AIM-HIGH Hits Low & Misses Target

Thanks to Dr. Peter G for pointing this out to me.  Last Thursday, the National Institutes of Health and its National Heart, Lung & Blood Institute announced the premature stoppage (18 months early) of its Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health (AIM-HIGH), aimed at studying the effect of 2,000mg daily of Niaspan brand of niacin in those patients with optimized LDL cholesterol (40-80mg/dL) on simvastatin +/- ezetimibe.  The 3,414 participants followed for 32 months were 64yo on average w/most also having diabetes, heart disease & hypertension.

Several thoughts came to mind as I read over the scarce information available in their press release.  First, don't assume anything.  As we were taught in medical school, assumptions make an a-- out of you and me (if you don't get this, look carefully at the spelling of assume).  So while heart attack risk has been inversely correlated to HDL in those w/optimized LDL, there have been no studies demonstrating any benefit from purposefully raising HDL.  Again, we only have observational data but nothing causative.

Second, just because it didn't work in this instance doesn't mean it won't work in another.  Now, I'm sure that will be the spin from Big Pharma.  But in fact, we've had to learn the hard way from studies like Women's Health Initiative and others that what's good for one specific group can't always be generalized to the public.  So perhaps, using niacin to raise HDL doesn't work in those w/pre-existing disease but might work in those without.

Third, perhaps they didn't raise HDL enough.  But that's pure speculation & BS on my part.  The press release reported that HDL was raised 22% on average but it didn't mention baseline HDL.  This was just a press release and, as such, has not been published in a peer-reviewed journal.  However, with a bit of sleuthing, I was able to find a description of the trial which noted inclusion criteria if HDL <40mg/dL in men & <50mg/dL in women.  With observational data, we tend to consider HDL normal when it is 40-59mg/dL, which implies average risk of heart disease; HDL is considered cardioprotective when >60mg/dL so perhaps we shouldn't have expected any benefit since HDL would only have increased from 39mg/dL to 47mg/dL at best.  Only time will tell when the complete data is published.

So what are we to do at this point?  Especially considering a slight increase in ischemic stroke . . . As always, do your research and have an in-depth conversation with your family physician so that you can make a decision that is best for your individual situation.

Thank You to Our Military

The Soldier: - By Charles M. Province

It is the soldier, not the reporter, who has given us freedom of the press.
It is the soldier, not the poet, who has given us freedom of speech.
If you can read this message thank a teacher,
If you are reading it in English of your own free will THANK A SOLDIER!
It is the soldier, not the campus organizer, who has given us the freedom to demonstrate.
It is the soldier, not the lawyer, who has given us the right to a fair trial.
It is the soldier, who salutes the flag, who serves under the flag, and whose coffin is draped by the flag,
who allows the protester to burn the flag.
To all the brave men and women who have dedicated or given their lives
to protecting this country and it's freedoms:
Thank you.

On this Memorial Day, I would like to take the time to acknowledge & thank all those whose personal sacrifice allows me to write what I wish and worship who, when & where I please, all without fear of reprisal.  I am also forever grateful to all the families who have sacrificed on all our behalf, especially those with children growing up without their mothers & fathers present and those raising children without their spouses.  We owe you a debt of gratitude which can never be fully expressed or repaid.  Thank you.

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Lungs & Bladder: What's the Link?

The good Lord must have had a funny sense of humor when he put Adam & Eve together.  Little did we know that S/He connected our lungs to our bladder!

How's that again?  In a nested case-control study published earlier this week in the Archives of Internal Medicine, amongst both men & women with chronic obstructive pulmonary disease (COPD), those who used inhaled anticholinergic drugs, whether short-acting or long-acting, had an increased risk of developing acute urinary retention severe enough to require hospitalization, same-day surgery, or an emergency department visit, compared to non-users.

Men with an enlarged prostate (benign prostate hyperplasia or BPH) had an even greater risk, which makes sense given the obstructive issues associated with BPH.  Worse, men who required the use of both short-acting and long-acting inhaled anticholinergic drugs to control their COPD symptoms had greater risk of acute urinary retention compared to those men who were taking one or the other, or none at all.

So now we have to choose between breathing a little bit more easily versus being able to empty our bladder adequately?  Well, that's where we, as family physicians, come in.  We're trained to look at the person as a whole, not just as individual organ systems independent of each other.  After all, how many patients live with just one chronic disease in isolation?  Most have two or more!  So family physicians (and geriatricians) take the time to involve the patient in his/her health decision making process after discussing the various risks, benefits & alternatives.  We just have to remember to add acute urinary retention to the list when we talk with our patients w/COPD.

Atrial Fibrillation Not So Benign For Women

Atrial fibrillation (AF) occurs when the heart loses it's pacemaker or symphony conductor, so to speak.  This loss manifests itself in a widely varying heart rate, often described as irregularly irregular.  The heart speeds up & slows down of its own accord w/o any rhyme or reason.  Unless one's heart rate becomes unreasonably fast which is then noticeable as racing beats, palpitations, or fluttering in the chest, or becomes unreasonably slow which is then noticeable as fatigue and/or (pre)syncope, it can often escape notice for quite some time.

AF is also associated with a not insignificant loss of cardiac efficiency, known as ejection fraction.  However, up until this week, what's most worrisome about AF is that it dramatically increases one's risk for stroke.  Luckily, this risk can be mitigated by proper anticoagulation, typically w/oral warfarin.  In fact, there are several online calculators available to determine both stroke risk from AF (CHADS2 & CHA2DS2VASc) and bleeding risk from warfarin (HAS-BLED).

So why the fuss & preamble?  In another analysis of the Women's Health Initiative published this week in JAMA, after following 34,722 predominantly Caucasian women, average age 53 years old, all free of AF & cardiovascular disease at baseline for median of 15+ years, the authors concluded that new onset AF was associated with an increase risk of all-cause mortality, cardiovascular mortality & non-cardiovascular mortality, at least double that of those without AF.

While the overall risk of developing AF is low, the fact remains that upon diagnosis, one's mortality increases substantially.  While this study makes no conclusions as to cause & effect and while there is no proof of any ability to modify mortality once AF is diagnosed, there is no reason not to aggressively prevent stroke & cardiovascular events from occurring.

Fluke or Trend: Coffee vs Prostate & Other Cancers

Also published 2 weeks ago was a prospective study of 47,911 men in the Health Professions Study followed for at least 20 years.  While the average consumption was just under 2 cups of coffee/day, those who drank >6 cups/day had an 18% lower risk of developing prostate cancer compared to nondrinkers.  And while there was no association between coffee and low grade prostate cancer, those who drank >6 cups/day had a 60% reduction in prostate cancer mortality compared to nondrinkers.

What's this mean for you & me?  Well, remember that this is the first study demonstrating a link, so perhaps this is just a statistical fluke.  On the other hand, in a cohort study published over 2 years ago, a cup or more a day of coffee amongst 38,679 Japanese was associated w/49% reduction in oropharyngeal & esophageal cancers.  Published late last fall, the large-scale cohort study, European Prospective Investigation into Cancer & Nutrition (EPIC) took 8.5 years of follow up to find 343 cases of brain cancer, specifically glioma along w/245 cases of meningioma.  Compared to controls, those who drank more than 100mL of coffee daily had a 34% lower risk of developing cancer.

In contrast, in a study published last summer, there was no difference in colorectal cancer rates between those who drank at least 6 cups of coffee per day compared to those who drank no coffee.

So if you don't already drink & enjoy coffee, I'd wait for another study to come out before purposefully starting to drink coffee for some purported benefit.  But if you do enjoy your morning cuppa joe, then feel free to continue doing so.

Fluke or Trend: Coffee vs Breast Cancer

Some days coffee is good for you, other days, it's not.  The pendulum has recently swung in favor of coffee consumption with a series of studies published demonstrating an association between more coffee and lower cancer risk.  Of course, the devil is in the details because coffee has a multitude of antioxidants, the amounts of which vary depending upon brewing method, and because cancer is not just one homogenous disease process.

With that in mind, a case-control study was released 2 weeks ago comparing 2,818 Swedish women with breast cancer to 3,111 without.  The authors concluded that drinking >5 cups of coffee daily was associated with 20% reduction in overall breast cancer risk and with 57% reduction in estrogen receptor negative breast cancer as compared to those who drank <1 cup/day.

In a study published last fall, the authors followed 64,603 Swedish men & women for 15 years and determined that those women who drank >4 cups of boiled coffee daily had a lower risk of developing breast cancer compared to those who drank <1 cup/day.  But again, it's important to analyze the details.  Specifically, the authors found that premenopausal filtered coffee drinkers had an increased risk of breast cancer while postmenopausal filtered drinkers had a decrease risk.  The study also looked closely at method of brewing and noted that overall, boiled coffee appeared to more protective than filtered coffee, the former having higher levels of antioxidants than the latter.

And in the spring of 2009, authors completed a meta-analysis of 9 cohort & 9 case-control studies that met strict inclusion criteria and concluded that drinking at least 2 cups of coffee daily might decrease breast cancer risk.

So what's the take home point, especially given the tendency of our daily newscasts to vacillate with the study du jour?  There appears to be a trend towards benefit from coffee consumption, especially more of the really strong stuff.  But remember that all these studies only demonstrate an association and therefore are good for developing hypotheses.  Given our limited knowledge, I'd recommend drinking coffee because you like it, not because you want to prevent breast cancer.  And don't forget Goldilock's approach.  Avoid drinking so much as to give yourself palpitations & tremors!

Sloth vs Hummingbird: Who Will Be the Survivor?

Sloths are known for taking it easy and just hanging around, presumably with a relatively low metabolic rate in light of their relative inactivity.  A lower metabolic rate would probably only be found in a hibernating bear.  On the other hand, hummingbirds are known for their high metabolic rate as they flap their wings at incredible speeds in order to stay aloft. In humans, our metabolic rates can vary dramatically depending upon whether we're active or not and whether we're hypothyroid, euthyroid or hyperthyroid.  In fact, our caloric intake can affect our metabolism as noted by those who recommend an ultralow caloric intake which appears to improve markers of lifespan.

In a study to be published next month, the authors followed 652 healthy, non-diabetic Pima Indian volunteers for over a decade after measuring resting metabolic rate (RMR) or 24 hour energy expenditure (24EE).  Their conclusion?  Higher metabolic rates, whether measured by RMR or 24EE, was associated with greater mortality.  The authors questioned how a faster energy turnover could accelerate aging as determined by mortality?  Perhaps from increasing oxidative stress?

Clearly this study opens up a can of worms since all other studies have demonstrated decreased mortality in patients w/more muscular body composition consistent w/increased RMR & 24EE, whereas obesity, and thus decreased RMR & 24EE, has been associated w/increased mortality.

The take home point from this study is that we don't have all the answers, just more questions.  But for now, I would consider this result a fluke rather than a trend.

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Say Goodbye to Rosiglitazone aka Avandia

Well, it's finally happened, and none too soon.  After study after study since 2007 pointed towards a greater risk of negative outcomes compared to its competitor, the FDA is finally pulling the plug on rosiglitazone, sold here in the States as Avandia, as of this coming November.  Interestingly, it won't be completely banned from use, but so many restrictions will be placed on it that the effect will be essentially the same.

So why do I feel so different about rosiglitazone as compared to acetaminophen?  As I mentioned yesterday, there's only one study linking acetaminophen to cancer, as opposed to it's well known liver toxicity when consumed in excess.  Plus, it is the only non-aspirin anti-pyretic.  In other words, while both can lower fever, acetaminophen stands in a class of its own, different from the many examples of non-steroidal anti-inflammatories, including aspirin & ibuprofen.

On the other hand, rosiglitazone has a competitor, pioglitazone, in its class, which is capable of doing all the things that rosiglitazone can do but with less risk.  Granted the side effect profile is the same, eg liver toxicity & fluid retention.  However, pioglitazone tends to raise HDL cholesterol rather than lower it and no increase in heart attack rates, congestive heart failure exacerbation, or mortality has been associated with it, unlike rosiglitazone.

Just in case you've failed to respond to pioglitazone but have done well on rosiglitazone, all is not lost.  Your physician just has to document as much and that you've been advised of your increased risk for a heart attack, exerbation of congestive heart failure, and/or death.

But let's not forget that the real solution is low glycemic nutrition & regular exercise, both aerobic & resistance.

Acetaminophen vs Cancer: What's the Link?

Sex sells.  So does sensationalism.  I'm sure many of you have already read about a new study just released that concluded that acetaminophen use is linked to hematologic cancers.  But so what?  It's an epidemiologic study that is useful in developing hypotheses.  It doesn't prove cause & effect.  It doesn't matter that the authors followed 64,839 patients 50-76 years old for 6-8 years.  It doesn't matter that no link was found between hematologic cancers and non-steroid anti-inflammatory use, aspirin included.

This type of journalism only serves to frighten & alarm the public while discrediting the medical profession when the next study presumably demonstrates no causal relationship such that we'll be accused once more of flip flopping & vacillating.

Will I continue to use acetaminophen when indicated?  You bet!  Will I worry about its well known & well documented liver toxicity when used in excess?  Absolutely.  As with all meds, remember my Goldilocks theory.  Use the right amount for the right reason; avoid using either an inadequate amount or an excessive amount, especially for the wrong reason(s).  Let's be sure to get more information before we pull this medication off the shelf!

Hormone Deficiencies vs Bone Mineral Density

We've known for a while that growth hormone deficiency (GHD) and sex steroid deficiency are individually associated with low bone mineral density (BMD). 

In a study published this month in the Journal of Clinical Endocrinology & Metabolism, the authors analyzed the 15,000+ GHD patients from 31 countries being followed in the KIMS database and found 1,218 men & women who had not yet received growth hormone replacement.  They then analyzed these patients' BMD and sex steroid levels.  Not surprisingly, in those GHD patients who had lower IGF-1 & sex steroid levels also had lower BMD. 

Individually we have studies demonstrating an increase in BMD when GHD patients are given growth hormone and when sex steroid deficient patients are given sex steroids.  What we're lacking is a study that demonstrates benefit from giving both growth hormone & sex steroids to those patients deficient in both.  Somehow I doubt that the findings from such a study are going to surprise any of us.

How to Prevent Alzheimer's Disease

It's been an amazing 10 months since I was first asked by the AAFP to develop a presentation on the latest research in Alzheimer's disease and then given the opportunity to present my findings at several state chapter meetings since then.  One of the first things that was reinforced was the concept of a deadline, such that once that date came & went, I was not allowed to change or update my presentation.  However, as you all know, a deadline doesn't stop the advancement of medicine, at least not if you review my posts regarding the latest research into dementia.  So oftentimes, I have had to talk about the latest research just published w/o benefit of any reference material.

When it comes to publishing a study, that same deadline concept applies.  So while it may have been disconcerting to recently hear on television and read in your newspaper that there's nothing that we can do to prevent Alzheimer's disease, please keep two points in mind.  The review study published last week in Archives of Neurology was based upon data reviewed & discussed during that NIA conference last  April 2010.  Much has been uncovered since then.

More importantly, while the conclusion was "insufficient evidence exists to draw firm conclusions on the association of any modifiable factors with risk"", the data analysis was congruent with what we've known for quite some time:  "Diabetes mellitus, hyperlipidemia in midlife, and current tobacco use were associated with increased risk of AD, and Mediterranean-type diet, folic acid intake, low or moderate alcohol intake, cognitive activities, and physical activity were associated with decreased risk."

Admittedly, the evidence may not reach the gold standard of randomized, double blind, placebo controlled trials, but I'll take what I can get for now.  Besides, there's no downside to any of these lifestyle recommendations.  At the very least, they'll minimize your risk for heart attack & stroke, which is always a good thing!

Bisphosphonates & Atypical Femur Fractures: Part 4

Earlier this month, the New England Journal of Medicine jumped into the growing controversy in osteoporosis management by publishing a case-control study that concluded that (current) use of bisphosphonates increased one's risk of atypical femur fracture by almost 50 fold.  With such a dramatic increase in risk, many of the major news outlets had to weigh in, including USA Today.

However, as usual, the devil is in the details and what was left out of the sensational reporting is the relative infrequency of these atypical fractures.  In fact, use of bisphosphonates would lead to an additional 5 atypical fractures for every 10,000 patient-years of use.  Put another way, we'd have to treat 2,000 patients in order to harm 1 (also known as number needed to harm).

On the other hand, the number of patients needed to be treated in order to prevent just 1 typical osteoporotic fracture is dramatically less.  In other words, use of bisphosphonates in patients w/osteoporosis is of net benefit.  However, the same cannot always be said for those w/osteopenia or low bone mass.

So know the strength of your bones before you start the medication.  In fact, to be sure that you really need this medication, ask your doctor to use the WHO Fracture Risk Assessment Tool, FRAX, to calculate your 10 year risk of sustaining an osteoporotic fracture after measuring your bone mineral density via DXA (dual energy xray absorptiometry).  Those who are osteoporotic with a T score < -2.5 warrant therapy while those who are osteopenic w/T score between -1 and -2.5 warrant therapy if their 10 year probability of a hip fracture is > 3% and/or their 10 year probability of any major osteoporotic fracture is > 20%.  Be sure your calculation is based upon data appropriate for your ethnicity!

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Wake Up Stroke: Now What Do You Do? Part 2

Remember yesterday's post regarding wake up strokes?  One of the major issues is the inability to determine how much time has elapsed since the start of the event (obviously because it happened while one was asleep).  Without any way to determine elapsed time, emergency department & stroke center physicians are unwilling to take the chance to offer this specific subset of patients thrombolytic therapy (clot busting drugs) out of fear for turning an ischemic event into a hemorrhagic one.  As a result, as noted in a study published online last week, the authors concluded that those patients who suffered a stroke while asleep had worse outcomes.

But here's the rub:  you need to get to the emergency department to get evaluated.  Don't be like the majority of stroke victims in a recent survey published last week who called a friend or family member rather than 911 when they noted FAST symptoms.  Why?  Perhaps they hoped the symptoms would resolve on their own or they thought the symptoms were not a big deal.  But if you ask me, sudden onset of facial asymmetry, lost of arm or leg function, and/or dysarthria would be a dramatic concern.  Maybe that's because I'm a family physician.  But any, even one, FAST symptom should raise an alarm in you to call 911 immediately.

Wake Up Stroke: Now What Do You Do?

I can't believe that we're already a third of the way through the month but it turns out that May is National Stroke Awareness Month, which explains the number of studies that have been published of late looking at this devastating disease.  

For a quick review, how many of you remember the FAST (face, arm, speech & time) mnemonic?  Should you be so unfortunate as to notice any of these symptoms, you need to get thee to an emergency department or stroke center immediately. 

If you can get evaluated within 3-4.5 hours of onset of stroke symptoms, you have a better change of receiving thrombolysis (clot busting drugs). 

But what if you wake up with one of the FAST symptoms?  How much time has elapsed since your stroke started?  You can't tell because it started while you were asleep!  Which means you probably won't be given thrombolytics out of fear for converting an ischemic stroke (think clogged pipe) into a hemorrhagic one (think burst pipe).  And if you don't get a clot busting drug, your long-term outcome isn't as good.  

This is exactly what the authors noted in a study published this week in which 14% of the stroke victims presenting to the emergency department woke up with stroke symptoms.  One solution, as proposed by cynics to prevent a stroke, is to avoid going to sleep!  Of course, that's not practical.  But why go to the emergency department if it's not likely that you'll receive optimal (thrombolytic) therapy?  Because we need to evaluate what caused the stroke in order to minimize the risk of another stroke occurring. 

If you're lucky enough not to have had a stroke, now would be a good time to review my December 4th and February 3rd posts regarding how to prevent strokes.

Exercise vs Diabetes: Aerobic, Resistance or Both? Part 2

Memory starts to fade as Thanksgiving was almost half a year ago.  I mention this because back in November, a randomized controlled trial (RCT) was published concluding that only a combination of aerobic exercise & resistance training was able to lower a diabetic's HgbA1c, the  running 3 month measure of sugar control.

In an attempt to weed out flukes & look for trends, a meta-analysis was published last week in JAMA, concluding that structured exercise was more effective at lowering HgbA1c than exercise advice, after culling 47 RCTs from 4,191 articles, by excluding those of shorter than 12 weeks' duration.  Specifically, physical activity of greater than 150 minutes/week was twice as effective at lowering HgbA1c compared to exercise programs of less than or equal to 150 minutes/week.

Lest you feel bad about only leading the horse to water but not making him/her drink, physical activity advice plus dietary advice was associated w/better sugar control compared to those who did not receive any encouragement.  So don't give up hope.  Just like continuing to encourage tobacco cessation at each outpatient visit in those who smoke, it's imperative that we encourage our patients w/diabetes to exercise & eat wisely.  Hopefully, we can then congratulate them when they actually take it upon themselves to become physically active more than 30 minutes/day, 5 days/week.

Levothyroxine & Fractures: Too Much of a Good Thing . . .

Remember my Goldilocks theory of medicine?  You want just the right amount, not too much and not too little.   In a nested case-cohort study published last week in BMJ, the authors concluded that levothyroxine dose is associated w/osteoporotic fracture in the elderly after following 213,511 patients >70 years old who were either currently taking, or had remotely taken, levothyroxine.  They noted that those on high (>93mcg/d) and medium dose (>44mcg/d but <93mcg/d) had more than 2-3x risk of fracture compared to those taking low dose (<44mcg/d) of levothyroxine.

One downside to the study, which the authors acknowledged up front, was their inability to ascertain the patients' TSH.  In other words, dose alone is not the final parameter for treatment of hypothyroidism but rather TSH within the normal range (again neither too high nor too low).  Admittedly, the higher one's levothyroxine dose the greater one's risk for iatrogenic hyperthyroidism.

The take home point is not to stop taking levothyroxine but rather to continue to monitor one's TSH even after years of taking the same dose, especially since one's physiologic requirement for levothyroxine decreases with age.  By the way, don't forget to take your levothyroxine on an empty stomach at night!  And don't forget your calcium & vitamin D, too, to maximize bone strength - just remember to take these at a different time than your levothyroxine!

Fluke or Trend? Calcium vs Heart Disease

Semmelweis.  Marshall.  Bolland?

It takes a lot of courage to go up against the establishment.  Semmelweis did this back in the 1840s to prove that washing hands would decrease puerperal fever (maternal-fetal mortality).  More recently, Marshall did this in the 1980s to prove that H pylori is the cause of peptic ulcer disease.  Now it appears that Marc Bolland and the BMJ have taken up the sword to convince all of us that too much calcium increases our risk of cardiovascular disease.

Back in February 2008, Bolland & his team noted that calcium supplementation was associated with greater risk of myocardial infarctions after randomizing 732 healthy postmenopausal New Zealand women to calcium & 739 to placebo, neither of whom received any vitamin D, over 5 years.

Then last July, Bolland & colleagues arrived at the same conclusion after performing a meta-analysis of 15 trials involving 8,151 female participants followed for close to 4 years.

Most recently, Bolland et al stirred up the hornet's nest last month by again associating calcium supplementation with cardiovascular events, regardless of whether or not vitamin D was consumed, after reviewing the available data from 16,718 female participants of the Women's Health Initiative study.

So are Bolland's findings a fluke or trend?  After 3 separate studies, it's difficult to dismiss his claims and renounce all calcium.  However, I'm concerned that he's the only one leading the charge (and that the BMJ is the only publication getting this into print).  I'll be more of a convert once others have been able to duplicate his findings - call me cynical but I've heard all too many false research findings announced as ground breaking news in our scientific assembly only to be denounced later on by their colleagues.

Fluke or Trend? Omega 3 Fatty Acids vs Prostate Cancer

When it comes to new, anomalous findings, it's best not to change medical strategies abruptly but rather to wait for confirmation.  In other words, we look for trends, rather than change on a whim based upon a fluke.

Case in point is the relationship between omega 3 fatty acids (most commonly found in fish) and prostate cancer.  Just last week, a case control study was published linking high levels of docosahexaenoic acid (DHA) to prostate cancer, quite contrary to what numerous previous studies have concluded.  The authors found 1,658 participants from the Prostate Cancer Prevention Trial who had actually developed prostate cancer over 7 years of observation and compared them to 1,803 controls matched for age, treatment & family history.  They then analyzed serum omega 3 fatty acids, omega 6 fatty acids, and trans-saturated fatty acids.  Because of all the well known benefits associated w/omega 3 fatty acids, the authors were not expecting to find DHA associated w/high grade prostate cancer.

But as one of my patients asked me, does this study mean that he should stop taking his (high dose) fish oil supplements?  In other words, is this finding a fluke or a trend? It turns out that back in November, three other authors concluded that fish consumption was associated w/63% reduction in prostate-specific mortality after performing a meta-analysis of 12 case-control studies involving 5,777 cases & 9,805 controls.  Similarly, an April 2009 case-control study demonstrated that consumption of dietary omega 3 fatty acids was associated w/decreased risk of aggressive prostate cancer after comparing 466 cases of aggressive prostate cancer to 478 age- & ethnicity-matched controls. An even earlier case-control study published in July 2007 also came to a similar conclusion that higher serum omega 3 fatty acids are associated w/lower risk of prostate cancer after comparing 476 cases to 476 controls.

So what are we to make of this latest study?  First, case-control studies are relatively weak forms of evidence upon which to base medical therapy.  Just like observational & epidemiologic studies, they're good for demonstrating association but not causation.  Therefore, they're most useful in generating hypotheses rather than directing therapy.  And given the preponderance of the data, I would posit that this latest finding is more fluke than trend.  Personally, I'm sticking w/my fish oil supplements.

Fluke or Trend? Salt vs Blood Pressure

Before you jump up & change your regimen with the latest whim published as scientific research, ask if the data is applicable and generalizable to you.  In other words, studies demonstrating that mammogams save lives probably don't apply to men.  Likewise, studies looking at PSA screening probably don't apply to most women.  This is pretty obvious, right?

But what about a new study published yesterday in JAMA in which the authors conclude that dietary salt restriction isn't necessary.  Does it mean that we can all go out & celebrate w/potato chips & lots of processed foods?  Probably not!

The authors followed for 8 years 3,681 participants w/o heart disease who had all been originally enrolled in 2 European studies.  Among the 2,096 w/o baseline HTN who were followed for 6.5 years, blood pressure was not associated with sodium excretion (and therefore dietary intake).  In fact, HTN developed in the same number of patients regardless of sodium excretion, which did not change over time, while blood pressure increased steadily.

So back to my original question:  is this study generalizable to you & me?  For instance, are you a Caucasian of European descent as were the participants in this study?  Not me!  Plus I'm already a decade past the average age of the participants.

Let's not forget that multiple studies have demonstrated outcome benefits from dietary sodium restriction in both men & women of all ages & ethnicities.  This study is the first to come to a completely different conclusion.  So while I may sneak an occasional potato chip, you won't find me eating processed foods or reaching for the salt shaker anytime soon.

Health Literacy: Does It Matter? Part 2

Based upon Monday's post, health literacy matters in obtaining better outcomes in heart failure (just like Wall Street uses terms like equities & asset allocation rather than stocks & diversification to help us investors reach our goals).  But when you think about it, health literacy is a higher order of understanding based upon, at the very least, basic English comprehension & literacy.  Sure it's up to those of us in the medical profession to explain difficult concepts without condescension (that's why I like analogies - for instance, glucose = speedometer, insulin = tachometer, and Hemoglobin A1c = average speed - however, it also helps if you're a gearhead, like me) but typically we use English as our language of choice, not one of more than 300 languages spoken in our country.

But what about those of us for whom English is not our native tongue?  What about those of us who have not yet had a chance to become proficient in reading, speaking & understanding spoken (American, not Australian, British, or New Zealand), much less, written English?  In a retrospective cohort study of 1,257 children less than 18 years old published online this week, it turns out that those w/parents w/limited English proficiency stayed in the hospital longer (average 6.1 days) than those whose parents spoke English well (average 4 days).  At $2,500/hospital day in the facilities studied, this leads to an increased cost to society of at least $5,000 per child per stay.  

Given that 1 in 5 residents speaks a language other than English at home, half of whom acknowledge limited English proficiency, the additional cost to our society is tremendous, especially in a time when Nevada is contemplating drastic cutbacks in funding for our elementary & high schools as well as our universities & medical school.  Lest I am misunderstood, I write this not from a xenophobic perspective but rather to urge our legislatures to think ahead about the potential repercussions of their budget cuts and instead to invest in our future, our children.  If our children don't get the education they need, our grandchildren may very well end up staying in the hospital far longer than necessary.

New Kid on the Block: Linagliptin (Tradjenta)

Never be the first to prescribe a new medication, but never be the last either. Despite Big Pharma's attempt to induce us to prescribe the newest & latest, too often me-too drugs, we teach our resident physicians to look deeper for meaningful reasons, eg outcomes that matter, to switch.  For instance, LDL lowering isn't enough - we want to see a decrease in cardiovascular events & mortality.

I mention this because the Food & Drug Administration just approved linagliptin (Tradjenta), another dipeptidyl peptidase-4 (DPP-4) inhibitor, for treatment of type 2 diabetes.  This latest drug is the 3rd in the class started by sitagliptin (Januvia) in 2006 and joined by saxagliptin (Onglyza) in 2009.  The beauty of this class is that the risk for hypoglycemic is low when used by itself or in combination w/metformin or a glitazone, eg pioglitazone (Actos) or rosiglitazone (Avandia).

These DPP-4 inhibitors work by inhibiting the breakdown of incretin.  Higher incretin levels thus leads to both lower glucagon & higher insulin levels, both of which lower glucose and tend to delay gastric emptying.  Alternatively, one can increase incretin by injecting either exenatide (Byetta) or liraglutide (Victoza).

The good news for our patients w/diabetes is that they have many options from which to choose to assist them in lowering their blood sugars and minimizing their risk for dying early or suffering from heart attacks, strokes, kidney failure, amputations, and erectile dysfunction.  However, as providers, we have to look long & hard to see if new therapies have any decided advantage over (slightly) older options, which by now have hopefully demonstrated safety.

So never be the first but never be the last to prescribe a new medication.  But above all else, do not harm.