Menopausal Symptoms vs Breast Cancer

Continuing the theme of breast cancer, a recent population-based case-control study looked at the presence & severity of menopausal symptoms compared to the later development of breast cancer.  Interestingly, they noted that those women who suffered from menopause and especially those who reported severe symptoms (presumably due to a dramatic decrease in estrogens) had a lower risk of developing breast cancer, regardless of whether or not they started hormonal therapy (!) and regardless of the timing of hormonal therapy (contrary to the study reviewed yesterday).  Granted, this study is good for demonstrating an association and for development of hypotheses, but it is of no use for stating causality.  

So why mention this study?  Mainly to show that well intended researchers looking over (different) data can come to different conclusions.  Also, perhaps our patients can re-interpret their symptoms given the positive outlook further down the road.

New Data Upends Timing Hypothesis

When the Womens Health Initiative came out almost 9 years ago, it really upset the traditional apple cart regarding the use of hormonal therapy to prevent heart disease.  Overnight, prescriptions & sales of estrogen/progestin products to combat menopausal symptoms went down the drain.  During the ensuing years, the pendulum has swung back towards the midline, as we've moved towards prescribing smaller doses for shorter periods of time.  Part of the swing has been due to subgroup analyses, discussions over bio-identical hormones vs non-bio-identical (still not an accepted & recognized portion of traditional medicine's lexicon), and to development of the timing hypothesis.

Specifically, the timing hypothesis addressed what appeared to be a decrease risk of cardiovascular disease in those women who received hormone replacement soon after entering the menopause, as compared to those who didn't receive any hormone replacement until they were at least 10 years out from menopause (and presumably completely asymptomatic at that time).

However, in a paper just released by the Journal of the National Cancer Institute to be published next month, a review of data from the United Kingdom's Million Women Study concluded that women who started hormone replacement therapy (either estrogen alone or estrogen + progestin) within 5 years of entering menopause had a significantly higher risk of developing breast cancer compared to those who started more than 5 years post-menopause.

The above findings relating to time of initiation are similar to those from a French cohort published almost 2 years ago.  Of note, when they specifically looked at those women who received progesterone, there was no increase risk of breast cancer compared to those who received other progestins.  Interestingly, the Million Women data also demonstrated an increase risk of breast cancer in those who received combination estrogen + progestin therapy compared to those who received estrogen alone.  This makes one question the effect of the non-bio-identical progestin on breast cancer risk.  Luckily, the authors also noted that risk of breast cancer returns to baseline within 3-4 years after cessation.

So what is one to do?  I suggest we continue what we've always done as family physicians:  have a heart-to-heart discussion w/our patients concerning the risks, benefits and alternatives, in this case possibly trading an increase risk of breast cancer early on for a lower risk of heart disease.  By the way, do you know what's the number cause of death in women?  It's not breast cancer - it's heart disease!

Vitamin D Review

The Institute of Medicine generated a lot of controversy 2 months ago with its recent recommendations for vitamin D.  Specifically, they were quite conservative in their recommendations but mainly because all the studies that demonstrate a link w/many chronic disease processes are observational in nature. 

In fact, there are very few, if any, randomized double blind placebo controlled trials demonstrating benefit.  The New England Journal of Medicine published a nice review of the data this past week that's easier to peruse than the IOM's monstrosity.  So did the Mayo Clinic in their Proceedings this month. 

My take is that given the strong (observation & epidemiological) associations with chronic disease, the relative lack of side effects when levels are monitored closely, along with the minimal expense, perhaps the benefit:risk ratio is in favor of optimizing one's vitamin D.  Because there is concern about skin cancer from too much sun exposure (which also increases vitamin D), we normally suggest supplementing w/vitamin D3 (a study published in December 2010 demonstrated vitamin D3 had better efficacy than vitamin D2).  Of course, when it's a sunny day at Heavenly Ski Resort . . .

Smoking Cigarettes Increases Risk of Breast Cancer

In a new study published this week, authors followed 111,140 active smokers of the Nurses Health Study for 30 years and 36,017 participants exposed to passive smoke for 24 years and concluded that, as expected, active smoking as denoted by number of years smoked (both current & past), number of pack-years smoked, younger age at smoking initiation, and premenopausal smoking were all associated with an increase risk of breast cancer.  The good news is that passive smoking was not associated with development of breast cancer. 

Last month, I discussed the Surgeon General's statement that smoking even one cigarette can kill you.  We've known for years that smoking increases one's risk for lung cancer, emphysema, heart attacks & strokes.  Now we've just uncovered a link w/breast cancer.  Do you really need another reason to quit?

Or better yet, never start!  Our Nevada Academy of Family Physicians Foundation sponsors & supports Tar Wars, our outreach & tobacco-free education program for our fourth & fifth graders.  So come out & help fund our Foundation by attending one of our wine tastings & silent auctions (August 5th in Las Vegas and August 26th in Reno).

Cookbook Medicine: Poor Quality of Evidence Behind Guidelines

You're only as strong as your weakest link.  In the world of evidence-based medicine, there are a number of ways to evaluate the strength of evidence.  Since May 2007, the United States Preventive Services Task Force (USPSTF), the most conservative body regarding the promulgation of evidence-based guidelines, has used levels of certainty to evaluate & grade the evidence behind their guidelines.  

For instance, recommendations for which they declare a high level of certainty are those such that "[T]he available evidence usually includes consistent results from well-designed, well-conducted studies in representative primary care populations. These studies assess the effects of the preventive service on health outcomes. This conclusion is therefore unlikely to be strongly affected by the results of future studies."  

Those recommendations for which USPSTF declares moderate level of certainty are those such that "[T]he available evidence is sufficient to determine the effects of the preventive service on health outcomes, but confidence in the estimate is constrained by such factors as the number, size, or quality of individual studies; inconsistency of findings across individual studies; limited generalizability of findings to routine primary care practice; and/or lack of coherence in the chain of evidence."

The American Academy of Family Physicians (AAFP) uses the ABC rating scale, where Level A (randomized controlled trial/meta-analysis) includes high-quality randomized controlled trials (RCT) that consider all important outcomes or high-quality meta-analyses (quantitative systematic review) using comprehensive search strategies.  Level B (other evidence) includes well-designed, nonrandomized clinical trials; nonquantitative systematic reviews with appropriate search strategies and well-substantiated conclusions; lower quality RCTs, clinical cohort studies and case-controlled studies with nonbiased selection of study participants and consistent findings; and other evidence, such as high-quality, historical, uncontrolled studies, or well-designed epidemiological studies with compelling findings.  Level C (consensus/expert opinion) is consensus viewpoint or expert opinion.

 Strength of Recommendation Taxonomy (SORT) grades the evidence as Level 1 (consistent, good quality patient-oriented evidence), Level 2 (inconsistent or limited quality patient-oriented evidence), or Level 3 (other evidence).  Note the focus on patient-oriented evidence.  For instance, patients don't really care that a medicine lowers their blood pressure, they just want to be sure they don't have a stroke.

I mention the above because when one considers the multitude of guidelines foisted anonymously upon us especially in our electronic health records (EHR), it would be nice know that the highest quality of evidence supports the recommendations.  However, as the authors in a study published this month noted, over half the recommended guidelines promulgated by the Infectious Disease Society of American were only Level III, based upon expert opinion only as opposed to the hoped for Level I based upon >1 randomized controlled trial.

The problem with all these guidelines is a temptation by many to view the practice of medicine as akin to following a cookbook, when indeed there is quite a bit of art even to interpreting & applying the science of medicine on an individual basis.  So lest we fall lockstep into performing every recommended guideline in our EHR, we still need to read the latest literature ourselves rather than have someone pre-digest & regurgitate it for us.  In fact, we should consider the source of said guidelines when choosing our federally-mandated EHR.

Disclosure:  I'm scheduled to give a presentation entitled "The EHR Challenge: How to Choose the Best Fit" tomorrow at our Nevada Academy of Family Physicians' 43rd Annual Winter Conference here in lovely South Lake Tahoe where the weather has been sunny and the skiing awesome.

What Did You Say?

The secret's out: primary care physicians (or PCPs such as myself when I wear my family physician hat) don't communicate very well w/our specialist colleagues (such as myself when I wear my geriatrician hat) about you, our patient.  Incredible, isn't it?!?!  Maybe not when you recall our stereotypically atrocious handwriting.
I mention this because a survey published last week of 4,720 physicians working at least 20 hours/week reported that only 69.3% of PCPs "always" or "most of the time" sent the appropriate paperwork to the specialist to whom they were referring.  Worst, it arrived only 34.8% of the time as reported by the specialists. 

Well, this is kind of like the pot calling the kettle black since only 80.6% of specialists "always" or "most of the time" sent their consultation results back to the referring PCP while only 62.2% of PCPs reported receiving said consult notes.

Have you ever been to a specialist who then asked you "Why are you here?" and really meant it?  And then returned to see your PCP who asked "What did s/he say?"  Isn't this lack of communication appalling?  And I thought we grew out of this after passing through adolescence!

Let's hope that technology in the form of electronic health records will improve the back & forth flow of information (as suggested in an accompanying editorial).  The study also recommends "adequate" visit time (don't hold your breath!) and nurse support for monitoring patients with chronic diseases.  In the meantime, be proactive and check w/each physician's office a day or so prior to your arrival to be sure they've already received the necessary paperwork.  Should that be your responsibility as a patient?  Probably not.  But in this day & age, we need to work together to improve the care we provide & you receive.

Disclosure:  I'm scheduled to give a presentation entitled "The EHR Challenge: How to Choose the Best Fit" this coming Thursday at our Nevada Academy of Family Physicians' 43rd Annual Winter Conference here in lovely South Lake Tahoe where the weather has been sunny and the skiing awesome.

EHR Adoption vs Quality of Care

As you're all probably aware, physicians are being enticed to purchase electronic health records (EHR) by both a carrot ($44K in Medicare incentives over 5 years if adopted by 2012) and a stick (penalties in the form of reductions in Medicare funding starting at 1% and climbing to 3% if not implemented by 2015).  Besides theoretical cost savings, another reason that's been proposed for adopting EHR is an increase in the quality of care delivered via clinical decision support (what should I do in this particular situation) and electronic guideline-based reminders (Mr/s. Jones is due for "x").

However, in a study just published online today, after reviewing over 255,000 ambulatory patient encounters, the authors found no association between EHR use and quality of care as denoted by previously developed & agreed upon quality indicators.  This is important because for physicians to receive reimbursement for their front-end purchase of said EHR, they must be able to document "meaningful use".  But what if "meaningful use" doesn't improve the quality of care provided?  Why purchase an EHR?

As with most scenarios, there's more than one perspective.  Perhaps there was no improvement because we're doing such a wonderful job of providing quality care already?  Now, don't everyone choke & gag all at once.  Or perhaps we can blame the EHR itself for not being user friendly.  After all, when an EHR is implemented, the physician/provider should not have to change his/her way of documenting the visit nor should the use of said EHR slow down the documentation process.  Yet, as the majority of EHRs are not designed with the end-user in mind, I hear too often that the EHR is really more a burden and hindrance than it is a boost to productivity and delivery of quality care.

We have to stop putting the cart before the horse and allowing the tail to wag the dog.  We need to speak up and let it be known how we want to interface w/our EHR to boost productivity and quality of care.  While there probably will never be one best EHR for every physician, we need to start looking critically at our options as our deadline looms closer & closer.

Disclosure:  I'm scheduled to give a presentation entitled "The EHR Challenge: How to Choose the Best Fit" this coming Thursday at our Nevada Academy of Family Physicians' 43rd Annual Winter Conference here in lovely South Lake Tahoe where the weather has been sunny and the skiing awesome.

Possible New Blood Test for Alzheimer's Disease

My friend & former colleague, Dr. Irene Hamrick, Chief of the Division of Geriatrics at the Brody School of Medicine, is flying into Tahoe to talk about "Dementia, Depression & Delirium" tomorrow to start off our Nevada Academy of Family Physicians' 43rd Annual Winter Conference.  I mention this because perhaps I was too harsh yesterday when I wrote about the use of florbetapir for the diagnosis of Alzheimer's disease.

After all, without an ability to make the diagnosis and follow its progression, it's difficult to search for potential cures.  So while florbetapir might not have direct clinical application on a day-to-day basis for the average clinician practicing in the trenches today, it could certainly be used to assess the utility of various preventive techniques and potential pharmaceutical agents.

Following that same line of thought, I decided that in all fairness, I should also mention an article published in that same issue of JAMA this past week looking at the efficacy of plasma beta amyloid levels to potentially detect & predict cognitive decline in 997 adults followed for 10 years.  More good news out of this study was that cognitive reserve (as approximated by years completed of schooling plus literacy level) appeared to attenuate the loss expected with a lower level of plasma beta amyloid. 

Now before you race over to your doctor and ask for the test, do realize that it's not ready for prime time.  In other words, it hasn't been approved by the FDA, much less been commercialized.  If anything, this is the beginning of a proof of concept that perhaps beta amyloid is the cause of Alzheimer's disease and not a by-product. 

However these two testing modalities turn out, I offer them as examples of our continued attempts to develop a more objective way to make the diagnosis, follow its progress, and find a cure.  While we have none of the three right now, hope is just over the horizon.  In the meantime, stay physically & mentally active and eat low glycemic, non-processed foods akin to the Mediterranean diet in our best attempt to prevent cognitive decline.

Florbetapir Helps Image Alzheimer's Disease

We now know that there's a link between insulin resistance and Alzheimer's disease.  And since insulin resistance is related to physical activity, that might help explain why physical activity has also been linked to Alzheimer's disease.  Admittedly, I'm stretching things quite a bit to fill our knowledge gaps but you have to admit, it's plausible.

But in the meantime, what do you do?  How do you know if you have it or not?  Back in the day when I was in training and we didn't have CT/MRI/PET scanners everywhere, we thought long & hard before sending someone for imaging.  After all, the radiographic image didn't so much as prove/confirm the diagnosis of Alzheimer's disease as much as it "ruled out" other conditions that also lead to memory loss.

More recent advances now allow us to consider hippocampal volume as well as functional metabolism, eg glucose uptake.  Pittsburgh Compound B is the first agent allowing us to look for beta amyloid plaque buildup, what's theorized as the cause of Alzheimer's disease.  However, it's general use is limited to due its very short half-life.

With time & money, more & more compounds are being studied as diagnostic imaging agents.  Research regarding the efficicacy of florbetapir was just published in this week's issue of JAMA.  Florbetapir, with a longer half-life than Pittsburgh Compound B, was able to confirm the presence & density of pre-mortem beta amyloid with post-mortem autopsies, the only true gold standard for diagnosing Alzheimer's disease, with 96% accuracy in 29 individuals tested an average of 99 days prior to death.

Coincidentally, the manufacturers of florbetpir took their product before the FDA yesterday.  But in a classic case of the glass is half empty/full, Medscape titled their post as FDA rejecting florbetapir while MedPageToday, writing about the same meeting & vote, titled their article as FDA approves florbetapir with caveat.  So which is it?  In fact, they're both right, in a way.  The FDA advisory committee did vote 13-to-3 against approving florbetapir.  However, in a second vote, they also voted 16-to-0 for approval if and only if the manufacturer stepped up with education & training to help radiologists interpret the images correctly.

So where does this leave us?  Don't forget that we still don't have a cure for Alzheimer's disease.  The four pharmaceutical agents broadly used today (five, if you count the original four-times-daily, potentially-dangerous-to-the-liver drug) only slow down the progression of disease, and that's only if you're lucky enough to be a responder and look at the statistics funny (just ask the folks at NICE who recently changed their minds without benefit of any new data).

Why spend money making a diagnosis when there really aren't any good treatment options available.  Why not just put those funds to use caring for the patient and family?  Or better yet, use those funds to encourage lifestyle changes to decrease one's risk of developing Alzheimer's disease!

Diabetes & Alzheimer's Disease: What's the Link?

With the prevalence of diabetes & obesity increasing exponentially, I've been trying over & over to encourage my sedentary patients to become more active by pointing out studies demonstrating mortality benefit and lower risk of diabetes.  If that hasn't convinced you yet, how about a new study just published concluding that insulin resistance may be a marker of Alzheimer's disease risk, even before the onset of mild cognitive impairment.

The authors examined 23 patients w/either pre-diabetes or undiagnosed diabetes compared to 6 euglycemic participants with positron emission tomography (PET) scan and noted that greater insulin resistance was associated with an Alzheimer's disease-like pattern in patients with either pre-diabetes or actual diabetes.

Other studies have already demonstrated that insulin resistance increases one's risk for developing Alzheimer's disease.  What this study adds is the pathophysiology in terms of a disease risk marker that might someday be used to predict future development before onset.  In the meantime, there's no reason why we can't use this study as yet another reason to become physically active to minimize our insulin resistance.

I Can't Even Eat 5 Servings A Day - Now You Want Me To Eat 8 Every Day?!?!

For quite some time, we've been exhorting our patients to eat more fruits & veggies, at least 5 servings a day (WHO 2003).  We teach our kids to eat the colors of the rainbow every day.  Recently, fruit & veggie consumption has been linked to lower risk of ischemic stroke, osteoarthritis, and even osteoporotic fractures.  Plus, I have yet to see a single study extolling the virtues of processed, calorie dense foods. 

So perhaps it should come as no surprise that another analysis of EPIC (European Prospective Investigation into Cancer & Nutrition) was published yesterday, this time of 313,074 previously healthy participants from 8 different European countries followed for 8.4 years, demonstrating a 22% lower relative risk of fatal heart disease in those 18% of the population able to consume 8 servings daily of fruits & veggies compared to those who ate 3 or less.  Moreover, each additional serving of fruits & veggies over 3 a day lowered the risk of cardiovascular mortality by 4%.  But it's not until one consumes the magical 5 servings daily that the results become statistically significant (in other words, 4 servings don't cut it), and primarily on the strength of the fruit consumption data.

My first reaction was the following:  are you kidding me?  8 servings a day?  I can barely squeeze in 5 on a good day!  Clearly, I'm not a vegan.  And it would appear that 4 out of 5 European participants agree w/me.  On the other hand, a strong point about this particular observation study is the diversity of the population - it wasn't isolated to just one race or ethnic group but rather spread out across Western Europe (although some might argue that this is still rather homogenous since, by definition, Africans, Asians, and Hispanics comprise a minority within the region).

Still, if this is all we have to do to prevent strokes, arthritis, osteoporosis, and now heart disease, this is an ounce of cure that I think is worthy of a pound of cure.

Post-Prostatectomy Incontinence: Is There A Better Option?

The odds aren't in my favor or yours, for that matter, if you have both an X and a Y chromosome.  In fact, we have a 1 in 6 lifetime chance of being diagnosed with prostate cancer.  But what does that really mean?  As I've mentioned previously, we're more likely to die with prostate cancer than from it.  On the other hand, who wants to go around knowing that they have a cancer in their body and then not really doing anything about?  Even if it's a localized tumor.  Perhaps, especially if it's a localized tumor, we're more likely to say, "Phew! Glad I caught it early and took care of it since you never can tell when it might spread." 

But that's where current studies are demonstrating the error of our thinking.  The downsides to treatment are tremendous.  From radiation, there's colitis & cystitis.  From androgen deprivation therapy, there's obesity, diabetes, cardiovascular disease, and increased mortality.  From radical prostatectomy, there's the obvious immediate surgical complications as well as post-prostatectomy incontinence and erectile dysfunction.  In fact, 2 out of 3 men continue to experience incontinence 5 years after surgery, regardless of the new techniques & technologies available, eg nerve-sparing robot assisted surgery.

In a study just published looking at 208 community-dwelling men 51-84yo w/post-prostatectomy incontinence, the addition of in-office biofeedback and home pelvic floor electrical stimulation to 8 weeks of behavioral therapy (pelvic floor exercises and bladder control strategies) did not improve incontinence any better than behavioral therapy alone compared to placebo/delayed treatment serving as control.  Granted, behavioral therapy alone resulted in a 50% reduction in incontinence, but that also implies that half the patients continued to suffer.

However, what I found quite intriguing was the editorial written by an academic urologist who opined that a better way would involve active surveillance (thereby avoiding the risk of incontinence) since 23-42% of patients diagnosed w/prostate cancer will die with it rather than from it and therefore are exposed to risks & side effects w/o additional benefit.  In other words, if you're diagnosed with a low risk cancer, why increase the risk of urinary incontinence (and most likely erectile dysfunction) if you don't have to?  Instead, consider active surveillance whereby you closely monitor your PSA on a regular basis, re-biopsy as deemed necessary, and consider more aggressive interventions only if the cancer turns moderate to high risk (as denoted by your Gleason score increasing above a specific mark).  The bigger question is whether you can handle the wait.

Candesartan vs Losartan: And the Winner Is . . .

All drug manufacturers would have you believe that their drug is distinctly different from all the others in the same class.  Pharmaceutical benefit managers would like you to believe that it's a class effect such that one (less expensive generic) drug can be substituted for another (more expensive brand) within the same class.  But who's right?

From my perspective, it appears that most manufacturers have some sort of gentleman's agreement to compare their products to placebos rather than their competitors so that it's often very difficult if not impossible to directly compare apples to apples.  Instead, we compare each product's efficacy to placebo vs another product's efficacy to placebo.  Or they focus on different outcomes (and even this changes w/time).

For instance, back in the day, the Zocor rep would discuss at length all the clinical outcome studies regarding their product.  On the other hand, the Lipitor rep would talk about how their product lowered LDL better than any drug on the market (this was in the pre-Crestor days).  Nowadays, however, the table's been turned.  Now the Lipitor rep talks about all the clinical outcome studies regarding their product while it's the Crestor rep who discusses how their product lowers LDL better than any drug on the market.  Yet, one rarely sees a direct head-to-head comparison of Crestor vs Lipitor regarding what really counts:  all-cause mortality, or at least cardiovascular mortality.

Therefore, I was quite surprised to see a study published this last week in JAMA comparing candesartan (2,639 patients) to losartan (2,500 patients) in those patients with heart failure w/reduced left ventricular ejection fraction followed for 5 years.   Their conclusion?  Lower all-cause mortality in those patients taking candesartan!

Now, before you start switching all your patients from any other ACE inhibitor and/or ARB to candesartan, realize that this population studied was a non-randomized registry (and not a randomized controlled trial) so there is plenty of room for tremendous bias.  However, as the authors concluded, there exists strong evidence that candesartan has benefits not found in other ARBs.  Only time and at least one randomized double blind placebo controlled trial will tell.  In the meantime, if I'm given a choice between candesartan & losartan . . .

Herpes Zoster Vaccination: Yes or No?

Dr. Andrew Schechtmann recently took me to task over the statistics used to gain approval for a new indication for the human papilloma virus vaccine.  And rightly so, as I agree that relative risk (which is the most commonly advertised result) only tells part of the story.  In fact, we really should try to look for the absolute risk reduction which can then be inverted into the number-needed-to-treat to see if the intervention really makes sense.

So let me attempt to make amends by discussing a freshly published retrospective cohort study of 75,761 vaccinees compared to 227,283 unvaccinated age-matched cases (all immunocompetent adults >60yo) in which there was a statistically significant 45% reduction in herpes zoster (shingles) diagnoses in those who received the vaccine (consistent w/previous randomized double blind placebo controlled trials) compared to those who did not.  Sure, this is impressive but consider that the rate of infection was 6.4 per 1,000 person-years in those vaccinated compared to 13.0 per 1,000 person-years in those not vaccinated.  The absolute risk reduction is therefore 6.6 per 1,000.  Take the reciprocal of 6.6/1,000 and you get an NNT of 152.  In other words, you'd need to vaccinate just 152 patients to prevent one herpes zoster diagnosis. 

Moreover, you're talking about a common disease entity (zoster/shingles) in a common group of patients (immunocompetent elderly) as compared to a relatively rare disease (anal cancer) in a much smaller group of patients (men who have sex with men).  Therefore, you can see the greater imperative here for us to vaccinate our elderly from a painful & potentially chronically disabling disease (postherpetic neuralgia).

Don't Just Sit There, Do Something! Part 2

When it rains, it pours.  While poring over my standard list of journals, I stumbled onto yet another study looking at the beneficial effects of regular physical activity.  In this population-based cohort study of 592 adults (avg 50yo at baseline) followed for 5 years just published in the British Medical Journal, the authors used pedometers to quantify the number of steps taken daily which they then compared to body mass index (BMI), waist-to-hip ratio (WHR), and insulin sensitivity.

Unfortunately, close to two-thirds of the participants walked less at the end of 5 years than at baseline.  Compared to those who walked less, those who walked more were more likely to have a lower BMI, lower WHR, and greater insulin sensitivity, all of which could again help explain the lower mortality that we associate with greater physical activity. 

Current recommendations are to take at least 10,000 steps daily.  If that's all it takes to prevent diabetes and premature mortality, I'd say that that's a small price to pay.  The bad news?  It'll probably take more than 30 minutes a day to accomplish.  But I still think that that's time well spent.

Don't Just Sit There, Do Something!

Right on the heels of a post from earlier this week linking screen time to mortality, here comes an NHANES analysis linking sedentary time to cardio-metabolic and inflammatory biomarkers as a possible explanation for the increased risk of mortality.

In this cross sectional analysis of 4,757 participants, an accelerometer was used to assess and quantify exactly how long someone was sedentary vs active.  The longer one remained sedentary without any physical activity, the greater one's waist circumference, the lower one's HDL, and the higher one's CRP, triglycerides, and insulin.

Taken in concert with the aforementioned studies, it's imperative that we remain as physically active as possible if we are to make a difference to our life expectancy.

Pain Relievers vs Heart Disease: What's the Link?

The World Health Organization (WHO) recommends a stepped approach to pain relief, consisting of acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) as the pharmacologic mainstay.  However, the downside to acetaminophen is its ubiquity, despite being the number one cause of hepatotoxicity (liver failure) in the US, enough so that the FDA will soon be limiting the amount of acetaminophen in combination narcotic medications.

But I digress. I wanted to review some of the safety concerns about NSAIDs.  It's been known for quite some time that traditional NSAIDs, such as ibuprofen, can increase one's risk for stomach ulcers and kidney damage.  That led to the development of cox-2 inhibitors, a subclass of NSAIDs that was supposed to have a lower risk of stomach ulcers.  However, as we found out w/Vioxx (rofecoxib) and Bextra (valdecoxib), which were pulled off the market due to an increase risk of heart disease, there's no free lunch.  This then led to a re-examination of all NSAIDs to determine each drug's individual risk of heart disease.

In a study just published in the British Medical Journal, the authors analyzed data from 31 trials of 116,42 patients followed for 115,000 patient-years and concluded that most, if not all, NSAIDs increased one's risk for heart attacks, stroke, death from heart disease, and death from any cause, with rofecoxib the worst offender and naproxen the least offensive.  I wouldn't be surprised if these findings hit the lay press shortly w/some rather inflammatory sound bites, such as "Pain Killers Cause Heart Attacks!"

Mind you I'm not here to defend the pharmaceutical industry, but while the statistics do support pulling rofecoxib from the market, the numbers are not statistically significant for most NSAIDs.  To understand this, we have to review the principle behind the 95% confidence interval (or credibility interval as used in the BMJ).  What this range tells you is that if you repeated the analysis 100 times, 95 out of that 100 times you'd have results within this range.  As long as both the upper & lower limits are on the same side of 1, your results are statistically valid.  However, as in the case for a number of the NSAIDs, when the upper limit is greater than 1 and the lower limit is less than 1, the implication is that 95 times out of 100, you might be better or worse than your comparator.  That's no better than flipping a coin!

So while the sound bite might report a doubling of one's risk for heart attack from lumiracoxib (not sold in the States), the fact that the 95% confidence interval ranges from 0.71 to 6.21 implies that the results are not statistically significant.  It says nothing about the risk of heart attack, just that I wouldn't want to mislead my patients.

Your TV Can Kill You! Part 2

Back in July, while I was writing for my previous blog, I reviewed a study published last January that followed 8,800 adults for 6+yrs and found that for every hour spent in front of the television, all-cause mortality increased by 11% and cardiovascular mortality increased by 18% compared to those who watched less than 2 hours/day.

Well, another study has just been published that arrives at the same general conclusion.  After following 4,512 adults for 4+ years, the authors noted that all-cause mortality increased by 52% while cardiovascular mortality more than doubled when comparing those who watched >4 hours/day to those who watched less than 2 hours/day of television.  Their definition of television watching extended to playing video games and sitting in front of a computer monitor. 

The above findings held true even after taking into account age, sex, ethnicity, obesity, smoking, social class, long-standing illness, marital status, diabetes, and hypertension.  Through statistics way beyond my comprehension, they concluded that 25% risk could be accounted for by BMI, CRP & HDL.  What really troubled me was that physical activity was unable to protect against the ravages of screen time.  In other words, exercising vigorously did not mitigate a time spent in front of the television.  Unfortunately, I find it difficult to imagine that even our grandchildren will consider the television a public health threat.

Sleep Apnea & CHF

In any group of friends, we all have a buddy with whom no one wants to share a hotel room on road trips.  Why?  Because s/he saws logs with enough enthusiasm to raise the dead, like the proverbial freight train rolling through your bedroom.  These days, we know snoring isn't all fun & games.  Luckily, not everyone who snores has sleep apnea.  But the vast majority of those w/sleep apnea do in fact snore.

And they feel miserable when they wake up, after a night of non-refreshing sleep due to too numerous to count micro-arousals.  So they never drift into deep enough sleep to release growth hormone.  As if this weren't bad enough, they also increase their risk for cardiac dysrhythmias, hypertension, pulmonary hypertension, heart failure and even sudden cardiac death.

The solution is often easier to prescribe than it is to comply:  continuous positive airway pressure or CPAP.  Basically, this uses air pressure to stent (keep open) your airway.  However, it also feels as if you're drowning in air since it's difficult to exhale against a column of air (one potential solution is BiPAP).  And that's if you can tolerate the mask or nasal pillows (work closely w/your sleep medicine physician).  Don't forget to ask for humidified air if you wake up w/cotton mouth.

Of course there are other options such as pharyngoplasty or dental appliances or in the most recalcitrant cases, jaw advancement.  But I thought I'd mention a nice review just published in JACC looking at how sleep apnea impacts heart failure so hopefully you can use this bit of information to improve your adherence.

Exercise vs Prostate Cancer: Does It Make A Difference?

So we now know that red meat doesn't affect prostate cancer risk.  But what about exercise?  After all, it's the beginning of the New Year and many of us make an annual resolution to exercise more every January.  Perhaps we need a stronger motivator?  

Well, the folks over at the Health Professionals Follow-Up Study looked at self-reported exercise in 2,705 men w/non-metastatic prostate cancer and followed them from 1990 to 2008.  Given the recent interest in active surveillance as a therapeutic option for diagnosed prostate cancer these days, it's interesting to note that of the 548 deaths in these men over this period of time, only 20% were due to prostate cancer.  In other words, as we've said all along, you're more likely to die with prostate cancer than from it.

Their conclusion?  Those men who self-reported as being physically active had lower all-cause mortality and prostate cancer specific mortality.  And those who were vigorously active had lower mortality than those who were non-vigorously active.  Duration of vigorous activity also made a difference at greater than 3 hours/week compared to less than 1 hour/week.  And vigorous exercise even prior to diagnosis also made an impact on mortality & survival.

Just what constitutes vigorous?  Biking, tennis, jogging or swimming were given as examples.  Even those men who reported walking at a normal to very brisk pace for 90 minutes/week had a lower risk of death compared to those reporting shorter durations at an easy walking pace.

So there you have it.  Exercise makes a difference in prostate cancer and all-cause mortality - just another reason to keep your New Year's resolution to exercise regularly.

Red Meat vs Prostate CA: Does It Make A Difference?

Red meat gets blamed for a lot of things these days, eg all-cause mortality, cancer mortality & cardiovascular mortality to name but a few as of March 2009.  But as you know, we all have to die from something.  So recently, researchers performed a meta-analysis of 15 studies looking at red meat consumption and another 11 studies evaluating process meat intake specifically with regards to prostate cancer.  Their conclusion?  No link.

So if you're worried about your prostate, go enjoy your Wagyu ribeye but only in moderation, since you'll still need to balance & somehow mitigate your all-cause and heart-related risk of death.  And if you're a vegan?  Then your risks are already significantly lower!

Colorectal Cancer: What's the best way to screen?

Depending upon how you run the numbers, heart disease & cancer are neck & neck for the top spot as the number one cause of death in the US.  As of this past September, colorectal cancer ranked as the 3rd highest number of new cancer cases & cancer deaths in both men & women.  I mention this bit of background because to a great extent, colorectal cancer deaths should be preventable with appropriate screening.  Our US Preventive Services Task Force strongest "A" recommendations offer a choice between fecal occult blood testing, sigmoidoscopy, or colonoscopy in adults 50-75 years old.  But given a choice, the question always comes up, which is best?

In a case control study published this week, the authors concluded that a colonoscopy w/polypectomy performed with the past 10 years lowered the risk of colorectal cancer by 77% after comparing 1,688 cases with 1,932 controls.  Just this past May, researchers followed for over 11 years 112,939 participant controls & 57,099 who underwent flexible sigmoidoscopy and noted a 23% reduction in colorectal cancer and 31% reduction in mortality.  191 persons needed to be screened to prevent one colorectal cancer diagnosis while 489 needed to be screened to prevent one colorectal cancer death.

Of the stool-based screening methods, immunochemical fecal occult blood testing was considered superior to traditional quaiac-based fecal occult blood testing in two separate studies published last November & last March.  The earlier study from last spring then went on to conclude that flexible sigmoidoscopy was superior to either fecal occult blood tests.  However, to paraphrase former US Surgeon General Dr. C. Everett Koop, any screening test for cancer can't work if you won't take it.

So what's the best way to screen for colorectal cancer?  Any way that you're willing.

Colorectal Cancer vs Glycemic Load

The latest in a series of studies looking for an association between glycemic load and colorectal cancer was just published following 73,061 Chinese women for an average of 9 years.  The answer appears to remain the same:  no link, whether you look at the PLCO study, Multiethnic Cohort study, or a recent meta-analysis of 12 other studies.  So while I don't advocate consumption of high glycemic load nutrition, at least there appears to be no harm with regards to colorectal cancer. 

By the way, glycemic load is defined as glycemic index multiplied by absorbable (or net) carbohydrates, which are based upon serving size.  So the more servings you eat of any food, the higher your glycemic load, even though the glycemic index of that item hasn't changed.  That's why that pint of ice cream is so bad for you - it actually contains several (usually four) servings that can easily be consumed by one person in one setting.  This also means that the higher the fiber content in your food item, the more likely it is to have a the lower absorbable carbohydrate compared to a similar portion of a similar food with less fiber. 

So learn to read ingredient labels.  Or at least avoid processed foods found in boxes & containers and choose fruits & vegetables from the produce section of your supermarket.  While it may not make a difference for your colorectal cancer risk, it will certainly improve other aspects of your health.

Milk: Does it deserve a bad rap?

Lately, milk has gotten a bad rap, at least amongst the complementary & alternative medicine arena.  There's talk of milk allergies, increased mucus production, and just basically how unnatural it is that humans, at least in the Western world, are the only mammalian form that continues to consume milk even after being weaned. 

Well, proof is in the pudding (pun intended).  In a meta-analysis of 17 prospective cohort studies involving 611,430 participants avg 56 years old, there was no association between milk consumption and all-cause mortality (the gold standard outcome).  There was even a hint of benefit regarding heart disease but this was not statistically significant. 

So if you drink milk regularly, go enjoy it and stop worrying.  And for those of you who avoid milk because you've noted some adverse outcome every time you consume dairy products, there's no evidence that you're missing out on some potential benefit.

And no, the National Dairy Council and Milk Advisory Board didn't pay me to write this.

Fruits & Veggies vs Low Trauma Fracture Risk

I've started 2011 by reviewing a series of studies looking at how what we eat affects us.  In this particular retrospective cohort study of 1649 men & 3539 women followed for over 6 1/2 years.  Based upon recall (again fraught w/error), 2 dietary patterns emerged, one that was nutrient dense, consisting of large amounts of fruits, vegetables & whole grains, versus one that was energy dense, consisting of soft drinks, potato chips, French fries, meats & desserts.  Even after accounting for body mass index, bone mineral density, falls & other demographic variables, the nutrient dense dietary pattern was associated with 14-17% lower risk of low trauma fracture, a euphemism for osteoporotic fracture.  So choose wisely.  You are what you eat and you don't want to break anything!

Q&A Session at Avvo.com

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Q&A Session at Avvo.com

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How to Make an Appointment with Me

An article in today's USA Today discusses how technology is making it easier to make an appointment to see your physician.  Well, if you're new to my practice and want to get a hold of me, just send me an email.  And if you're already a patient of mine, either send me an email or call me directly. 

Sure, I might not pick up the phone if I'm on the line with another patient, but I guarantee that your name will pop up on my caller ID and I'll call you back just as soon as I can.  The only reason you'll need to wait a few weeks to see me is your schedule, not mine.  If you want to chat with me today, I'll speak with you today.  Maybe not Monday afternoons while I'm over at the School of Medicine, but I will make time for you either beforehand or afterwards.  Just call or email me!  Simple as that!

Fish Consumption vs Diabetes

Yin & yang.  Good & bad.  There're always two sides to the proverbial coin.  In this case, I recently reviewed 2 diffferent studies demonstrating that higher fish consumption lowers heart attack & stroke risk.  Today, however, I have to tell you the rest of the story in that authors recently concluded that eating more fish just might increase your type 2 diabetes risk (T2DM), at least if you're a postmenopausal female.

Specifically, they followed 36,328 women partipants of the Women's Healthy Initiative study for an average of 12.4 years.  Those who consumed >0.2g/d of marine omega 3 fatty acids or >2 servings/d of fish had a statistically significant increase risk of developing T2DM regardless of blood pressure.  Interestingly, plant-based omega 3 fatty acids were not associated with T2DM risk.  While this is news to me, apparently this finding is consistent with those from both the Nurses' Health and the Iowa Women's Health studies.

But how does this impact us?  Well, just ask yourself, how many of you actually eat more than 2 servings of fish a day?  Most recommendations are for just 2 servings a week.  So eating fish every other day probably isn't going to raise your diabetes risk as much as it will lower your heart attack & stroke risk.  As with most things in life, too much of a good thing might actually be bad for you.  Time will tell if this really applies to fish consumption.

Flash: It's Snowing in Las Vegas!

Fish Consumption vs MI

Did you eat some fish today?  In a case-control study (not good for proving causation but useful to demonstrate association & develop hypotheses), Swedish researchers compared 431 patients who had suffered a heart attack (myocardial infarction or MI) to 499 controls matched for body mass index, tobacco use, alcohol consumption, fruit & veggie consumption, and physical activity level. 

Based upon self-report, fish consumption, ironically, was not associated with heart attack risk.  However, plasma EPA+DHA (shorthand for specific omega 3 fatty acids in fish oil) did correlate inversely w/heart attack risk.  In fact, plasma EPA+DHA was also associated with  mercury (Hg) level, one of the heavy metal contaminants over which many are concerned, such that high Hg was associated w/lower heart attack risk, contrary to what was expected. 

How do we interpret these results?  Well, self-reported food consumption is fraught w/error while bio-markers, such as plasma EPA+DHA & erythrocyte Hg, more accurately reflect true consumption.  The fact that plasma EPA+DHA correlates w/erythrocyte Hg makes sense, too, because the more fish you eat, the more Hg you ingest.  But the good news is that the beneficial effect of fish consumption appears to override any negative effects from Hg.

One last bit of detail:  cod & perch are considered lean fish while fatty fish (loaded w/EPA+DHA) are herring, lavaret & salmon. So again, just as with stroke risk, choose your fish carefully.

Fruits & Veggies vs OA

I trust y'all had a wonderful start to 2011!  I thought we'd begin the year by reviewing a small study published last year (December, actually, but it sounds more impressive to say last year) in which the researchers performed a cross-sectional study of over 1,000 twins to assess their dietary patterns vs their risk for hip OA.  It turns out that those who ate more fruits & veggies, especially cruciferous vegetables, eg cabbage, broccoli & cauliflower, and alliums, eg garlic, leeks, shallots, chives & onions, while avoiding fried potatoes, had a 25-30% relative lower risk of developing hip OA regardless of whether they were monozygotic or dizygotic.  This association persisted even after adjusting for age, body mass index & physical activity.  So it looks as if making better food choices to lower your arthritis risk & fend off vampires also lowers your stroke risk.  Resolve in 2011 to eat healthier!