As we were putting together this year's top 10 list, uncertainty
became a motif. Here at the beginning of the flu season, we don't
really know if the H1N1 flu pandemic will stay controlled by
public health measures, or take off in some unexpected way. Will
the yearlong debate over health care reform result in something
significant — or wind up being political sound and fury,
Even when a large randomized clinical trial seems to have settled
an important matter, it's hard to say how the findings will be
applied exactly. Results from a large study of intensive care
unit patients showed that controlling blood sugar levels too
tightly was a bad idea (number 7 on our list). But finding the
right level of control — that's a work in progress. The JUPITER
study may usher in a new era of cardiovascular disease prevention
that emphasizes inflammation and lowering C-reactive protein
(number 8). But how will those goals be combined with
tried-and-true cholesterol control? Also a work in progress.
More black-and-white answers would be nice, but learning to live
with gray areas is, perhaps, the beginning of wisdom, and not
just in health and medicine.
1. No panic about this pandemic
After the first several weeks of uncertainty, most of the news
about the 2009 H1N1 "swine flu" pandemic has been reassuring.
Much of that has to do with the nature of the H1N1 virus itself,
which spreads easily and makes people sick, but so far rarely in
a life-threatening way. And the word pandemic is misunderstood: a
disease is considered pandemic if it has spread globally and
affects a larger-than-usual proportion of the population. The
disease needn't be severe.
But a major reason for the calm has been the measured public
health response. Plenty of information has been made available
(this is the first Internet-age pandemic). A vaccine was
developed and put into production, although shortages are a
serious concern. Health officials gave us simple, concrete things
to do to protect ourselves and others: cough and sneeze into your
sleeve, wash your hands often, get vaccinated with both the
seasonal and H1N1 flu vaccines, stay home if you're feeling sick.
This wasn't the flu pandemic that the experts were expecting. For
years, they've eyed the H5N1 bird flu virus circulating in Asia
to see if it would mutate and become transmissible among humans.
Instead, H1N1 emerged in Mexico with a complicated quadruple
pedigree: two strains of swine flu, a human strain, and a bird
one. Hospitalization and death rates from the new virus have been
high in healthy young adults and quite low in people older than
60. One explanation for that pattern is that older people may
have some immunity left over from exposure to a previous version
We have months of flu season ahead of us. Much could go wrong.
Flu viruses are more contagious and more likely to produce severe
illness in cold, dry air. They can mutate. Still, early
indications were that this pandemic will stay manageable. As
expected, flu rates in the Southern Hemisphere returned to normal
in the fall. When we went to press, the worldwide death toll was
about 5,000 — a modest number, all things considered. And most
Americans were going about their business, with cleaner hands
than ever before.
2. Health care reform: Half a loaf
The final version was still taking shape as we went to press, but
some basic elements of health care reform looked to be in place.
A mandate requiring individuals to buy health insurance seemed
likely. We may also see tighter regulation of the health insurers
(no turning away people for pre-existing conditions) and creation
of computerized "exchanges" where people and small employers can
shop for affordable policies. About 46 million Americans lack
health insurance, and these and other reforms should shrink that
number. By how much depends on details like the subsidy levels
for those who can't afford insurance and whether a new government
insurance program, the so-called public option, comes to be.
Expanding coverage will be no small feat, but it's a breeze,
politically, compared with reining in spending. Chances are that
2009's reforms won't do enough on the cost side, and there's no
consensus on how to proceed. Technology (new drugs, new tests)
has been the driving force behind health care spending for
decades. Some economists see technology's effects as easing up
and that it could even save money in the future. Let's hope
3. Bad fat, good fat
In real estate, it's location, location, location. The same may
be true for body fat — and color makes a big difference, too.
The visceral fat — the fat located in our abdomen — churns out
inflammatory factors and hormones. By comparison, the
subcutaneous fat, which lies under the skin, is metabolically
sedate. Findings published in 2009 further implicate visceral fat
as a source of health woe, while largely exonerating the
subcutaneous deposits. For example, Framingham Heart Study
researchers reported that visceral, not subcutaneous, fat was
associated with calcium deposits, a marker for atherosclerosis,
in the body's main artery, the aorta.
White fat cells store fat, and most of the fat in our bodies —
visceral and subcutaneous — is white fat. But there are also
brown fat cells that actually burn fat. We have brown fat as
newborns to help with the regulation of body heat, but it's long
been believed that it soon disappears. A surprising trio of
articles published in The New England Journal of
Medicine used PET scans to show that we actually retain
appreciable amounts of brown fat as adults in an area between the
shoulder blades, and that the more brown fat an adult has, the
more likely he or she is to be lean with healthy metabolic
Researchers are now studying how brown fat cells can be increased
or activated. The visceral fat findings are shifting attention to
waist size as a measure of obesity, although it's not so simple:
subcutaneous fat also contributes to waist size, especially in
women. Still, the notion that diet and other habits should be
judged by their effect on waist circumference is gaining
4. Curbing the doctor-industry relationship
Companies — particularly drug manufacturers — spend billions each
year promoting their wares to doctors. In 2009, a wave of new
rules and regulations went into effect to slow down the flow of
gifts (all those logo-emblazoned pads and pens), free meals, and
payments to physicians. The changes were made in response to
criticism that industry largesse was creating conflicts of
interest. Too often, there was a risk that the doctor-industry
relationship would taint the doctor-patient one.
Large teaching hospitals, including the Harvard-affiliated
Partners HealthCare system, barred their faculty from accepting
gifts and meals and participating in speaker bureaus. Industry
groups and professional societies revised their codes of conduct.
Massachusetts and several other states stepped in with gift bans
and disclosure requirements. And there is a good possibility that
the health care reform legislation will include a requirement
that drug and device makers report their payments to doctors on a
public Web site.
Industry funding is important in medicine, especially when it
comes to research. But it should be aboveboard, for all who are
interested to see. The moves toward full disclosure and the end
of cheesy gifts designed to curry favor are steps in the right
5. At last, maybe an alternative to warfarin
Millions of people depend on warfarin (Coumadin), especially
those with atrial fibrillation, a common heart rhythm disorder.
By blocking vitamin K, the drug reduces the risk for blood clots
and, in turn, for stroke and other life-threatening, clot-related
disorders. But warfarin interacts with dozens of drugs, herbs,
and foods. Frequent blood tests are often necessary to make sure
the blood's clotting capacity is in a safe range. Patients and
their doctors have accepted these drawbacks for lack of a good
alternative. But in 2009, one might have been found.
Dabigatran, which is already approved in Europe for limited
purposes, acts directly on thrombin, one of the key players in
the formation of blood clots. No blood monitoring is needed, and
because of the way the drug is metabolized, there are far fewer
interactions to worry about.
A large, industry-sponsored study (18,000 atrial fibrillation
patients in 44 countries) was organized several years ago to test
two different doses of dabigatran (110 mg and 150 mg) against
warfarin. The results show that dabigatran matches up well
against warfarin. At the smaller dose, it was just as effective
at preventing strokes and caused fewer major bleeds. At the
larger dose, it was more effective than warfarin at stroke
prevention and caused a similar number of bleeds. The news wasn't
all good: heart attacks and gastrointestinal side effects were
more common among those taking dabigatran than those taking
The FDA is expected to approve dabigatran in 2010. It will
undoubtedly be more expensive than warfarin, although blood tests
won't be needed, so that might help offset some of the additional
expense. People who don't need frequent blood tests and dose
adjustments may be better off sticking with the old standby,
warfarin, but the convenience and efficacy of dabigatran is
likely to be a real advantage for many patients.
6. These micros are major
Messenger RNA reads the DNA of our genes and uses that code to
assemble proteins, the building blocks of all forms of life. In
the mid-1990s, researchers discovered small bits of RNA, now
known as microRNA, that attach to the messenger version and
switch it off, so the protein doesn't get made.
Already microRNAs are playing an important role in helping cancer
doctors make more accurate diagnoses and prognoses and choose
more effective treatments. For example, in 2009, researchers
reported that liver cancer patients whose tumors had lower levels
of a particular microRNA, called miR-26, had a much worse
prognosis, but also a better response to one kind of treatment.
Promising results for macular degeneration and respiratory
syncytial virus infection have been reported in humans, and
successful treatments using microRNAs have been achieved in mice.
Results of a mouse study showed that delivering miR-26 to liver
cancer cells made them behave more like normal cells. Another
study in mice showed that delivering a different microRNA to
breast cancer cells prevented them from metastasizing.
Compared to drugs, microRNAs are easy and cheap to manufacture.
For cancer, they would mean treatment targeted at the root cause
of the disease: mutated genes promulgating wayward proteins. And
researchers have high hopes that microRNA medicine will yield
pinpoint control, so only diseased cells would be affected. But
there's also reason to mix in some caution with the optimism.
MicroRNA research is, after all, in the beginning stages and has
a good ways to go before maturing into full clinical reality.
Toxicity could be a big hurdle if therapeutic microRNA
accidentally interferes with messenger RNA that shouldn't be
7. Blood sugar levels: Seeking the sweet spot
High blood sugar levels aren't just a problem for people with
diabetes. Elevated blood sugar is associated with worse outcomes
for heart attack and stroke patients and, in fact, for hospital
patients of all kinds. Several years ago, Belgian researchers
published results showing that the sickest of the sick — patients
in intensive care units (ICUs) — fared far better if their blood
sugar levels were very tightly controlled. That study was
influential, partly because it fit so nicely with the
conventional wisdom about the perils of sugary blood. Guidelines
were revised, so tight blood sugar control, accomplished with
intravenous infusions of insulin, became a priority in ICUs
throughout the country.
Now it's looking like those guidelines may need to be revised
again. Results from a large randomized trial (too cutely called
the NICE-SUGAR trial) showed that the death rate for tightly
controlled patients was higher than it was for patients
controlled to more conventional levels. The difference was 2.6
percentage points (27.5% vs. 24.9%), which may not seem like much
but translates into many deaths given the number of ICU patients.
Doubts about the wisdom of aggressive blood sugar levels aren't
limited to the ICU. Study results featured in our top 10 list for
2008 suggested people with diabetes might be harmed, not helped,
by overly ambitious goals for blood sugar control (an HbA1c goal
of below 6%).
Overdoing blood sugar control in the ICU might be harmful for
several reasons. Low targets result in more episodes of extremely
low blood sugar, or hypoglycemia, which can trigger a cascade of
events with mortal consequences. The insulin used to achieve low
blood sugar may have negative effects. Blood sugar control
doesn't make the sugar disappear; it goes into cells. That surge
of sugar may disrupt normal cell functions that wind up affecting
the heart and other vital organs.
Doctors aren't going to completely abandon controlling the blood
sugar of ICU patients. But to paraphrase one commentator on the
trial results, they'll now be looking for the "sweet spot"
between control that is too tight and too loose.
8. CRP: Ready to make an entrance?
Late in 2008, results from the industry-funded JUPITER trial
showed that people with normal LDL cholesterol levels (less than
130 mg/dL) but relatively high CRP levels (2 mg/L or higher)
could cut their risk of having a heart attack or stroke in half
by taking a high dose (20 mg) of a powerful statin drug,
rosuvastatin (Crestor). CRP stands for C-reactive protein, a
chemical in the blood that's a good indicator of inflammation.
Statin drugs are taken primarily to lower LDL levels, but this
was added proof that they also calm inflammation.
That first round of JUPITER results made a big splash, but it
left room for debate about how CRP testing and lowering should
fit into cardiovascular care.
Subanalyses of the JUPITER data published in Lancet
helped clarify if not completely settle matters. People in the
trial who reached a very low LDL level (less than 70 mg/dL) cut
their risk of having a cardiovascular "event" (heart attack,
stroke, and so on) by 55%. But those who achieved a sub-70 LDL
and a CRP of less than 2 mg/L lowered their risk by 65%. And
reaching a CRP of less than 1 mg/L lowered it by 79%.
Many unanswered questions remain. What are the long-term
consequences of taking high doses of potent statins like
rosuvastatin? Might changes in diet, or increased physical
activity, achieve the same thing?
Still, the JUPITER results add to the evidence showing that
cardiovascular disease is fundamentally an inflammatory process.
The official LDL-centric guidelines haven't changed, but many
doctors are going ahead and ordering CRP tests for their patients
with cardiac risk factors, even if their LDL levels are normal.
If two tests show the CRP level is high, they may prescribe a
high dose of a potent statin.
9. Screens with holes
Fresh doubts emerged about the wisdom of the current screening
tests for breast and prostate cancers. A provocative analysis in
The Journal of the American Medical Association (JAMA)
came to the conclusion that the past 20 years of screening
mammography for breast cancer and prostate-specific antigen (PSA)
testing for prostate cancer has led to detection and treatment of
many cancers that pose minimal risk while achieving only modest
reductions in the number of more advanced cases. Earlier in the
year, results from two large studies of PSA screening were
The logic of cancer screening is impeccable: catch the disease
early, while it's most treatable. The problems come when a test
finds slow-growing, "indolent" cancers that could have gone
untreated without causing harm but wind up getting treated
anyway, so people needlessly suffer through the complications of
The American Cancer Society was sticking to its screening
recommendations: women ages 40 and older should have annual
mammograms, and men should discuss the pros and cons of prostate
cancer screening with their doctors. But the group was reportedly
working on public statements that would make people more aware of
the pitfalls of screening. The authors of the JAMA
article had several suggestions for how breast and prostate
cancer screening could be improved: development of better tests
that would differentiate between low- and high-risk tumors; more
conservative treatment of low-risk tumors; targeting screening
and prevention efforts at people in high-risk groups. They also
suggested not calling low-risk tumors cancer, but referring to
them as indolent lesions of epithelial origin, or IDLEs, instead.
That rebranding might not catch on, but it's getting at the right
10. Do your friends make you fat?
We know, we know: we gain weight because we don't eat the right
foods and don't exercise enough to burn off the calories. But a
new wave of research is showing that the causation of weight gain
and a variety of other health-related behaviors has a social
dimension, spreading through social networks as if they were
contagious. Social networks are the vast webs of relationships we
find ourselves in: friends and relatives; their friends and
relatives, the friends and relatives of those friends and
relatives, and so on.
Network analysis has roots in sociology, anthropology,
mathematics, and several other disciplines. Dr. Nicholas
Christakis, a Harvard Medical School professor, and James Fowler,
a University of California political scientist, have applied the
techniques from those fields to health-related issues. They
started by painstakingly mapping out a social network based on
information supplied by participants in the famous Framingham
Heart Study. Their obesity findings in 2007 made headlines. In
2008, they used the same network to show how happiness ebbs and
flows through social connections. They've popularized their ideas
in a book titled Connected.
Their work has piqued people's interest partly because of some
unexpected twists. For example, their obesity study found that
your friend's obese friend may increase your chances of becoming
obese, even if your friend is not heavy. And in the happiness
study, the happiness of friends seemed to rub off on people, but
the happiness of coworkers did not.
How behavior could follow infectious patterns is uncertain,
although Christakis and Fowler say subtle social messages of
acceptance may get passed along from one person to another. Some
say social network researchers are leveraging interesting
correlations into causation. A related criticism is that network
research has dressed up the time-honored observation that in
social matters, like attracts like: clusters of behavior form
because we are favorably disposed toward people who behave like
we do. Regardless, viewing health-related behavior as a
collective phenomenon is fascinating and opens up new avenues for
research and experiments in intervention.
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