Sunday, March 11, 2012

"Women present atypically."

A recent study got a bit of press, and it got me to thinkin'. Specifically, it got me to thinking about those clinicians who  say stuff like "Women typically present atypically," and stuff like that. Like they're a whole other species when it comes to matters of the heart.

Now, I was going to go through the results, look at the past literature, put things in context... Boring! The heck with that - I'm going in a different direction.

I figure that if women are so different from men when it comes to ACS, then they must have different symptoms with a bunch of other diseases as well. Right?  So here goes!

Why don't we talk about how men and women present differently with pancreatitis? Both the heart and the pancreas are visceral organs, with indirect transmission of nociception, and are subject to hormonal influence. Although there is a clear divide in etiology based on gender (men drink, women get gallstones), there doesn't appear to be any difference in the symptoms.

Extensive Pubmed and Google searches turned up only one somewhat relevant paper. Unfortunately, they only studied the relationship of patient gender to disease severity, and made no comments about symptoms at presentation.

Bottom line: Absolutely no data in the literature, on way or another. Anybody need a research project?

Pulmonary embolism
So, just like MI, this is a bad one to miss. Just like the heart, the symptoms can be protean and vague, and hormones like estrogen are often implicated. Should be a slam-dunk for a difference in symptoms!

Swiss researchers combined the results of 3 prospective trials, looking at the clinical presentation of 3414 outpatients with suspected PE. When they looked at the all the data, they found that, apparently, women and men presented with about the same symptoms (small exception - men more often had a concomitant symptomatic DVT). Warning - big slug of data here:

Note that men and women both had chest pain at about the same rate - very reassuring! There are some small differences, but aside from DVT symptoms, nothing is statistically significant. In addition, both the Wells and Geneva scores showed comparable performance in both genders.

Bottom line: It's only one paper, but it has a great design.

Along with STEMIs and major trauma, stroke is one of the big three time-dependent, resource-intensive, emergency medicine priorities. Now, given that the history and physical exam are so crucial in our evaluation of tPA candidates, it would be good to know if we had to adjust our diagnosis to the gender of the patient. There have been 3 recent studies, with different methods, that all speak to this issue.

Looks sort of sketchy, right? Stuffed animals, adult woman... (source)
Lisabeth 2009 used interviews, asking the patient what symptoms had brought them to the hospital. These interviews were conducted after admission, but despite the potential for recall bias, few differences were found: Only "mental status change" rose to (marginal) significance.

Gargano 2009 was also performed in Michigan, but used registry data from almost two thousand admissions. Instead of interviewers, they abstracted data from ED documentation.

There appear to be few significant differences between the sexes here. Men having slightly more "balance/dizziness" problems than women, which seemed to drive the marginal difference in "Any warning sign or suspect stroke." Even the authors concede that:
 "Overall, the sex differences in symptoms we identified were relatively minor..." 
A Tasmanian study, Gall 2010, also showed some minor differences, but nothing clinically significant.
Women were significantly less likely to have dysarthria, ataxia, or paresthesia at stroke onset than men, but more often had incontinence, loss of consciousness, visual deficits, and dysphasia. ...  Despite sex differences in the prevalence of signs and symptoms, the ranking of the top 5 symptoms was similar for men and women.
Bottom line: Minor differences, of little clinical significance across a number of sites and study designs. Here, at least, men act like women. Or the other way around.

No only is the hormonal milieu different in this case, but the anatomy as well! With all the added adnexa & "stuff," the differential diagnosis is expanded, and the evaluation, and especially imaging choices, can be quite different for the boys and the girls.

And cylons.  Cylons definitely have atypical presentations.
So it's reasonable to think that the presenting symptoms would be significantly different as well. I only found 2 studies that fit the bill, however, and they have some disappointing shortcomings.

Guss 2000 looked at 196 ED patients who ended up with a diagnosis of appendicitis. Now this is the funny thing - the women had longer diagnostic work-ups before operation, but the men had higher rates of perforation. Apparently, though, they presented in much the same manner:

Oddly, there is no mention of RLQ tenderness here. Although the methods described how tenderness at McBurney's point was to be included, no mention is made in the results. Strange omission...

A similar study was done by McGann-Donlan 2009, comparing 137 men and women, by chart review, who had received a diagnosis of appendicitis. Rather than a surgical diagnosis, the CT scan was taken to be the "gold standard" of diagnosis. (By contrast, only 3 patients in Guss 2000 had CTs!)

Hmm, shouldn't there be some p's kicking around? Perhaps a SD or two, or even, heaven forfend, some confidence interval? Ah, no. Let me quote (italics from the original):
Females more commonly had nausea (66% of females vs 43% of males), vomiting (37% of females vs 32% of males), and diarrhea (18% of females vs 7% of males). Females less commonly had RLQ (right lower quadrant) pain (77% of females vs 88% of males) and fever (1.5% of females vs 7% of males). There was no difference in anorexia between genders (29% of females vs 30% of males)
Apparently italics are the new p-value. Brady, did you already know this?

Now, the problem with these two studies is that they only looked at patients with diagnosed appendicitis - they didn't look at patients with suspected appendicitis.

Eskelinen 1994 took a whole other approach. They collected data prospectively from over a thousand patients presenting with abdominal pain (not just those with confirmed appys), and tried to construct gender-specific prediction models (unlike, e.g., the MANTRELS score). Through multivariate analysis they determined the independent predictive elements for men and women. The elements in the "B" column are the regression coefficients - the higher the number, the higher the weight that element contributes to the score. Comparing men % women, we find:

Well, it looks like RLQ pain is the most important element for both genders. Most of the other symptoms washed out of both models - migration, intensity, anorexia, etc.

Bottom line - There appears to be no consistent, clinically significant difference between the genders in appendicitis.

On one hand, you wouldn't expect Borrelia to show up differently in men & women, since it's a freakin' bacteria. What does it know?

That's how B. burdorferi rolls.

On the other hand, this disease was first diagnosed in CT after one mother insisted that her child's disease that was being misdiagnosed. Since that dynamic (i.e. doctor vs lay-woman) is part & parcel of the Lyme disease history, you might expect some gender-based analysis in the literature.


"Sex differences in the clinical and serologic presentation of early Lyme disease" supposedly demonstrates that both women and men have similar symptoms in early Lyme, but have different immune responses. I'm not going to use this paper to prove any points, for a few reasons.

First, the lead author is employed at the Lyme Disease Research Foundation, which is an organization founded & run by the last author, Aucott. In other words, the last author is the boss of the first author.

Boss? Time for a gratuitous picture of my hero!
Second. it's kind of a crap paper. All the Lyme symptoms were diagnosed by 1 doctor - Dr. Aucott.

Last, it has an agenda. Many proponents of "chronic Lyme" believe current immunologic techniques of diagnosing Lyme disease do not work. (This notion, by the way, has no support from people who actually did fellowships in ID.) The paper here will likely be used to suggest that such tests discriminate against women, even in early disease. They're using the shield of "gender-based medicine" to advance their chronic Lyme agenda. For example:

(The lead author, Stricker, has had an article retracted from the NEJM for falsifying data. Not a trustworthy doctor. Nowadays he's an expert on Morgellons.)

Okay, now I'm ranting. Time to wrap this up!

Whatever your take on the cardiology literature is, I found little evidence that demonstrated that women evince significantly different symptoms than men in a number of other acute diseases.

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