Being a woman versus being womanly: the implications after heart attack

For the video version of this post, click here. There are two elements you can expect to see in almost any study: the first is some effect size - a measure of association between an exposure and outcome. The second is a subgroup analysis - a report of how that effect size differs among different groups. Sex is an extremely common subgroup to analyze - lots of things differ between men and women. But a really unique study appearing in the Journal of the American College of Cardiology suggests that sex might not matter when it comes to coronary disease. What really matters is gender.

The study, with cumbersome acronym GENESIS-PRAXY, examined 273 women and 636 men of age less than 55 who were hospitalized with Acute Coronary Syndrome (ACS). Sex was based on self-report, and was binary (man or woman). But gender isn’t sex. Gender is a social construct that represents self-identity, societal roles, expectations and personality traits, and can be a continuum - think masculine and feminine.

The authors created a questionnaire that attempted to assign a value to gender. Basically, questions like - “how much of the child-rearing do you perform” or “are you the primary breadwinner for your household” - in other words these are based on traditional gender norms - but that’s as good a place to start as any. A score of 100 on the gender scale was “all feminine”, and a score of 0 “all masculine”.  Most of the males in the study clustered on the masculine end of the spectrum, while the females were more diverse across the gender continuum.

What was striking is that the primary outcome - recurrence of acute coronary syndrome within a year, was the same regardless of sex - 3% in men and women.  But a greater degree of “femininity” was significantly associated with a higher recurrence rate. Feminine people (be they male or female) had around a 5% recurrence rate compared to 2% of masculine people. This was true even after adjustment for sex, so we’re not simply looking at sex in a different way - gender is its own beast.

What does it all mean?  Well, it shows us that our binary classification of sex may be too limited in the biomedical field. Of course, there will always be hard and quantifiable physiologic differences between men and women. But what is so cool is that it’s the more difficult to quantify gender-related differences that may matter most when it comes to health and disease.

Of course, this conclusion is way too big to be supported by one small study with a 3% event rate. But given the surprising and really interesting nature of the results, I’m sure we’ll have many more studies of this sort following close behind. 

Is there anything coffee can't do?

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Coffee. It’s hard not to be biased when it comes to the ubiquitous drink. Many of us, myself included, depend on the stuff to start our day, continue our day, and give us something to do when we should otherwise be working. Studies linking coffee to better health get a lot of press. A few months ago, a big splash was made when a study linked coffee consumption to lower risk of melanoma (though they failed to account for sun exposure). Now, we have coffee staving off colon cancer.

The paper, appearing in the Journal of Clinical Oncology, examined roughly 1000 individuals with stage 3 colon cancer, who had been through at least the first round of surgery and chemotherapy. Each of them filled out a detailed food-frequency questionnaire within a couple months after the initial treatment, and they were followed prospectively for cancer recurrence or death.

The majority of the cohort reported drinking 1-3 cups of coffee per day. A small number, 6%, reported taking more than 4 cups per day. Heavy coffee drinkers were more likely to be male, white, and smokers, and had a higher level of physical activity.

After around 7 years of follow-up, 35% of the patients had experienced cancer recurrence or died. Among those who drank 4 or more cups of caffeinated coffee per day, the overall risk of recurrence or death was reduced by about 50% after adjustment for confounders.

Let that sink in a minute. 50%. Has one of the most potent anti-cancer agents been literally sitting under our nose all these years? Well, as much as I’m a java fan, I might need to cool this off a bit.

First off, these patients were part of a clinical trial evaluating the role of adding irinotecan to standard adjuvant chemotherapy for colon cancer. Clinical trials recruit very specific patients - these results may not hold for your typical colon cancer survivor. 

Another issue: Food frequency questionnaires generate a ton of data - you can't possibly control for everything people eat. The authors adjusted their results for total caloric consumption, but it is possible that foods that correlate with coffee intake are the actual drivers of the relationship here. Put simply, it's just as likely that this is a biscotti effect as a coffee effect.

Finally, the big issue: What do we mean when we say coffee? Is an espresso the same as a venti caramel macchiato? Does it matter where the beans come from? How they are roasted? How much sugar you add to it? This is the central problem of dietary research, and one that can only be overcome by randomized trials.

So let’s do it. There seems to be enough data now to justify actually trying this under controlled settings. My prediction is that we won’t see a 50% reduction in recurrence of colon cancer, but we may see something. After all, coffee is a drug. A wonderful, tasty, necessary drug that goes great with pie.

You operate on appendicitis, right? Right?!

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If Grey’s Anatomy has taught us anything, it’s that you have to operate on appendicitis. This fact is imbued in the cultural zeitgeist - it’s the first book of the Madeline series for crying out loud. But paradigms, even one as inertial as this one, can shift.

Appearing in the Journal of the American Medical Association, a clinical trial attempted to show that, for appendicitis, antibiotic treatment alone may be no worse than a surgical approach.

Finnish researchers, led by Paulina Salminen, took 530 individuals with uncomplicated appendicitis (no perforation or appendicolith, basically), and randomized them to go to the operating room, or to get antibiotics instead: 3 doses of ertapenem (a broad-spectrum, IV antibiotic) followed by a week of oral levofloxacin and flagyl.  After about a year of follow-up, the big question was how many people in the antibiotic group would have had to undergo surgery.

Of the 257 patients in the antibiotic group, 15 got operated on during the initial hospital stay. Another 40 would be operated on within the following year, a total of roughly 27% of the group.  This missed the pre-specified non-inferiority target, but there are still some interesting numbers to look at.

First of all, let’s consider why there was a surgical group at all. The only reason, really, is to look at the complication rate so we can see what antibiotics might help us avoid.  Of the 273 people in the surgical group, 20% had complications, about half of which were surgical site infections and the remainder were due to pain and abdominal complications. Surgery has risk - and avoiding those risks, even in just 73% of cases, might be worthwhile.

But major caveat here: Almost all of these appendectomies were performed using an open technique, not laparoscopically. This is sort of crazy.  Laparoscopic appendectomies lead to fewer infections, fewer abdominal complications, and a shorter length of stay. In speaking with some surgeons, I was told that the only reason they’d consider an open technique is for cases of complicated appendicitis, cases which were specifically excluded from this trial.

The authors write that they encouraged open appendectomies since resource-poor areas of the world might not have laparoscopic equipment, but this really ends up stacking the deck against surgery. If I were given the choice of a quick laparoscopic appendectomy with guaranteed results versus a 25% recurrence rate with antibiotics, I might take the surgery.  But if my only choice was open surgery - with a risk of adhesions, obstruction, infection - well, antibiotics might just make the cut.