Friday, December 31, 2010

Dietary Antioxidants vs Stroke Risk

"Le bon Dieu est dans le d├ętail" (the good God is in the detail) - Gustave Flaubert (1821–1880).  

I thought this quote a propos given how loosely trial results are translated into headlines & sound bites.  In the EPICOR  study to be published next year (doesn't that sound so far off in the distance?), researchers of the Italian cohort of the European Prospective Investigation into Cancer & Nutrition followed 41,620 participants for an average of 7.9 years and concluded that those who consumed the most dietary antioxidants had the lowest risk of ischemic stroke but not hemorrhagic stroke.  That's the difference between the water pipes in your house clogging vs bursting.  

In fact, there was a 47% relative risk reduction by comparing those who ate the most to those who had the lowest total antioxidant capacity.  Please note, however, taking a handful of pills hasn't been proven to be equivalent to the daily & regular consumption of larger amounts of coffee, wine, fruit, chocolate, vegetables & soups, tea, and fruit juices as dietary sources of antioxidants. When broken down further, vitamin C was found to be especially helpful in preventing ischemic strokes while vitamin E was associated with increase risk of hemorrhagic strokes.

The take-home message hasn't changed over these past 12 months.  Make better, healthier, food choices, eg eat your fruits & veggies every day.  A little bit of wine & some high cocoa-content dark chocolate appears to be good for you, too.  So make a resolution to lower your stroke risk in 2011.  A votre sante!

Thursday, December 30, 2010

FDA Approves Fortesta (Testosterone) to Treat Hypogonadism

Endo Pharmaceutical announced yesterday that the FDA has approved their Fortesta brand of 2% testosterone gel for men suffering from hypogonadism for application to the thigh to minimize accidental transfer to spouses & children.  Hypogonadism or andropause or low T is a clinical syndrome comprised of loss of energy, loss of libido (sex drive), erectile dysfunction, increase in fat despite appropriate nutrition, loss of muscle despite appropriate exercise, depression, cognitive dysfunction, and/or osteoporosis, in a person with confirmed low testosterone levels.  So now, men can choose from transdermal testosterone (Androderm, Androgel, Fortesta & Testim), pellets, injections, and buccal patches (Striant).

Wednesday, December 29, 2010

HDL vs Heart Disease

You can't rely solely on your statin to prevent heart disease.  Just last week, authors analyzed 20 randomized controlled trials including 543,210 person-years of follow up and noted that after accounting for LDL (bad cholesterol), age, blood pressure (hypertension), diabetes, and tobacco use, lower HDL (good cholesterol) was associated with an increase risk of heart attacks, regardless of whether statins were used or not.  

For every 10mg/dL decrease in HDL, there was a 7.1-8.3% increase risk of heart attack in statin users & non-users, respectively, without either threshold or ceiling effect.  In other words, while we've said in the past that normal HDL is >40mg/dL, it turns out that a progressively lower risk of heart attack exists the higher one's HDL, even above 60mg/dL.  Conversely, there's a progressively greater risk for heart attacks w/HDL <60mg/dL.  So the question you need to ask yourself is whether you want to be normal or whether you want to be optimal.  The choice is yours.  

Tuesday, December 28, 2010

How to Prevent Falls in Our Elderly

As I've mentioned in previous posts, the US Preventive Services Task Force (USPSTF) is a stickler for evidence-based medicine.  Unless they have enough studies demonstrating cause & effect, they won't make recommendations or at least give strong ones based upon epidemiologic data alone.  This is both their strength & their weakness.

When it comes to caring for our elderly, especially when considering healthy aging, optimizing health & preventing debilitation & frailty, the USPSTF concluded last week that it's difficult to arrive at definitive recommendations because there are so many risk factors to take into account, so many interventions & outcomes to consider, and most importantly, a scarcity of elderly participants in many clinical trials.

Which isn't to say they haven't tried.  For instance, in the very same issue, USPSTF analyzed 19 randomized controlled trials to determine interventions to prevent falls in the elderly.  It's worth noting that they actually had to screen 3423 abstracts and 638 articles to find fair-to-good quality studies.

Their conclusions:  exercise & physical therapy can reduce falls by 13% while vitamin D can reduce falls by 17% (take that, IOM!).  Multifactorial fall assessment, the geriatrician's bread & butter, showed a non-statistically significant 6% trend towards fall reduction.  Unfortunately, the individual components, medication use, visual acuity, home environment, and gait/balance assessment, demonstrated no benefit in isolation.  The good news?  No serious harm was noted as an outcome of the interventions.

The obvious question:  how much exercise and how much vitamin D is necessary?  Given the debacle over their recommendations for mammogram screenings, the USPSTF is opening up their draft recommendation statements to public comment at www.uspreventiveservicestaskforce.org/tfcomment.htm prior to making definitive final recommendations.  But there's no reason that we can't continue to recommend exercise & vitamin D for our patients now.

Sunday, December 26, 2010

Gardasil Vaccine Prevents Anal Cancer

As physicians, we weigh the pros & cons of each therapeutic option with our patients daily.  What may be of benefit to one individual may be too dangerous for another to undertake.  I wish it were that simple but too often, emotions complicate our logic & science.  How else do you explain the 3,000-49,000 patients who refuse their yearly influenza vaccination and then end up paying the price of hospitalization & death for their illness (new reporting standards from the CDC this year).  Let's not forget the $10 billion in lost productivity and direct medical expenses and another $16 billion in lost potential earnings as a result of this preventable illness.

More recently, there has been a tremendous backlash against the use of Gardasil to prevent human papilloma virus (HPV) infections, first in women, and now in men.  Why the hesistance?  After all, multiple studies demonstrate that when administered properly, Gardasil can prevent cervical, vulvar & vaginal cancer in women, and genital warts in both men & women, all due to HPV.  Perhaps because HPV is considered a sexually transmitted illness and a vaccination against a sexually transmitted illness could be considered an e-ticket to have sex & promiscuity.  Of course it doesn't help that the vaccine is not inexpensive and that most insurance companies don't cover it.  But we're talking about preventing cancer, folks!

So in a gesture of holiday largess, the FDA just announced the approval of Gardasil for the prevention of anal cancer due to HPV types 6, 11, 16 & 18, to be administered to men & women 9-26yo (same age group as for the other above mentioned indications).  While anal cancer is not common, its incidence is increasing with the American Cancer Society estimating that 5,300 persons will be diagnosed in the coming year.  In the study used to substantiate Merck's request for another indication for their vaccine, Gardasil was shown to decrease the risk of anal cancer by 78%.

I don't know about you, but I look at this 78% reduction in cancer risk and its attendant surgery, radiation, & chemotherapy treatment and complications as being worth the relative cost of Gardasil and the risk of vaccine related side effects, such as fainting, pain at the injection site, headache, nausea, and fever.  Bottom line, for my kids, Gardasil is an ounce of prevention worth the proverbial pound of cure.

PS Don't be surprised if Gardasil receives an indication in the future to prevent HPV-related oral cancers given our society's generalized increased acceptance of oral sex.

Saturday, December 25, 2010

Fish Consumption vs Stroke

Hope y'all had a very merry Christmas today!  Or happy holiday for those of you who celebrate something else. 

Exactly 3 weeks ago, we talked about how to avoid your 1st stroke.  Now comes a new study to be published next month in which the authors studied the dietary habits of 21,675 participants >45yo and discovered that less than one in four consumed at least two servings of non-fried fish weekly as suggested by nutritionists.  The chances of meeting this requirement were worst for those (African-Americans) who lived in the Stroke Buckle of the Stroke Belt which may account for the racial & geographic differences we find in stroke risk.  Ironically, African-Americans consumed more fish than Caucasians but unfortunately most of it was fried.  And those living in the Stroke Belt & Stroke Buckle were more likely to consume greater than two servings of fried fish weekly.

Let's be clear, this study does not establish causality.  In other words, this study doesn't prove that eating fried fish causes strokes.  However, the results are consistent with what we know, that fried foods aren't good for us.  But perhaps it's the omega 3 fatty acid content that's important.  Fatty fish such as salmon, herring & mackeral have significantly more of the omega 3 fatty acids EPA & DHA than their lean counterparts, eg catfish, cod & haddock, which are usually fried.  Another point that's been raised about farmed vs wild-caught salmon is also mentioned in this study regarding catfish:  farmed catfish has less EPA & DHA than its wild-caught counterpart.

So, details do matter.  We need to eat more non-fried fatty fish, not fried lean fish.  What a bummer.  I really love my fish & chips!

Friday, December 24, 2010

Andropause Part 5: Latest Research

On this Christmas Eve, I am most grateful to all of you for tuning in to my television debut and 20+minutes of fame this week on local NBC affiliate KSNV Channel 3's Healthline Today.  And many thanks to Dr. Jim Lenhart for giving me this invaluable opportunity just as I start up my private practice.  Without further ado, here is the final segment devoted to the latest research regarding andropause.  Wishing all of you the happiest & healthiest holiday yet!

Monday, December 20, 2010

My Television Debut!

Several friends informed me that they saw my andropause interview on KSNV Channel 3 earlier today.  Unfortunately, as my wife & I were still rangling 8 girls for our daughter's birthday slumber party, neither one of us caught the airings.  Luckily, the television station has made a copy available for your viewing pleasure at http://www.mynews3.com/story.php?id=34311&n=27237.  The 4 minute video is also available on YouTube under "alvinblin".  Part 2 airs tomorrow during the 6AM, 9AM and 12 noon news programs.

What to Do for the Common Cold?

The problems with studying herbal supplements include product variability (both as to content of active ingredient as well as potential contaminants) and the wide variety of protocols used for any given indication.  For instance, some claim that the leaves are the active portion of the plant, rather than the root, seeds or flowers, or vice versa.  Others might claim that the manufacturing process removes the active ingredient.  As recently pointed out by the FDA, one also has to monitor for potential contaminants, some of which can be deadly in isolation while others are if taken in conjunction w/other meds & supplements.  Proponents might claim benefit due to chronobiology, in other words, some feel that it matters what time of day you take the supplement.  Or perhaps a loading dose is required.  Complicating the above for us non-botanists, many different plant species are known by a common name, ginseng, for instance.  With all these variables, it's no wonder that studies of herbal supplements have such disparate results.

In the latest salvo to be published tomorrow, the authors randomized 713 patients 12-80yo who self-presented w/upper respiratory symptoms, eg common cold, to either no treatment, unblinded echinachea pills, blinded echinacea pills, or blinded placebo pills.  They self-assessed the severity of their symptoms and underwent objective measures of their immune response.

While the results were not statistically significant, there was a trend towards better symptom scores and shorter duration of illness for those randomized to echinacea (although there was no difference noted with regards to impact upon immune response).  The good news to report is that the product studied was of good quality as per the American Botanical Society and the dose/regimen was appropriate.  The bad news is that given this information, one would have hoped for better statistically significant results.

Will the above results dissuade someone from taking echinacea for the common cold?  Probably not.  But I would certainly have great difficult recommending it to anyone over rest & fluids.  In the meantime, wash your hands religiously because the best way still to treat a cold is to prevent it in the first place.

Saturday, December 18, 2010

Exercise Affects Your Weight Gain & Waist Circumference

Figure. BMI at Each CARDIA Visit by Habitual Activity Category

File a study published in this week's JAMA under "been there, done that" in which the researchers followed for 20yrs 3,554 men & women 18-30yo at baseline and concluded that those who were the most physically active gained the least in both weight & waist circumference over the following two decades. 

The algorithm used to determine physical activity took into account intensity, frequency & duration leading to an activity score in exercise units, 300 of which was deemed equivalent to the suggested 150 minutes/week recommendation of moderate intensity.  However, it turns out that men in the lowest tertile of physical activity averaged just this amount, while men in the highest tertile, those who gained the least in body weight & waist circumference, were more than twice as active.  For the ladies, 300 exercise units only placed them in the middle tertile while twice that much garnered them a place in the highest tertile.

There are two take home points from this study.  First, everyone gained weight & expanded their waist circumference as they aged from young adulthood into middle age, regardless of physical activity.  Second, it takes quite a bit of activity to minimize said gain & expansion, more than double what is currently recommended.

Friday, December 17, 2010

FDA Says Stop Taking Contaminated "Man Up Now"

Fresh off the press:  FDA is now warning consumers to avoid taking the "Man Up Now" dietary supplement which is marked as an "all natural" and/or "herbal" alternative to Cialis, Levitra & Viagra, which are prescription medications indicated for erectile dysfunction. 

However, as I mentioned in an earlier posting, Cialis, Levitra & Viagra are members of a class of medications, phosphodiesterase inhibitor type 5 (PDE-5 inhibitor), that should not be taken in conjunction with nitrates & nitroglycerins as the combination may cause an abrupt drop in blood pressure leaking to loss of consciousness and possibly death.  Most physicians know to avoid prescribing this combination so patients who take nitrates & nitroglycerins (typically those with heart disease caused by blood vessel blockage which also blocks the blood vessels to the penis) are forced to search for alternatives. 

Unfortunately, mass marketers are aware that we tend to look more favorably upon "all natural", "herbal", and "organic" products, especially compared to "synthetics" and thus label their products as such.  The problem arises when their products actually contain either prescription medications or substances chemically similar to said prescription medications.  Thus the unsuspecting patient takes this "all natural", "herbal", and "organic" product in conjunction with his nitrates & nitroglycerins and ends up dead.  In the case of "Man Up Now", the FDA analyzed the dietary supplement and found it to contain sulfoaildenafil, a chemical similar to sildenafil, the active ingredient in Viagra. 

If you need help in achieving an adequate erection while also taking nitrates & nitroglycerin for your heart such that you can't take any PDE-5 inhibitor, consider checking your testosterone level.  Many studies demonstrate an association between testosterone and heart health (more is better).  In case you're told you don't qualify for testosterone supplementation because you're normal and passing, ask yourself, do you want to settle for being normal or do you want to be the best that you can be?  Do you want to settle for a "C" or "D" grade or do you want an "A" or "B" grade?  Just saying . . .

Risk of Dying After a Stroke

Just under 2 weeks ago, I reviewed how to avoid your 1st stroke.  Besides the obvious loss of function, a study published online yesterday points out something even more compelling: an increase risk of death soon thereafter.  The researchers followed 91,134 participants (avg 79yo) for 3yrs.  6.1% died while hospitalized, 14.1% within the 1st 30 days, and 31.1% within the 1st year.  In other words, 1 out of 3 patients who were hospitalized for their 1st stroke were dead within a year.  So go back and review that list of how to avoid your 1st stroke.

Thursday, December 16, 2010

BMJ & Christmas III: Bicycle Weight vs Speed

I'm just as guilty as the next cyclist who's willing to spend tens if not hundreds of dollars in order to shave grams off one bicycle component or another.  But my body weight?  It's pretty steady.  The bigger question is whether this expensive mechanical weight reduction really matters, at least to a recreational cyclist, over a relatively short distance.

Thus, in this 3rd of a series of humorous studies published online in the BMJ, the author timed himself on a 27 mile roundtrip from his home to the hospital & back.  So as not to allow a chance spurious ride to throw the results, he averaged his times over 809 miles on his 30 pound steel frame bicycle and another 711 miles on his 21 pound carbon frame bicycle.  From personal experience, I can tell you that the 9 pound difference in weight costs on the magnitude of thousands of dollars.  Yet the average difference in time for his ride was just an 32 seconds (1:47:48 vs 1:48:21 in hours:minutes:seconds) with the confidence interval anywhere from 3 minutes slower to 2 minutes faster on any given day regardless of the bicycle ridden.

So go buy the brand new carbon kevlar titanium bike because you can't stop drooling over it.  Just don't rationalize that it'll make you a faster rider, at least not over 27 miles.  Even the seven time winner of the Tour de France, Lance Armstrong, said "It's not about the bike".

Wednesday, December 15, 2010

BMJ & Christmas II: You Can't Get Drunk With Your Feet In Alcohol

Here's another study just published online in BMJ's Christmas issue.  Apparently there's a Danish urban myth that one can get drunk by leaving one's feet in alcohol.  At least that's what the 3 authors posited in order to determine if the legend is indeed true or false.  Anything in the name of science!

In essence, they wasted perfectly good vodka by soaking their feet in 2,100ml of 37.5% alcohol by volume for 3 hours, all the while checking their blood alcohol levels every 30 minutes.  They also assessed how they felt, whether they were more confident, more voluble, or more spontaneously given to hugs.  Alas, their blood alcohol levels did not budge one iota and their were no symptoms of intoxication.  Chalk one up for the mythbusters! 

And in honor of the holiday season and the cardiology field which is known for the catchy acronyms given to its studies, the authors declared this the PEACE ON EARTH (or Percutaneous Ethanol Absorption Could Evoke Ongoing Nationwide Euphoria And Random Tender Hugs) study.  God bless us, every one!

BMJ & Christmas: Beauty Rest

The British are known for their wry sense of humor.  That's why I look forward to the Christmas issue of the British Medical Journal (BMJ) each year as it's filled with unique, shall we say, studies.  For instance, published online this week, the author's asked whether beauty sleep is real or just a phrase.

In fact, by randomly comparing the photographs of 23 healthy participants after a normal (8 hours) night's sleep and then again after 31 hours of consciousness after just 5 hours rest, 65 untrained observers were able to distinguish sleep status based upon appearance alone without actual knowledge as to when each photo was taken.

In other words, the participants appeared less healthy, less attractive, and more tired in the latter sleep deprived state compared to their former rested status.  So getting one's beauty rest isn't an excuse after all!

Tuesday, December 14, 2010

HDL vs Alzheimer's Disease

Known knowns.  Known unknowns.  Unknown unknowns.  Hmmm . . . We know that higher levels of physical are associated with lower risk of Alzheimer's disease (AD).  Multiple studies have demonstrated this over & over again.  We also know that physical activity tends to increase HDL, the good cholesterol.  But is there a link between HDL & AD?  As of this month's issue of Archives of Neurology there is!

The authors studied a cohort of 1,130 elderly (avg 76yo) free of cognitive impairment followed for just 4+yrs.  Those whose HDL was in the highest quartile (>56mg/dL) had a 60% lower risk of developing AD or probable AD compared to those in the lowest quartile (<38mg/dL), regardless of age, sex, education, ethnicity, and APOEe4 genotype. For what it's worth, average age at diagnosis was 83yo.

Ironically, there weren't enough cases of vascular dementia to arrive at a statistically significant answer, but the results suggested once more that high HDL is associated w/lower risk of vascular dementia, too.

Hmmm . . . that chocolate is looking pretty good to me right now to raise my HDL.

40% Tax on Sugar-Sweetened Beverages?

 A few days ago, I jokingly referred to George Orwell's "1984" after noting that Australia expected to save quite a bit of money if they could legislate lower salt content in process foods.  Well, I laughed a bit early since some authors published yesterday that a 40% tax on carbonated sugar-sweetened beverages could potentially generate $2.5B annually in additional tax revenue, mostly from high-income households they theorized, while leading to a 0.59kg/yr loss in weight per person because of a reduction by 12.4kcal/d per person.  Don't hold your breath but stranger things have been known to happen, especially given our current dire economy.

Levothyroxine Administration: AM or PM?

I've come to accept that some medications need to be taken on an empty stomach while others do better w/(specific) food.  For instance, bisphosphonates need to be taken on an empty stomach since they're so poorly absorbed.  Calcium is best absorbed in its carbonate form if someone doesn't have their stomach acid suppressed by either an H2 blocker or a proton pump inhibitor.  On the other hand, if one needs to take one or both types of those medications, calcium is better absorbed in its citrate form.  Likewise, studies have demonstrated that levothyroxine should be taken on an empty stomach to achieve the narrowest thyrotropin range.

But time of day?  I always thought that as long as you're consistently taking a medication every 24hrs, then it doesn't really matter if you choose AM or PM.  Well, a pilot study of 12 participants published almost 3 years ago demonstrated that timing does matter w/bedtime better than morning for levothyroxine.

And a study published this month corroborates this after the authors elegantly randomized 90 patients already taking levothyroxine to a twice daily regimen, one of which was the real thing and the other a placebo in a double blind fashion (thus, in this cross over design, they acted as their own controls).  This continued for 3 months at which time unbeknownst to the patients, their levothyroxine was switched for the placebo & vice versa for another 3 months.  Upon analysis, thyrotropin levels were substantially lower (by 1.25mIU/L and both total triiodothyronine and free thyroxine were higher whenever the participants took their levothyroxine in the evening compared to the morning.

What's interesting to note is that lipid values & quality of life scores did not change regardless of the timing of dose administration.  Yet, the authors recommended changing dose administration time in an attempt to achieve better (lower) thyroxine numbers w/o any clinical rationale.  Remember that we're here to treat the patient, not just the numbers.

Monday, December 13, 2010

Nature vs Nurture re Diabetes & Obesity

Genomics.  Genetics.  A rose is still a rose . . . It turns out that when we speak of genetics, we're talking about one specific gene making a big difference, whether autosomal dominant or recessive in the classic Mendelian manner.  However, with new technology, we are now able to delve into genomics, where multiple genes are involved in disease risk.  This week's issue of NEJM has a nice review of our current state of knowledge regarding how genomics affects our risk for diabetes & obesity.  While new advances might help us individually tailor treatment in the future, we're not there yet, not by a long shot.  So let's not forget the old nature vs nurture debate.  Rather than using this study as an excuse to give up, let's refocus on our ability to control our genomic destiny to a great extent by making positive lifestyle choices.

Sunday, December 12, 2010

Testing Testosterone Part 2: Apples vs Oranges

Here's a little factoid for you:  those testosterone tests that we run for men aren't necessarily all that accurate for women.  So states a study published this month in JCEM.  More specifically, there's no standardized assay method for testosterone in women.  We use the same technology as we do for men but it's scary to consider the (lack of) accuracy.

First, you have to understand (trust?) that women in most age groups have a normal range of 20-60ng/dL compared to men's 300-1000ng/dL.  Granted you might see slightly different values for either the upper limit of normal or the lower limit of normal but just get a feel for the ballpark difference.  There are certain clinical conditions in which women might have substantially higher testosterone levels than usual but still not into the male range.

Second, there are many different ways to measure testosterone, each with its own reference range.  While your lab might publish a reference range, there are in fact no age & gender normal ranges, nor is there an assay upon which to base this standard.  That's why I mentioned last month that the Endocrine Society and Centers for Disease Control & Prevention are developing a plan to come to a consensus.

But which testing method is most accurate?  The authors took blood samples from 596 women with a condition (polycystic ovarian syndrome or PCOS) that should raise their testosterone levels high enough to minimize as best we can assay difficulties.  These samples were each then divided individually into 3 aliquots.  Two went to two different academic facilities and one went to a commercial facility.  One methodology was used by both an academic facility and its commercial counterpart while a different method was used by the other academic facility.  Got it?

In an ideal world (which we clearly don't live in), all three values would be exactly the same.  For your purposes & mine, getting 90+% correlation would be satisfactory.  However, using the same testing methodology (LCMSMS), the closest the academic and commercial facilities could come to each other was just 83%.  Worse, when compared to a different method (RIA), the academic facility only achieved 79% correlation while the commercial facility was only 67% accurate.  And the lower the testosterone level, the worse the correlation.

Funny then that the study concluded that the LCMSMS & RIA methods are "comparable".  Like an apple to an orange, I think.  At least they admitted there's significant variability between assay methods.  Bottom line for you & me?  Treat the patient, not just the numbers.  And have your blood tests run at the same place using the same technology each time.  So you can compare apples to apples.

Saturday, December 11, 2010

Save Money, Save Lives! Eat Less Salt!

Sometimes it helps to repeat myself.  At least that's what I think when it comes to my kids.  But maybe it's true regarding salt, too.  Remember the Cochrane Collaboration (Database & Library), the extremely well respected group promulgating evidence-based medicine?  They just announced that after analyzing 13 studies involving 75 participants w/T1DM and 158 w/T2DM, a reduction in daily salt consumption by 8.5g/d was associated with a decrease in systolic blood pressure by 7mm Hg and in diastolic blood pressure by 3mm Hg.  This is at least equivalent to taking any first line blood pressure medication with huge potential cost savings.

Of course that's great news.  However, my first gut reaction was who in the world eats that much salt every single day in this age of health consciousness?  Obviously, these individuals missed the study published in February that projected that reducing dietary salt intake by just 3g/d could decrease the number of new diagnoses of heart disease by 60,000 to 120,000, stroke by 32,000 to 66,000, heart attacks by 54,000 to 99,000, and all-cause mortality (the Holy Grail for physicians) by 44,000 to 92,000 ANNUALLY!  

Just released last month for publication this month, a study evaluating individual accountability in Australia projected a median cost-effectiveness of A$100,000/DALY (disability adjusted life year).  They then went on to claim that population health could improve by 20x that amount if the government would step in and legislate lower salt limits in processed foods.  1984 anyone?

Cannabis for Diabetic Cardiomyopathy? Sure, If You're A Mouse!

All too much seriousness this week.  Time for something fun.  Like marijuana?  In a study prepublished for next week, the authors demonstrated that cannabidiol has benefit for diabetic cardiomyopathy in both a mouse model and in human heart cells (cardiomyocytes).  Why does cannabidiol sound familiar?  Well, it's the most abundant nonpsychoactive ingredient in marijuana.  

Now, the applicability of mouse & celllular experiments is so far removed from our everyday world that I normally wouldn't make a big deal about these types of studies, press releases and announcements.  But I'm sure someone is going to extrapolate from this study and make a huge leap of faith to light one up.  Or at least help improve the economy in Northern California's Emerald Triangle. 

Selenium for a Healthy Thyroid

Those practicing complementary, alternative, integrative, functional, anti-aging medicine or whatever descriptive term you want to use have known forever about the importance of selenium for thyroid health.  For without a healthy thyroid, our metabolism gets out of whack, we gain weight w/o reason, and lose a substantial amount of energy, all the while becoming constipated & unable to think clearly.  It's a bit of a domino or house of cards effect.

Those of us in the traditional realm have typically patched & whitewashed this w/levothyroxine but haven't looked further as to the cause.  Just published this month is a nice review article in a mainstream journal (JCEM) documenting the importance of selenium for thyroid health.

Besides multivitamins & supplements, where should we look for natural sources of selenium?  Shellfish, crabs, kidney, liver, and Brazil nuts are all rich sources.  I don't know about you, but I'll pass on the organs and focus on the Brazil nuts & seafood.  That multivitamin isn't looking so bad now compared to kidneys & liver!

Friday, December 10, 2010

Bisphosphonates vs Atypical Femur Fractures

What's life without controversy?  Are bisphosphonates good for you or not?  Before we answer that question, you need to know that doctors typically try to do their best but are always limited by the current state of science & knowledge (not to mention lack of time!).  And most of us left our crystal balls at the cleaners.  In other words, if we knew something bad was going to happen, if we knew that someone would have a negative side effect from the medication, if we knew that the procedure wouldn't work, if we knew that we couldn't help you live any longer just more miserably, you get the idea, we wouldn't have done what we did at the time.  But we can't practice medicine in hindsight.  Just like we can't drive forward down the road by only looking in the rearview mirror.  Sure we look in the rearview and in our side view mirrors every now & then, but mostly we look forward to see where we're going, trying to guess if that bozo rocking out in the car in front of us, texting, eating, and shaving, is aware of the truck pulling out ahead.  

Ok, enough of my ranting and raving for today.  But my introduction is to discuss the current hot topic of bisphosphonates.  We've known for quite some time that as we get older, our bones become weaker and we have a greater risk of sustaining fractures.  And unfortunately, we typically never recover to our previous baseline function.  So when we discovered bisphosphonates, we all jumped up & down because here was something we could finally offer to our patients to prevent fracture-induced debility.  Little did we know that a decade or more down the road, we'd have to worry about bisphosphonates linkage to osteonecrosis of the jaw, atrial fibrillation, esophageal cancer, and most recently as of this month's study, atypical femoral fractures.

So is it true?  Do bisphosphonates cause atypical femoral fractures?  Well, we're still not absolutely clear.  But the American Society for Bone & Mineral Research (ASBMR) is looking into this as of last month.  An article published in October in JAMA mentioned considering 12 months off after 5 years on treatment to minimize atypical fracture risk.  An earlier analysis published this May in NEJM stated that the risk is small but clearly didn't deny it either.  As far back as June 2008 in my personal archives, researchers were already considering the possibility of atypical skeletal fragility.

So what are we to do as clinicians?  Exactly what was discussed in that USA Today article published 3 days ago:  improve our communication with our patients!  Tell them what we know.  Tell them what we don't know.  And help them decide what's best for our patients as an individuals.

Vitamin D vs Frailty: Too Much of a Good Thing?

Don't kill the messenger.  I'm a big fan of vitamin D.  After reading quite a bit of research over the last year or so, I believe that we generally don't have enough vitamin D which can severely impact our health.  So we mostly agree that not enough vitamin D is bad.  The disagreement comes when we try to figure how much is enough.  Just last week, I chastised the IOM (yeah, as if they had any idea who I am or even cared) because I thought they were overly conservative in their vitamin D recommendations.

Well, in a study published this month, the authors performed a cross sectional & longitudinal 4 year study of 6,307 women >69yo.  Not surprisingly, those with the lowest vitamin D (<15ng/mL) were at the greatest risk of becoming frail (which in itself opens up another can of worms regarding how one defines frailty).  Those with vitamin D ranging from 15-19.9ng/mL were intermediate in risk of becoming frail compared to those with levels 20-29.9ng/mL.  But surprisingly, those with levels >30ng/mL also had a greater risk of becoming frail such that the authors described a U shaped curve in terms of frailty vs vitamin D level.

How to explain this if you're in vitamin D's corner?  Perhaps, they studied participants too late for vitamin D to make a difference.  But regardless of baseline functional status, the lower one's vitamin D, the greater one's risk for becoming frail.  Perhaps, those who were already frail were taking lots of supplements to remedy their condition.  No one knows right now.

Please understand that correlation does not imply causation.  However, while many other studies have demonstrated negative outcomes associated with low vitamin D, there have been no randomized double blind placebo controlled studies (this is the gold standard for proof) demonstrating a higher ceiling effect. 

As with many things in life, perhaps too much of a good thing isn't good for you?  Perhaps, we should strive for just right, rather than too much?  Let's learn from Goldilocks!

Thursday, December 9, 2010

Surgeon General: One Cigarette Can Kill You!

The Surgeon General has spoken:  even just one cigarette can kill you!  Secondhand smoke can cause immediate DNA damage (leading to cancer later on), trigger an acute cardiovascular or cerebrovascular event (heart attack or stroke), and generally make it difficult for your body to fight off illness.  I used to tell my patients that a pack or two a day habit was bad but that I couldn't in good conscience tell someone that they couldn't smoke just one teeny tiny cigarette socially when out with their friends once a month, much less once a year.  Well, I guess I can now!  You can read the Executive Summary here or peruse the full report here.  And let's not forget that tobacco use was linked to Alzheimer's disease just two months ago.  So don't light up, not even just one!

Vitamin A & Childhood Mortality

The Cochrane Collaboration and Library is the epitome of evidence-based medicine.  They sort through volumes of data and innumerable studies to arrive at a consensus derived from science rather than expert opinion.  Of course, that limits what statements they're willing to make.  But when they speak, to paraphrase E. F. Hutton, you should listen.

In this particular instance, Cochrane just released their meta-analysis of 43 trials of over 215,000 children 6mo-5yo and concluded that vitamin A would reduce all-cause mortality by 24% compared to placebo, mostly from death due to diarrheal illnesses & measles.  Cochrane felt so strongly that they stated that no more randomized double blind placebo controlled studies of vitamin A for all-cause mortality were necessary in this age range.

Cochrane also warned that high-dose vitamin A would be followed by vomiting over the next few days.  At least here in the States, there's probably no need for high dose vitamin A but rather a daily multivitamin should suffice without unnecessary risk.

Wednesday, December 8, 2010

Sex and the Older Male

Yesterday, I mentioned the FDA recall of an over-the-counter supplement to aid those with erectile dysfunction. Besides the lack of 3rd party oversight & accountability, why is this an issue?  It turns out that in a survey published this week of 2,783 Australian men 75-95 years old followed for 13 years, almost half (48.8%) considered sexual activity at least somewhat important and almost 1 in 3 (30.8%) reported at least 1 sexual encounter in the last 12 months. Slightly more than half (56.5%) were satisfied with their frequency of sexual activity with the remainder wishing for more.  

Now, before you turn up your nose, roll your eyes and say "Ewww", think about how you'll feel when you (hopefully) reach that age.  It's really no one else's business but yours (and your partner's - or is it partners'?).  While the 1 in 3 statistic made the press, they overlooked the factors that affected the results.  For instance, age, partner's lack of interest, partner's physical limitations, osteoporosis, prostate cancer, diabetes, antidepressant use, and beta-blocker use were all associated with less frequent sexual activity.  

What I found intriguing was that higher testosterone levels were associated with increased sexual activity.  Rather than focus on a specific number (to achieve), just know that every increase in testosterone by 1 standard deviation increased the odds of having sexual activity by 20%.  Because this study was observational & cross sectional in nature, there is no way to prove cause & effect.  But as I've noted previously, there appears to be something good about having higher levels.

So rather than reaching for Cialis, Levitra or Viagra, and especially rather than reaching for a potentially contaminated over-the-counter supplement, consider checking your testosterone level.  And ask yourself if you'd be satisfied with a normal level, passing at a "C" or "D" grade, or would you rather see how you'd feel after being tutored to an "A" or "B" level?

By the way, when are we going to see a study on the sexual preferences & activities of older women?

Tuesday, December 7, 2010

Duro Extend Recalled by FDA

As I've mentioned before, dietary supplements and herbals are not beholden to any 3rd party oversight unless voluntarily requested by the manufacturer.  The rules & regulations are such that our FDA, which does monitor prescription & over-the-counter medications (a subtle but very important distinction), is hamstrung when it comes to these dietary supplements and herbals.  Unless someone gets hurt or there's enough evidence to support wrong doing, it's a bit of a crap shoot when it comes to supplements and herbals.  Not that there aren't good brands backed by excellent companies that value their reputation, but unfortunately, the rotten apple does tend to spoil the barrel.

Case in point is the recall of yet another "natural" alternative to the prescription erectile dysfunction drugs.  This time, the FDA is recalling Duro Extend as it found an analog of sildenafil, the active ingredient in Viagra, inside this purported natural compound.  So what, you ask?  Remember the scene between Jack Nicholson's lecherous lothario and Keanu Reeve's emergency room physician in "Something's Gotta Give"?  The combination of Viagra (or its competitors) and nitroglycerin can dangerously lower one's blood pressure, leading to death in the extreme case.  It turns out that family physicians have been warned against prescribing Viagra and its ilk to anyone who takes nitrates, eg nitroglycerin, and/or some other drugs.  So the patient then turns to his vitamin store clerk with minimal education and asks for a "natural, organic" substitute.  If he takes Duro Extend contaminated with this sildenafil analog, another one bites the dust.  Caveat emptor!

Monday, December 6, 2010

Aspirin vs Cancer

It used to be pretty easy.  Take two aspirin and call me in the morning.  Then, everyone over a certain age was told to take aspirin.  There was even talk about putting it in the water.  However, after further analysis, it turned out that aspirin isn't actually as safe as we'd previously thought.  In large enough doses, it can actually increase your risk of stomach ulcers or bleeding in the brain (hemorrhagic stroke), neither of which are benign consequences.  Furthermore, the benefits aren't quite as clear cut.  It appears that aspirin protects men from heart attacks and women from (ischemic) strokes but not vice versa. 

In a study to be released tomorrow, authors analyzed the data from several larger studies involving over 25,000 patients randomized to varying doses of aspirin (75-500mg daily) vs placebo and followed for at least 4 years.  With a wave of the pencil and the punching of calculator keys, they concluded that aspirin was associated with a decrease risk of death from cancer.  The time required before one could expect benefit - at least 5 years.  The relative risk reduction varied depending upon the specific cancer but the good news is that the reduction in the cancer death rate was unrelated to sex, smoking & aspirin dose.  In other words, 75mg daily worked just as well as 500mg daily, but with less potential side effects.  More incredible, the older the patient, the greater the benefit!

Just last month, the same authors analyzed data from several previously published studies (involving over 14,000 patients followed for 18 years) and concluded that aspirin 75mg daily would reduce the risk of colorectal cancer and death from said cancer, especially that from the right (proximal) side, which are not found by sigmoidoscopy but only by colonoscopy assuming adequate preparation. 

So do we all need to start popping baby aspirin like candy?  Probably not yet.  Why? These are associative studies, not causative.  Yes, the data is compelling but it's not definitive.  However, if you're mature enough (read Medicare-age), have a strong Family History of cancer, are male with heart disease or female with stroke, then you probably should review these studies with your family physician and have a good discussion about your individual risks and benefits.  Unfortunately, this isn't going to be easy in the time typically allotted for a follow up visit.  But keep trying.  We really do want to listen to you!

Sunday, December 5, 2010

(Fish + AREDS Supplements) vs ARMD

We've known for a while that we should eat fish regularly to protect our hearts.  There's also mounting evidence that adding fish to our list of protein sources will also help minimize our dementia risk.  As if you needed another reason to consume our fishy friends, out pops a study published this month concluding that fish consumption decreases one's risk for age related macular degeneration (ARMD), the most common form of blindness in the elderly.

The authors came to this conclusion after evaluating fish & shellfish consumption frequency in 2,520 participants. Therefore, the weakness of this study is it's associative nature, rather causal.  It is also a retrospective cross sectional study, rather than a prospective randomized double blind placebo controlled study.  Again, nothing against the study, just be aware of its limitations.  Use it as a jumping off point for a larger study with proper controls & procedures in place.

But for those of us who can't wait, consider adding fish to our daily dose of AREDS (age related eye disease study) supplements available over-the-counter from different manufacturers.  After all, there's no down side.  And besides, you're already eating fish for your heart & brain, right?  Don't forget to check the Amsler grid regularly.

Saturday, December 4, 2010

How to Avoid Your 1st Stroke

It's all in the mind of the beholder, but I can't think of too many conditions worse than having a stroke.  While I don't relish developing a dementing illness, I'm currently thinking that at least I wouldn't be aware (although clearly the suffering will be upon my family & caregivers).  But if I suffered a stroke, I'd be fully cognizant that I can no longer perform all the things that I can currently do but take for granted.  Not a very happy image.

So rather than treating a stroke (2o prevention) & preventing its complications (3o prevention), we really ought to try to prevent one from happening in the first place (1o prevention).  Obviously, there are some immutable risk factors which can't be changed/altered: age, sex, low birth weight, race/ethnicity, and family history.  But in the American Heart Association and American Stroke Association's newest guideline to be published next February, they review the evidence supporting modification of the following risk factors:

don't smoke/quit smoking
control blood pressure
control cholesterol (lower total & raise HDL)
control sugars
take anti-coagulant if suffering from atrial fibrillation
consider endarterectomy for asymptomatic carotid stenosis
avoid postmenopausal hormone therapy if possible
consider non-hormonal form of contraception if possible
alter diet to decrease sodium & increase potassium
limit alcohol consumption to <2 drinks/d for men and <1 drink/d for women
become physically active (at least 30min/d moderately intense activity)
avoid obesity
avoid/treat heart disease
treat sleep disordered breathing, eg wear your CPAP mask if you have sleep apnea

Now, don't get me wrong.  Some of these recommendations are controversial.  Plus there are other risk factors that are less well documented, but given the list above, I'd start there first before looking for more trouble.  Who knows?  But the stroke that's avoided may be yours & mine if we're so lucky.

Friday, December 3, 2010

5ARIs: An Ounce of Prevention vs A Pound of Cure

It has been said that "an ounce of prevention is worth a pound of cure".  However, the FDA holds the ounce of prevention to a higher standard than the pound of cure and posits that any side effects are intolerable in prevention since there's no guarantee that one will succumb to the potential condition that one is attempting to prevent.  Therefore, their Oncologic Drugs Advisory Committee just voted 17-0 with one member abstaining to reject finasteride as a chemoprophylaxis against prostate cancer.  They also voted 14-2 with two members abstaining against the use of dutasteride for the same proposed indication.

The background and premise certainly was tantalizing back in July 2003 when the Prostate Cancer Prevention Trial (PCPT) was published evaluating the 7yr effect of finasteride 5mg daily vs placebo randomized to 9,060 men w/PSA 3.0ng/mL.  In this particular population, the risk of low grade prostate cancer was reduced by 24.8% (absolute reduction from 24.4% on placebo down to 18.4% on finasteride) but at the cost of increase risk of high grade tumors (Gleason >7) from 22.2% on placebo to 37.0% on finasteride.  To add insult to injury, sexual side effects, eg loss of libido, erectiledysfunction, reduced ejaculate volume & gynecomastia, were more common in those randomized to finasteride (while lower urinary tract symptoms were more common in those randomized to placebo).  Several papers published since this original study have concluded that the increase in high grade tumors was a statistical anomaly and not likely the cause of finasteride.

Earlier this April, the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial was published evaluating the 4yrs effect of dutasteride 0.5mg daily vs placebo randomized to 6,729 men w/PSA 2.5-10 s/p negative biopsy.  The authors concluded that there was a 22.8% relative risk reduction in prostate cancer, similar to that of finasteride.  But likewise, there was a statistically significant increase in high grade tumors (Gleason >8), decrease/loss of libido, erectile dysfunction, decreased semen volume, gynecomastia as well as heart failure! 

In their wisdom, the advisory panel recommended the ongoing use of 5 alpha reductase inhibitors to treat lower urinary tract symptoms (where benefit exceeded risk) but against use to prevent prostate cancer (where risk exceeded benefit).  Sometimes that ounce of prevention just isn't worth it.

Thursday, December 2, 2010

Body Mass Index (BMI): When Is It Too High?

A few years ago, the CDC reported that, contrary to conventional wisdom, being overweight was ok, possibly even healthy, although they did agree that being obese wasn't good for you.  Obviously, this stirred up quite a bit of controversy.  First, you have to understand that, for statistical purposes, overweight & obesity are defined strictly by weight divided by height squared in the metric system so that the units for body mass index (BMI) come out as kg/m2.  Quite obviously, this simple calculation won't take into account those with more muscle and less fat, eg athletes, bodybuilders, etc.  However, think about how many muscular athletes & bodybuilders there are, at least compared to the US population.  So by and large, this calculation & definition using BMI works.

With that in mind, the authors of today's study did some fancy statistical analysis of 1.46 million baseline healthy Caucasian adults (why? because that's the data that they had to work with) avg 58yo with avg BMI 26.2 (overweight) and followed for 10yrs.  In the ladies, they noticed a J-curve with lowest all-cause mortality at BMI 22.5-24.9, increasing on either side as much as 2.5x for those with BMI 40-49.9 (morbidly obese).  Most important to note is the statistically significant 13% greater risk of death from any cause even in those with BMI 25-29.9 or overweight.  Morbidly obese men fared worse with risk almost 3x that of those with normal BMI.  The other point to notice is that being rail thin isn't healthy either.

It would appear that the CDC study was more likely a fluke since multiple studies have since demonstrated findings similar to today's publication.  For instance, one study published in August concluded that in those men with heart disease, BMI was similarly related to mortality with risk starting at 25kg/m2 and up.  Another study published that same month but analyzing over 424,000 participants, came to similar conclusion of increased cancer mortality for both overweight & obesity.  Back in March 2009, another study of over 890,000 participants avg 46yo followed for 13yrs demonstrated lowest mortality in normal BMI even after taking into account the usual suspects with mortality increasing at BMI >25kg/m2.

The moral of the post is this:  BMI is just like Goldilocks, who wanted everything just right, not too much, not too little.

Wednesday, December 1, 2010

Canada 3, IOM 1

 The controversy regarding the IOM's recent RDA for vitamin D isn't going to go away any time soon, not when our neighbors to the north plan to ignore it.  The Canadian Cancer Society, the Canadian Pediatrics Society, and Osteoporosis Canada have all come out against the absurdly low recommendations.  Instead, all 3 are united in pushing for high doses of vitamin D (anywhere from 800-2,000IU daily) to ward off chronic disease, including cancer.  It will be interesting to see if anyone else takes on the IOM.

Prostate Cancer: To Watch Or Not To Watch

If you knew that you had a cancer in your body, would you be willing to just "watch" it?  I think our gut reaction is to cut it out, irradiate it, take chemo, do something, anything.  Well a recent series of studies has been published that turns this thinking on its head.

In today's JAMA, the authors evaluated quality of life vs quantity of life.  More accurately, they assessed quality-adjusted life years (QALY) for active surveillance vs initial treatment in 65yo men with low-risk, clinically localized prostate cancer.  Compared to those who might have elected radical prostatectomy vs intensity-modulated radiation therapy vs brachytherapy, those choosing active surveillance enjoyed 11.07 QALY vs 10.23 QALY for surgery, 10.51 QALY for external beam radiation and 10.57 QALY for seed implants.  There was no mention of androgen deprivation therapy, which is typically offered for those with metastatic disease, and has recently drawn scrutiny due to its association with increased all-cause and cardiovascular mortality.

Before you go ballistic and toss virtual tomatoes at me, understand that the authors looked specifically at otherwise healthy 65yo men with localized low risk disease, eg PSA <10ng/mL, Gleason <6, and stage <T2a.  This calculation does not apply to either younger or older men or those with potentially more aggressive disease.

Well, we're pretty clear as to what's involved with surgery, external radiation & seed implants.  But what exactly is active surveillance?  In this model, the protocol consisted of physical examination, PSA measurement, and rebiopsy at 1yr after diagnosis and every 3yrs thereafter.  Active treatment/intervention with one of the other 3 options was performed at progression to Gleason score >7, other evidence of progression, eg PSA doubling time, or patient preference.

So who's crazy enough to watch & wait once a cancer has been diagnosed.  Well, consider the downside of treatment: impotence, eg erectile dysfunction, urinary difficulty, eg incontinence, and bowel problems, eg proctitis and incontinence.  For some men, the risk isn't worth the benefit.  But isn't this just a model?

Earlier this summer, a study of 6,849 men <70yo w/PSA <20ng/mL, Gleason <7 and stage T1-2 followed for 10yrs demonstrated 3.6% cancer-specific mortality in the surveillance group vs 2.7% in the curative intent group.  For those in the low risk group, cancer-specific mortality was 2.4% in the surveillance group vs 0.7% in the curative intent group.  More interesting was the other-cause mortality of 19.2% in the surveillance group vs 10.2% in the curative intent group.  In other words, the patients were 5-10x more likely to die with prostate cancer rather than from it.  So those authors deemed active surveillance a suitable option in this very narrowly defined population.

Last spring, authors followed 262 men <75yo w/PSA <10, Gleason <6 and stage T1-2a for 29mo and deemed active surveillance safe in this well defined group with low risk for clinical & systemic progression.

So is active surveillance for everyone?  Absolutely not!  But if you have the cojones to handle this and the psychological stress of waiting isn't going to give you an ulcer, then there appears to be plenty of evidence to support doing so.  In which case, you don't have to worry about erectile issues or incontinence.  After all, quality of life matters, not just quantity of life.  As always, it's a personal decision that must be made only upon review of all the information available with one's family & physicians.

Tuesday, November 30, 2010

Vitamin D 2010 RDA: IOM Lays An Egg

News flash!  The Institute of Medicine (IOM) just released their long awaited (13 years in the making) pronouncement regarding the recommended daily allowance (RDA) of vitamin D and calcium.  Many of us were waiting to see the RDA increased from 400IU daily to 1,000IU daily or even 2,000IU daily.  Maybe the IOM would even increase the upper limit of 10,000IU daily.

Instead, the IOM laid an egg.  That's my opinion (plus that of the Vitamin D Council).  Now, I make no claim as to being a vitamin D expert, although in my prior position as Senior Institute Physician and Executive Director of Physician Education at Cenegenics Medical Institute, I wrote 8 reviews regarding the benefit of vitamin D over the past 3 years.  However, I remember fondly the paraphrase attributed to Newton (who probably pilfered it from Salisbury) about standing on the shoulders of giants.  That's why, rather than re-invent the wheel, I direct you instead to the Vitamin D Council's response.  It's a great summary & rebuttal.

Q&A session at Avvo.com

I live in northern california and my doctor left her practice to work on an air force base. Now I am jammed up to find a Doctor. - Avvo.com

Q&A session at Avvo.com

I'm 16 years old and my boyfriend is 19. We had a bit of an accident and I may be pregnant. - Avvo.com

Q&A session at Avvo.com

Can an elderly person endure dangerous side effects from being medicated daily with multi drugs including 3 anti-depressants? - Avvo.com

Q&A session at Avvo.com

My mom is in her 70's and she is sometimes loses her balance or her hand or arm will just go limp and she drops things. - Avvo.com

Monday, November 29, 2010

Exercise vs Brain (Size & Function)

Exercise.  We spit it out like it's a 4 letter word.  Most of us loathe it.  Yes, there are the dedicated few who actually make use of their gym membership for which they have funds withdrawn painlessly every month.  But for the vast majority of the population, our physical activity consists of walking to the feeding trough to stuff our faces and pointing the remote control to change the TV channel.  Thank goodness for Wii, and now PlayStation Move & XBox 360 Kinect to get some of us off our bottoms.  I'm ranting about this since a recent study demonstrated that walking more was associated with greater brain volume and lower risk of cognitive loss.

The authors followed 299 adults (average 78 years old) who were free of cognitive impairment at baseline.  Brain MRI was performed at baseline & year 9 followed by reassessment of cognitive function at year 13.  All the while, they evaluated the amount of walking performed on a regular basis.  The range of walking varied from none to 300 blocks per week with an average distance of 56 blocks (or 8 blocks per day 7 days per week).  However, the authors concluded that one needed to walk 72 blocks weekly or 10 blocks daily without fail in order to preserve and actually increase brain volume.  This greater amount of gray matter was then associated w/significantly lower risk of cognitive impairment just 4 years later.

Take home point?  Physical activity is protective of brain function as we age which is imperative as our Baby Boomers reach retirement and the age at which risk of dementing illnesses increases dramatically.  But I can hear it now.  How long is a block?  Here in Las Vegas, the major street intersections are a mile apart (granted there are more frequent intersections in between).  But the authors did declare the 72 blocks equivalent to 6-9 miles. 

Now if this study isn't convincing enough to get you off your sofa, a study published in July came to a similar conclusion in women.  Likewise studies from August 2009, September 2008, July 2008, May 2008, and October 2006 all point towards the same conclusion that an increase in physical activity is associated with an increase in cognitive function & lower risk of dementia.  So that you won't later forget that you should have.

FDA Approves Underarm Application of Testosterone

The FDA just announced their approval of Axiron, a 2% topical solution of testosterone that is applied via metered dose pump at 30mg per actuation.  The plan is to apply 1 squirt to each armpit daily (more if necessary), wash hands & get dressed.  Yes, you still need to avoid skin-to-skin contact with your kids & partner.  You should also avoid bathing & swimming for at least 2 hours after application although, hopefully, you already completed the former prior to squirting yourself.  Whether you choose to apply deodorant or antiperspirant is up to you (and your close contacts!) as neither will affect absorption but they recommend applying either one before the testosterone.  And no, you don't have to shave (your pits).  But you might have to wait a while for it to actually hit the market.

In any case, you now have a wide choice of FDA-approved oral & buccal tablets, subcutaneous pellets, transdermal patches, injections, manually applied topical gels/creams, and now, metered dosing to the axilla.  Of these, the only ones I avoid are the oral tablets (due to increase risk of liver irritation) and subcutaneous pellets (difficult to obtain/maintain proper level & requires minor procedure for placement), but that's just me.

Yet Another Q&A session at Avvo.com

I've had a left side pain just above the waist, for several days. It's not a sharp pain, but it is there all of the time. - Avvo.com

Another Q&A session at Avvo.com

Weird pain under shoulder left side, near armpit on back side. - Avvo.com

Q&A from Avvo.com

What is the average testosterone level for a 58 yr. old man? - Avvo.com

Q&A from Avvo.com

How long is too long for hormone therapy for prostate cancer? - Avvo.com

Q&A from Avvo.com

Incontinence in men? - Avvo.com

Q&A from Avvo.com

i cant stop myself from urinating - Avvo.com

Sunday, November 28, 2010

HDL vs Chocolate

Just the other day, I reviewed a study looking at the benefit of high cocoa content chocolate on chronic fatigue syndrome.  Yesterday, I reviewed another study looking at the benefit of low carbohydrate caloric restriction on HDL levels.  In the skewed logic of my children, one might then ask whether high cocoa content chocolate might have an impact upon HDL.

In a small, short study published this month (and yes, I do review larger, longer studies, too), the authors randomized 12 participants with well-controlled Type 2 diabetes (average HgbA1c 6.4%) to placebo vs 15g three times daily of 85% cocoa content chocolate for 8 weeks, followed by a 4 week washout period, and then crossed over for a final 8 weeks.  This randomized double blind placebo controlled cross over study allowed each of the subjects to also serve as their own controls.  Parameters were checked at baseline, after the first 8 weeks randomization, after the 4 week washout & after the 8 week cross over.

The first bit of good news?  Despite adding 45g daily of chocolate, the participants did not gain weight, lose glycemic control, or worsen their insulin response.  More importantly, compared to their results from placebo, the consumption of high cocoa content chocolate increased HDL from 1.16mmol/L (45mg/dL) to 1.26mmol/L (49mg/dL) & lowered cholesterol:HDL ratio from 4.4 down to 4.1, both statistically significant findings. In fact, this 10% increase in HDL is equivalent to the results obtained from less tasty pharmacologic assistance.

What's this mean for our patients with T2DM?  Conventional wisdom has always stated that diabetics should avoid candy but this study throws that thought out the window.  High quality, eg 85% cocoa content, chocolate in moderation (15g three times daily) can be a healthy adjunct to their meals.  Given what we know about all the other benefits of this type of chocolate, there's really no reason to avoid it unless you're allergic.  In the meantime, I'll see if I can find a large, long-term study of low carbohydrate caloric restriction vs chronic fatigue syndrome.  But don't hold your breath!

Testosterone vs Heart Failure

Click here for April 19, 2012 update!

I mentioned in an earlier post that I was attending a CME conference last week. One of the lectures covered evidence-based, state of the art care of patients with heart failure. The presenter reminded us that ACE inhibitors, beta blockers & aldosterone antagonists, separately and in combination, have been demonstrated to improve heart failure mortality. He also reviewed evidence that the benefit from beta blockers is not a class effect since there are real differences between the individual drugs. Cardiac resynchronization therapy plus implantable cardioverter-defibrillators has also been demonstrated to improve outcomes.

All told, he pointed out a 77% cumulative risk reduction if all four of these therapies were applied with 27% absolute risk reduction. This translates into treating only 4 persons in order to save 1. Given that heart failure exacerbation is one of the leading causes of (re)hospitalization and that hospital care accounts for the greatest percentage of medical costs, it's clear that we need to be more aggressive in optimally treating our patients with heart failure.

However, he also pointed out that current ACC guidelines do not recommend hormonal therapies other than to replace deficiencies. Based upon the preponderance of new information, I have to disagree. For instance, in a study published just last month, researchers randomized 36 elderly women with stable heart failure (NYHA III without hospitalization in immediate past 3 months with 33% ejection fraction) on maximal medical management to either testosterone transdermal patch (300ug twice weekly) or to placebo and followed them for 6 months.

Those who received testosterone walked further in 6 minutes (standard testing protocol), increased their maximum oxygen consumption (that's a good thing), and strengthened their legs.  If you ask me, that's a touchdown or home run, especially when your average age is 68-69yo.  Even better, no side effects were reported from this dose besides minor allergic dermatitis, common to all patch delivery systems.

Not surprisingly, these findings are consistent with those published last September in which 70 elderly men (average 70yo) with heart failure (NYHA II or III with 32% ejection fraction) responded to intramuscular testosterone for 12 weeks on top of maximal medical management.  They, too, demonstrated improvement in exercise capacity, muscle strength, and even glucose metabolism.  And just as important, the therapy was well tolerated.

In January 2006, 76 men (average 64yo) with heart failure (NYHA II-IV with 32% ejection fraction) were randomized to receive Androderm 5mg daily vs placebo for 12 months.  The authors reported significant improvement in functional capacity as born out by decrease in NYHA classification.  The only issue noted was intolerance to the patch.

Finally, a study in May 2003 demonstrated in 12 men with heart failure that testosterone 60mg via buccal mucosa increased cardiac output immediately.

Now, I'm not suggesting that everyone with heart failure go out and start taking testosterone.  However, I think that the research thus far points to a need for a larger scale study of longer duration to confirm/disprove these consistent results using a very inexpensive drug.  And in the meantime, for those of you waiting for the outcome of said study, perhaps you can discuss the above findings with your cardiologist or primary care provider.