CDC Sounds the Alarm about Antibiotic Resistance

CDC: Antibiotic resistance threats in the United States, 2013A recurrent theme of my posts is the increasing danger of antibiotic-resistant germs and the harmful consequences of antibiotic overuse. This week the Centers for Disease Control and Prevention (CDC) released Antibiotic Resistance Threats in the United States, 2013, a detailed report assessing the current state of antibiotic resistance and recommending actions to limit the problem.

The report begins with an attempt to estimate the current harm from antibiotic-resistant organisms. Using very conservative estimates that are likely to undercount relevant cases, the CDC concludes that over two million people in the US develop infections that are resistant to antibiotics and that over 23,000 deaths result from these infections.

The report also has a diagram explaining the development and spread of antibiotic resistance.

In the mid-90s while I was going through my residency, infections with antibiotic-resistant bacteria were relatively uncommon and were limited to hospitalized patients. Now, as antibiotic resistance is becoming more common, and as hospitals have taken measures to reduce the spread of resistant organisms, more infections with these dangerous organisms are being seen in non-hospitalized patients.

In some bacteria, like drug-resistant gonorrhea and carbapenem-resistant Enterobacteriaceae (CRE), the realistic near-term threat is that no available antibiotics will be able to treat these infections. The threat of severe drug-resistant infectious spills beyond the risk to the affected patients. Many important medical treatments have the possibility of being complicated by infections. Surgeries and immunosuppressive medications for organ transplantation or for auto-immune diseases can increase the risk of infections. These therapies are only undertaken because we know that we can treat the infections that might result. That calculation may change as infections become less treatable. Who will want a heart valve replacement or a kidney transplant if we get to the point that a tenth of the patients suffer an untreatable infection as a result?

The report also estimates the threat from the most relevant antibiotic-resistant organism. The three bacteria who were assigned the highest threat level are Clostridium difficile (C. dif.), drug-resistant gonorrhea, and CRE. If you haven’t read enough to be terrified of these critters, browse the part of the report that discusses them.

Finally, the report recommends four actions to slow the spread of resistance. The first is infection prevention through vaccination, hand washing, safe food preparation and handling, and infection prevention measures in healthcare settings. The second is tracking of drug resistance by the CDC. The third is using antibiotics more responsibly. Up to half of the courses of antibiotics prescribed in the US are unnecessary. And fourth, new antibiotics and new diagnostic tests must be developed. Though the need for new antibiotics has never been more urgent, fewer new antibiotics are in the drug pipeline now than in previous years.

Some experts have hypothesized that antibiotics will be a temporary technology, like phone booths or audio cassette tapes. We might look back at the 1940s to the 2040s as the antibiotic century. But unlike phone booths or audio tapes, if antibiotics become obsolete it will not be because of their replacement by a better alternative. It will be because they will cease to work. Then we’ll be back to worrying that every cut, every infected tooth, every sore throat could be fatal.

Learn more:

Untreatable: Report by CDC details today’s drug-resistant health threats (CDC Press Release)
Antibiotic resistance threats in the United States, 2013 (CDC report)
Antibiotic-Resistant Infections Lead to 23,000 Deaths a Year, C.D.C. Finds (NY Times)
Taking antibiotics you don’t really need might kill you (Washington Post Wonkblog)

Some of my previous posts about drug-resistant bacteria and unnecessary antibiotics:

A New Weapon against Hospital-Acquired MRSA Infections
Azithromycin Might Kill You, but That’s Not Why You Shouldn’t Take It
The Pathogens on Cupid’s Arrow
Untreatable Gonorrhea – The Next Infectious Threat
Relearning What We Knew: Antibiotics Don’t Help In Sinus Infections
Serious MRSA Infections More Common

Some of my previous posts about C. dif.:

Clostridium difficile Infections on the Increase
Curing Clostridium difficile with, um, Feces

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A Better Understanding of Sex Hormones in Men

A body builder. Would more testosterone make him stronger? Credit: Wikimedia Commons

Testosterone is one of the most over-prescribed and poorly understood medications. It is prescribed to millions of men for myriad indications, many of them unproven. Athletes believe it will improve their muscle mass and strength. Older men look to it as an anti-aging remedy. Men with flagging libido hope it will restore their sex drive. Testosterone has developed a mythology of masculinity. This is very similar to the notions we had a generation ago about estrogen being a fountain of femininity before anyone actually studied it.

Part of the difficulty in deciphering the actions of testosterone has been that testosterone is naturally metabolized in men’s bodies to estrogen. The concentration of testosterone in our blood is ten thousand times greater than that of estrogen, but estrogen clearly has important effects in men which are independent of the effects of testosterone. Sorting out which hormone does what has been challenging.

This week the New England Journal of Medicine (NEJM) published a very cleverly designed study that helps untangle the roles of testosterone and estrogen in middle-aged men.

The study enrolled 400 healthy men between the ages of 20 and 50 who had normal testosterone levels. They all received monthly injections of Zoladex, a medication that shuts off testosterone production in the testes. They were then randomized to 5 different groups. One group applied placebo gel to their skin daily. The next four groups each applied increasing doses of testosterone gel daily, from one quarter the typical testosterone replacement dose to twice the typical dose. That means that these men had their native testosterone production halted, and were replaced with 5 different amounts of testosterone ranging from zero to twice the typical amount.

Half of the men in these five groups were also randomized to receive Arimidex, a medication that blocks conversion of testosterone to estrogen. So these half were deprived of estrogen, regardless of how much testosterone supplement they were receiving. The men receiving Arimidex experienced severe hot flashes from the absence of estrogen.

The men were followed for 16 weeks. They answered questionnaires about their physical function, health status, and sexual function. They did leg presses to measure leg strength. They had CT scans to measure body fat and lean body mass.

By the way, spare a kind thought for the intrepid men who volunteered for such a study. For the reward of only $1,000 and the knowledge that they have served science, they agreed to have their sex hormones altered for 16 weeks. That means the placebo group essentially underwent a temporary castration for the fee of $31.25 per week per testis.

The findings were definitive and surprising. Muscle size and strength were found to be (as expected) due only to testosterone. Estrogen played no role in muscle mass or strength. Interestingly testosterone levels had to get very low before muscle size and strength were affected, suggesting that testosterone supplementation for men with testosterone levels even near the lower limit of normal may not improve their strength. Very little testosterone is all the muscles need.

Body fat turns out to be entirely estrogen dependent, with body fat increasing as estrogen declines. So just as women gain body fat during menopause, men probably gain body fat as their estrogen levels decline with age.

Sexual function was clearly dependent on both testosterone and estrogen. It declined in men deprived of testosterone, but declined even more in men deprived of both hormones.

I know what you’re thinking. “My libido hasn’t been great recently. I should start taking some of my wife’s estrogen supplement.” That’s a terrible idea. The doses your wife takes would likely cause you to grow breasts. Your wife’s reaction to that would likely more than outweigh whatever increase in libido you may experience.

This study doesn’t give us any immediate help in treating patients, but it suggests that checking estrogen levels in men with symptoms of hormone deficiency may be reasonable. And it elucidates which hormones are responsible for which symptoms. The Testosterone Trial is an ongoing study in older men with low testosterone that will help demonstrate the health benefits and harms of testosterone replacement. The results are expected in about a year and will give us much more practical information about who may benefit from treatment.

In the meantime we should remember that masculinity isn’t a molecule. Youth isn’t a medicine. The difference between men and women can’t be prescribed. And even if everyone else is jumping on the latest unproven fad, we are wise to wait for the data. That takes real balls.

Learn more:

Middle-Aged Men, Too, Can Blame Estrogen for That Waistline (NY Times)
Male Sex Drive Depends on Both Estrogen and Testosterone (Bloomberg)
Gonadal Steroids and Body Composition, Strength, and Sexual Function in Men (NEJM article)
Mechanisms of Action of Testosterone — Unraveling a Gordian Knot (NEJM editorial)

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Anticipating Autumn

Photo credit: Arivumathi / Wikimedia Creative Commons License

Fall is upon us with its much-anticipated wonders. Giddy parents are gently pushing anxious children onto school buses and then enjoying their first child-free hours in months. The temperature is dropping into the 70s. The leaves on the palm trees in Beverly Hills are staying exactly the same color. An occasional cloud dots the sky.

We Jews are anticipating the arrival of the New Year by taking stock of our most recent loop around the sun and contemplating our fates during the next loop. We ask ourselves anxiety provoking unanswerable questions about what will befall us and our loved ones in the year to come. Will our businesses prosper? Will our children stay healthy? Will there be peace or war? Will the inevitable exhaustion of the sun’s fuel in billions of years that wipes out all life on the planet occur after humans have colonized other solar systems? Will my cat stop throwing up on our rug? Why did I ever agree to get a cat? If humans colonize other solar systems, will they take cats with them?

These autumn ruminations are ultimately unproductive, but there is one very practical harbinger of fall that takes minutes and can go a long way to keeping you healthy in the coming year – a flu shot. Our office just received our batch.

The flu vaccine is recommended for everyone over six months. The Centers for Disease Control’s Key Facts About Seasonal Flu Vaccine webpage will answer most of your questions about the flu shot.

To those celebrating I wish a sweet and healthy year. And to all of us I wish a happy Labor Day and a flu-free winter.

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On Stinting On Stents

Former President Bush holds up his bike before a ride in 2007. Credit: White House Archives
Former President Bush holds up his bike before a ride in 2007. Credit: White House Archives

Former President George W. Bush underwent an angioplasty this week, and the details sparked a public debate about the controversies of heart disease treatments.

His spokesman stated that he underwent a routine physical exam and had no symptoms of heart disease. A stress test showed EKG changes and a CT angiogram found a blocked artery. He was transferred to another hospital and underwent an angioplasty, a procedure in which a stent (a wire mesh tube) is inserted into the blocked artery and pushed against the artery walls to prop it open.

Before delving into the details of the ensuing controversy, let me make clear that we don’t have enough details about Bush’s care to make any judgments about it, and the rest of the post will be about angioplasties in general, and not about Bush’s case specifically.

Whenever a public figure undergoes a medical procedure there is a concern that the public will misunderstand the details and assume that the procedure is also right for them. (A recent example is Angelina Jolie’s revelation of her double mastectomy.)

The controversy regarding Bush’s care centers on the fact that while angioplasties are known to be lifesaving during or immediately after a heart attack, in patients with stable heart disease they have no advantage over medications other than for relief of chest pain. We are told that Bush was not experiencing chest pain, and he is known to be an active athlete, having hosted and participated in several lengthy bicycle rides since leaving office. So the justification for the angioplasty is unclear.

Our best evidence comparing angioplasty to medications in patients with narrowed coronary arteries comes from the COURAGE trial which published its findings in 2007. The trial showed that rates of heart attack and death were the same whether patients with blocked arteries underwent angioplasty or were put on optimal medications.

This is where the media sometimes distorts the story. The press coverage of Bush’s angioplasty had frequent questions about the necessity of the angioplasty and the cost of such a procedure. That is precisely not the point, and gives the public the incorrect idea that angioplasties are expensive and beneficial luxuries. BMWs, after all, are unnecessary and expensive, but very nice. And if a VIP gets something unnecessary and expensive, shouldn’t I want one too? The point of the evidence about angioplasties is that in most patients they have no benefit. Focusing on “necessity” misses that point.

It is entirely possible that Bush’s care was flawless. One possibility was that his stress test was extremely abnormal. Such very abnormal tests were excluded from the COURAGE trial, and we have no definitive evidence whether medications or stenting is best in those cases.

The important thing for the public to understand is that VIPs sometimes get terrible care. I’ve personally seen that myself. Physicians often over-test and over-treat celebrities, wrongly thinking that this will protect them from blame for any adverse outcome later. It’s much easier to tell a prominent patient that we will fix your problem with a high-tech and very expensive solution, rather than taking the time to educate the patient that we should start a few very old and very inexpensive medicines which have been proven to save lives. Paradoxically, we’re frequently much more comfortable doing the right thing for patients who will not draw public attention.

I wish the former president continued good health. I wish the rest of us a careful review of the evidence before we burst into our doctors’ office demanding a stress test.

Learn more:

Did George W. Bush Really Need A Stent? (Forbes)
Former president’s stent surgery revives debate on heart care (Chicago Tribune)
President George W. Bush has stent procedure (Salon)
George W. Bush Gets Angioplasty and Stent – Was It Necessary? (The Voice in the Ear, a blog about stents)

My previous posts about angioplasty:
For Most Heart Patients Medicines are as Good as Angioplasty
Is There a Patient Educator in the House? (About a study which showed angioplasty patients did not understand the benefits of the procedure)

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Cyclosporiasis Outbreak Sickens Hundreds

Cyclospora
Cyclospora visualized by ultraviolet fluorescence microscopy. (Credit: CDC DPDx)

Cyclosporiasis is the name of the intestinal illness caused by the single-celled microscopic parasite Cyclospora cayetanensis. It is spread through ingestion of food or water contaminated by stool. (Oh, sorry. I hope you’re not reading this over lunch.) In the US, outbreaks of cyclosporiasis have usually been linked to contaminated imported fresh produce. It is not spread directly through contact from person to person.

The onset of the illness occurs about seven days after ingestion of contaminated food or water. Typical symptoms include prolonged watery diarrhea, abdominal cramping and nausea. Cyclosporiasis is treatable with antibiotics though most people with healthy immune systems recover without treatment.

The Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA) are investigating a recent outbreak of cyclosporiasis that has so far sickened 285 people in eleven states. (California is not among them.) Most of the illnesses started between mid-June through early July. 18 of the patients have been hospitalized. There have been no deaths.

The source of the outbreak has not yet been identified, though the investigation is ongoing.

Why am I bringing this to your attention? Just as an excuse to remind you to wash your hands and food preparation surfaces with hot soapy water before handling food, and to wash fresh produce thoroughly before eating it.

Learn more:

U.S. Health Officials Still Tracking Source of Stomach Bug Outbreak (US News)
Investigation of an Outbreak of Cyclosporiasis in the United States (CDC)
Parasites – Cyclosporiasis (CDC)
FDA Investigates Multistate Outbreak of Cyclosporiasis (FDA)

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Marie Curie Helps Patients with Metastatic Prostate Cancer

Marie Curie. Credit: Wikipedia
Marie Curie. Credit: Wikipedia

Anytime you or I feel particularly content with our achievements, we would be well advised to review the biography of Marie Curie. We would then quickly realize that we are unambitious mediocrities who should be much more productive. The magnitude of her accomplishments is dizzying. Virtually everything we know about radioactivity rests on the work of Madame Curie and her husband Pierre. The Curies coined the term radioactivity. She discovered the elements polonium and radium. She received two Nobel Prizes. Your last broken bone was diagnosed thanks to her pioneering work on x-rays.

This week’s news relates to Madame Curie’s discovery of radium-226 over a century ago. She even published a paper describing that tumor-forming cells were destroyed faster than healthy cells when exposed to radium. Radium emits alpha particles which are much more lethal to living cells than x-rays or gamma rays but penetrate living tissue less than a tenth of a millimeter. This would seem to be an ideal treatment for cancer if the radium could be transported to the tumor and not to healthy tissues. The insurmountable problem at Curie’s time was that radium-226 has a half-life of over a millennium and decays to radioactive radon gas, a substance you don’t want inside you.

Fast-forward to the present. Advanced cyclotrons now allow production and purification of specific isotopes that Madame Curie could only dream about, like radium-223. Radium-223 also emits alpha particles, but has a half-life of 11 days and decays to stable chemicals. That means that in a month only about an eighth of the original amount remains. Radium appears chemically to the human body a lot like calcium, so the body transports it rapidly to the bones, especially to areas where bone is being destroyed and rebuilt. Given the tiny tissue penetration of alpha rays, that would seem to be a perfect way to irradiate bone tumors.

This week the New England Journal of Medicine (NEJM) published the results of a fascinating study testing the effects of radium-223 in patients with metastatic prostate cancer in whom hormonal treatment had already failed. Patients with prostate cancer that has spread to the bone eventually develop bone pain which can be severe, and are at high risk for disabling fractures. Once their cancer stops responding to hormonal medicines, their life expectancy is about a year. That means these patients typically have both very little life expectancy and a miserable quality of life.

The study randomized over 900 such patients to receive intravenous injections of radium-233 or placebo every four weeks for six total doses. The primary endpoint measured was survival, but measures of quality of life like fractures and bone pain were also recorded. The patients given radium survived an average of 14 months, while those who received placebo survived an average of 11 months. That may not seem like a big difference, but I suspect it’s a huge difference to someone who has only 11 months to live. It’s also a very important difference because cancer treatments that prolong survival (rather than just shrink tumors) are notoriously difficult to find. The patients receiving radium also had fewer adverse events – like fractures – and had better quality of life. The radium did not cause serious side effects.

This is a very exciting finding, and not only for patients with advanced prostate cancer. It is the first time alpha rays have been used to treat disease. Given the excellent tolerability of radium-232 future trials should test it earlier in the course of metastatic prostate cancer. The treatment of other cancers that spread to bone should also be tested. Madame Curie would have been delighted by this advance, and would be quite impatient for us to get to the next discovery.

Learn more:

Radium-223 and Metastatic Prostate Cancer (Summary video from the editors of NEJM)
New Radiation Therapy Prolongs Prostate Cancer Survival (NY Times)
New Drug May Extend Survival for Some Prostate Cancer Patients (US News)
Fighting Prostate Cancer with Radium-223 — Not Your Madame’s Isotope (NEJM editorial)
Alpha Emitter Radium-223 and Survival in Metastatic Prostate Cancer (NEJM article)

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Even More Studies You Should Ignore

Fish oil capsules. Image credit: Wikimedia Commons.
Fish oil capsules. Image credit: Wikimedia Commons.

Back when I was a medical student (in the Cretaceous Period) we were taught that someone once did a study comparing folic acid levels in the blood of cancer patients compared to the blood of healthy patients. The cancer patients had, on average, significantly lower folic acid levels. And the ones with the largest, fastest growing tumors tended to have the lowest folic acid levels. “Aha,” they thought. “Something about folic acid deficiency predisposes them to cancer. We should give folic acid to cancer patients.” Bad idea. A randomized trial showed that cancer patients given folic acid died sooner than those given placebo.

What happened? Low folic acid levels are a consequence, not a cause, of cancer. Folic acid is needed to synthesize DNA, and DNA synthesis is necessary for one cell to divide into two cells. So folic acid gets used up by rapidly dividing cells – like cancer cells. Giving cancer patient folic acid just gives their tumor a helping hand. (This roundabout insight led to medications that block folic acid metabolism which are used as chemotherapy to this day.)

The main lesson here is that correlation tells us almost nothing about causation. That means if A and B occur together, we say that they are correlated, but we have to be very careful not to assume that one causes the other. A might cause B, or B might cause A, or they may both be caused by some other factor that we’re not paying attention to. This is the cognitive error that the farmer makes when he notices that the daily number of deaths of his livestock correlates with sales of ice cream in the town’s ice cream parlor. He figures that some waste from the ice cream is contaminating his feed or water. He lobbies the legislature to ban ice cream sales around his farm. He doesn’t realize that the rise in ice cream sales and his livestock deaths are both caused by very hot days.

This week a study was published that encourages just such a mistake. It should be universally ignored, but a handful of patients have already emailed me about it, and it’s receiving a fair amount of confused media attention.

Before we look at the study, we need to learn a little about omega-3 polyunsaturated fatty acids. Omega-3 fatty acids are the predominant molecules in fish oil. They have been proven to lower triglycerides. They have gained popularity in the last few years, though the most recent trials (reviewed last year by The Medical Letter) have failed to show that they prevent stroke or heart attacks. There is certainly no convincing reason for the general population to be taking fish oil.

This week’s study, published in the Journal of the National Cancer Institute, compared blood levels of omega-3 fatty acids in patients with prostate cancer to those levels in healthy adults. Prostate cancer patients had higher levels of omega-3 fatty acids. Note that the study had nothing to do with fish oil supplements or diet. None of the study subjects were asked about supplements or how frequently they ate fish. The only comparison was blood levels of omega-3 fatty acids of people with prostate cancer to healthy people.

This should remind you of the ancient folic acid study.

The study authors conclude that this should make us worry about the risks of increasing omega-3 fatty acids in our diet, and some of the media coverage warns that fish oil supplements may increase the risk of prostate cancer, but the study proves no such thing. Other possibilities are that prostate cancer patients produce elevated levels of omega-3 fatty acids, or that some unknown metabolic defect both increases prostate cancer risk and elevates omega-3 fatty acid blood levels.

The only way to know for sure is to randomize lots of people to fish oil capsules or to placebo, follow them, and count the resultant prostate cancer. That study hasn’t been done, but that study would deserve our attention.

So am I saying that fish oil is safe and everyone should resume taking it? No. It has no proven benefits (except possibly for elevated triglycerides). That the connection to prostate cancer is unproven isn’t a reason to take it.

Who knows? Maybe after a randomized trial is done and the biological connection is meticulously worked out this might lead to a new prostate cancer test or treatment. Then medical students not yet born will learn about it as an example of the importance of not confusing correlation with causation.

Learn more:

Hold The Salmon: Omega-3 Fatty Acids Linked to Higher Risk of Cancer (Time)
Too Much Fish Oil Might Boost Prostate Cancer Risk, Study Says (US News)
Plasma Phospholipid Fatty Acids and Prostate Cancer Risk in the SELECT Trial (Journal of the National Cancer Institute article, abstract available without subscription)
Fish Oil Supplements (The Medical Letter, by subscription only)

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Weight Loss Doesn’t Decrease Strokes and Heart Attacks in Overweight Diabetics

Photo credit: Wikimedia commonsDoctors spend a lot of time recommending diet and exercise for weight loss. If you’re my patient, unless you’re quite fit, you’ve probably heard me ask you to exercise more and eat less. There is good reason for this. Many short term studies have convinced us of multiple benefits of weight loss – better sugar control in diabetics, lower blood pressure, improved mood, higher quality of life.

Nevertheless, there is little data about the long term benefits of weight loss. If you were to design a trial looking to measure the cardiovascular benefits of weight loss you would want to focus on a group of people who would benefit most, a group at high risk for strokes and heart attacks. Overweight diabetics would be a great choice.

Last week the New England Journal of Medicine (NEJM) published the results of a long term trial testing whether intensive lifestyle modification aimed at weight loss would prevent strokes and heart attacks in overweight patients with type 2 diabetes.

Over 5,100 middle aged and elderly patients with type 2 diabetes were enrolled. They were all overweight or obese (BMI 25 or over). They were randomized to two groups. One group was counseled about diet and exercise. They were educated to exercise for about 3 hours per week and consume 1,200 to 1,800 calories daily with less than 30% of the calories from fat. The control group was not given specific targets for calories or exercise. Both groups had their diabetes and other medical problems managed by their own physicians, and their medications were not controlled by the study.

Both groups were followed for an average of 9.6 years to see if one group had fewer strokes, heart attacks, or death due to cardiovascular causes.

Not surprisingly, the lifestyle intervention group lost more weight than the control group. After one year the intervention group lost on average 8.6% of body weight, compared to 0.7% in the control group. After the first year, the intervention group regained some weight, a common occurrence in weight-loss studies (and in the personal experience of dieters). Still, by the end of the study the intervention group lost 6% of their initial body weight, compared to 3.5% in the control group. The intervention group had lower glucose levels (i.e. better diabetes control), was on less medication, and had less serious kidney disease, depression, and sleep apnea.

That’s not bad, right? If I had diabetes I would exercise regularly and eat less for those benefits.

So you would think that with all those benefits including the pretty impressive weight loss, the intervention group would have had fewer strokes and heart attacks. They didn’t. The numbers of strokes, heart attacks, and deaths in the two groups were not significantly different.

Across the scientific land there was wailing and gnashing of teeth. What happened? Surely, we can’t throw in the towel on diet and exercise.

An editorial in the same NEJM issue suggests possible explanations. Perhaps the weight loss achieved in the study was simply too small to decrease cardiovascular risk. That would be a very depressing explanation since the weight loss achieved in the study is greater than most people are able to maintain. Hoping that a larger weight loss is needed for cardiovascular benefits would not be very realistic for real patients. Another possibility is that the cardiovascular benefits only accrue after a longer delay, and that following the patients for longer than 10 years is needed to measure this benefit.

The explanation I find most plausible has to do with the medications the patients were taking. Again, the medications taken by the patients were not controlled by the study; they were left up to each patient’s physician. As it turned out, blood pressure medicines, statins (a family of cholesterol-medicines), and insulin were used more frequently in the control group than in the intervention group. One result of this is that LDL (the most important cholesterol molecule) was lower in the control group.

It’s easy to see how this might have happened. Imagine two overweight diabetics with elevated cholesterol. One is in the control group. He’s not making much progress losing weight, so his doctor starts him on a statin. Statins have solid evidence that they prevent strokes and heart attacks. The other patient is in the intervention group. He’s making good progress losing weight with diet and exercise, so the doctor delays starting the statin, choosing instead to recheck his cholesterol in a few months. Maybe his cholesterol eventually drops or maybe it doesn’t but the proven statin therapy is delayed despite the high cholesterol because of the optimism generated by the impressive weight loss. The delayed statin use negates whatever benefit the weight loss would have caused, and the two groups end up with equal numbers of strokes and heart attacks.

To put it another way, I think current medical treatment for high blood pressure, diabetes, and high cholesterol is so effective in preventing strokes and heart attacks that it is very difficult to find an intervention that will decrease cardiovascular risk even further. Perhaps the most positive thing that can be said about the weight-loss group is that it had the same cardiovascular outcomes as the control group which was taking more medications.

So my lesson is that overweight diabetics should diet and exercise, but medications to aggressively lower their blood pressure, sugar and cholesterol should not be delayed due to optimism about their weight loss. Lose some weight, but take your statin.

Learn more:

Disappointing Results for Weight Loss and Diabetes (Wall Street Journal)
Weight loss, exercise didn’t affect heart outcomes in Look AHEAD (Internal Medicine News)
Weight loss does not lower heart disease risk from type 2 diabetes (National Institutes of Health)
Cardiovascular Effects of Intensive Lifestyle Intervention in Type 2 Diabetes (NEJM article)
Do Lifestyle Changes Reduce Serious Outcomes in Diabetes? (NEJM editorial)

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Hepatitis A Outbreak Linked to Frozen Berry and Pomegranate Mix

Product label of Townsend Farms Organic Anti-Oxidant Blend frozen berry and pomegranate mix
Click for larger image. Image credit: CDC

Hepatitis A is an illness which affects the liver and is caused by a virus. (You’ll be shocked to learn it’s called the hepatitis A virus.) It is usually transmitted through food and water contaminated by human feces, even in microscopic amounts. In the US outbreaks have frequently been linked to food workers who have hepatitis A and contaminate food with their hands. The disease typically causes fatigue, abdominal pain, jaundice (yellowing of the skin and eyes), and dark urine. Patients typically recover completely without lasting damage to the liver. Unlike other forms of viral hepatitis, hepatitis A does not cause chronic infection. After the patient has recovered, the virus is cleared from the body and the patient is no longer infectious. Recovery is followed by lifelong immunity.

An outbreak caused by a negligent restaurant worker is bad enough, but we live in an interconnected international food marketplace. Contamination of the food supply can happen anywhere from the farm to the consumer’s hands; the farther upstream the contamination, the more people may be affected.

The most recent food-borne hepatitis A outbreak has been sickening people since March. This week the Centers for Disease Control and Prevention (CDC) updated their findings from their ongoing investigation. The outbreak has been linked to Townsend Farms Organic Anti-Oxidant Blend frozen berry and pomegranate mix. As of Wednesday 97 people have become ill in eight states including California. About half of those affected have been hospitalized. There have been no deaths. The berry and pomegranate mix is sold at both Costco and Harris Teeter, though all the affected people who recall eating the berry mix bought it at Costco.

The product has obviously been removed from store shelves. If you have any, discard it immediately. If you have eaten this product in the past two weeks and have never been vaccinated against hepatitis A, contact your doctor immediately. Vaccination may lower your chance of becoming ill.

I’ve written previously about food-borne illness, about the lack of evidence that anti-oxidants have health benefits, and about the lack of evidence that organic food is healthier than food grown with industrial fertilizer and pesticides. This is an unfortunate story in which these topics intersect. The recent media coverage of the outbreak included an interview with the wife of one of the people sickened with hepatitis A. She expressed surprise that organic food could become contaminated. But there has never been any suggestion that organic food is less likely to bear infectious diseases than food grown with pesticides. Even organic food producers have never made such a claim. If anything, the withholding of industrial fertilizers may increase the likelihood of food contamination if animal waste is used instead and if it is not cleaned off the food.

So please wash all uncooked fruits and vegetables before eating them, even frozen produce. Please wash your hands after using the bathroom. And please feel free to buy organic food because you think it tastes better, or because you’d like to spend more money on food, or because you know it will impress the intriguing hipster checking out your shopping cart. But don’t do it for health benefits.

Learn more:

Multistate outbreak of Hepatitis A infections potentially associated with “Townsend Farms Organic Antioxidant Blend” frozen berry and pomegranate mix (CDC)
Advice to Consumers (CDC)
CDC: 87 Now Sickened in Hepatitis A Outbreak (WebMD)
Hepatitis A victim shocked organic berries almost led to liver transplant (CBS News)
Hepatitis A (review article by the Mayo Clinic)

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A New Weapon against Hospital-Acquired MRSA Infections

Scanning electron micrograph of MRSA bacteria. Credit: Janice Haney Carr/CDC

The bacterium Staphylococcus aureus can live on our skin and in our noses without causing disease. Such a condition is called bacterial colonization, to contrast it from infection in which the bacteria causes illness. When the skin is broken or when host immunity is weakened Staph. aureus can enter the blood stream or other body spaces and cause life-threatening infection. Because medical procedures frequently involve puncturing or cutting the skin, Staph. aureus accounts for more health care-associated infections than any other germ.

That would be bad enough, but one strain of Staph. aureus, called methicillin-resistant Staph. aureus (MRSA), has developed resistance to many of the antibiotics most commonly used against Staph. infections, making it particularly difficult to treat. Controlling the spread of MRSA in health-care settings has become a national priority. Many hospitals have implemented programs to remind staff to wash their hands before and after contact with patients and to identify and isolate patients colonized with MRSA. Hospital-acquired MRSA infections have actually declined in recent years, perhaps due to these efforts, but in 2011 they still affected 62,500 patients and killed more than 9,000.

ICU patients are especially vulnerable to life-threatening hospital-acquired infections, for two reasons. First, they are the sickest patients in the hospital and their immune system is frequently not working well. Second, they undergo many invasive procedures that cause potential portals of entry for infection. Some hospitals screen all patients (or all ICU patients) for MRSA by swabbing their nose. Those who test positive are then placed under contact isolation – they are moved to a private room and all staff must don gloves and a disposable gown prior to coming into contact with them. Nine states have mandated by law such MRSA screening and isolation procedures.

But is this the best way to protect hospitalized patients from MRSA infection?

Other hospitals have stepped up their MRSA efforts even further. They screen all patients for MRSA. Those who test positive are isolated and also undergo decolonization – an attempt to kill the MRSA on their skin and in their nose. This is usually done with an antibiotic gel that is placed in the nostrils and antibacterial wipes that are used to clean the patient’s skin.

Last week the New England Journal of Medicine published a very clever experiment that tried to elucidate the best way to minimize ICU-acquired MRSA infections.

Rather than randomize patients, they randomized whole hospitals. 43 hospitals were randomized to three different MRSA strategies for their ICU patients. Hospitals in the first group employed the traditional screen-and-isolate strategy. All ICU patients were screened for MRSA and those who were found to be colonized were placed under contact isolation. The second group used a screen-and-decolonize strategy. All ICU Patients were screened for MRSA and those who tested positive were placed under contact isolation but also underwent decolonization with the antibiotic nasal gel and the antibacterial skin wipes. The third group had the simplest strategy – universal decolonization. Their ICU patients did not get tested for MRSA. Instead, all the patients were decolonized with the antibiotic nasal gel and the antibacterial skin wipes.

Hospitals in the third group had the fewest MRSA infections. They also had the fewest blood-borne infections from any germ. That makes sense given that the antibacterial wipes would be expected to kill many pathogens, not just MRSA. The authors calculated that 181 patients would need to undergo decolonization to prevent one MRSA infection, and 54 patients would need to undergo decolonization to prevent one bloodstream infection from any pathogen.

Besides being the most effective, universal decolonization had another important advantage; it eliminated the need for swabbing everyone’s nose. This eliminated the expense of doing all those tests for MRSA and also eliminated the delay of waiting for the test result, since decolonization could proceed immediately.

Occasionally fortune smiles on us and the simplest solution turns out to be the most effective. The practicality of this approach makes it possible to implement it in virtually any hospital immediately.

There are some possible drawbacks. The most serious is that universal use of the antibiotic nasal gel and the antibacterial skin wipes could eventually lead to bacterial resistance to either of them. If they were to be used universally, some program to test for resistance should be also implemented. But a more immediate hurdle is that eliminating screening for MRSA would run afoul of state law in nine states.

An editorial in the same issue of NEJM states

[T]he folly of pursuing legislative mandates when evidence is lacking has been shown, and laws mandating MRSA screening should be repealed.

That is indeed a worthy goal. If this were generalized to the repeal of all “legislative mandates when evidence is lacking”, the effects of this study would be revolutionary.

Learn more:

Winning the MRSA Battle in Hospitals (Well, NY Times health blog)
New Tack in Preventing Hospital Infections (Wall Street Journal)
Disinfect All ICU Patients To Reduce ‘Superbug’ Infections (Shots, NPR health blog)
Targeted versus Universal Decolonization to Prevent ICU Infection (NEJM article, by subscription)
Screening Inpatients for MRSA — Case Closed (NEJM editorial, by subscription)

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