The Doctor Weighs In

"Most heart attacks in women are preventable," is the headline of an article posted on NBC.com.  The article describes a study, published in the Archives of Internal Medicine, that was done by the researchers at the Karoinska Institute in Sweden.  Dr. Agneta Akesson and colleagues looked at the diet and lifestyle patterns of almost 25,000 postmenopausal women.  At the time of enrollment none of the women had heart disease, diabetes or cancer.

The researchers asked the women to fill out "food frequency" questionnaires to identify how often they ate 96 different foods.  The researchers analyzed the data and found four major dietary patterns:

• Healthy - vegetables, fruits, and legumes
• Western/Swedish - red meat, processed meat, poultry, rice, pasta, eggs, fried potatoes, and fish
• Alcohol - wine, beer and some snacks
• Sweets - sweet baked goods, candy, chocolate, jam, and ice cream

Other information collected included family history of heart disease, education level, physical activity, and body measurements.

The women were followed for an average of 6 years.  During that time, 308 women had heart attacks.  The investigators found that two of the dietary patterns (healthy and alcohol) were associated with a decreased risk of heart attack.  Women who drank less than a quarter ounce of alcohol daily (that is just a splash in the bottom of your glass) and ate lots of veggies, fruit, whole grains, legumes, and fish had a 57% lower risk of having a first heart attack.  That is a whopping big difference.

If women added three other healthy lifestyle habits into the mix (not smoking, being physically active, and avoiding too much weight gain), they had a 92% lower risk of heart attack.  In other words, most heart attacks in women are preventable by making healthy lifestyle choices.

Now, it is one thing to say, eat healthy, drink in moderation, exercise and maintain a healthy weight.  It is quite another thing to actually do all of those things over the course of an entire lifetime.  On the other hand, if you look at the amount of money the US (and, indeed, the entire world) spends to treat cardiovascular disease, I believe you would find there is enough there to buy each and every person a personal cook and a personal trainer (I believe this is the secret to Oprah's weight loss and maintenance).

I say this tongue in cheek, but it does make the point that we aren't spending our "health" care dollars on the right things.  We spend generously to fix disease, but we are very stingy when it comes to funding health.   It is time to get this right.  There aren't enough dollars in any treasury to treat all of the heart disease we are going to see as a result of the global epidemic of obesity and physical inactivity.  This must be  a top priority of policy makers and health reformers.  Studies, like the Karolinska study, should be used to promote changes in public policy - such as healthy school foods, ensuring that all neighborhoods have access to fresh fruits and vegetables and that they have safe places where kids and adults can move their bodies (without worrying about getting shot in the process).

Every politician, health reformer, and policy wonk ought to know about this study and others that prove that healthy lifestyles mean fewer heart (expensive) attacks - not just in women, but in men as well.  The bottom line is most heart attacks are preventable!

by Dov Michaeli

Sometimes revolutionary developments come out of the most unexpected corners. There is new branch is medical research called regenerative medicine.

The “old” way of treating disease (which we are still practicing today) is through drugs that treat the consequences of the disease. For instance, anti-inflammatory drugs to treat arthritis, or statins to lower cholesterol through inhibition of its synthesis, or chemotherapeutic drugs to kill tumor cells.

The bold vision of investigators in the regenerative medicine field is to simply replace the ailing organ with a healthy one. I am not talking about transplantation; I am talking about stem cells that can be programmed to replace an injured muscle, a severed spinal cord, or damaged pancreatic beta cells that can no longer synthesize insulin. This is a breathtaking paradigm shift that promises to revolutionize the way medicine will be practiced in the not so distant future.

Out of left field

As our attention was riveted on “the big stuff” of stem cells, a barely noticed report, published in the February issue of The Archives of Dermatology (vol. 143, pp. 155-163, 2007), looked at the mode of action of a dermal filler used in cosmetic medicine to treat facial wrinkles. The report, by a group from the department of Dermatology at the University of Michigan, showed that contrary to the belief that the material (Restylane is made up of a substance called cross-linked hyaluronic acid) acted simply by physical expansion of the skin volume, it actually had a biological effect.

What is a wrinkle?

The skin is made up of a thin outer layer of cells called epidermis, and a much thicker layer called dermis. The bulk of the dermis is composed of a protein called collagen, as well as smaller amount jelly-like materials, hyaluronic acid being one of them. Collagen is synthesized by special skin cells called fibroblasts.

In a young person the fibroblasts have a stretched appearance and secrete copious amounts of the collagen, enough to make up for the continuous degradation of skin collagen by an enzyme called collagenase. In older people the fibroblasts become more relaxed and rounded, and secrete less collagen, not enough to counteract the losses due to the degradation by collagenase. Slowly but surely, enough collagen is removed, the dermal structure collapses, and we get the dreaded wrinkles.

What the investigators found is that the hyaluronic acid in Restylane caused the re-stretching of the fibroblasts, causing them to increase their synthesis of collagen. As a bonus, the material also reduced the activity of the enzyme collagenase. The key to achieving this effect was the repeated injection of the material, 6-12 months apart, until enough stretching of the fibroblasts took place. How long would this effect last? This is still unknown, but the thought is that as long as the injected material is present the fibroblasts would remain stretched and synthesize more collagen.

Why is it exciting?

First, if confirmed, it promises to make us look young forever, or at least as long as we live. Isn’t that what all aging boomers look for?  But more importantly, here is the first realization of the regenerative medicine dream: use of the body’s own cells to regenerate damaged organs.

I love this study, because out of the limelight of the titanic stem cell struggles a relatively unknown group of dermatologists found a simple, and vastly more practical solution then stem cells to rejuvenation the sagging skin—simply stretch the old fibroblasts.   The study used Restylane only because it was started before a similar product, Juvéderm, was available. In my estimation, both products should work equally well; but the proof will require another study.

Here is another interesting aspect of progress in medicine. The material was originally intended as a physical filler; nobody had any grandiose thoughts about profound biological effects. After all, collagen itself was used as a filler to treat wrinkles, and indeed that is all it was—a filler, which degraded with time.

Hyaluronic acid, quite unexpectedly, opened new avenues for research in tissue regeneration. Would we be able soon to grow pre-existing brain neurons in Parkinson’s or Alzheimer’s patients by simply injecting ‘brain filling material’? If you asked this question a few months ago you’d be laughed out of the room. It is now totally plausible. Isn’t that exciting?

Dov Michaeli MD Ph.D. is in the biotech industry, engaged in drug development.

by Pat Salber, MD

In the early days of the clinical practice guidelines movement, doctors used to complain that it was “cookbook medicine.” As a pretty good cook, who still uses cookbooks, I say, great – when you follow the directions of experts, instead of “winging it,” you increase the odds of getting a good outcome.

So it should be not a surprise that a new study, in the July 23 issue of Archives of Internal Medicine, found that outcomes of hospitalized heart-failure patients are improved when hospital personnel follow clinical guidelines.

OPTIMIZE-HF (“Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure”) is a heart failure guidelines/quality improvement program adopted by the American Heart Association (and sponsored by drug maker GlaxoSmithKline). The program provides hospitals with tools to help improve the reliability of care, including standardized admission orders, discharge checklists, pocket cards, medical chart stickers, best-practice algorithms and critical pathways. It is currently being used by 259 hospitals across the US.

The study, led by Gregg Fonarow, MD from UCLA’s Department of Medicine, looked at data entered into an online OPTIMIZE-HF performance improvement registry. Admission, hospital, discharge care, and outcomes (death and hospital readmission rates) data on 48,612 heart failure patients were entered into the registry between March 2003 and December 2004. A subgroup of 5,791 patients were followed for an additional 60-90 days after they were discharged from the hospital.

The researchers found statistically significant improvements in three of four of the Joint Commission on Accreditation of Healthcare Organization's performance measures used to gauge the quality of heart failure care in hospitals. They included:

· Better patient discharge instructions. The rate of giving complete medical instructions to patients increased from 46.8 percent at the beginning of the study to 66.5 percent by the study's end.

· Smoking cessation counseling. Hospitals provided smoking cessation counseling to 75.6 percent of the patients at the end of the study, compared with 48.2 percent in the beginning.

· Left ventricular function assessment. Evaluating the heart's left ventricle systolic function rose from 89.3 percent to 92.1 percent.

A fourth measure, the rate of angiotensin-converting enzyme inhibitors (ACEIs) prescribed to eligible patients at discharge was 75.8% at baseline. This rate did not improve during the 2-year study.

There was a statistically significant reduction in the mean length of stay for these patients, going from 7.5 days at baseline to 6.2 days at the end of the study. In addition, were trends for reduction of in-hospital mortality, postdischarge death, and combined postdischarge death and rehospitalization, but they did not reach statistical significance.

So patients did better and hospital days were reduced (and so were costs presumably). What’s not to like? According to the lead author, Dr. Fonarow, as quoted in the Washington Post:

"If similar improvements had occurred at hospitals nationwide, this would translate to 40,000 less deaths and 1.4 million costly hospital days eliminated per year. Despite compelling scientific evidence and national guidelines for use of key life-prolonging agents and lifestyle changes, gaps exist in heart failure treatment. We hope more hospitals will adopt this validated model for enhancing heart-failure patient care."

Amen.

It has been well-documented that women could reduce their risk of being diagnosed with breast cancer by eating vegetables and fruits, exercising and keeping a non-obese BMI (>25). But the pervasive feeling among physicians (yours truly included) was that once cancer is diagnosed, changes in life style are too little too late. But a recent study (Journal of Clinical Oncology, vol. 25, pp. 2345-2351, 2007) looked at this issue, and the results were totally unexpected.

How the study was done

A prospective study was performed of 1,490 women diagnosed and treated for early-stage breast cancer between 1991 and 2000. Enrollment was an average of 2 years postdiagnosis. An analysis of the effect of interaction between different factors on survival (called multivariate analysis) found that a combination of exercise, equivalent to a 30 minute walk six times a week, and a diet rich in vegetable and fruits (five or more daily servings) had the biggest effect on survival. There was no effect of obesity per se on survival; as long as the woman exercised and ate well her chances of survival were significantly increased.

How big was the effect?

Very big! Women who adhered to the diet and exercise regimen had a 50% reduced risk of dying, compared to women who did not.

Mind you, these were women with end stage disease. To keep things in perspective, when we get say, a 20% increased survival with a new chemotherapy drug, this is grounds for accelerated approval by the FDA. Here is a completely natural and healthy way of prolonging survival, with the only ‘side effect’ being… feeling much better. Not bad.

The usual caveats

The study was prospective, which is the gold standard for good clinical trials. It was also multi-institutional (UCSD, Stanford, Kaiser Permanente, Arizona Cancer Center in Tucson , and the M.D. Anderson Cancer Center in Houston , TX ), which avoids the possibility of institution-specific confounding factors. The patients were all end-stage, which avoids the ‘contamination’ of the sample with early stage, curable cancer.

On the downside, the study was relatively small (1,490 patients), although the results were statistically significant, because the effect was so big. If the effect was smaller, a much larger sample would have been necessary. Still, the authors rightly conclude that further study is needed.

I agree. A larger population size may have canceled out confounding factors that have not been considered. For instance: The women were entered into the study 2 years post diagnosis, and after receiving chemotherapy. If the diet/exercise regimen did not make any difference in mortality, then it would not have made any difference in the outcome. But if we assumed that it did, then during the 2 years preceding enrollment the women who did not follow the regimen got sicker and entered the trial in poorer shape, increasing their chances of dying earlier. The net effect would have been to exaggerate the magnitude of the effect, not necessarily negate it.

Having said that, I think this study is of tremendous importance because it showed the role of lifestyle not only in the prevention of cancer, but also in therapy. This is novel, encouraging, and requires a major research effort in order to incorporate it in the treatment of breast and other cancers (for instance colon cancer) that have shown a relationship to diet, exercise and obesity.

I recently came across an article in the April 23 issue of the Archives of Internal Medicine (vol. 167, pp. 802-807; 2007) describing a newly-discovered connection between depression and diabetes type 2 in older adults. The study enrolled 4,681 non-diabetic men and women over age 65, and followed them for 10 years. The participants filled out every year a questionnaire to measure their depressive symptoms, and every 2-4 years had their blood pressure measured. After removing confounding factors that are well known to increase the incidence of diabetes, like increased body mass index, alcohol consumption, and smoking, they discovered that even a single report of high depressive symptoms is highly associated with increased risk of diabetes type 2. In fact, there was a 60% increased chance of developing diabetes after reporting one incidence of high depression; this is significant by any measure.

Is it a good study?

I think it is an excellent study. The study group was ‘clean’, namely all diabetics and pre-diabetics were excluded from participation in the study. It was longitudinal, following the 4,581 participants for 10 years. The numbers were large enough and the observation period long. Furthermore, the authors accounted for all the obvious confounding factors, like obesity, smoking status, alcohol consumption, and anti depressant use. What is most convincing is that there was a relationship between the score of depression and the likelihood of developing diabetes, what we call in experimental medicine a ‘dose/ response’ relationship. The highest score had the highest increase in risk (60%).

How could depression cause diabetes?

There could be several explanations for this observation, and the answer is not really known. But if we look at the hormonal changes that accompany depression, we may find a possible link to diabetes. Cortisol is a stress hormone that is elevated in depressive states. Cortisol also happens to inhibit the secretion of insulin from the beta cells in the pancreas. Lower blood insulin would in turn lead to higher blood sugar, a hallmark of diabetes.

Caveat emptor

As always, when I speculate I feel obliged to caution that what ‘makes sense’, in biology it ain’t necessarily so. Biology is so complex, and largely still unknown, that any attempt to ‘dry lab’ it is an exercise in futility. Still, using speculation to form a testable hypothesis is how science works. For instance, we could test the cortisol hypothesis by measuring its blood levels in patients reporting an episode of depression and see if there is a correlation between it and the onset of diabetes. Or an experiment could be devised in which any participant reporting a depressive episode would be immediately treated with anti depressive drugs. Would that reduce the risk of developing diabetes?

I am sure many of you have other suggestions to study the depression/diabetes relationship. Send in your suggestions; we promise to publish and critique them.

Dov Michaeli, MD, Ph.D.

The President has indicated that he will veto the bill on Monday when he returns to Washington, DC. Please tell the President to uphold his duty to the 70% of Americans who support embryonic stem cell research and not to veto S. 5....send a fax to the White House and ask President Bush not to veto hope!"

Here is how you can help:  Send a simple email to President Bush today at comments@whitehouse.gov or fax (202-456-1111).  Your message doesn't need to be long (he probably won't read it anyway) or complicated.  Just be clear about what you want. 

Here is some sample language:

"President Bush,

Don't veto hope.  Americans want sensible, sensitive stem cell research.  S-5 provides for that.  This legislation is life-affirming.  Let it stand.

Sincerely,"

Please help.

Pat Salber, MD

Given the drawbacks of the current commonly used diabetes screening methodology – fasting blood glucose – and the fact that more than 20 million people are thought to have undiagnosed diabetes in the US alone, an easier and more convenient screening test would be a very welcome addition to the diabetes testing armamentarium.

Fasting Plasma Glucose

The limitations of using fasting plasma glucose (FPG) as a screening test for diabetes include the following factors:

• You have to fast overnight before having the test – that means you have to get yourself to a clinic or laboratory in the morning before going to work. Hmmm. Not such an easy thing to do when you have to get the kids to school and yourself to work. So, if you are like me you keep putting it off and putting it off – it doesn’t mean you are ignoring the need to have the test – it is just a fact that today’s crowded lives don’t mesh well with yesterday’s screening technologies.

• You need to have blood drawn. Again, no big deal for some people, but a dreaded experience for others. I have seen great big guys faint on the spot when they see their blood sucked up into that little tube. So, again, it can be one more reason to put “diabetes screening” on the bottom of the “to do” list.

• The test misses quite a few cases of diabetes. It only detects elevated glucose when a person is fasting. It does not detect abnormal elevations of glucose after a meal. An even more inconvenient Oral Glucose Tolerance Test (OGTT) is needed for that. This test involves having blood drawn, drinking a standardized glucose-containing solution and then having blood drawn again 30, 60 and 120 and, sometimes, 180 minutes later.

So, you may be thinking, what’s the big deal if you put off screening for diabetes. It is because diabetes complications mount up as diabetes remains undiagnosed year after year. That is the reason that many diabetic patients will have one or more irreversible complications at the time they are diagnosed (Harris MI, Diabetes Metab Res Rev 16:230-236, 2001).

Enter SAGE

SAGE is a new diabetes screening technology. It is short for “Spectroscopic measurement of dermal AGEs.” AGEs are “advanced glycation end products” that form when glucose levels, over time, are elevated. AGEs serve as biomarkers for diabetes.  Their levels correlate with existing complications of diabetes and have been shown to predict future complications, such as diabetic kidney or eye disease

Like A1C (a blood test that measures glycosylation of hemoglobin), but unlike a spot glucose blood test, AGEs are not affected by acute increases in glucose. Therefore, a test that measures skin AGE levels can be performed regardless of whether the individual has fasted or just eaten. This fact, combined with the fact that there is no need to draw blood, makes this technology highly attractive.

AGEs are measured using a spectroscope that measures skin fluorescence. AGE accumulation impacts flourescense. Since skin naturally accumulates AGEs over a person’s lifetime, it is necessary to apply an algorithm to correct for age.

How does SAGE compare with FPG and A1C testing?

Maynard and his New Mexico colleagues, as reported in Diabetes Care May 2007,  performed a head-to-head comparison of SAGE with both FPG and A1C testing. 351 people were tested with the SAGE technology in the fasting and fed states. They also underwent FPG , A1C and OGTT testing. The idea was to see how many of the people who had abnormal OGTT tests (the most sensitive of the diabetes diagnostic tests) also had abnormalities in the other tests. Here is what they found:

• The SAGE test identified almost 29% more individuals who were OGTT “positive” compared to FPG and 17% more than A1C testing

If these results hold up and if the testing equipment can be made to be both easily transportable and affordable, then this technology could make highly sensitive diabetes screening tests accessible to the millions of individuals who cannot or will not avail themselves of FPG testing. Early diagnosis of opens up opportunities for early intervention and prevention of diabetes complications.  This is really exciting.

As always, you must be aware that there is a caveat about this study. The lead author, John D. Maynard, MS works for VeraLight, a for-profit company that is manufacturing the SAGE instruments. Catriona Nguyen, another author on the paper is affiliated with InLight Solutions, a related company. Although VeraLight’s mission is to

“help stem the tide of the worldwide diabetes epidemic by driving early diabetes detection, thus enabling initiation of therapies that can prevent diabetes or reduce its complications”

we, nevertheless, need to be cautious about placing too much hope on technology "proven effective" by industry funded and/or affiliated publications…..we have been burned before.

Pat Salber, MD

Would you believe it? I found this report on a three-decade study of wine drinkers on Wine Spectator Online. The study itself was published in a respected peer-reviewed medical journal, the Journal of Gerontology. The results are the stuff wine-marketers (and wine lovers) dream about: Wine drinkers had a lower mortality rate compared to drinkers of other alcoholic beverages.

No, the study was not performed in California's Napa Valley nor in the Loire Valley in France. Rather it was done in Finland (there's wine in Finland?) by Timo Strandberg and colleagues, researchers at the University of Oulu. At the start of the study in 1974, 2,468 businessmen and male executives, ages 40-55, were assessed at the Institute of Occupational Health in Helsinki for cardiovascular risk factors and alcoholic beverage preferences.  Only 131 of these men did not use alcohol, 455 did not report a single beverage preference, and 694, 251, and 937 preferred beer, wine, and spirits, respectively.

 The researchers tracked these men down for a re-assessment in 1985 and again in the year 2000. As you can imagine, some of these guys were a bit “long in the tooth” by the end of the study. Others had died or just dropped out (of the study).  Study subjects were included in the final calculations only if they were constant in their preference for one type of alcohol (e.g., wine, beer, or spirits) over the others.  By the time of the second stage of the study, in 1985, only 1,369 men were available to be reassessed. Some dropped out of the study, some changed alcohol habits and 93 of the men had died. By the time of the final calculations, in 2002, there were 1,127 men left in the study who drank three or less drinks per day and had not changed their drinking preferences over the course of the study.

Here are the results:

The men remained pretty constant in their choice of alcoholic beverage and there was not a significant difference in the amount they drank between the different beverage groups.

 Men with wine preference had the lowest total mortality of the three groups due to lower cardiovascular mortality. Compared to the spirits drinkers, wine drinkers had a 34% lower total mortality.  Beer drinkers had a 9% lower mortality than spirits imbibers.  Should we break out a bottle of pinot to celebrate the good health of wine drinkers? 

Best keep the cork in the bottle for now. There are some confounding variables. It turns out wine drinkers had healthier habits than beer and spirits guzzlers. They exercised more and smoked less, both factors associated with better health and lower mortality.   In other words, it may not have been the wine that led to a good long life, rather wine drinkers might be more health conscious.

Here's how the Strandberg, the lead researcher, sums it up:

"Is it the drinker rather than drink characteristics, as healthier men preferred wine?" It could also be that "spirit preferrers may lead a more dangerous life, with more risk factors, and all hidden aspects may not be culled in an epidemiologic study." What he is pointing out, rightfully so, is that care has to be taken in interpreting the results of this type of study.

Oh well. It did sound too good to be completely true -- kind of like reading that dark chocolate lowers blood pressure, but only if you don't eat so much that you get weight-related hypertension. 

Back to the fruits and veggies.

Pat Salber, MD

Last week we looked at the complex interactions of genes, brain circuits, hormones, psychology and culture in forming the mass killer’s persona. But keep in mind, most killers don’t have genetic or anatomical defects that we know about, although some new ones may be discovered in the future.

Obviously then, psychology and culture must be playing a major role in the seemingly unprecedented wave of violence we are experiencing.  Unprecedented? Not quite.

Scriptural violence

Here are a few choice nuggets from the Bible:

• Lot , a pious man living in Sodom, took into his home some traveling strangers who stopped for the night. No sooner than did the men retire for the night, a rumor spread around town that the men were homosexual.
  The destruction of Sodom and Gomorrah by John MartinThe enraged Sodomites assembled in front of Lot ’s house and demanded that he surrender his guests. When he refused, they forced their way in and, well, sodomized them. The first recorded anti-gay crime. But unlike today, the punishment was swift and terrible: God rained fire and brimstone on the town and obliterated it off the face of the earth. Don’t worry about Lot , God warned him to leave immediately.

• Moses, who spoke to God himself, transmitted His injunction to “wipe the Amalekites off the face of the earth”. Who are those terrible Amalekites that deserved what we call today ‘genocide’? They apparently were a nomad tribe in the desert who raided the Israelites as they made their way to the Promised Land. In fact, Moses was denied entry to Canaan, according to a later biblical exegesis, after leading his people in the desert for forty years, because he failed to completely annihilate them.

The story of the concubine in Gibeah: an academic study.

The Concubine of Gibeah 3 by Janet ShafnerThere once was a man and his concubine from the tribe of Ephraim who were traveling in the land Benjamin, another Israelite tribe. As the couple dined in the city of Gibeah , a mob assembled outside and pounded on the door. The mob captured the concubine, then raped and beat her to death. The man collected her corpse the next day and traveled home. The other tribes of Israel were outraged at the crime, assembled an army and razed several Benjaminite cities, killing every man, woman, child and animal they could.

Brad Bushman, a social psychologist at the University of Michigan in Ann Arbor, is the lead author of a study, "When god sanctions killing: effect of scriptural violence on aggression," published in the March issue of Psychological Science (vol. 18, pp. 204-207; 2007).  He had about 500 students read the tale about the tribe of Ephraim in order to study the role of “higher authority” in the propagation of religious violence. For half the students he added another passage:

When the man returned home, his tribe prayed to God and asked what they should do. God commanded the tribe to “take arms against their brothers and chasten them before the Lord”.

The students then took part in an exercise designed to measure aggression. About half of the study participants were from Brigham Young University , and almost all of them were religious Mormons. The other half were from the Free University in Amsterdam . Of the Dutch group, only 50% believed in God, and 27% in the Bible (astonishingly high percentages, for Europeans).

But for both groups, regardless whether they lived in the U.S. or the Netherlands , or whether they believed in God or not, the trends were the same:

Those who were told that God had sanctioned the violence against the Israelites were more likely to act aggressively in the subsequent exercise.

What does the study mean?

First, what it doesn’t mean: one cannot conclude that religious people are more aggressive than non-religious people. But it does suggest that people are more prone to aggression when they feel that it is sanctioned by some higher authority, be it God, or his clergy.

Jihadist terrorism and the silence of religious authorities.

One could quote passages from the Bible and the Koran that would make it sound like these were manifestos of some violent cults. In fact, modern religion tries to de-emphasize the violent aspects of the scriptures. The story of the Amalekites was edited out of many versions of modern Hagaddahs, and in others its violent message is softened with an injunction to be charitable to the stranger among us. But with the notable exception of a few courageous Moslem women, there is a deafening silence coming out of the religious community. The feeble voice of moderate Moslem clergy and intellectuals is almost invariably accompanied by their loud protestations of American aggression or Western social permissiveness. Western clergy and intellectuals, being "sensitive" and "politically correct", are not much better—they are experts at diffusing the responsibility: it is not the religion and its leaders that are at fault; it is the “root causes” whatever they are, it is poverty, or Western cultural imperialism, or insensitivity and intolerance toward other cultures. It fell to a Saudi security official to state, after reporting the foiling of a vast Al Qaida plot and the arrest of 172 young jihadists, to add: "unless we change the ideology (of religious extremism), more young people will fall pray to terrorism".

If we ever needed rigorous academic proof that religious authorities can, and sometimes do, propagate aggressive and violent behavior—now we have it in the study by Bushman and his coworkers.

It is time to speak up and tell the unvarnished truth—a culture that justifies violence in the guise of religion is intolerable in the 21^st century. Religious leaders need to raise their voices against this perversity.

Traditional abdominal surgeries leave large (8 to 10 inch) abdominal scars. Laparoscopic surgical procedures
Famous Levine cartoon of LBJ showing his gallbladder scarhave successfully reduced the size of the scars and also the lengths of stays in the hospital after the surgery -- laparoscopic gallbladder surgeries are now more common than traditional large incision cholecystectomies.

But now, cutting edge surgeons are proposing eliminating visible scars all together by operating through natural orifices.  Ok, here is the squeamish part. Natural orifices in the human body are the mouth, the vagina, and the anus.

Already natural orfice surgeons in India have removed an appendix through the mouth (imagine that). And, recently, a Columbia University Medical Center Surgeon, Dr.Marc Bessler, has removed the gallbladder of a patient through her vagina. That’s right – a vaginal cholecystectomy.

These are not a one time events. Surgeons are actively pursuing natural orifice surgery as a viable alternative to traditional abdominal and even laparacopic surgery. In fact, they have formed an organization, the Natural Orifice Surgery Consortium for Assessment and Research (or NOSCAR). As I mentioned earlier this week, when doctors form professional organizations, they are getting serious about advancing the mission of the group.

Here is language from NOSCAR's website:

[The NOSCAR Olympic Research Fund is] a joint initiative supported by the American Society for Gastrointestinal Endoscopy (ASGE) and the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES).

It is unique in one’s career in medicine to see a true paradigm shift that significantly changes patient management. This generation experienced such a paradigm shift with the introduction and development of laparoscopic surgery. It is possible that we are on the verge of another paradigm shift - Natural Orifice Translumenal Endoscopic Surgery (NOTES)™.

To address this emerging technology, a working group consisting of expert laparoscopic surgeons from the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) and a group of expert interventional endoscopists representing the American Society for Gastrointestinal Endoscopy (ASGE) came together for a meeting in New York City in July 2005. This group identified itself as the Working Group on Natural Orifice Translumenal Endoscopic Surgery. The overriding goal of the meeting was to produce a document that would serve as a guide for the responsible development of NOTES.

Often breakthroughs in medicine and surgery are viewed skeptically.  Rightfully so. Some work and some don't.  This might be one of those breakthroughs that actually changes practice forever and for the better.

Weird, yes.  I am sure I wouldn't want to be see pictures of my appendix being delivered through my mouth or my gallbladder through my vagina.  But if these procedures not only eliminate a belly scar, but also reduce the serious complications of abdominal surgery, such as prolonged hospitalizations, post-operative bowel obstructions, and post-op pain, then so be it.  I think patients can get used to, and even welcome, anything that provides good outcomes with less discomfort and risk.  The NOSCAR approach is worth evaluating and embracing, if it can deliver on the early promises....yuckie or not.

Natural orifice surgery...who would have thought it possible?

Pat Salber, MD, MBA

Thanks to Skip McGinty for alerting me to this development: “Researchers Developing Automatic Oral Drug Dispenser”

According to a report by Reuters, the European Union is funding a project to develop a "cybertooth," a
Getting my cybertooth!cybernetic oral device that attaches to a tooth and automatically administers the appropriate dosage of medication as programmed by the patient's physician.

Supposedly the device is designed to help chronically ill people, including those with Alzheimer’s disease, who have physical and/or mental reasons why they miss their medication doses. I, for one, find even with my faculties more or less intact, that it is tough to remember to take those pills, particularly if you have to take them more than once a day. I am always forgetting the pill I am supposed to take in the evening even though I have used lots of little tricks to help me remember, like putting it in a bowl right next to my toothbrush. Hey, just give me a cybertooth and be done with it.

According to Ben Beiski, one of the developers of the device at the Assuta Medical Center in Tel Aviv, Israel, the device could contain up to several weeks of doses of most drugs and administer more than one type of medicine, The device also would transmit information to a remote receiver when it is about to become empty and needs to be replaced.

(from livingpictures.org)Now, we are going to have to wait a while to get our hands on this nifty device. So far it has only been tested in pigs. But those tests found that high levels of the drugs were administered and distributed evenly throughout the pigs’ blood. Beiski, a colleague, and scientists in Europe plan to conduct clinical trials of the device and hope to market it in three years.

Yes, somebody has actually studied how physicians view the role of religion and spirituality on health outcomes. The results are very interesting, but not really surprising. The more religious the doc, the more likely he/she is to believe that God intervenes in patients’ health, prevents “hard” negative outcomes (like heart attacks), and, in general, influences health.

The study, “Physicians Observations and Interpretations on the Influence of Religion and Spirituality on Health,” was published in the April 9, 2007 issue of the Archives of Internal Medicine. The authors, led by Farr A. Curlin, MD from the MacLean Center for Clinical Medical Ethics, surveyed a random sample of 2,000 U.S. physicians about their attitudes about religion and spirituality. The survey had an excellent response rate (63%), although non-religious physicians were somewhat more likely to fill out the survey than religious physicians.

Doctors' religiosity was determined by their response to two questions from the Hoge’s Intrinsic Religious Motivation Scale (I had no idea there was such a thing). The questions asked whether they agreed or disagreed with the following statements:

• “I try hard to carry my religious beliefs over into all my other dealings in life.”

• My whole approach to life is based on my religion.”

Doctors who answered “yes” to both questions were rated as high in intrinsic religiosity (IR), those who answered “no” to both were low in intrinsic religiosity, and those with only one “yes” were rated as medium in intrinsic religiosity.

Physicians were also categorized by their stated religious affiliations:

• None (they listed none, atheist, or agnostic)
• Protestant
• Catholic
• Jewish
• Other (Buddhist, Hindu, Mormon, Muslim, Eastern Orthodox, etc)

Because religiosity varies by where you live (folks in the South and Midwest are more religious than people from other geographies), the doctors were asked to report where they live and practice.

Here are some of the key findings of the study:

• In general, 56% of physicians believe that religion and spirituality (R/S) have much or very much influence on health
• Only 6% believe that R/S often change “hard” medical outcomes (i.e., prevents a heart attack)
• Three-quarters of doctors believe that R/S helps patients cope and gives them a “positive state of mind.”
• A bit more than half felt that R/S provides “emotional and practical support via the religious community”

Physicians who rank “high” on intrinsic religiosity overwhelmingly believe that R/S strongly influences health. They also believe that God intervenes in patient’s health and that R/S helps patients cope. Interestingly, 31% of these same highly religious physicians feel that R/S sometimes, often, or always “causes negative emotions.”

On the flip side, physicians of low intrinsic religiosity report that patients rarely mentioned R/S issues to them (19%) and although 27% and 22% respectively thought God intervened in health or prevented negative hard outcomes, 61% felt that R/S helped patients to cope with their medical condition.

An interesting point in this paper is the discussion of concordance of physician/patient attitudes related to geographic prevalence of religiosity. Docs and patients who live in the South are more likely to talk to each other about their issues related to R/S. Conversely, docs who live in the West, where I live and trained, are less likely to talk to patients about religion and spirituality.

To me, the take away of this study is that physicians' attitudes about R/S influence not only how they interpret the role of religion and spirituality in patient’s lives, but also how willing they are to explore (and patients to disclose) their beliefs in this very personal and often private aspect of human life.

When I was a medical intern, a patient I spent many hours caring for died. He had been in the CCU for weeks and had one complication after another. It was a slow and painful death. I had met the family, of course, but as the intern on the “case”, I was more engaged in the daily “scut” work (drawing blood, fetching lab results, and writing lengthy notes) of medical practice than I was in developing a personal relationship with the patient or his family.

After the patient died (despite our best efforts), this man’s family asked me to pray with them. Being “low" on the intrinsic religiosity scale -- although I got on my knees, closed my eyes, and held their hands -- I was very uncomfortable in the role this grieving family was asking me, their loved one’s most identifiable doctor, to play in their efforts to deal with their loss. Of course, I wanted to do “the best” for my patient and his family, but I couldn’t really provide the religious support they wanted from me. I think, in retrospect, that I may have let them down (after, not before) the death of their loved one. But I really couldn’t help it. My beliefs are my beliefs and theirs are theirs.

I do want to point our that I do not think all doctors need to have a religious or spiritual response to illness. I, for one, would be highly offended if my doctor told me my health was in “God’s hands” or, if I had cancer, that my remission  after rounds of chemotherapy was because God ordained that for me. On the other hand, acknowledging that a lot of medicine is still more about relationships than actual science is, once again, worth affirming.

The American Association of Medical Colleges (AAMC) recommends that physicians “recognize that their own spirituality might affect the ways they relate to and provide care to patients" [and I might add how they relate to their patients' families and friends].

As we continue to explore how much of the effectiveness of medicine is because of the science and how much is related to the “art,” perhaps we need to explicitly talk much more openly about the role of religiosity and spirituality of patients and physicians on the spectrum of health outcomes (physical, psychological and spiritual) instead of just assuming that “one size fits all.”

Isn’t life wonderful and don’t we always have so much more to learn?

Pat Salber, MD

Every once in a while a medical research study is published that significantly alters clinical practice. The paper on percutaneous coronary intervention (PCI) in patients with stable coronary artery disease, published in the prestigious New England Journal of Medicine on March 26, 2007, is one such study.  The results show that PCI plus optimal medical management (lifestyle changes and drugs) are no more effective than optimal medical management alone at preventing heart attacks and death in individuals with stable coronary artery disease.

 In the NY Times’ story about the study, Steven E. Nissen, MD, President of the American College of Cardiology, describes the study as a blockbuster. And, indeed it could lead to some folks’ blocks being busted (particularly stent companies, such as Boston Scientific and the Cordis Cardiology division of Johnson and Johnson, as well as invasive cardiologists who perform these procedures).

The name of the study is COURAGE, an apt description for a study that is likely to be attacked vigorously by people who stand to lose in the high stakes arena of invasive cardiology. COURAGE stands for “Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation.”

Understanding plaque

In order to understand what these researchers were trying to determine, it is important to understand a bit about what causes heart attacks. Years ago, we used to think heart attacks were caused because one or more blood vessels supplying the heart became progressively more narrowed by atherosclerotic plaques, perhaps even closed off completely, thus, depriving the heart muscle of oxygen.

As we have learned more about the anatomy and physiology of coronary artery plaques, we have discovered that the plaques that cause heart attacks and other acute coronary syndromes, such as unstable angina, are prone to rupture, lead to clot formation, and, in that manner, block the coronary artery.

These vulnerable plaques, according to the NEJM article, tend to “have thin fibrous caps, large lipid cores, fewer smooth muscle cells, more macrophages [inflammatory cells], and less collagen” than stable plaques. They also tend to grow outward in the coronary artery wall, thus, before they rupture, they actually cause less blockage (stenos is) of the coronary artery lumen than stable plaques.

Stable plaques can cause symptoms of shortness of breath and chest pain with exertion, but they are less likely than unstable plaques to cause a heart attack or the worst outcome, sudden death.

This is an important point so I will repeat it by quoting from the article:

“…unstable coronary lesions that lead to myocardial infarction are not necessarily severely steno tic, and severely steno tic lesions are not necessarily unstable.”

The study

The study is a well designed randomized trial with enough participants, 2287 in all, to detect small differences between the two groups. 1149 patients were assigned to undergo PCI with optimal medical therapy and 1138 to receive optimal therapy alone. The primary outcome was non-fatal heart attack or death from any cause.  Participants were in the study between 2.5 to 7 years (median 4.6 years).

There were 211 of the above described primary events in the PCI group and 202 in the medical therapy group. This translated to a 4.6 year cumulative primary-event rate of 19% in the PCI group and 18.5% in the medical therapy group. There were no significant differences between the PCI group and the medical-therapy group in the composite of death, heart attack, and stroke, nor in the percent hospitalized for an acute coronary syndrome, such as unstable angina, nor in the percent that had myocardial infarctions.

The PCI group did have a greater decrease in symptoms (shortness of breath or chest pain) compared with the medical management group. But it is important to note that there was a substantial reduction in angina in both groups during follow up and, by 5 years, the percent free of angina was similar in both groups. Fewer individuals (21.1% vs 32.6%) had to undergo a subsequent revascularization for angina (chest pain) unresponsive to maximal medical therapy or when there was worsening ischemia (oxygen deprivation of heart muscle).

The critics

Advocates for PCI are going to try to find reasons why PCI should still be used to prevent heart attacks. In the NY Times article, Dr. David Kandzari of J&J’s Cordis Cardiology (stent company) points out that the individuals in the trial were largely from the Veterans Hospitals in the US and Canada and, therefore, usually get their medications for free. Yeah, so that is a reason for a $25,000 procedure instead of finding a way to get those at risk the relatively inexpensive generic medications used in this study.

Others will point out that bare metal stents were used in most of the patients in the study. Drug-eluting stents were not available until the end of the study. Perhaps, there would have been a greater difference in symptoms if the drug-eluting stents were used. Maybe, but there is no evidence that drug-eluting stents prevent deaths or heart attacks in stable patients and there is the recently described problem of late-forming clots that has led some cardiologists to switch back to bare stents.

Another important lesson from the study

I do think there is another very important take away lesson from this study. All you doctors out there should study Table 2 of this study carefully. These people were aggressively managed. This is not usual care. LDL levels were lowered from about 100 to the mid 70s after five years. Average blood pressure went from a 130/74 range to 122 to 124/70-72. HDLs increased slightly and Hemoglobin A1cs were maintained in the low 7s. There was a substantial increase in individuals following the American Heart Association diet and there was an increase in percent of people who participated in moderate physical activity.

Now, we all know that it is hard work for people with heart disease to take a bunch of medications and change their lifestyles. It is also hard work for docs and other clinicians to provide support for people as they try to make these changes. On the other hand, if we could take even a portion of the $25,000 spent on each PCI and apply it to buy support for people trying to make these changes; we probably could help folks in the general population achieve the same remarkable adherence to an optimal medical regimen. How many hours of nutritional counseling and personal training could be bought for even a fraction of that amount…week after week, for years? Not only would it be affordable in the long haul, there probably would be enough money left over to buy or subsidize the generic medications as well.

Isn’t it time we to start paying for the right stuff in healthcare?

Pat Salber, MD, MBA

We know that diet and exercise can prevent the onset of type 2 diabetes in people with impaired glucose tolerance. We also know that healthy lifestyle measures are more effective than even the most effective drugs. That being said, we also know that in the real world with Mickey Ds and Starbucks on every corner, long work hours, longer hours in front of the computer, and way too few hours exercising our body parts, that medications will be a part of the treatment armamentarium utilized to prevent type 2 diabetes.

So the question before us today is which drug should be used. An editorial in the March 20, 2007 issue of the Annals of Internal Medicine takes a stab at answering that question.

David Nathan, MD from the Massachusetts General Hospital Diabetes Unit and Michael Berkwits, MD, Deputy Editor of the Annals review the results of the DREAM trial (AKA, the Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication trial --- seems like you can’t have an important trial nowadays without a cute acronym).

The DREAM trial randomly assigned more than 5,000 patients with impaired fasting glucose (>110 mg/dL, but less than 126 mg/dL) or impaired glucose tolerance (a glucose level 2 hours after an oral glucose load between 140 mg/dL and 199 mg/dL) into one of four groups. One group received ramipril (an ACE inhibitor), one received rosiglitazone (an insulin sensitizer), one group received both drugs, and one group received a placebo.

The participants were evaluated after 2, 6, and 12 months and annually thereafter to determine if they had either developed diabetes or died. They were also evaluated to see if their glucose levels improved during those time frames. The participants were middle-aged and they were obese (mean BMI 31 kg/m2).

Here is what the study showed:

• Participants taking the drugs had a significant reduction in the progression to type 2 diabetes
• The reduction was entirely attributable to taking rosiglitazone.
• More patients taking rosiglitazone regressed to normal blood glucose levels (almost 39% in the rosi group compared to 20% in the placebo group.
• Although both medications were generally safe, rosiglitazone was associated with a higher prevalence of peripheral edema (swollen ankles) and a ~ 2.2 kg weight gain. In addition, there was an increased frequency of heart failure in a small number of patients (0.5% in the rosi group compared to 0.1% in the placebo group)

The authors talk about what clinicians (and patients) should do in light of this new information. First of all, they point out that rosiglitazone is expensive and has some uncommon but serious side effects. There are, they remind us, other medications that have been shown to prevent progression from impaired glucose tolerance to type 2 diabetes.

Metformin is available as an inexpensive generic formulation. At least in people with BMIs of 35 or higher, the percent reduction in progression to diabetes is only slightly lower than that described with rosiglitazone (53% vs. 60%). In addition, it is well tolerated except for some minor gastrointestinal symptoms, and it is much cheaper. The other effective drug, acarbose, is poorly tolerated because of adverse GI side effects.

So what’s a clinician to do?

• Continue to counsel and support patients with impaired glucose tolerance or impaired fasting glucose to adhere to a healthy lifestyle (you know, diet and exercise).
• For patients unable to unwilling to make these changes, they recommend considering metformin, as opposed to rosiglitazone, as a medication to prevent type 2 diabetes.

It is noteworthy, that Dr. Nathan lists GlaxoSmithKline, makers of Avandia, the brand name for rosiglitazone, as a potential financial conflict of interest. His recommendation to not go with rosi as a first line diabetes prevention drug must surely have caused some heartburn in GSK marketing circles.

Pat Salber, MD

Remember how shocked we were when we first heard about Dr. Moon and Dr. Realyvasquez. These are the heart doctors who performed unnecessary cardiac procedures, including coronary artery bypass surgeries, at a Tenet Hospital in Redding, California.

These guys may have been at the far end of the spectrum when it comes to driving inappropriate cardiac care, however, a study in the March 7, 2007 issue of JAMA adds to the growing body of evidence that suggests that cardiac procedure rates are strongly influenced by competitive market dynamics and not just patient need.

A group of well-respected health services researchers, led by Brahmajee Nallamothu at the University of Michigan Medical School took a careful look at the impact of introduction of specialty heart hospitals in geographic areas that represent distinct markets for tertiary (advanced) cardiac care. As opposed to general hospitals, specialty