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Saturday, April 30, 2011
Friday, April 29, 2011
Testosterone's Effect in Women
We've known for known for a while that testosterone (T) increases bone mineral density (BMD) & lean body mass (LBM) while decreasing total body fat in men. But what about in women?
In a study published in this month's Journal of Clinical Endocrinology & Metabolism, the authors evaluated 232 healthy community-dwelling women between the ages of 67-94 who had enrolled in the Cardiovascular Health Study and noted that total T was associated with lumbar spine & hip BMD and that free T was associated with hip BMD, LBM, and total fat mass.
But let's not forget that association is not the same as causation. This study allows us to develop the hypothesis that increasing T levels in women might serve to increase BMD & LBM while decreasing body fat. The bigger issues will be deciding in whom to supplement and for what duration.
Clearly, we understand (some of) the risks associated w/supplementation in men but they might not apply to women (at least we won't have to worry about prostate cancer in the ladies!). Let's hope Proctor & Gamble gets more information based upon their world-wide sales of Intrinsa before they come back to the FDA to try again for approval (for indications unrelated to above).
In a study published in this month's Journal of Clinical Endocrinology & Metabolism, the authors evaluated 232 healthy community-dwelling women between the ages of 67-94 who had enrolled in the Cardiovascular Health Study and noted that total T was associated with lumbar spine & hip BMD and that free T was associated with hip BMD, LBM, and total fat mass.
But let's not forget that association is not the same as causation. This study allows us to develop the hypothesis that increasing T levels in women might serve to increase BMD & LBM while decreasing body fat. The bigger issues will be deciding in whom to supplement and for what duration.
Clearly, we understand (some of) the risks associated w/supplementation in men but they might not apply to women (at least we won't have to worry about prostate cancer in the ladies!). Let's hope Proctor & Gamble gets more information based upon their world-wide sales of Intrinsa before they come back to the FDA to try again for approval (for indications unrelated to above).
Thursday, April 28, 2011
Progesterone vs Progestins
You say either and I say either
You say neither and I say neither
Either, either, Neither, neither
Let's call the whole thing off.
You like potato and I like potahto
You like tomato and I like tomahto
Potato, potahto, Tomato, tomahto
Let's call the whole thing off.
- Let's Call The Whole Thing Off
by Louis Armstrong
by Louis Armstrong
The above comes off better when you get a chance to listen to him sing the lyrics but I think you get the idea. Sometimes it doesn't matter, but other times it does.
For instance, bio-identical hormones. Progesterone is what our bodies produce (out of the class of steroid hormones known as progestogens). In a very small study published in this month's Journal of Clinical Endocrinology & Metabolism, the authors demonstrated that oral progesterone given nightly can help restore normal sleep pattern (whereas currently marketed sedative-hypnotics tend to inhibit deep sleep). In fact, they noted that progesterone actually improved growth hormone release.
On the other hand, in a case-cohort study just published in the British Medical Journal, the authors noted a doubling of the risk for non-fatal venous thromboembolism in those women who took oral contraceptives containing drosperinone compared to those who received contraception containing levonorgestrel. Granted both drospirenone & levonorgestrel are non-bio-identical progestins, but it would appear that the latter is significantly safer than the former.
Given that women have a large number of (oral) contraceptives from which to choose, we might want to consider safety & side effect profile in addition to efficacy. However, before abruptly stopping one's oral contraceptive (since pregnancy & delivery are fraught w/health risks), one needs to review one's options w/one's prescribing physician, be it your family physician or obstetrician.
So while potato & potahto and tomato & tomahto may refer to the same things, remember that progesterone and progestins don't.
One last item: in another study also published in this month's JCEM, the authors found no increase risk of heart disease regardless of the type of progestin used in contraception and regardless of the route of administration of said progestin. I'll take good news any way I can.
Wednesday, April 27, 2011
Energy Drinks + Alcohol = Combination Best Avoided
Remember that recent commentary published in JAMA discussing the phenomena of "wide-awake drunkeness"? In a study just released online, some authors randomized 56 participants to either alcohol alone, energy drink alone, combination of alcohol plus energy drink, or placebo. Baseline objective performance as well as subjective self-assessment was performed prior to imbibing and then repeated after quaffing their drinks. As expected, those who consumed alcohol demonstrated worsening of performance.
However, those who consumed the combination of energy drink mixed with their alcohol increased their self-reported sense of awakeness but did nothing to improve their objective performance. Thus, the authors felt that the combination was even riskier than consumption of alcohol alone in that the caffeine & sugar fought off the sedating effects of the alcohol without improving performance.
However, those who consumed the combination of energy drink mixed with their alcohol increased their self-reported sense of awakeness but did nothing to improve their objective performance. Thus, the authors felt that the combination was even riskier than consumption of alcohol alone in that the caffeine & sugar fought off the sedating effects of the alcohol without improving performance.
Tuesday, April 26, 2011
Excessive Alcohol Consumption vs Laparoscopic Skills
Just over a year ago, researchers demonstrated that excessive alcohol consumption (>11% via breath analyzer) would affect cognitive function the following day. They theorized that under similar circumstances, physical performance might fail.
So earlier this month in Archives of Surgery, authors randomized 16 students to excessive alcohol consumption vs placebo after first teaching them baseline laparoscopic skills. They also monitored 8 laparoscopic experts before and after consuming excessive alcohol. As expected, performance skills lagged at 9AM and even 1PM. But in the biggest surprise, laparoscopic performance failed to return back to baseline by 4PM after the equivalent of a night on the town.
So earlier this month in Archives of Surgery, authors randomized 16 students to excessive alcohol consumption vs placebo after first teaching them baseline laparoscopic skills. They also monitored 8 laparoscopic experts before and after consuming excessive alcohol. As expected, performance skills lagged at 9AM and even 1PM. But in the biggest surprise, laparoscopic performance failed to return back to baseline by 4PM after the equivalent of a night on the town.
The point of mentioning this study is not so much to denigrate all surgeons but to increase awareness that cognitive impairment & loss of physical performance might last well into the following afternoon after a night of excessive alcohol consumption. So think twice before going out for a binge, especially if you have something important to do the next day, whether cognitive or physical!
Monday, April 25, 2011
Heart Disease Risk Factors in India
But when I think of the major cause of death in other parts of the world, I think more of infection & trauma rather than of chronic diseases. However, in just a few years, that image may soon change with the continued population explosion of India, which is predicted to surpass China in terms of population by the year 2025.
In a study just published last week in the Journal of the American College of Cardiology, the authors document the rapid worsening of cardiovascular risk factors after following for just 7 years the remaining 1,100 participants of the New Delhi Birth Cohort, while aging from 29yo to 36yo on average .
Specifically, the authors noted that body mass index increased by 2-3kg/m2 in both men & women while waistlines increased by 6cm in both over such a remarkably short period of time. What's problematic is that prior to the increase, these individuals were already considered overweight by the International Obesity Task Force criteria for Asians (BMI >23kg/m2) and met International Diabetes Federation criteria for central obesity in South Asians (waist >90cm in men and >80cm in women), both of which are considerably more strict than for Caucasians.
Systolic blood pressure was noted to increase by 12mm Hg in both men & women, moving from normal into pre-hypertension in the former. While total cholesterol increased by 5mg/dL in both men & women, luckily LDL cholesterol did not change in either, although fasting glucose changed from normal to impaired fasting in men only.
We know from experience that unless acted upon (inertia anyone?), these cardiovascular risk factors will only get worse with the passage of time. And with progressive worsening, we can only expect a dramatic increase in cardiovascular events (which accounted for 25% of deaths as of January 2008). The fuse is lit and it is short. Given the difficulty we have dealing w/heart disease in America, I can only begin to imagine the nightmare of heart disease in India in just 2 decades.
Sunday, April 24, 2011
Saturday, April 23, 2011
Friday, April 22, 2011
Memantine: Is It Worth It?
Memantine is the only NMDA receptor antagonist approved in the US for use in Alzheimer's disease (AD). However, despite it's indication for use in moderate-to-severe AD alone, it is widely prescribed off-label in combination with acetylcholinesterase inhibitors, even in mild AD. But one must remember that statistically significant improvements in objective cognitive testing don't necessarily correlate with or lead to clinically significant improvements in outcome. Which begs the question, why pay for a very expensive drug?
Sure, in one study from 2009 of 943 patients w/probable AD, use of memantine delayed nursing home placement even beyond that of acetylcholinesterase inhibitors used in isolation. But as far back as July 2005, the Food & Drug Administration refused to expand the indication for memantine to include mild AD, much less mild cognitive impairment. Now, in a meta-analysis of 3 trials published online this month in Archives of Neurology, the authors found no benefit demonstrated in 431 patients w/mild AD and very minimal benefit in 697 patients w/moderate AD.
And in case you've now learned to follow the money, it should be no surprise that the manufacturer was not involved in this study, but rather the California Alzheimer Disease Center and the University of Southern California Alzheimer Disease Research Center, the latter funded through a National Institutes of Health grant. Makes you wonder, doesn't it?
Sure, in one study from 2009 of 943 patients w/probable AD, use of memantine delayed nursing home placement even beyond that of acetylcholinesterase inhibitors used in isolation. But as far back as July 2005, the Food & Drug Administration refused to expand the indication for memantine to include mild AD, much less mild cognitive impairment. Now, in a meta-analysis of 3 trials published online this month in Archives of Neurology, the authors found no benefit demonstrated in 431 patients w/mild AD and very minimal benefit in 697 patients w/moderate AD.
And in case you've now learned to follow the money, it should be no surprise that the manufacturer was not involved in this study, but rather the California Alzheimer Disease Center and the University of Southern California Alzheimer Disease Research Center, the latter funded through a National Institutes of Health grant. Makes you wonder, doesn't it?
Thursday, April 21, 2011
New Guidelines re Alzheimer's Disease
The National Institute on Aging and the Alzheimer's Association just published a revision to their original 1984 guidelines regarding the diagnosis of Alzheimer's disease. One would think that after 27 years of research and advancement, there might be some dramatic changes & updates. Surprisingly for those of us in the trenches in routine practice, there's really nothing new!
While diagnostic accuracy, beyond clinical examination & patient/caregiver reports, can be improved upon with genetic testing, PET scans using amyloid binding ligands, and cerebrospinal fluid assays for beta-amyloid, it's still recommended that such testing be reserved for research only.
So why test for these changes? From a research perspective, we need to know if someone we've enrolled in a preventive study is actually at risk by dint of the above tests. In fact, a whole paper was published looking at how to define such a preclinical stage of AD, even before the onset of mild cognitive impairment due to AD. This is continuum of disease is consistent with the ability to predict AD via brain atrophy 10 years prior to clinical manifestation as pointed out 2 days ago.
But for most patients already presenting w/memory loss affecting cognitive function w/demonstrable loss from a previously higher level of function, in the absence of any findings consistent with vascular dementia, dementia w/Lewy bodies, and/or frontotemporal dementia, we can comfortably make a diagnosis of AD after a standard work up, including neuroimaging.
If your patients like the NY Times or WSJ, those papers have a nice write up. So, too, does USA Today. Or they can watch CBS Early Show and most any other TV news channel. But whatever you & your patients read/watch, check out Generation Alzheimer's as the oldest of the Baby Boomers turns 65yo this year, of whom 1 in 8 will develop AD. While we can't absolutely prevent AD, we can certainly lower our risk. Personally, I'd rather spend my time urging my patients to live a healthy lifestyle in order to improve their odds against AD, and in doing so, also against heart disease, stroke, and cancer.
Wednesday, April 20, 2011
Huperzine A: An Alternative to Prescription Meds for Alzheimer's Disease?
Another question that comes up often regarding Alzheimer's disease (AD) is with regards to treatment & prevention. Randomized, double blind, placebo controlled studies have demonstrated on more than one occasion that aspirin, conjugated equine estrogens, ginkgo biloba, and vitamin E neither prevent nor treat AD. That's not to say that you shouldn't take aspirin if you have heart disease or hormone therapy if you suffer from intolerable vasomotor instability. But be sure you're doing what you're doing for the right reason.
With that said, epidemiological & observational studies have demonstrated a link between activity (both physical & cognitive), fish consumption, and the Mediterranean diet when it comes to lowering AD risk. Don't get me wrong. There's no proof of cause & effect here. But we've been telling our patients all along to make healthier lifestyle choices to minimize their risk for cardiovascular & cerebrovascular disease, so I see no harm in dangling the possibility of AD prevention as another reason to choose wisely.
As for treatment, we have 3 acetylcholinesterase inhibitors (4 if you include one that's very rarely prescribed these days) and 1 NMDA receptor antagonist from which to choose in an attempt to treat AD, essentially closing the barn door after the horses have escaped. However, as I've mention over & over again, statistically significant improvements on objective cognitive testing doesn't imply clinically significant outcomes. Moreover, these medications are all very expensive and come with an array of side effects.
Thus, not surprisingly, the next question that arises is for a natural supplement that might prevent or treat AD. While huperzine A is a natural acetylcholinesterase inhibitor and NMDA receptor antagonist used by the Chinese for thousands of years, is more potent than prescription-only tacrine & galantaimine, has good brain penetration, and is relatively free of cholinergic side effects, it has never been demonstrated in a randomized, double blind, placebo controlled trial to be of benefit in AD. In fact, a study published in Neurology this month, failed to show any benefit when taken at a dose of 200mcg twice daily by 210 patients w/mild-to-moderate AD for 24 weeks.
And in case you're following the money, the study was jointly sponsored by the National Institutes of Heallth/National Institute on Aging and Neuro-Hitech, a biopharmeutical company interested in bringing Huperzine A to the market.
With that said, epidemiological & observational studies have demonstrated a link between activity (both physical & cognitive), fish consumption, and the Mediterranean diet when it comes to lowering AD risk. Don't get me wrong. There's no proof of cause & effect here. But we've been telling our patients all along to make healthier lifestyle choices to minimize their risk for cardiovascular & cerebrovascular disease, so I see no harm in dangling the possibility of AD prevention as another reason to choose wisely.
As for treatment, we have 3 acetylcholinesterase inhibitors (4 if you include one that's very rarely prescribed these days) and 1 NMDA receptor antagonist from which to choose in an attempt to treat AD, essentially closing the barn door after the horses have escaped. However, as I've mention over & over again, statistically significant improvements on objective cognitive testing doesn't imply clinically significant outcomes. Moreover, these medications are all very expensive and come with an array of side effects.
Thus, not surprisingly, the next question that arises is for a natural supplement that might prevent or treat AD. While huperzine A is a natural acetylcholinesterase inhibitor and NMDA receptor antagonist used by the Chinese for thousands of years, is more potent than prescription-only tacrine & galantaimine, has good brain penetration, and is relatively free of cholinergic side effects, it has never been demonstrated in a randomized, double blind, placebo controlled trial to be of benefit in AD. In fact, a study published in Neurology this month, failed to show any benefit when taken at a dose of 200mcg twice daily by 210 patients w/mild-to-moderate AD for 24 weeks.
However, it's worth noting that some benefit was seen at a dose of 400mcg twice daily. More importantly, in this Phase II study, there were no short-term safety & tolerability issues noted. Just beware that nutritional supplements are manufactured & sold without third-party oversight, so you may not be getting the dose you paid for and your product might also be contaminated. But on the other hand, there does appear to be some benefit to huperzine A at higher dose.
And in case you're following the money, the study was jointly sponsored by the National Institutes of Heallth/National Institute on Aging and Neuro-Hitech, a biopharmeutical company interested in bringing Huperzine A to the market.
Tuesday, April 19, 2011
Brain Volume: Does Size Matter?
As I've mentioned previously, I've been criss-crossing the country recently giving an update on Alzheimer's disease (AD) to fellow family physicians. One of the bigger questions that often comes up is with regards to neuroimaging. In other words, why should we obtain a CT or MRI of the brain?
The practical matter is that while we cannot prove a diagnosis of AD based upon currently available radiologic studies (although cutting edge contrast agents & ligands may be available at research facilities), we can look for masqueraders, such as vascular dementia (from one or more strokes), infection, subdural hematoma, normal pressure hydrocephalus, and even cancer, all of which can alter cognitive function.
With that said, researchers have already started linking brain volume (specifically, hippocampal) & atrophy to cognitive decline. Back in January 2008, those with greater cognitive reserve were shown to have larger brain volume. That same month, white matter hypertensities, presumably from small vessel disease due to vascular risk factors, was associated with a progression from normal cognition to mild cognitive impairment (MCI), while decrease brain volume predicted the conversion of MCI into dementia.
So it should come as no surprise then that in a study published in Neurology this month, brain volume & atrophy, specifically cortical thinning, was able to predict AD in asymptomatic, cognitively intact individuals 10 years prior to onset of cognitive decline & dementia. Granted, this study was rather small, composed of two cohorts of 25 cognitively intact patients each, followed for 11 and 7 years, respectively, of whom 8 patients developed AD in one set and 7 developed AD in the other.
No we're not quite ready to predict AD based upon neuroimaging for brain volume & atrophy. However, we do have data that diabetes, conjugated equine estrogen +/- medroxyprogesterone acetate, reduction in lean mass, and an increase in visceral adiposity have been associated with less brain volume while B vitamins, endogenous sex steroid hormones, and physical activity have been associated with greater brain volume. So it appears that we do have some control over our destiny. And perhaps size does matter. But I'd rather not wait to find out how little I can get away with.
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Monday, April 18, 2011
Vascular Risk Factors vs MCI Conversion into Alzheimer's Disease
One of my slides talks about treating vascular risk factors aggressively to minimize stroke risk. However, in an online release published in Neurology this last week, the authors observed that those patients with VRF were more likely to progress from mild cognitive impairment (MCI) to AD compared to those without VRF. But more intriguing, those who aggressively managed all their VRF were less likely to progress from MCI to AD compared to those who only managed a few of their vascular risk factors.
Granted, these findings were observed in 837 patients w/MCI followed for 5 years, so there's been no randomized, double blind, placebo controlled trial as of yet to demonstrate causation. But when you think about it, is there any reason to accept "good enough" care any longer? We need to strive for optimal care for all our patients!
Sunday, April 17, 2011
Saturday, April 16, 2011
Friday, April 15, 2011
Follow the Money Trail! Part 2
We always want to be the best, the most handsome, the richest, whatever the superlative. And as physicians, we like to think that we're better & more skilled than the average physician and more independent of external (financial) influence than the rest. Yet, when I now look back upon some (all?) of my writings & presentations, the sad truth is that perhaps I was only fooling myself into seeing what I wanted to see.
In a follow up to yesterday's post, I stumbled upon a review published in PLoS Medicine last month in which authors with industry affiliations were more than twice as likely to promote continued use of hormone therapy after publication of the Women's Health Initiative study than those without such financial ties. The good news is that regardless of affiliation, most of the articles reviewed were scientifically accurate. The bad news? Almost two thirds of the articles reviewed were also promotional in nature.
And of the 18 studies that were non-promotional in nature, 11 were authored by those without industry ties. The fact that 3 of the authors with industry ties had large blocks of text self-plagiarized repeatedly without acknowledging or citing the original source makes one suspect medical/scientific ghost writing, which has been another major issue of late.
Now I'm sure (or at least I'd like to believe) that none of these authors put pen to paper thinking explicitly that they needed to put a positive spin on the hormone controversy to continue to receive research money, speaking fees, and/or consulting honoraria. But isn't it ironic that those not beholden to Big Pharma were less promotional, even critical?
As I noted yesterday, we need full disclosure of any and all potential and real conflicts of interest. Just because there is a potential conflict of interest doesn't mean that it will manifest itself. But the public, our patients, needs to make that judgement, that decision, for themselves. It's time we stopped hiding on top of our (academic) pedestals.
In a follow up to yesterday's post, I stumbled upon a review published in PLoS Medicine last month in which authors with industry affiliations were more than twice as likely to promote continued use of hormone therapy after publication of the Women's Health Initiative study than those without such financial ties. The good news is that regardless of affiliation, most of the articles reviewed were scientifically accurate. The bad news? Almost two thirds of the articles reviewed were also promotional in nature.
Granted it's always a good idea to be critical of new study outcomes that contradict the accepted, but when study after study thereafter comes to the same conclusion, perhaps it's time to accept a new course direction. Yet, of the 32 articles supporting & promoting the continued use of peri-menopausal hormone therapy, 30 were authored by those with potential conflicts of interest, eg financial ties to Big Pharma as evidenced by payment for research, speaking, and/or consulting.
And of the 18 studies that were non-promotional in nature, 11 were authored by those without industry ties. The fact that 3 of the authors with industry ties had large blocks of text self-plagiarized repeatedly without acknowledging or citing the original source makes one suspect medical/scientific ghost writing, which has been another major issue of late.
Now I'm sure (or at least I'd like to believe) that none of these authors put pen to paper thinking explicitly that they needed to put a positive spin on the hormone controversy to continue to receive research money, speaking fees, and/or consulting honoraria. But isn't it ironic that those not beholden to Big Pharma were less promotional, even critical?
As I noted yesterday, we need full disclosure of any and all potential and real conflicts of interest. Just because there is a potential conflict of interest doesn't mean that it will manifest itself. But the public, our patients, needs to make that judgement, that decision, for themselves. It's time we stopped hiding on top of our (academic) pedestals.
Thursday, April 14, 2011
Follow the Money Trail!
Depression has always been a major issue. It's pharmacologic therapy has been even more problematic given that early medications were rife with side effects and risk of overdose high. Thus, treatment was mainly left to the psychiatrists until the advent of the selective serotonin reuptake inhibitor (SSRI) class, which was noted for its much lower side effect profile and overdose potential, and which has allowed for its widespread prescription by non-psychiatrists, namely primary care physicians, such as family physicians and internists.
Now, after two decades of use, we have a less sanguine view of SSRIs with their withdrawal syndrome, serotonin syndrome, and even an increase risk of suicidality in children & teenagers necessitating a black box warning. Lately, there has been some concern & controversy about a possible link between antidepressant use and an increase risk of breast & ovarian cancer.
But what I find intriguing is the conflict, which at face value is not new in the medical world. However, it's interesting to note that in a study published last week in PLoS ONE, one's ties to Big Pharma appeared to influence the conclusion of one's research. Of the 61 studies that were reviewed, one third reported an association between antidepressants and cancer. The remaining two thirds reported no association or possibly even an antiproliferative effect.
However, the authors with industry affiliations were much less likely to report a link between antidepressant use and cancer compared to those authors without industry ties. Maybe there's no real link but doesn't it appear suspicious that someone is hiding something?
However, the authors with industry affiliations were much less likely to report a link between antidepressant use and cancer compared to those authors without industry ties. Maybe there's no real link but doesn't it appear suspicious that someone is hiding something?
We may accept cloak & dagger secrets when it comes to business & government but not with regards to our science & medicine. However, despite our many attempts to develop & enforce conflict of interest policies, there are still too many reports of breach & loss of faith in our medical profession to maintain the public's trust. We must absolve to free ourselves of any hint of bias and place our patients' interests above our own. Yes, medicine is a business. But it is a business in which the customer must always come out a winner and believe in the word of the owner/physician.
Wednesday, April 13, 2011
The Pen is Mightier than the Sword
Medical management or surgical intervention? For some conditions, it's clear cut. In diabetes, the surgeons don't have much of a role (unless you consider bariatric surgery). Same with hypertension (unless you're looking at renal artery stenosis or pheochromocytoma). The shoe's on the other foot when it comes to appendicitis (although there are some folks considering antibiotics alone). In the middle is heart disease. Over the last few years, we started to look more closely at medical management.
Just last week, a study was published in the New England Journal of Medicine that concluded that medical management was equivalent to coronary artery bypass grafting for ischemic heart failure with regards to all-cause mortality. Granted those who underwent a CABG had a slightly lower risk of cardiovascular death. But when you think about it, we have to die from something at some time, so all-cause mortality is key.
How did they come to this conclusion? In the international study, STICH, they followed 1,212 men w/heart disease (specifically coronary artery disease amenable to CABG) and heart failure <30% ejection fraction. But what does this tell us about the mortality risk for those with heart failure but without ischemic disease. Nothing. For now, it's imperative that we offer standard of care medical management when it comes to treating those with heart failure, regardless of the type chosen.
Just last week, a study was published in the New England Journal of Medicine that concluded that medical management was equivalent to coronary artery bypass grafting for ischemic heart failure with regards to all-cause mortality. Granted those who underwent a CABG had a slightly lower risk of cardiovascular death. But when you think about it, we have to die from something at some time, so all-cause mortality is key.
How did they come to this conclusion? In the international study, STICH, they followed 1,212 men w/heart disease (specifically coronary artery disease amenable to CABG) and heart failure <30% ejection fraction. But what does this tell us about the mortality risk for those with heart failure but without ischemic disease. Nothing. For now, it's imperative that we offer standard of care medical management when it comes to treating those with heart failure, regardless of the type chosen.
Tuesday, April 12, 2011
Menopausal Estrogen: Good or Bad?
As I noted back towards the end of January, hormone replacement has received quite a bad rap since the Women's Health Initiative study was first released. It's unfortunate, however, that the lumpers put conjugated equine estrogen (CEE) in the same group as bio-identical estradiol. Likewise, they did the same with medroxyprogesterone acetate (MPA) and bio-identical progesterone, which is chemically distinct. Ironically, traditional medicine and the press downplayed any benefit from the use of CEE alone in those women who had been hysterectomized. But those of you who paid close attention theorized that perhaps the bad news was due to MPA rather than CEE.
So here it is nearly a decade later and a study was released last week in JAMA concluding that almost 6 years use of CEE alone did not change (increase or decrease) heart disease, stroke risk, venous thromboembolism risk, colorectal cancer or total (all-cause) mortality. Interestingly, those who took CEE alone did demonstrate a lower risk of breast cancer as noted in the initial study.
What does this mean for our female patients? If your peri-menopausal symptoms are bothering you enough, take the lowest dose for the shortest period of time without any fear of negative outcomes over the ensuing 10 years. But don't take it because you're trying to improve or prevent some health outcome. And while you're at it, consider a bio-identical transdermal estradiol, rather than conjugated equine estrogen. Studies demonstrate safer physiologic responses and better outcomes w/bio-identical transdermal estradiol products.
But what do you do if your patient doesn't believe in Big Pharma products (and you don't believe in compounded estradiol)? Consider branded bio-identical transdermal estradiol products such as Vivelle-Dot or Climara (not Climara Pro which contains non-bio-identical levonorgestrel). That way you and your patient can have the best of both worlds.
Monday, April 11, 2011
Help Train Future Physicians: Say Yes to Interns & Residents - Part 3
As a follow up to last Friday's post, I'd have to venture that working 80 hours a week is still a bear. But it's better than working more than 80 hours a week! However, if we were to look at work hour limitations from the interns & residents perspective, that's still averaging more than 11 hours a day, 7 days a week. I mention this little tidbit because in a study published last week in the Annals of Internal Medicine, the authors concluded that the more hours one spends at work, the greater one's risk for heart disease.
What's this mean for us? Sleep is important, sure. But, so is time off from work. No one ever claimed on their deathbed that s/he wished s/he'd worked more. The problem for those of us dedicating ourselves to our jobs is the sacrifice & loss of our own health.
They came to this conclusion after following 7,095 men & women w/o heart disease for more than 12 years. Those who worked 11 or more hours per day had a 67% greater risk for heart disease compared to the more than half who worked 7-8 hours/day. Furthermore, adding hours worked per day to the Framingham Risk Calculator improved its accuracy in reclassifying and better predicting those who would later develop heart disease.
What's this mean for us? Sleep is important, sure. But, so is time off from work. No one ever claimed on their deathbed that s/he wished s/he'd worked more. The problem for those of us dedicating ourselves to our jobs is the sacrifice & loss of our own health.
Sunday, April 10, 2011
Saturday, April 9, 2011
Friday, April 8, 2011
Help Train Future Physicians: Say Yes to Interns & Residents - Part 2
Recently, an air traffic controller at Washington Reagan National Airport failed to respond to radio & phone calls for 20 minutes or so. Two days later, he admitted to having fallen asleep because he was working his fourth consecutive overnight shift. What's not clear to me is whether he had worked four straight 24 hour shifts or simply switched to 4 consecutive night shifts without allowing for physiologic circadian adjustment.
I mention this because until recently, due to federal mandate, we (the medical profession) prided ourselves on our mental toughness and ability to go for days (and nights) on end w/o little-to-no sleep. After all, when I trained many moons ago, it was common to be on call every other night during some rotations. And to prove our machismo, we complained that we were disappointed because we would miss half the cases!
However, we have since learned that sleep deprivation is a bad thing that impairs both clinical judgment and fine motor coordination. Most notably, the death of Libby Zion resulting from allegedly overworked & under-supervised resident physicians lead to the passage of work hour limits in New York in 1989. This was followed by national work hour limits in 2002 so while the clock for overtime for most hourly employees starts after 40 hours worked in a week, we are now prohibited from allowing our residents to work more than 80 hours a week. Back in the day (imagine chest thumping here), we routinely put int 50% more hours, spending most waking hours in the hospital without much conscious time outside (time off work was spent asleep getting ready for another shift). In fact, my then-girlfriend-now-wife still recalls that I fell soundly asleep at the table during our first Valentine's Day dinner.
So here we are many years later and it's good to find out that, in a review of 72 studies published last month in the British Medical Journal, reducing the work hour limit to 80 hours a week has not made a negative impact on either patient outcomes or physician training. Unfortunately, if you like your glass half empty rather than half full, the converse of this study is that patient outcome (read safety) hasn't improved either. In Europe, there are already scattered attempts to further reduce work hours to a more humane 56 or 48 hours a week. The jury is still out as we gradually step off our sleep pedestal and allow our residents the sleep we recommend for our patients.
I mention this because until recently, due to federal mandate, we (the medical profession) prided ourselves on our mental toughness and ability to go for days (and nights) on end w/o little-to-no sleep. After all, when I trained many moons ago, it was common to be on call every other night during some rotations. And to prove our machismo, we complained that we were disappointed because we would miss half the cases!
After I started teaching, the work hour limits came into play. Academia struggled with how to balance these new regulations with providing quality care and a sound educational experience. The initial solution was the attending physician filling in for the residents, enough so that my wife commented that I was working harder as an attending than as a resident! So a new rotation (night float) was designed whereby one's only responsibility was to work nights for a month or two, covering overnight call for one's fellow residents. But at what cost (some estimate as much as $1.6B annually) as another rotation's learning experience was sacrificed.
So here we are many years later and it's good to find out that, in a review of 72 studies published last month in the British Medical Journal, reducing the work hour limit to 80 hours a week has not made a negative impact on either patient outcomes or physician training. Unfortunately, if you like your glass half empty rather than half full, the converse of this study is that patient outcome (read safety) hasn't improved either. In Europe, there are already scattered attempts to further reduce work hours to a more humane 56 or 48 hours a week. The jury is still out as we gradually step off our sleep pedestal and allow our residents the sleep we recommend for our patients.
Thursday, April 7, 2011
Bisphosphonates & Atypical Femur Fractures: Part 3 - Take Teriparatide!
We've taken a hard look at bisphosphonates lately, first in December and then in February. The consensus now is to take them only if necessary (and only after clearance from your dentist) and then only for about 5 years with the understanding that bisphosphonates do lower the risk of osteoporotic fractures which overrides the extremely low risk of an atypical fracture (although admittedly it is increased).
But what if you're too late to heed this new bit of advice? Let's say you've been taking your bisphosphonate for over a decade, even 13 years. And to make matters worse, what if you were just diagnosed w/bilateral femoral stress fractures?
In a case report to be published in the June issue of the Journal of Clinical Endocrinology & Metabolism, the authors reported healing after bringing this 63 year old female patient's vitamin D level back into the normal range and then offering her teriparatide, the daily injectable recombinant parathyroid hormone, for 16 months.
Now, don't get me wrong. I'm not recommending that you start teriparatide based upon one patient's experience. But if you (or your patient) find yourself in a similar situation, consider looking at the study in detail.
Wednesday, April 6, 2011
Telomeres & Childhood Obesity
Telomeres are those endcaps on the tips of our chromosomes that are purportedly linked to our health & death. Some propose that the length of the telomere limits cell division (and thus ongoing life). In fact, shorter telomeres have been linked with heart disease & hypertension, diabetes, including insulin resistance & impaired glucose tolerance, and even cancer. Granted, we haven't figured out the chicken & egg relationship, whether shorter telomeres predisposes us to disease or vice versa, disease shortens telomeres.
But some would like us to act upon this now. In fact, based upon one short trial in a small number of subjects, they would like to sell us a nutritional supplement (if they called it a medicine, they'd have to past FDA muster) that promises to lengthen our telomeres for the princely sum of $2,000 per month.
Unfortunately, most would rather depend upon taking fish oil, multivitamins and vitamin D to lengthen their telomeres. But just where did our lifestyle inertia come from? In a study to be published next month in the Journal of Clinical Endocrinology & Metabolism, the authors demonstrated an association between obese children and shorter telomeres, with longer telomeres found in their non-obese cohorts.
What could you do with an extra $2,000 every month? Pop 4 pills every day? Or invest that sum in proper nutrition & regular physical activity for both you & your family. It's never too early to start!
But some would like us to act upon this now. In fact, based upon one short trial in a small number of subjects, they would like to sell us a nutritional supplement (if they called it a medicine, they'd have to past FDA muster) that promises to lengthen our telomeres for the princely sum of $2,000 per month.
But what if you don't have $2,000 burning a hole in your pocket every month? After all, there's a world-wide recession going on the last time I looked. Well, proper nutrition & lifestyle have been associated w/longer telomeres in women. And so has IGF-1 in both men & women (presumably resulting from growth hormone - so don't forget strenuous exercise & a good night's rest), especially since physical activity has been directly linked to longer telomeres. Even exercise capacity, as a measure of physical activity, has been associated with longer telomeres.
Unfortunately, most would rather depend upon taking fish oil, multivitamins and vitamin D to lengthen their telomeres. But just where did our lifestyle inertia come from? In a study to be published next month in the Journal of Clinical Endocrinology & Metabolism, the authors demonstrated an association between obese children and shorter telomeres, with longer telomeres found in their non-obese cohorts.
What could you do with an extra $2,000 every month? Pop 4 pills every day? Or invest that sum in proper nutrition & regular physical activity for both you & your family. It's never too early to start!
Tuesday, April 5, 2011
Please Turn Off The Light, Honey, I Don't Want Cancer
How many of you fall asleep with the TV on? Or with room lights on? In a study published in last month's Journal of Clinical Endocrinology & Metabolism, researchers concluded that exposure to room light while asleep decreased melatonin by 50%. Furthermore, room light (compared to dim light) in the 8 hours preceding bedtime delayed melatonin release and shortened melatonin duration.
Why is this important? Melatonin is a hormone produced by the pineal gland, our primitive third eye, which helps us regulate our sleep-wake cycle to coincide with our surrounding environment (daytime & nighttime). There is also a body of research looking at melatonin as an antioxidant w/anti-cancer properties of some sort. In fact, an observational study has shown that women who are blind and thus cannot perceive light vs dark have a lower risk of breast cancer (presumably b/c their body is in a perpetual state of nighttime which allows for more melatonin).
Conversely, two analyses of the Nurses Health Study (NHS) have demonstrated an association between working night shift (just 3 a month for 15 years or more) and an increase risk in both colon cancer and breast cancer. Another observational study came to a similar conclusion linking night shift work to increased breast cancer risk.
Of course science is never clear cut & crystal clear. Case in point, another analysis of NHS showed that working the night shift was protective against skin cancers, particularly melanomas. Perhaps working night shift prevents ultraviolet radiation's mutagenicity which is more critical for skin cancer while the decrease in melatonin allows colon & breast cancers to develop.
Whatever the explanation, in October 2007, the International Agency for Research on Cancer felt strongly enough about the available data to conclude that "shift-work that involves circadian disruption is probably carcinogenic to humans".
So what are we to do? Someone has to work those night shifts. And the fact of the matter is that just about everyone of us turns on the lights in our homes after it gets dark inside (and outside). I doubt that we're going to return to our ancestors' ways of working from dawn to dusk and resting (sleeping) from dusk to dawn. But we could at least turn off the lights (and TV) before we go to sleep.
PS Those low wattage/lux night lights don't count. We don't want you tripping and breaking something!
Monday, April 4, 2011
Prostate Cancer Screening May Not Be As Effective As We'd Like To Believe
The Times They Are a-Changin' - Bob Dylan
There once was a time when prostate cancer was most often diagnosed late in the course of the disease after the patient presented complaining of back pain w/absurdly elevated prostate specific antigen (PSA) levels. Then someone had the bright idea to screen for prostate cancer by checking PSA levels (in addition to digital rectal examinations) in asymptomatic men after arbitrarily deciding to call all levels >4ng/mL abnormal. However, we've never really proven that this early screening makes a difference in mortality. After all, if we cure a disease that isn't going to affect mortality, what good are we doing.
Sure, we always read about the men who die from or because of prostate cancer, such as Frank Zappa (52yo), Johnny Ramone (55yo), Jerry Orbach (69yo), Telly Savalas (70yo), Dennis Hopper (74yo), Earl Woods (74yo), and Pierre Elliott Trudeau (80yo). And we hear even more often from those who were successfully treated, such as Robert DeNiro (now 8 years post-diagnosis), Rudy Giuliani (10 years), Roger Moore (18 years), General H. Norman Schwarzkopf (18 years), Louis Farrakhan (20 years), and Senator Bob Dole (20 years). But have we helped them live any longer than if we'd just watched & waited? And at cost were these men "cured" with life changing side effects, eg incontinence, erectile dysfunction, proctitis & diarrhea.
In a study just published in the British Medical Journal, the authors concluded that over 20 years of follow up, mortality did not differ between those who were screened (1,494 individuals) and those were not (7,532 controls). Perhaps, this finding was an anomaly. But in fact, a systematic review & meta-analysis published last September (also in the BMJ) of 6 randomized controlled trials involving 387,286 individuals arrived at the same conclusion: no statistically significant effect of screening on prostate specific and all-cause mortality. Back here in the States, the ongoing Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial also came to the same conclusion in March 2009 after following 76,693 men for 7-10 years.
When you think about it, these findings are consistent with the spate of studies suggesting that active surveillance is a reasonable option in those w/localized, low grade diagnosis. Which might explain why a study in JNCI questioned the value of a prostate biopsy based just upon PSA velocity. If anything, this really begs the question as to why screen at all? Sure, maybe if you have a family history of aggressive cancer leading to death at any early age. But for the rest of the population, are we really doing them any good?
There once was a time when prostate cancer was most often diagnosed late in the course of the disease after the patient presented complaining of back pain w/absurdly elevated prostate specific antigen (PSA) levels. Then someone had the bright idea to screen for prostate cancer by checking PSA levels (in addition to digital rectal examinations) in asymptomatic men after arbitrarily deciding to call all levels >4ng/mL abnormal. However, we've never really proven that this early screening makes a difference in mortality. After all, if we cure a disease that isn't going to affect mortality, what good are we doing.
Sure, we always read about the men who die from or because of prostate cancer, such as Frank Zappa (52yo), Johnny Ramone (55yo), Jerry Orbach (69yo), Telly Savalas (70yo), Dennis Hopper (74yo), Earl Woods (74yo), and Pierre Elliott Trudeau (80yo). And we hear even more often from those who were successfully treated, such as Robert DeNiro (now 8 years post-diagnosis), Rudy Giuliani (10 years), Roger Moore (18 years), General H. Norman Schwarzkopf (18 years), Louis Farrakhan (20 years), and Senator Bob Dole (20 years). But have we helped them live any longer than if we'd just watched & waited? And at cost were these men "cured" with life changing side effects, eg incontinence, erectile dysfunction, proctitis & diarrhea.
In a study just published in the British Medical Journal, the authors concluded that over 20 years of follow up, mortality did not differ between those who were screened (1,494 individuals) and those were not (7,532 controls). Perhaps, this finding was an anomaly. But in fact, a systematic review & meta-analysis published last September (also in the BMJ) of 6 randomized controlled trials involving 387,286 individuals arrived at the same conclusion: no statistically significant effect of screening on prostate specific and all-cause mortality. Back here in the States, the ongoing Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial also came to the same conclusion in March 2009 after following 76,693 men for 7-10 years.
When you think about it, these findings are consistent with the spate of studies suggesting that active surveillance is a reasonable option in those w/localized, low grade diagnosis. Which might explain why a study in JNCI questioned the value of a prostate biopsy based just upon PSA velocity. If anything, this really begs the question as to why screen at all? Sure, maybe if you have a family history of aggressive cancer leading to death at any early age. But for the rest of the population, are we really doing them any good?
When the facts change, I change my mind. What do you do, sir? - John Maynard Keynes
Sunday, April 3, 2011
Saturday, April 2, 2011
Friday, April 1, 2011
Help Train Future Physicians: Say Yes to Interns & Residents
I've been "in" medicine for close to a quarter century now (pretty scary) on both sides of the table & auditorium, first as a student, then as an intern (1st year resident), resident (in family medicine) & fellow (in geriatrics), and finally as an attending physician, training our future providers of care. In retrospect, I am very grateful to all the patients who allowed me to participate in their care and gain the experience necessary to care for and pass onto others. Without their permission, I would not be where I am today.
Thus, I've always struggled with how to respond when informed of patients who request that no physicians-in-training, whether med students, interns, residents, and/or fellows, be involved in their care. Luckily, there aren't too many of these patients (at least not at the School of Medicine where my family and I receive our care). I guess they self-select in that those who don't want trainees go to private hospitals, whereas those who don't care, don't know, or don't have a choice go to teaching hospitals, where it's expected that trainees (of all kinds) will be involved.Therefore, I'm happy to report that a study published just last month concluded that resident participation was associated with lower mortality. Specifically, the American College of Surgeons reviewed 607,683 surgical cases and found greater morbidity with resident participation in vascular procedures, pancreatectomy, esophagectomy, and colorectal resections. On the other hand, and more important at that, there was a slight decrease in mortality. In the final analysis, resident involvement was associated with 6.1 additional morbid events but 1.4 fewer deaths per 1,000 procedures.
Granted, I'm not a surgeon, but it's good to know that surgical training doesn't negatively impact patient care & outcome. And let's not forget that surgeons (and physicians) continue to learn new procedures & techniques even after finishing their formal training. Without patients willing to have a physician learn & practice his/her newly acquired skill, progress could not be made (or at least not at its current rate). So thank you to all of you who have helped train physicians.
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