Monday, February 28, 2011

Heart Disease in Women: Lifestyle Interventions

As this year's American Heart Month comes to an end, it seems appropriate to point out a new guideline from the American Heart Association about to be published next month regarding the prevention of cardiovascular disease in women, as heart disease remains their number one cause of death, far out pacing all cancers combined, including breast cancer.

Specific recommendations include not only cessation of tobacco use but also avoidance of environmental tobacco smoke (which may not be the easiest thing to do given one's work situation - which therefore makes it imperative that we step in from a legislative perspective).

The AHA recommends 150 minutes/week of moderate exercise, 75 minutes/week of vigorous exercise, or some combination of the two.  Additional cardiovascular benefits can be obtained by increasing moderate-intensity exercise to 300 minutes/week or 150 minutes/week of vigorous-intensity physical activity.  All this is supported by Class I, B Level of Evidence.

As for nutrition, the AHA recommends a diet rich in fruits & vegetables; whole-grain, high fiber foods; and oily fish (at least twice weekly), while limiting intake of saturated fats, cholesterol, alcohol, sodium & sugar, and avoiding trans-fatty acids completely.

There is a specific recommendation for 1,800mg/d of EPA (a specific form of omega 3 fatty acids) in those with hypercholesterolemia (high cholesterol) and/or hypertriglyceridemia (high triglycerides) for both 1o and 2o prevention.  Please note, however, that most omega 3 products, eg fish oil capsules, are only 30% pure and thus only contain 300mg EPA+DHA out of 1,000mg fish oil.  And of that 300mg EPA+DHA, typically only 180mg are EPA (the other 120mg being DHA).  So, unless you look for higher grade supplements, you'll need to consume at least 10 capsules of standard over-the-counter fish oil daily to meet AHA recommendations.

None of the above is shocking or a revelation.  But we have to empower the women in our lives to act upon this information, if not for them, then selfishly, at least for us.

Sunday, February 27, 2011

Bisphosphonates & Atypical Femur Fractures: Part 2

Remember my December 10th post about bisphosphonates?  Of course, you don't.  That's ancient history, at least by medical standards.  Well, here's the latest chapter, which needs to be entitled "Relative Risk vs Absolute Risk".  Just released this past week in JAMA, in a population-based, nested case-control study of 205,466 Canadian women >68yo, the authors concluded that use of bisphosphonates increased (more than doubled) the risk of atypical subtrochanteric or femoral shaft fractures after 5yrs of use compared to non-users.  But this is relative risk.  The absolute (or true) risk was actually quite low, only 0.35% or 716 women.  
And lest you decide to stop taking your bisphosphonate because of a misguided fear of this rare fracture type due to misinterpretation of statistics, the authors also found 9723 women who'd sustained a more typical femoral neck or intertrochanteric fracture despite bisphosphonate use, which actually lowered the relative risk of fracture by 24% after taking the usual suspects into account.

Let me put it another way and give you a different example.  Let's say the risk of something bad happening was 4 out of 100 or 4%.  If you took some medicine that could lower your risk to 2 out of 100 or 2%, you would have achieved a 50% relative risk reduction.

Likewise, let's say the risk of something else bad happening was only 4 out of 1,000 or 0.4%.  And if you took some medicine, you could lower your risk to 2 out of 1,000 or 0.2%.  In reality, you would've achieved the same 50% relative risk reduction.

So while it may sound impressive in both situations to claim that you lowered the relative risk of a bad occurrence by 50%, in actuality, the absolute risk reduction was minimal in the 2nd scenario.

Returning to our situation with bisphosphonates, prolonged use >5yrs might double the risk of a rare fracture while truly minimizing your risk of a more common fracture.  As a result of this study and the others already mentioned 2 months ago in my earlier post, it appears the consensus is moving towards limiting bisphosphonate use to just 5 years.  We'll see whether that actually becomes a guideline shortly.  In the meantime, as with all new findings, please discuss your individual situation with your family physician before abruptly stopping some regimen based upon the lay press.

Saturday, February 26, 2011

Cannabis Use: Is It Really Safe?

No, I don't condone the use of illicit substances.  But I do find it curious as to how some are considered licit while others are illicit.  For instance, we know that there are very few benefits to the use of tobacco (are there any at all?) compared to all the down sides from its use, yet it's still sold legally here.  Alcohol is trickier since many studies demonstrate some benefit when consumed in moderation.  However, there's a very visible minority that enjoys their alcohol in excess to the detriment of others.  That's where I draw the line because when your business becomes my business, it's no longer a matter of individual rights & freedom.

Any way, I digress.  I wanted to review a meta-analysis (study of studies) published this month in the Archives of General Psychiatry  looking at the recreational non-medicinal use of cannabis (marijuana).  More importantly, I wanted to see if the authors reported any downside to the use of cannabis since most recreational users state that it causes no harm.  Turns out that cannabis users had an earlier psychotic break than non-users, almost 3 years earlier.  Alcohol and other substances did not play a role in onset of psychosis.

Ironically, in my previous life, exactly 3 short years ago, I wrote two posts regarding the use of marijuana, the first on February 5, 2008 and the second on February 18, 2008, the latter in response to some input from colleagues.  Concordant with my posts, an earlier analysis in the Lancet also concluded that use of marijuana increased the risk of psychosis later on in life.

Of course, one could always argue for an associative effect rather than causal in nature.  But the authors of this month's study concluded that the current evidence support a causal relationship.  In other words, use of marijuana increases one's risk of (earlier) psychosis.  So think twice before you light up!

Part 2
Part 3

Friday, February 25, 2011

More Controversy: Menopausal Symptoms vs Heart Disease

Just over 3 weeks ago, I looked over a study that concluded that vasomotor symptoms, hot flashes & night sweats, were associated with lower risk of breast cancer.  Now, a new study just released this week in the journal Menopause, concludes, contrary to conventional wisdom, that early vasomotor symptoms were actually associated with lower risk of stroke, all cardiovascular events, and most importantly, all-cause mortality.

With all studies, but especially those that are contrary and controversial, I always suggest looking at how the study was performed and how significant were the statistics.  In this particular situation, the authors followed 60,027 women in the observational arm of the Women's Health Initiative (WHI).  Granted, there's been a lot of negative press about WHI, especially from the alternative & complementary medicine folks, but remember that this specific analysis was observational in nature.  So one can't argue over horse-derived estrogen vs natural estrogen.

What's this mean for you & me?  Well, probably just confusion for you but lots of confusion plus controversy for me since this study just opened up Pandora's box (again).  Conventional wisdom over the last 2-3 decades has been that estrogen is protective of the heart (which is why women tend to have their heart disease manifest after menopause, typically 10 years later than men) which is why we previously thought that estrogen replacement would be protective.  Now comes a new spin that less estrogen (leading to hot flashes & night sweats) is actually good for you!

The authors rightly concluded that they need to perform more studies (how else will they put food on the table?) but more importantly, whether the individual's timing of menopausal onset represents distinct processes and different risk profiles.  Only time will tell.  But as I mentioned 3 weeks ago, perhaps our patients can re-interpret their early symptom onset given the positive outlook further down the road.  As for treatment with estrogen with(out) progesterone, that requires more space than I have to type (and more time for an informed discussion with your healthcare provider to understand your individual risks).

High PSA Velocity vs Prostate Cancer: To Biopsy or Not to Biopsy?

Argh!  I hate controversy!  Give me a clean, straightforward answer.  Unfortunately, medicine isn't like that.  We continue to refine our understanding as we gain more knowledge.  We can only make predictions based upon what we know today, not what we may know in the future.  As I've said many times before, our crystal ball is in the shop (at least mine is).

Therefore, it was with some irony that on the same day that I heard back from a close colleague/friend/relative that his prostate biopsy came back negative, the same diagnostic procedure for which I pushed mightily given his rather dramatic & persistently increasing PSA velocity, the Journal of the National Cancer Institute published a study that prostate biopsies performed due to PSA velocity alone did not improve accuracy of diagnosis in a group of 5,519 men.  I wish I'd known that over the last 2 months as I worried about the sudden increase in his PSA that was not amenable to an empiric trial of antibiotics.

Their conclusion was that using PSA velocity as the sole indication for prostate biopsy in the setting of low PSA and normal digital rectal exam lead to one in seven men (more typically, only one in twenty men) being biopsied without statistically significantly increasing the chances of finding a high-grade cancer (Gleason score of 7 or greater) and/or clinically significant cancer (using Epstein criteria).

Their conclusion goes against both the National Comprehensive Cancer Network (you first need to register for free) and the American Urological Association's guidelines.  This controversy and lack of clarity is why medicine is such a difficult profession to undertake, especially in our litigious society.  We're damned if we do and damned if we don't.  Helping a patient make an informed decision based upon our current scope of knowledge isn't enough.  We are expected to be correct 100% of the time, yesterday (in the shortest period of time) and tomorrow, while consuming the least possible resources, after which we receive (threats of) declining reimbursements.  We're being pecked from all sides.  No wonder we're sitting ducks for the malpractice lottery.

Thursday, February 24, 2011

Cheers! Let's Drink for Heart Disease!

Cheers!  A votre sante!  Gam bai!  Two studies were just published yesterday in the British Medical Journal adding to the evidence that alcohol is beneficial in heart disease.

In the first systematic review & meta-analysis, the authors filtered through 4,690 studies to read 124 full articles from which 63 were selected but only 44 had data on the desired biomarkers.  Of those evaluated, the authors concluded that moderate alcohol consumption led to statistically significant beneficial effects on HDL (good cholesterol), apolipoprotein A1, adiponectin & fibrinogen, which may explain alcohol's cardioprotective effect.

In the second systematic review & meta-analysis, another group of authors sifted through 4,235 studies from which they culled just 84 for inclusion.  Their conclusions?  Alcohol consumption lowered cardiovascular mortality by 25%, incident coronary heart disease by 29%, coronary heart disease mortality by 25%, and all-cause mortality by 13% compared to tee-totalers.  Incident stroke and stroke mortality did not demonstrate a statistically significant association with alcohol consumption.

Of course, by now everyone wants to know just how much alcohol can be consumed, right?  The second article again demonstrated the presence of a J-curve when it comes to alcohol consumption.  In other words, consuming <1 drink/day was enough to garner statistically significant benefit whereas moderate-to-heavy consumption actually increased hemorrhagic stroke risk. 

So, remember Goldilocks when you go out w/your buddies.  You want the right amount, not too much, but clearly, not too little either.  Moderation is key.  By the way, saving it all for the weekend blow out does you no good either. 

Another (Off-Label) Way to Increase Testosterone

Did you ever hear the story about the girl who asked her mom why she always cut both ends off the roast before cooking it?  Her mom said b/c that's how Grandma does it.  So the girl then asked her Grandma why she cut both ends off the roast before cooking it.  Her Grandma said b/c that's how Great-Grandma does it.  Luckily, their family is long lived, so the girl asked her Great-Grandma why she cut off both ends off the roast before cooking it.  And her Great-Grandma answered b/c she didn't have a pan large enough!  At least that's how I recall the tale.

The moral of the story is that just as in medicine, we do what we're taught, rarely exploring the boundaries.  We stay within our comfort zones and never stretch ourselves or venture beyond the line drawn in the sand.  As much as I try to stay up-to-date and practice evidence-based medicine, I'm as guilty of that as anyone else.  So it's a good thing students & colleagues ask questions.  In this particular instance, I'm particularly indebted to Dr. S who asked about the off-label use of clomiphene to increase testosterone (and sperm). 

In fact, clomiphene, a selective estrogen receptor modulator, blocks estrogen receptors at the hypothalamus and pituitary, thus decreasing estrogen's inhibition of gonadotropin secretion, ergo more testosterone production.  Many studies (amongst them published in June 2003, May 2008 & December 2010) demonstrate increases in testosterone levels with some even showing an improvement in semen parameters, but apparently without any change in pregnancy rates (although it continues to be used off-label towards this endpoint).  Physicians have also commented online about the off-label use of clomiphene.

I mention this, not so that someone can become a professional bodybuilder, but so that those who are clinically hypogonadal can have another option for therapy.  Let's not forget that offering testosterone (whether in oral, sublingual, topical, pellet, or injectable form) to someone essentially renders them infertile and dependent upon (more) exogenous testosterone, whereas offering either hCG, anastrazole, or clomiphene is a way to potentially stimulate testicular production of more testosterone (assuming that the patient is not suffering from primary hypogonadism or testicular failure).

Again, I can't emphasize enough the need to work closely with a clinician who is experienced in this field of medicine and willing to provide close & regular monitoring.  Let me repeat:  this is not a do-it-yourself project.

Wednesday, February 23, 2011

Cell Phone Use vs Brain Fxn: Conspiracy Theorists Unite!

My brother asked me a while back what I thought about putting up some cell phone & radio towers/antennas on top of our parents' building complex.  After all, it would help shore up the home owners association's coffers.  His main concern, however, was the possible theoretical effect of cell phone radiofrequency signals on our health.  Now, I was never a huge X-Files fan, unlike my wife.  However, most observational & epidemiologic studies have not demonstrated any effect, positive or negative, from the use of cell phones, despite persistent anecdotal rumors to the contrary.

Ironically, as just noted on CNN and in USA Today, a randomized crossover study just released today in JAMA noted that 50 minutes of cell phone use next to the ear was enough to increase glucose metabolism in the two parts of the brain closest to the antenna.  Moreover, the larger the radiofrequency electromagnetic field, the greater the increase in glucose metabolism.  However, overall brain metabolism was not affected.

But what does this mean to you & me, a colleague, Dr. D, asked?  Just like the authors concluded, the findings are of "unknown clinical significance".  In other words, we don't know.  Cell phones have only been around for a little over 2 decades and over this period of time, designs have changed dramatically (not to mention power output).  I still remember when I was in medical school and my best friend had just purchased one of those old brick-style phones.  We were too cool driving around calling everyone we knew, unaware that that phone was putting out several times as much signal power as my current Samsung Epic 4G. 

The editorialists suggest that more studies are needed.  I agree.  But in the meantime, I'm going to more conscious about using my Bluetooth earpiece even while I'm at home.  And maybe it would be safer(?) to leave those antenna buffer cases off your iPhone4.  After all, a lower/lost signal is less likely to affect your brain!

Shhhh . . . What About Hospice & Palliative Care?

I try to focus this blog on health rather than disease by writing about all that we can do to optimize our wellness.  But death is the 800 pound gorilla in the room.  We can't escape its grasp, yet too often, we ignore it and won't discuss it, even when it's near.  It's as if by mentioning it by name, we're committing someone to a sure death.  But I have a surprise for you:  even if we don't talk about death, we will still die, sooner or later.

Sure, physicians and lay people alike aren't very good at using their crystal balls to predict the exact time of death.  But with certain diseases and conditions, we've developed enough experience to narrow our guess down to weeks-to-months or sometimes days-to-weeks or so on.  You get the idea.

Cancer is one of those illnesses where we can often make a credible guess.  Yes, we've made tremendous strides over the last few decades against this dreaded diagnosis.  In fact, some forms that were once as good as a signed death sentence are now manageable.  With others, we even dare breathe that other "C" word, cure.  But still too often, cancers either present too late, having already spread to different parts of the body, or become resistant to all the surgeries, chemotherapies, and radiation that we can throw at it.  

These patients, the ones with metastases, are the ones for whom we should discuss hospice and palliative care earlier rather than later.  Realistically, we should offer palliative care even at the beginning of any treatment to help all patients and their loved ones cope with side effects and adverse reactions.  But later on, once it's clear to us, the physician, that things aren't going so well, rather than consider death the equivalent of defeat, we really need to take the initiative and start discussing hospice & palliative care, even as we consider another "Hail Mary" pass to rally the troops.  In truth, we never win.  Death always trumps life.

The American Society of Clinical Oncology just released a new statement that care needs to be individualized for patients with advanced cancer.  That's code for actively involving the patient in his/her care, specifically asking for their individual goals and care preferences.  For many, it's not death that is feared, but rather the final days right before.  Patients don't want to suffer (however, one defines that physically, mentally, emotionally or spiritually) or to be left alone in the hospital's cold sterile environment.  Most want to be at home surrounded by loved ones after having checked a few more items off the bucket list.  This is where hospice and palliative care medicine step in, to offer comfort and compassion, when no cure is possible/realistic, to both the patient and the family.

Incredible as it may sound, in the case of metastatic non-small cell lung cancer, in a study published in the New England Journal of Medicine last August, those patients randomized to early palliative care had less aggressive care at the end of life (as expected by definition), yet reported better mood, better quality of life, and surprisingly, longer survival, living on average almost 3 months longer (11.6 months compared to 8.9 months) compared to those who received standard oncologic therapy alone.

So it's about time that we acknowledge that 800 pound gorilla.  To get the conversation started, a nice piece was written online yesterday in the USA Today.  Let's start talking about hospice and palliative care options.

Disclaimer:  I serve as a Medical Director for Infinity Hospice Care's Las Vegas program.

Tuesday, February 22, 2011

6 Months After Stopping Testosterone . . .

What happens when you quit doing something?  The effect/result usually goes away, right?  For instance, if you decide to stop filling your car's gas tank w/gas, eventually it stops running.  If you stop eating, the sensation of satiety is replaced by hunger.  In the case of stress incontinence, if you stop performing your Kegel exercises regularly, your incontinent episodes return (as many of patients have discovered on their own).

Following that same line of thinking, researchers recently decided to look into whether short-term testosterone supplementation could lead to long-term benefits.  Unfortunately, while numerous studies have demonstrated the ability of testosterone to increase muscle mass (peaking at 6 months) and then maintain said gains with continued treatment for up to 3 years, in this situation, all gains in body composition, muscle strength & quality of life resulting from 25-75mg/d of testosterone gel for 6 months were lost by 6 months after cessation.

So what did we learn from this study?  That just like many other situations in life, short-term testosterone is not enough to provoke long-term benefit.  So if you're going to commit, be ready for the long haul.  But let's be clear that long-term testosterone supplementation requires close monitoring by an experienced clinician familiar with all the possible downsides of supraphysiologic testosterone so as to be able to prevent, treat, and mitigate any potential side effects.  It's doubtful that you'll receive that kind of care by answering a few questions online in order to obtain a prescription.

Monday, February 21, 2011

Growth Hormone Receptor Deficiency & Laron Syndrome

Now, don't get me wrong.  I'm not an endocrinologist, much less a growth hormone specialist.  However, the discussion of tesamorelin the last few days led me to a recent news article published last week in the Los Angeles Times about a small group of Ecuadoreans with Laron Syndrome (an autosomal recessive growth hormone receptor deficiency) followed by researchers whose findings were just published concluding that growth hormone receptor deficiency protected these people from cancers and diabetes compared to their normal relatives.  What's truly exciting is that the serum of these patients with Laron Syndrome protected DNA from breakage, which is one long-standing theory behind aging.  It also lead to increased programmed cell death or apoptosis (which is a good thing).

But what about ending up relatively short compared to your peers, say growing to a height of only 3-4' tall?  In this day and age, I'm not convinced that that's an acceptable side effect.  Most surveys & studies report that taller height (within reason) makes a difference in most things in life after all other factors are taken into account.  But what of the researchers and LA Times reporter's conclusion that lower growth hormone is better.

It turns out that long term 10 year studies demonstrate no increase in mortality in those patients with growth hormone deficiency who are given growth hormone.  Specialists in growth hormone were actually incensed enough to write a letter to the editor stating the same.  Likewise, a 20 year follow up study of survivors of childhood cancers who have since received growth hormone demonstrate favorable overall safety profile (although there is a subset that might be at higher risk of secondary neoplasm).

Moreover, growth hormone is released in response to strenuous exercise.  If growth hormone suppression were such a good thing, one might as well recommend limiting exercise and physical activity, when in fact all available data demonstrates lower mortality the more active one becomes over a lifetime.  Furthermore, we have data that growth hormone is important in bone mineral density, body composition, coronary disease, and most of all, quality of life.  Yes, future data may alter our current way of thinking but given what we have available to us now, I vote for (naturally) increasing growth hormone (within the normal reference range) as a means to live a high quality disease-free life for as long as possible, not necessarily to just live longer for duration's sake.

Sunday, February 20, 2011

Q&A Session at

how can i get rod of belly fat?

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Will she be okay?

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I hurt my lower back sledding - home care options

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I had gained about 70 lbs due to a medicine I was taking I am four foot eleven an have always weighed about 125 to 135

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Misshapen left testicle that is painful.  Please help!

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What to do about incontinence?

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My mother is going to be 90.  My dad passed away going on 8 yrs.  She has health problems but is not taking her medication for he

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My grandmother is taking certain medications that are inflaming her gout. Causing her pain.

Saturday, February 19, 2011

Q&A Session at

Hi, my grandma is experiencing Peripheral Artery Disease! :( How to treat it at home?

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We need a geriatric psychiatrist who speaks Farsi and is located in the Bay Area.

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Is there a test for Alzheimer's.  My husband is 68 and has virtually no short term memory and confusion processing information.

Tesamorelin (Egrifta) Part 2

Given the FDA's November 10, 2010 approval of Tesamorelin (Egrifta) for use in HIV-positive patients w/lipodystrophy, I thought that I would give more background information and run through a quick review of this agent.

It's predecessor, Sermorelin (Geref), has been around a while and used in testing for growth hormone (GH) deficiency by attempting to stimulate the pituitary to produce more GH.  Since the end result in most otherwise healthy patients is GH production & release, it was then offered as a less expensive, off-label option to recombinant human GH (rhGH) in the anti-aging and age management medicine arena.  That's where the politics and legal issues surrounding this compound get a bit murky.  It is no longer available since Serono pulled back its marketing support here in the US although some compound pharmacies still make it available for use.

I first stumbled upon this compound when a study was published in December 2007 in the New England Journal of Medicine documenting its ability to decrease visceral fat and improve lipid profiles in HIV-positive patients when used for 26 weeks.  A year ago, another study concluded that tesamorelin could reduce visceral fat in HIV-positive patients without significant side effects or hyperglycemia.  Then last September in the Journal of Clinical Endocrinology & Metabolism, yet another study concluded similarly that tesamorelin would reduce visceral adipose tissue for an additional 26 weeks after the initial 26 week trial and more importantly, without causing hyperglycemia.  It should be noted that up to a quarter of the participants in this last study were also taking testosterone (in some form) concurrently.  Also, note that all reductions in adipose fat have been from the visceral component, not subcutaneous.  However, you'll recall that it's the visceral adipose that leads to the metabolic syndrome, diabetes, and coronary disease.

Which brings me to a rather small but significant study published in JCEM last month.  Specifically, the authors gave tesamorelin to 13 healthy men, average age 45 years old w/body mass index 27.3 (overweight but not obese), for 2 weeks.  Growth hormone levels increased as expected with an increase in IGF-1 (insulin-like growth factor-1) by an astounding 181ug/L (or more common ng/mL) without changing fasting glucose or insulin-stimulated glucose uptake.

My conclusion?  We now have a legal manner in which to increase growth hormone with minimal impact, if any, on sugar control (although I've really downplayed the potential side effects as noted in the product insert).  We still don't have long-term data (longest duration mentioned above was 52 weeks) on large numbers of patients.  What about cost?  Last June, one financial analyst put the cost at $36K/year which is 3x what most growth hormones now cost. lists Egrifta at $46/1mg vial.  Since the prescribing information dictates 2mg/day, you'll need 2 vials/day or $92/day.  They do offer volume discount so that 60 vials or a month's worth of Egrifta might go for $2,300, which means $27,600/year.  However, one can't prescribe growth hormone off-label.  Aye - there's the rub!

So there you have it.  All you wanted to know about Tesamorelin but were afraid to ask.

Friday, February 18, 2011

Tesamorelin (Egrifta) is now FDA-approved!

Thank goodness for good friends & colleagues like Dr. C who asked me about tesamorelin today.  I'd been following this growth hormone releasing factor analog for a while as it wended its way thru FDA Phase I thru III trials in HIV-positive patients.  I even remember discussing its implications back in May 2010 when it went before the FDA.  Well, then everything went to h-ll in a hand basket as my employment status became murky to say the least.  So from August to November, I really didn't peruse the literature as I usually try to do since I no longer had an outlet to post my thoughts.  Of course, that's when the FDA approved the use of tesamorelin (Egrifta) for lipodystrophy in HIV-positive patients.  Boy, did I ever miss the boat on this - I'm 3 months late!  So I'm eternally grateful to Dr. C for keeping me on my toes.

So what good is tesamorelin?  Up until this past November, we'd been restricted (and still are) from using recombinant human growth hormone off-label.  Of course, this is all very political because traditionally, physicians have been given free-rein to use any and all other medications off-label once they're approved for at least one indication by the FDA.  For those physician playing by the rules, you had to subject your patient to growth hormone stimulating tests, one of which could be a risky session involving insulin leading to hypoglycemia.

Well, we now have an agent that can be used off-label to increase growth hormone release and thus measurable insulin-like growth factor-1 without the requirement for undergoing invasive & risky stimulation testing.  I must admit to surprise that this medication came out without much fanfare, at least in the anti-aging and age management medicine arena as I attended two major meetings this past winter w/o mention of this medication.  And having just perused the Internet, I didn't find much celebration & elation.

In any case, don't be surprised if your anti-aging or age management physician starts recommending Egrifta to increase your IGF-1.  Just be aware that we still don't have long term (safety) data.  Plus, there's always the cost issue.  Stay tuned!

Thursday, February 17, 2011

Testosterone vs Prostate Cancer: Malpractice or Act of God?

Given yesterday's diatribe regarding defensive medicine, I thought it useful to return to an older review article published exactly 3 years ago in the Journal of the National Cancer Institute with the corresponding press release stating clearly that "Sex Hormones [Are] Unrelated to Prostate Cancer Risk".

Why?  Most clinicians are so overworked that keeping up with the literature is an impossibility.  Thus, they still ascribe to their medical school teachings as published by Huggins in 1941 concluding that because removal of testosterone decreased prostate cancer mortality, then testosterone must be the root cause of prostate cancer.

By definition, most of us describe the practice of defensive medicine as ordering unwarranted tests or prescribing unnecessary antibiotics.  However, another definition of defensive medicine is avoiding performance of procedures & interventions out of fear of potential litigation.  Keeping this in mind, think about these clinicians who haven't read about the strong association between higher testosterone and lower mortality or about the fact that androgen deprivation therapy for prostate cancer leads to higher all-cause mortality in those with heart disease.  They're practicing defensive medicine when they refuse to offer testosterone supplementation to clinically hypogonadal men simply because their testosterone is just above the lower limit of normal and therefore is good enough for their age.  After all, they don't want to cause prostate cancer, right?

Even without the above studies, a simple analysis of human demographics should demonstrate clearly that testosterone, in and of itself, does not cause prostate cancer.  Why?  If high testosterone caused prostate cancer, then prostate cancer should be a disease of teenage boys and college-age males.  Instead, we know that prostate cancer is a disease of old(er) men, typically with testosterone levels substantially lower than in their prime or youth.

Now, don't get me wrong.  I'm not advocating that we put testosterone in the water or give it out indiscriminately. However, I think that rather than saying "no" with a closed mind, we should have a thorough discussion with our clinically symptomatic patient (and ideally, their family & loved ones, too) about the potential risks and benefits of testosterone supplementation after a thorough physical exam and review of the laboratory results.

And patients and their family & loved ones must understand that should they develop or be diagnosed with prostate cancer after testosterone supplementation, said supplementation was not malpractice and did not lead to or cause the cancer.  It was just an act of God.  Until we reach that level of trust and understanding, we will never be able to fully treat hypogonadism.

Wednesday, February 16, 2011

Practicing Defensive Medicine: Our System is Broken

Well, the gig's up & the secret's out.  We physicians practice defensive medicine, at least as reported at the American Academy of Orthopedic Surgeons annual meeting today.  What's that, you ask?  That's where we order tests, prescribe medications, and generally do things, not because we believe it to be indicated and called based upon our training and the evidence before us, but rather, because we're afraid of being sued.  Sometimes we even avoid doing things just out of fear of litigation.  How's that for some apples?  We all want the best care in the shortest amount of time at the cheapest cost.  It turns out we can have two out of the three at any given time, but probably not all three all at the same time. 

The Pennsylvania Orthopaedic Society got 72 of its members to agree to note why they were ordering tests over the course of 2,068 patient encounters.  Whether the patient was evaluated in the office, emergency room, or other setting, the orthopedic surgeon checked a box to denote testing either for clinical reasons or for defensive purposes.  It turns out that 20% of all tests ordered were for the latter rationale, accounting for 35% of total costs ($113,369 out of $325,309 for this small cohort).

Why?  Think about the prevailing thought process under which we physicians work:  it's not a matter of if we're going to be sued, but when we're going to be sued.  As expected, the surgical specialties like obstetrics & neurosurgery are more likely to be involved in litigation due to poor outcomes.  Where else are we expected to be perfect each & every time (not that I'd settle for less) getting everything done yesterday (immediately) for the least cost possible while knowing that our reimbursement will be pennies on the dollar and while Congress threatens to dramatically cut Medicare payments each year.  Something's gotta give and it's our system - it's broken!

How's this all tie in together?  When your expectations aren't met, we get sued.  So what's a doc to do?  Practice defensive medicine.  The problem is that this drives up costs (estimated at $100B-$178B in 2005) that are then passed back to you & me (approximately $, while exposing you to excess, unnecessary radiation, procedures, and medication side effects.  Here's the worse part:  in a study published in the New England Journal of Medicine in May 2006, 37% of claims did not involve any medical errors and no injuries occurred in 3%.  Yet, we continue to work under threat of litigation.  Now, I'm not claiming that all doctors are bad.  There are plenty of bad apples out there (we here in southern Nevada have our share).  But the way our system now works, all physicians are penalized for the outlandish behavior of a few.

Moreover, there are, using insurance parlance, acts of God.  Many poor outcomes are just that, acts of God, not due to negligence.  Yet, patients have developed an attitude that they are owed something just because something bad (might or might not have) happened.  Since when did I deserve something just because some bad luck befell me?  Yes, we need a system to assist those devastated by bad outcomes.  But not on the backs and at the expense of good physicians trying to do their best for you, their patient, day in and day out.  No wonder we keep looking over our shoulders and practicing defensively.  I'm not condoning this but I can certainly empathize.

One more thought about our broken system:  malpractice litigation really is a lottery, not just for the patient but also for the attorney.  If you win, they win (big).  Attorneys pocket 30-40% of the total award, so the plaintiff never sees all that money.  Therefore, attorneys must learn how to judge potential outcomes before "investing" in a case (like trying to predict dice at the craps table).  However, given our current economy, apparently there's less funding to go around.  So the latest twist to our derelict system is the advent of investment companies putting up the capital to allow attorneys to bring forth malpractice litigation with the promise of a percentage of the winnings.  If you want to diversify your investments, you can now consider malpractice in addition to stocks, bonds, real estate and precious metals.  Let's just hope President Obama can overhaul our medical tort system as promised on Monday before our system breaks down further.

Brain Volume vs Antipsychotics: Does Size Matter?

We've known for quite some time that there's a long list of side effects associated with taking antipsychotic medications, ranging from uncontrollable movements to diabetes and weight gain.  You can now add loss of brain volume to that list, at least in patients with schizophrenia.

In a study published this week, the authors followed 211 patients with schizophrenia who received on average 3 scans of their brains over the ensuing 7+ years of observation.  They concluded that those who were adherent with their antipsychotic regimen, especially larger doses for longer periods of time, had a notable loss of brain volume, compared to those who were less adherent.

But as the joke goes, does size matter?  We can't be too sure since the authors didn't include cognitive assessment in their study.  Given the option, I'd prefer to maintain my brain size.  What's worrisome to me is the increasing use of antipsychotics beyond schizophrenia and bipolar affective disorder.  New indications include depression unresponsive to traditional antidepressants alone while I've seen too often off-label use as a sedative-hypnotic to treat insomnia.  Even before this study, I wasn't convinced that this class of pharmaceuticals should be used for chronic insomnia.  Now, I'm even less inclined.

Tuesday, February 15, 2011

More Fiber = Lower Death Rate

We've known for a while that fiber is good for you.  Roughage, our parents called it.  Many observational studies demonstrate an association between higher fiber intake and lower heart disease & cancer rates.  However, nihilists would argue that we have to die from something, so maybe a quick death from a heart attack wouldn't be such a bad thing.  The problem is that we can't necessarily control whether we succumb to cancer or from post-stroke complications.  That's why I'd rather hedge my bets and lower my risk as best I can.

Now comes new evidence, just published online yesterday in the Archives of Internal Medicine, after following 567,169 men & women 50-71yo for 9+years, that higher dietary fiber is associated with 22% reduction in all-cause mortality (the Holy Grail for studies) in both men & women.  More intriguing was a link to statistically significantly lower rates of infectious & respiratory, as well as cardiovascular, causes of death, by 24-56% in men and 34-59% in women.

The next question then is how much?  It turns out that the lowest risk for men was in those who consumed on average over 29g fiber/day while lowest risk for women was in those who consumed on average close to 26g fiber/day.  Granted, those who consumed more fiber were also more likely to exercise vigorously, less likely to smoke, while drinking less alcohol and consuming less red meat, but the association remained intake after taking all the usual suspects into account.

Given that lofty daily goal, some of you will inevitably reach for the bottle . . . of fiber supplements.  After all, we're a nation in love with the quick and easy answer, always looking for a shortcut.  In this case, the authors pointed out the most of the infectious & respiratory disease benefits came from fiber obtained from whole grains.  Therefore, they recommend substituting whole grains (full of fiber) for refined carbohydrates (which can spike your blood glucose).

If you're a lumper, like me, rather than a splitter, this study supports a variation on the theme of low glycemic nutrition, Mediterranean diet, Paleolithic diet, etc.  In other words, this isn't earth shattering evidence but rather another piece piece of the nutrition puzzle.  So think carefully before you take that next bite.

Monday, February 14, 2011

Energy Drinks Part 2

Happy Valentine's Day!  Do you know what you're going to quaff over your romantic dinner tonight?  Hopefully not an energy drink, at least not if you're a child, adolescent or young adult.  Why?  In an review article published online today in Pediatrics, the authors pointed that consumption of these sources of caffeine has been associated with liver damage, kidney failure, respiratory disorders, agitation, seizures, psychotic conditions, rhabdomyolysis, tachycardia, heart failure, and even death.  This doesn't even take into account the more common & unreported nausea, vomiting, abdominal pain, jitteriness, agitation, and racing heart sensation (w/o documented tachycardia).  These adverse events are a world-wide phenomena reported in Geman, Ireland, and New Zealand, amongst other countries.  In Australia, 5 energy drinks were banned for containing more than 320mg/L caffeine. Both Denmark & Turkey prohibit energy drinks altogether, which I think is overly restrictive.  The solution?  Monitor your children & adolescents (30-50% self-report consumption) and beware of the consequences should you decide to mix yours w/alcohol.  Just saying!

Sunday, February 13, 2011

Erectile Dysfunction vs Heart Disease: Chicken or Egg?

We know that men w/heart disease are also predisposed to have erectile dysfunction (ED).  We understand the pathophysiology, too:  both conditions are due to lack of adequate blood flow.  However, the big question is whether one leads to the other; more specifically, whether ED predicts heart disease later on.

Multiple studies over the last decade have essentially led to the conclusion that ED, in fact, predates heart disease.  Worse, the younger one reports ED, the greater one's chances of having clinically manifest heart disease.  Granted, there are often psychological reasons for ED, but in general, most physicians now agree that ED leads to heart disease.  In fact, a very nice review of the available data was just published.

The next step then is to make ED an acceptable diagnosis and take it out of the closet, just like we've managed to do w/mental illness (although we're still far from our goal there, too).  Once we can acknowledge ED, we can then start screening for heart disease at an earlier subclinical stage where we can make (population level) changes to minimize the impact of heart disease on our families, our nation, and our economy.

Of course, by screening, we spend more money (which we don't have).  The flip side is that we're stimulating the economy, right?  Well, we can't screen everyone, at least not right now, it's just not practical.  But this review posits a simple algorithm to stratify those with ED into low, intermediate, and high risk of heart disease based upon age and other known cardiovascular risk factors.  The author focuses specifically on those in the intermediate risk group for further evaluation with our current set of tools.  And just who are those men?  Anyone w/cardiovascular risk factors (that's obvious) regardless of erectile function as well as those men <60yo w/ED who may (or may not) have cardiovascular risk factors.

Saturday, February 12, 2011

Family History - It's in Your Genes

Have you ever wondered why medical students are taught to ask so many questions when they perform their history & physicals?  For that matter, why your own (family) doctor might be asking about your parents & siblings' health when it's you, after all, who's sitting in front of him/her with a medical concern, not your relatives.  Worse, your family doc then continues on ad nauseum asking about the health of your aunts, uncles, grandparents, etc.

In other words, why is it so important to know your family history?  Well, like begats like.  We've known for a while that strokes in female 1st degree relatives increase the risk for ischemic stroke (the most common kind - due to blockage) in women.  But how does it affect heart disease risk?  Especially since that variable is left out of both the Framingham risk calculator and the Reynolds Risk calculator (the latter specifically asks for a family history of heart attack, not stroke).

In a study released online this month, the authors compared those who had suffered a heart attack to those who had suffered a stroke and concluded that a family history of stroke in the mother was associated with an increased (more than doubled) risk of heart attack in the daughter.

So the next time you attend one of your boring family gatherings, start asking questions (non-judgmentally, of course) to develop & understand your family tree.  With just a bit more information, the life you save may be yours.

Friday, February 11, 2011

Time is Brain!

I've spent the last several days talking about how to prevent strokes.  But what if you're not so lucky?  Or rather your luck is bad rather than good?  Would you know you were having a stroke if you had one?  You need to think fast! Or in this situation, act FAST!  

F = face.  Is your face droopy or asymmetric, especially if you try to smile or raise your eyebrow?  Or perhaps one side is quite numb & tingly as if you just returned from the dentist full of Novacaine(r).

A = arms.  Does one drift or appear significantly weaker than ordinary?  Is one numb & tingly?

S = speech.  Is your speech slurred?  Are you having difficulty making yourself understood?

T = time.  Time is most important because if you notice any or all of the above, you need to call 911 to get yourself to your emergency department as soon as possible (ideally within 3 hours of any of the above - so don't dilly-dally waiting to see if you're going to get better).  Preferably, your emergency department would also be a certified stroke center, where they'd be prepared to take you in for neuroimaging as soon as you rolled thru the doors and then get you set up for thrombolysis immediately afterwards (ideally within 60 minutes of your arrival).

Why is time so important?  Think of a stroke as a brain attack, similar in nature to a heart attack.  We all know that time is of the essence when someone is suffering from a heart attack.  For all intents & purposes, most (80%) strokes are similar in nature to heart attacks and are due to clot formation.  So we perform a head CT to prove that the stroke isn't due to a ruptured blood vessel (20%) and then start medication to break up the clot if we're within a specific time frame (3 hours, sometimes more depending upon newer European guidelines).  After all, just like time is myocardium (heart tissue), time is brain, too.  So the sooner we can break up the clot and get blood flowing, the better your chances of surviving the ischemic stroke w/minimal long-term disability.

Unfortunately, in a study just published online yesterday and announced at the American Stroke Association's annual conference, only one out of four patients who even received thrombolysis (remember, most didn't get to the hospital in time!) got therapy within 60 minutes of arrival.  We need to do better than that.  But you also need to know where to go (quickly)!  So while you're exercising, eating right, and controlling your blood pressure, look around and know which of your nearest emergency departments is a certified stroke center.

Thursday, February 10, 2011

Diet Sodas & Stroke: What's the Link?

In another announcement from the American Stroke Association's annual conference, researchers proclaimed to the lay press that those who drank diet soda daily had a 48% greater risk of having a stroke or some other vascular event

Unfortunately, the study has not yet been published so there hasn't been an adequate opportunity to evaluate the statistics behind their conclusion.  So it's difficult to make recommendations for the whole population based upon what could very well be a statistical fluke.

For instance, we do know that the authors followed 2,564 participants, average 69yo, from the Northern Manhattan Study for an average of 9+years.  Of these, only 116 drank diet soda daily, a small fraction of the total number of participants.  Do these 116 really represent all of us?  Maybe or maybe not.  I would still suggest reconsidering one's libation of choice to determine if indeed there might be a better, safer option, eg water.  Just sayin' . . .

Wednesday, February 9, 2011

Different Strokes for Different Folks

Having a stroke is no longer a disease of just our parents & grandparents.  Strokes are now occurring at a higher frequency in our youth & middle-aged over the past 10 years as reported at the American Stroke Association's annual meeting this week. 

While the overall risk is still low at 14.8 per every 10,000 hospitalizations among men 15-34yo during 2006-2007, that's still a significant 51% increase compared to just 9.8 back in 1994-1995.  Amongst men 35-44yo, the rate increased by 47% from 36 to 52.9 per 10,000 hospitalizations.  

For comparison's sake, the incidence of strokes dropped by 25% from 404 down to 303 per 10,000 hospitalizations amongst men 65yo & older during this same period of time.  Similar trends were noted amongst women in like age groups.

Is the glass half full or half empty?  Yes!  Compared to our parents & grandparents, the risk of stroke is just 1/20th in our youth & middle-aged but the fact that we're increasing while they're decreasing doesn't portend good things for us and our children. 

Remember the ASA guidelines to prevent your first strokeI reviewed them 2 months ago.  How many of you have made even one change as suggested?  Just last week, I reviewed the European version of how to prevent your first stroke.  Anyone change their lifestyle as suggested?

Don't allow yourself to become a statistic.  Do something to avoid having a stroke.

Tuesday, February 8, 2011

Sleep Duration vs CV Outcomes

I truly believe in the Goldilocks theory of medicine - everything needs to be just right, not too much, not too little.  This is particularly evident when discussing hormonal optimization b/c what's right for one person isn't necessarily correct for someone else.  The same dose may be either too much or too little for another patient.

Interestingly, this also appears to apply to sleep duration versus heart disease and stroke as reported in an analysis released yesterday in the European Heart Journal of 15 prospective studies involving 24 cohort samples of 474,684 men & women followed for 7-25 years.  Both short duration of sleep and long duration were associated with a greater risk of heart disease and stroke.

We've had our suspicions regarding poor sleep quality for awhile especially when looking at the link between sleep apnea and heart disease.  But sleep quantity regardless of quality?  While we leave the researchers to ponder the association, the question on everyone's mind is just how much is the right amount?

It turns out that 7-8 hours/night was the reference and that short duration was <5-6 hours/night and long duration was >8-9 hours/night.  So for whatever the reason, maybe those lazy weekend mornings sleeping in aren't so good for us after all, and just maybe we need to set an alarm even on the weekends!

Monday, February 7, 2011

Energy Drinks: Chug, Sip or Avoid?

I trust all you Packers fans are recovering from your celebratory debauchery.  Likewise, I hope that all you Steelers fans have recovered after drowning your sorrows in your favorite libation.  Out of curiosity, did anyone mix an energy drink w/their alcohol?  I'm not talking about a simple rum & Coke(r).  You know what I mean, it's all the rage these days. 

Energy drinks are those concoctions full of caffeine, vitamins, herbal supplements, and often sugar.  The problem that the FDA is most concerned about is the amount of caffeine in these energy drinks, especially those that already contain alcohol (but which have since been pulled off the market as of last November), since the former can mask the effects of the latter.

For comparison's sake, typical colas contain 34-54mg of caffeine per 12 ounce serving, and are limited to 71mg per 12 ounce serving by the FDA.  A 6 ounce cup off coffee (obviously not brewed at Starbucks given the small volume!) typically contains 77-150mg of caffeine.  However, energy drinks have been tested at up to 500+mg per serving!  The lower volume "shots" test out at 100-350mg of caffeine in each 1-2 ounce serving.  Imagine chugging a half dozen of those!

So who hasn't consumed a full pot of coffee while pulling an all-nighter or after being on call for 24-36 hours?  Remember how miserable you felt?  Imagine adding excessive amounts of alcohol to that situation.  The problem with mixing large amounts of caffeine with alcohol is that it can potentially alter your interpretion of your true state of inebriation, allowing you to become even more drunk than you would normally get, possibly reaching a state of "wide-awake drunkeness" as pointed out in a commentary published in JAMA

Now, I'm all for individual rights and minimal governmental intrusion but it seems to me that if we limit our colas to 71mg of caffeine, perhaps we should limit our energy drinks to the same.  Or raise the caffeine limit of our colas to 500+mg per serving.  At least we should be consistent as we educate our patients on what to drink when.  Just remember to limit your consumption.  And have someone else drive you home.

Friday, February 4, 2011

The Heart Truth

Since 1963, Congress has designated February as American Heart Month and the first Friday of every February is National Wear Red Day.  The Department of Health & Human Services plus the American Heart Association want to get the message out that "Heart Disease Doesn't Care What You Wear—It's the #1 Killer of Women."  I know it's hard to believe, but although we're all too familiar with the pink ribbon, 7-8x more women died from heart disease than from breast cancer in 2007, in fact , more than all cancers combined

Get your own Red Dress Pin and help focus more attention & awareness on heart disease in women.  Then do something so that you and/or your loved ones won't have to suffer needlessly given all the advances we've made in the last few years.  Listen to your body and make sure your doctor listens to you.  Most of all, choose a healthier lifestyle b/c not only will it prevent heart disease, it will most likely lower your risk of cancer, diabetes, and Alzheimer's disease, too.  You can't lose if you make the right choice!

Thursday, February 3, 2011

How to Avoid Your 1st Stroke, Part 2

Two months ago, I reviewed the American Heart Association and the American Stroke Association's recommendations on how to prevent that first stroke.  Earlier this week, the European Heart Journal reviewed the currently available evidence and concluded 70% of first strokes are avoidable & preventable with lifestyle modification, especially those that lower blood pressure.  They also noted that while the evidence for the role of lipids in heart disease is quite strong, the linkage is not so clear cut with regards to lipids and stroke.  Both heart failure and atrial fibrillation are considered high risk for cardiac embolism as a source of ischemic stroke.  While we only have observational data as to the link between blood pressure and stroke, it's not too far fetched to consider optimizing one's blood pressure, rather than settling for just good enough.  So keep a close eye on your blood pressure.  And in the meantime, Happy Chinese New Year (it's the year of the rabbit/hare).

Tuesday, February 1, 2011

USDA Dietary Guidelines 2010

The US Department of Agriculture released its Dietary Guidelines yesterday.  As expected, it recommended consumption of more fruits & vegetables, whole grains, oils, and fish/chicken/beans while limiting solid fats, added sugars, refined grains, and sodium.  In general, they recommend nutrient-dense foods compared to our current calorie-dense choices.

The USDA briefly reviewed various known diets, eg Okinawan (Asian), Mediterranean, DASH (Dietary Approaches to Stop Hypertension), and vegetarian.  While they pointed out the benefits of each and the commonalities in all, the USDA glossed over the one major selling point behind the Mediterranean diet over all the rest -- that of  lower all-cause mortality.  Yes, they're all associated w/lower rates of heart disease, some w/lower rates of hypertension, diabetes and/or stroke, but only the Mediterranean diet has been repeatedly associated w/lower all-cause mortality, cancer, and dementia, in addition to the aforementioned diseases.

Granted, the world would be a pretty dull place if we all ate the same thing over & over again w/o regard to ethnic, cultural or religious preferences and especially if we didn't indulge in the occasional dessert to celebrate a birthday or anniversary.  But unlike the quote that it's always 5 o'clock somewhere as the rationale to start drinking, while it's always someone's birthday and/or anniversary, we need to make better choices on a more regular basis and minimize our indulgences as best we can.