. colitis is antibiotics.  But since antibiotics don’t allow the normal gut bacteria to return, recurrence of C. dif. diarrhea after treatment is completed is a frequent problem.  In hospitals and nursing homes spread of C. dif. has become a menace.

A study published in this issue of the New England Journal of Medicine offers hope against this worsening problem.  The study randomized 200 patients with C. dif. diarrhea.  All patients received conventional antibiotic treatment.  Half the patients also received a new intravenous antibody directed at C. dif. toxin; the other half received intravenous placebo.  The results were encouraging.  Only 7% of the patients that received the intravenous antibody developed another episode of C. dif. infection, compared to 25% receiving placebo.  That means that for every about six patients that receive the antibody, one recurrent infection is prevented.

This new treatment will have to undergo larger trials before it is approved.  In the meantime the cornerstones of C. dif. prevention remain judicious antibiotic use and preventing spread between patients in hospitals and nursing homes.

Learn more:

New England Journal of Medicine article:  Treatment with Monoclonal Antibodies against Clostridium difficile Toxins

New England Journal of Medicine editorial:  Clostridium difficile — Beyond Antibiotics

Forbes post on The Science Business:  Why You Should Care About Treatment with Monoclonal Antibodies against Clostridium difficile Toxins

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To Clot or to Bleed?

Aspirin has long been known to prevent strokes and heart attacks in patients with a previous stroke or heart attack.  But aspirin has potentially serious side-effects.  Aspirin can cause stomach ulcers, and it inhibits blood clotting raising the risk of life-threatening bleeding.

If we knew in advance that a patient was going to be in a car accident or have a bleeding stomach ulcer, we would discontinue the aspirin a week before the event and minimize the bleeding risk.  (This is exactly what we do in anticipation of routine surgery.)  But of course such events don’t herald themselves, so doctors are left reacting to adverse events after they occur.  If a patient has life-threatening bleeding we stop the aspirin and consider that the risk may outweigh the benefits.  If the patient months or years later has a stroke we reconsider restarting the aspirin.  But this strategy is irrational.  What is needed is a way to balance risks and benefits of aspirin based on the likelihood of future events, regardless of which event happened most recently.

A study published in this issue of Annals of Internal Medicine examines the wisdom of the current practice of discontinuing aspirin after bleeding from stomach ulcers.  The study followed 156 patients who had been taking aspirin for stroke or heart attack prevention and developed bleeding stomach ulcers.  All patients had endoscopy to determine the site of bleeding and to stop the bleeding.  They were all then started on acid suppressing medication to decrease the risk of future bleeding.  Half the patients were randomized to continue 80 mg of aspirin daily and the other half to placebo.

The patients were followed for 8 weeks to test whether the patients on aspirin had more recurrent bleeding than those on placebo.  The hope was that the acid blocking medication would make the aspirin safe.  It didn’t.  Significantly more patients had bleeding on aspirin than on placebo.  But surprisingly, more patients died on placebo than on aspirin.  The reason was that more patients had strokes and heart attacks on placebo.

This study is too small to reach definitive conclusions, but its results should rattle our current thinking.  Rather than stop aspirin because an adverse effect occurs, the right course may be to remember why we recommended aspirin in the first place.  After all, strokes and heart attacks are much harder to fix than bleeding ulcers.

Learn more:

Annals of Internal Medicine article:  Continuation of Low-Dose Aspirin Therapy in Peptic Ulcer Bleeding

Annals of Internal Medicine editorial:  Aspirin Withdrawal in Acute Peptic Ulcer Bleeding: Are We Harming Patients?

Tangential miscellany:

My post last week, Antidepressants for Mild Depression May Not Help Much, generated many interesting comments, some from the handful of psychiatrists and psychologists who are my patients.  Many comments pointed out important limitations of the study I wrote about.  Two psychiatrists pointed me to the following New York Times articles which make the case that antidepressants are more beneficial than the study I cited suggests.  I’m grateful to all who wrote to me.

New York Times article:  Before You Quit Antidepressants …

New York Times Op-Ed:  The Wrong Story About Depression

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Antidepressants for Mild Depression May Not Help Much

Treatments for depression are difficult to study.  First, depression is a condition that can improve without treatment.  So any treatment must be compared to placebo to see if the treatment is responsible for the improvement or if the depression improved on its own.  Also, depression can not be measured objectively.  There is no objective test like an X ray or a blood test that can diagnose depression.  (At least not yet.  As our understanding of brain function improves, such a test is certainly conceivable.)  For now, the most reliable measures of depression used in research are standardized questionnaires.  Another difficulty is that depression has a high response rate to placebo, so demonstrating that a treatment is better than placebo isn’t easy.

Because of these difficulties, most randomized trials testing antidepressants tend to study severely depressed patients, and they clearly show that antidepressants are beneficial.  But is the benefit the same in patients with milder depression?  A study in this issue of the Journal of the American Medical Association answers that question.

The study collected the data from six trials which randomized a total of 718 patients with depression to an antidepressant or to placebo.  It then compared how much more improvement antidepressants offered over placebo in patients with different levels of depression severity.  Surprisingly, for patients with mild or moderate initial symptoms, the difference between antidepressant and placebo was not significant.  The benefit of antidepressants over placebo grew in those with more severe symptoms.

The authors conclude:

The magnitude of benefit of antidepressant medication compared with placebo increases with severity of depression symptoms and may be minimal or nonexistent, on average, in patients with mild or moderate symptoms. For patients with very severe depression, the benefit of medications over placebo is substantial.

What does that mean in practical terms?  First, it’s another reminder that antidepressants help patients with severe depression.  But for patients with mild symptoms it suggests that the visit with an attentive doctor, the anticipation that the medication may work, and the simple passage of time help more than the medicine itself.

Learn more:

Wall Street Journal article:  Effectiveness of Antidepressants Varies Widely

LA Times article:  Study finds medication of little help to patients with mild, moderate depression

Journal of the American Medical Association article:  Antidepressant Drug Effects and Depression Severity

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End of Year Cheer

Short work weeks make for short posts, doubly so when virtually all the health-related news is about the healthcare bill in Congress. So I’ll end the year with two unrelated bits of good news.

The first is that the H1N1 flu pandemic is mostly behind us. The peak numbers of people getting sick both nationally and in California was about two months ago, with decreasing numbers ever since. As predicted by yours truly in April, the world did not end (though a bunch of my patients were plenty miserable).

The second bit of good news is that Americans are living longer then ever. In 2007, the most recent year for which statistics are available, average life expectancy at birth crept up to a record high of 77.9 years. That’s an average, so many of us will live longer. So for everyone who had a mediocre 2009, here’s hoping you have many better years ahead.

Tangential miscellany:

Posting will be suspended next week and will resume in the New Year. Merry Christmas to all who are celebrating, and to all of us a prosperous, healthy and happy 2010!

Learn more:

Follow the H1N1 flu trends at the Centers for Disease Control FluView Weekly Report or at Google Flu Trends

The statistic about your increasing life expectancy is from the LA Times Booster Shots post: U.S. birth rates back on the rise

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Mollified about Mercury (or Calm about Catfish)

Mercury in high doses is known to be toxic.  So if you were thinking about breaking your glass thermometer and drinking the contents on a lark, I beg you to reconsider.  This has raised concern about possible harm from eating seafood since many species of seafood are known to contain trace amounts of mercury.  Much hand-wringing has ensued.  Should we shun salmon?  Avoid albacore?

The most recent issue of The Medical Letter, a publication I frequently cite, summarizes the scientific literature and attempts to clarify the issue.

Mercury exposure during pregnancy has been associated with problems with neurological development in the developing babies, though the results of studies of the effects of seafood intake during pregnancy have been mixed.  Still, because neurodevelopment appears to be the biggest effect of mercury toxicity, concern has focused on pregnant and breastfeeding women and small children.  The FDA (see link below) has recommended that pregnant and breastfeeding women limit their intake of seafood high in mercury.

In non-pregnant adults, no harm has been shown from mercury exposure from seafood.  One possible reason is that the omega-3 polyunsaturated fatty acids (PUFAs) in fish oil have a beneficial protective effect that could outweigh any harm from the mercury in fish.

The authors of the article conclude:

Public health agencies have recommended limiting the intake of seafood with a substantial mercury content during pregnancy. Since the typical US seafood diet has a healthy ratio of omega-3 PUFAs to methylmercury and PCBs, the net effect of eating fish in the US is likely to be a protective one.

This is reassuring.  I’m going to celebrate with a jar of herring.

Learn more:

The Medical Letter article:  Mercury in Fish (by subscription only)

FDA advisory for Women Who Might Become Pregnant, Women Who are Pregnant, Nursing Mothers and Young Children:  What You Need to Know About Mercury in Fish and Shellfish

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Expired Medications (or Medicines From The Mesozoic)

Every primary care physician occasionally encounters questions similar to the following.

“I just found some of my blood pressure medicines.  The container fell behind the couch a year ago.  The expiration date was last month.  Can I still use them?”

or

“I know you just prescribed amoxicillin for my sore throat, but I just found some amoxicillin in my cupboard that I bought during the Nixon administration.  Can I take that?”

The bigger question is, what happens to medications after they expire?  Fortunately this issue of The Medical Letter reviews this ever-fresh topic.

The first reassuring fact is that medications are not more harmful as they degrade.  So medicines don’t deteriorate into something toxic, just something ineffective.  Any side-effects you get from taking an expired medicine are just the side-effects from the active medication, not from the process of degradation.

So all we have to worry about is whether the expired medication will still work, not whether it will harm us.  The efficacy of medicines in tablets lasts much longer than that of liquid medications.  Liquid medications that have become cloudy, discolored or have solid particles forming in them should not be used. The shelf life of eye drops is limited not by the stability of the medication, but by the preservative which eventually stops working and allows germs to grow in the solution.  Epinephrine in epinephrine autoinjectors is particularly unstable and degrades shortly after the expiration date. Since epinephrine is a rarely-used but life-saving medicine, it should be replaced promptly at the expiration date.

Tablets on the other hand frequently retain most of their efficacy for years if kept in a dry location in reasonable temperatures.  In their original unopened containers, many medications keep 90% of their potency 5 years after their expiration date.

So the recently expired blood pressure medications in the question above should be fine.  The 35 year old amoxicillin is likely to be ineffective, but not toxic.  And since amoxicillin is cheap, I would recommend purchasing a brand new twenty-first century batch.

Tangential miscellany:

A bright and joyous Hanukah to all my Jewish readers!

Learn more:

The Medical Letter article:  Drugs Past Their Expiration Date (by subscription only)

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Lemierre Syndrome: Rethinking Pharyngitis in Young Adults

One of the first outpatient problems a primary care trainee learns to manage is sore throat.  The current algorithm is fairly simple.  Most sore throats are caused by viruses and will not improve with antibiotics.  Symptomatic medication for pain and fever is the best we can offer.  But a significant minority of sore throats is caused by a bacterium called group A β-hemolytic streptococcus.  These cases are more commonly known as “strep throat”.  In strep throat antibiotics shorten the duration of symptoms by a day or two, but more importantly antibiotics prevent acute rheumatic fever, a potentially dangerous complication of untreated strep throat.

So the algorithm for evaluating sore throats is: decide if it’s strep.  If it is (or has a reasonable likelihood of being) strep then treat with antibiotics; otherwise don’t.

An article in this issue of Annals of Internal Medicine suggests that this algorithm is inadequate in adolescents and young adults.  The reason is that about 10% of sore throats in patients between 15 and 24 years old is caused by a bacterium called Fusobacterium necrophorum.  (Please memorize that name and mention it at your next holiday party.)  F. necrophorum also causes Lemierre Syndrome, a bacterial infection of the internal jugular vein that results in the bacteria spreading elsewhere in the body.  Lemierre Syndrome frequently results in permanent harm and is sometimes fatal.  Though much remains unknown about F. necrophorum, it appears to cause sore throats as commonly as strep in adolescents and young adults, and Lemierre Syndrome in this age group appears to be more common than acute rheumatic fever.

Diagnosing F. necrophorum pharyngitis is problematic.  F. necrophorum doesn’t grow on a standard throat culture.  (It’s anaerobic, meaning it only grows in the absence of oxygen.)  And specific molecular tests for it are not commercially available.

So the author recommends that antibiotics be prescribed for 15 to 24 year olds with sore throats and at least 3 of the following 4 findings.

  • history of fever
  • pus on the tonsils
  • swollen tender lymph nodes in the neck
  • absence of cough

(Note for doctors: use penicillins or cephalosporins.  Macrolides are ineffective against F. necrophorum.)

In that age group worsening symptoms or neck swelling should be alarm signs that F. necrophorum is present.

Our simplest clinical problem just got more complicated.  That’s a good sign that we’re learning something.

Learn more:

Annals of Internal Medicine article:  Expand the Pharyngitis Paradigm for Adolescents and Young Adults

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Happy Thanksgiving!

I’m grateful to all the readers of my weekly posts for all the stories you’ve pointed me to and all your valuable feedback.  Thanks for reading.

I’m grateful to my partners Dr. Rubencio Quintana and Dr. Dorothy Lowe for making our office a happy and intellectually stimulating place to work.

I’m grateful to Jaymes, Nancy and Jill for helping us take great care of our patients.  I couldn’t dream of a better support staff.

I’m grateful to my parents for bringing me to the US, where we are judged by our destinations, not by our origins.

I’m grateful to my wife for raising our kids, taking care of me, and working much harder than I do.

I’m grateful to my patients for letting me support my family by doing what I love (and in last year’s economy, I’m doubly grateful).

As is my tradition, I waive all of my patients’ dietary restrictions for 24 hours.  Count blessings, not calories.  Happy Thanksgiving!

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New Mammogram Recommendations Betray Women, Doctors and Science

This week the US Preventive Services Task Force (USPSTF) revised their recommendations for screening mammograms.  Their recommendations have ignited much controversy and have weakened the credibility of a formerly objective scientific body.

This post is longer than usual.  It deals with an important subject in some detail.  For the readers who like to delve into the details and see the data, set this aside for when you can give it some time, follow the links, and check out the articles yourself.  If you just want an executive summary, skim for the bold face type and read the conclusion.

What did the USPSTF recommend?

My regular readers know that the USPSTF is a national body of scientists who periodically assess the medical literature and provide recommendations about preventive tests and treatments.  Because they are unaffiliated with any specific interest group, the USPSTF developed a reputation as the most objective and unbiased source of medical recommendations.  For every test or therapy they reviewed, they weighed patient benefit against the potential for patient harm (regardless of cost) and reported whether the intervention was beneficial, harmful or that there is insufficient evidence to decide. I personally looked to their recommendations and wrote about them frequently.

The USPSTF’s last review of the literature regarding mammograms was in 2002.  At that time they recommended a mammogram every one to two years for women aged 40 and older.

This week, in the Annals of Internal Medicine they published their new recommendations, supported by two articles detailing the scientific evidence that was reviewed to reach their conclusions.  Their current recommendation (link 1 below) for mammograms is

The USPSTF recommends against routine screening mammography in women aged 40 to 49 years. The decision to start regular, biennial screening mammography before the age of 50 years should be an individual one and take into account patient context, including the patient’s values regarding specific benefits and harms.

The USPSTF recommends biennial screening mammography for women between the ages of 50 and 74 years.

The USPSTF concludes that the current evidence is insufficient to assess the additional benefits and harms of screening mammography in women 75 years or older.

So the major changes from 2002 are that

  • mammograms are no longer recommended between the ages of 40 and 49,
  • between 50 and 74 mammograms are recommended every two years, rather than every one to two years, and
  • there is insufficient evidence about the benefits and harms of mammograms in women 75 years and older.

Shockingly, the first two points are entirely contradicted by the scientific evidence on which the recommendations are based.

What are the benefits and harms of mammograms for women in their 40s?

The article which examines the harms and benefits of mammograms in different age groups can be found at link 2, below.  Table 1 (Pooled Risk Ratios for Breast Cancer Mortality From Mammography Screening Trials for All Ages) is a very helpful review of the pooled data from all the randomized trials for mammography in different age groups.  The table shows how many women are needed to be invited to undergo mammograms in each age group to prevent 1 death from breast cancer.  The numbers for women in their 60s are terrific.  377 women in their 60s need to be offered mammography to save 1 life from breast cancer.  (The lower the number of women who must undergo mammograms to save one life, the more beneficial the intervention.)  In their 50s 1,339 women must be screened to save a life, and in their 40s 1,904 must be screened.  So mammography is still life-saving for women in their 40s it just saves fewer lives than for women in their 50s and 60s. In fact, the abstract of the article concludes

Mammography screening reduces breast cancer mortality for women aged 39 to 69 years.

So if mammograms have a life-saving benefit for women in their 40s, albeit a much smaller one than for women in their 50s or 60s, why would they not be recommended?  Perhaps the harms caused by mammograms in that age group outweigh the benefits.

The article also methodically reviewed harms caused by mammograms.  The risk posed by radiation exposure due to mammograms was studied without conclusive evidence of significant harm.  The pain, anxiety and distress associated with undergoing mammograms and being told about potentially abnormal results were also studied.  Most women surveyed reported that the pain and anxiety would not deter them from future mammograms.  The most important harms that may result from mammography is a biopsy to determine if an abnormality is benign or malignant, additional imaging that may be required, and overdiagnosis, which means the diagnosis of breast cancer that is so slow-growing it is unlikely to shorten the woman’s lifespan.

Table 2 (Age-Specific Screening Results From the Breast Cancer Surveillance Consortium) summarizes the potential harms by age per 1,000 women screened.  We would expect the harms in women in their 40s to outbalance the benefits and lead to the recommendation against mammograms at that age.  The left column in the table deals with women in their 40s.  Recall that it takes 1,904 women to be screened to save one life from breast cancer in that age group.  Since the table shows the harms per 1,000 women screened, if we multiply each number by 1,904/1,000 we discover the harms that result from saving one life in this age group.  So to save one life from breast cancer by screening women in their 40s with mammograms we would have to inflict 186 women with false positive mammogram results (abnormal mammograms without any cancer present), 161 women would have to undergo additional imaging and 18 women would have to undergo biopsies.

Now, I don’t want to minimize the misery involved in an unnecessary breast biopsy (unnecessary only in hindsight, of course).  The procedure itself is uncomfortable and waiting for results is torture.  Still, 18 biopsies to save one life strikes me as a wonderful trade-off, especially given that saving a life in the 40s yields many years of additional living.  How can the USPSTF possibly judge that these harms outweigh the benefits?  They hedge their recommendation by saying that the decision should be individualized for each patient, but that’s true for all medical decisions.  Why then recommend against it?

Because it’s sometimes difficult to understand the numbers involved, I ask you to do the following thought experiment.  You are a physician addressing an auditorium of 1,904 women in their 40s.  You tell them “If you all have mammograms before you turn 50 one of your lives will be saved from breast cancer compared to just waiting until you all turn 50.  Some of you will get breast cancer and die of it whether you get mammograms or not, and most of you won’t get breast cancer.  If you start mammograms now, 18 of you will get biopsies, and a lot of you will get incorrect initial mammogram results requiring more mammograms or ultrasounds or MRIs.  But only one of you will have her life saved from breast cancer.”  Each woman can and should decide for herself but they’d like a recommendation from you.

I can’t imagine not recommending mammograms under this circumstance.  Of course some women may choose against mammography, but to me the harms seem minor compared to the benefits.

How frequently should women have mammograms?

The decision to recommend biennial mammograms is based on a study published in an article at link 3, below.  The study uses various models to compare the harms and benefits from different mammogram frequencies.  But this article does something that has generally been outside the purview of the USPSTF.  It considers cost.

The results state that having a mammogram every two years had 81% of the benefit of annual mammograms with far fewer false-positive results, unnecessary biopsies and additional imaging.  And they state explicitly that annual mammograms consume more resources than mammograms every other year.

There are two important objections to this.  First of all, getting only 81% of the life-saving benefits of annual mammograms may not strike many women as a victory.  Why not capture all the benefits by having the test annually?  The answer might be the additional harms, but as we’ve seen in the previous section, the harms are quite modest and most women would not be deterred by them.  The second objection is that previously the unique value of the USPSTF was that it advised physicians about the value of tests regardless of costs.  That allowed us to give patients the best advice we could, and allowed patients to decide if the cost was worth the benefit.  Now, the USPSTF is deciding for us that annual mammograms are too expensive.

Conclusion

So, I and many other physicians will advise women to have annual mammograms starting at age 40.  And in my opinion they should continue to do so until they are ill or frail enough that a new diagnosis of breast cancer would be unlikely to shorten their lives.  For some women this might be in their 70s, for others, in their 80s.

But the broader outrage is that a group that I used to turn to without hesitation for objective review of the scientific data, a group that informed my daily advice to patients, has provided recommendations inconsistent with their own data and motivated by economics.  Patients and physicians have neither the skills nor the time to scour the world literature on important topics.  Who will fill the role that the USPSTF abandoned?

Learn more:

Scientific articles:

(1)  Screening for Breast Cancer: U.S. Preventive Services Task Force Recommendation Statement

(2)  Screening for Breast Cancer: An Update for the U.S. Preventive Services Task Force

(3)  The Annals of Internal Medicine article studying how frequently mammograms should be done:  Effects of Mammography Screening Under Different Screening Schedules: Model Estimates of Potential Benefits and Harm

Media coverage:

New York Times article:  Panel Urges Mammograms at 50, Not 40

LA Times article:  Mammogram guidelines spark heated debate

Wall Street Journal Editorial:  A Breast Cancer Preview

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