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In this issue we are pleased to bring you the exciting news that Dubai Healthcare City will launch a world-class tertiary care teaching hospital. This story has been developing for several months, as faculty from HMI, health care leaders in Dubai, a team of architects from a top firm, and clinical and administrative experts from throughout the Harvard medical community have worked together to design every component of the University Hospital.
Around Harvard
This article originally appeared in the December 2007 Harvard Health Letter and is provided courtesy of Harvard Health Publications.
The top 10 health stories of 2007
In an essay on scientific discoveries, the former editor in chief of Science magazine, Daniel E. Koshland Jr., noted that most important breakthroughs don’t come in a single “Eureka!” moment. More often it’s a matter of several discoveries coming together in just the right combination. Koshland, who died in 2007, used Sir Isaac Newton as an example: to put his theory of gravity on a firm footing, he also had to develop calculus and the laws of physics he described in his Principia.
So it is with our 10 nominees for health and medical significance in 2007, although we don’t mean to invite any comparisons to Newtonian genius. Several items on our list have come about because of the slow, steady accretion of basic research findings and trial results. Some involve politics, which is almost always a grind — especially when it comes to health care. And with a couple of others we’re intentionally marking trends, not a single event. Sometimes the Eureka moments come when you realize that there isn’t always a splashy breakthrough but many events on a continuum — a lot that came before and even more to follow.
1. Did we learn a lesson from Avandia?
The FDA is supposed to allow drugs on the market only if they are safe and effective. In 2007, rosiglitazone (Avandia), became the latest medication found to have serious side effects that weren’t apparent when it was approved.
No drug is entirely safe, and it would be impractical to require studies large enough to identify all of a drug’s problems as a condition of approval. Instead, the FDA needs more money — and clout — to make sure drugs are monitored for safety after they’re on the market and to take prompt action if necessary. Congress passed legislation in 2007 that would give the agency that funding and power, as well as make some other important reforms (a requirement that all clinical trials be recorded in a central registry, for example). Time will tell whether these changes make a difference and restore lost confidence in medication safety.
2. Genome-wide association studies: Neighborhood searches
The human genome — all of our genes collectively, as well as noncoding parts of our DNA — consists of three billion chemical bases strung in a sequence, like letters forming the words in a very long book. The first diseases linked to genetic “misspellings” involved a single gene. But what happens when the candidate gene is not obvious, or the disease is caused by misspellings in multiple genes, as is so often the case? To find all of the genes, scientists would have to read the entire three billion letter genome. And to firmly establish a link to a disease, they’d have to read the genomes of hundreds, if not thousands, of people with and without the disease. Talk about finding a needle in a haystack.
Genome-wide association research is a shortcut that takes advantage of the discovery of unique “flags” flying in each neighborhood of the genome. Researchers find the flags associated with disease and then conduct an intensive search for genetic miscues just in that neighborhood. That’s a lot more efficient than a dragnet through the entire genome.
There’s been a flurry of genome-wide association studies in 2007. The technique has identified genes important for everything from type 2 diabetes to multiple sclerosis to natural resistance to HIV infection. More discoveries are sure to come.
3. Genome sequencing in a jiffy — and getting cheap, too
Sequencing genomes — identifying all the chemical base pairs of all genes — is expensive, but rapidly becoming cheaper. In 2003, sequencing all three billion base pairs of the human genome cost $10 million to $25 million. In 2007, the entire genome of James Watson, co-discoverer of the DNA double helix, was sequenced for $1 million. Some experts are predicting that the price will drop to $1,000 per genome by 2017.
One of the new gene sequencing techniques that may make rapid and inexpensive scanning possible involves shattering the DNA of the genome into millions of pieces and sequencing the letters simultaneously. After this “massively parallel” sequencing is finished, computers knit the fragmented data into a single sequence. This technology is already being used in genome-wide association studies. Once the neighborhood where problem genes lie has been identified, ultra-fast gene sequencing can rapidly check all the genes just in that area of the genome.
In the future it may become routine for children to have their genomes sequenced, enabling doctors to tailor health advice and medical treatments to each individual’s genes. Along with the opportunities come moral and ethical pitfalls. One of the great challenges of this century will be harnessing this explosion in genomic information so it won’t be used to discriminate, persecute, or invade privacy.
4. Waking up to a new health habit: Sleep
None of us needs a study to tell us that we feel better after a good night’s sleep. But research is showing that getting enough sleep — between seven and nine hours a night for most people — is one of the pillars of good health, along with exercise, eating plenty of fruit and vegetables, and staying slim.
No one study made a big splash in 2007, but the evidence has reached a critical mass. Studies have linked short and poor sleep to many modern maladies: diabetes, heart disease, high blood pressure,
inflammation, stroke. Short sleep may be a factor in the obesity epidemic: sleep lab studies have shown that it alters the activity of leptin, the “fullness” hormone, and ghrelin, the “appetite” hormone.
Meanwhile, scientists are beginning to understand the sleeping brain and the role it plays in our mental lives and health. One popular theory is that we need sleep to store — and possibly attach meaning to — our memories. So if you make sleep a priority, you might improve your memory and your health.
5. Health is going global
Perhaps all politics are local, but American medicine and health are going increasingly global. Students at American medical schools and schools of public health are flocking to seminars, courses, and programs devoted to global health. Hospitals have established global health residencies that allow doctors to train overseas. Medical journal editors are getting involved. In October 2007, more than 200 journals throughout the world simultaneously published articles devoted to the topic of poverty and human development. Celebrities like Oprah Winfrey (AIDS in Africa) and George Clooney (Darfur) have attached themselves to global health causes, giving them glamour and media attention. Others, like Drs. Paul Farmer and Jim Kim of the Harvard School of Public Health, are well known because of their work in the field.
Money is pouring in, too. The Bill and Melinda Gates Foundation has committed $8 billion to global health projects since its founding in 1994. In 2007, governments pledged $9.7 billion to the Global Fund to Fight AIDS, Tuberculosis and Malaria, less than the original goal of $15 to $18 billion, but still a major commitment.
Some of the motivation for the concern is enlightened self-interest. Severe acute respiratory syndrome (SARS), avian flu, and, of course, AIDS have shown how disease can travel easily from country to country, and around the globe, in an era of almost frenetic trade and travel. There’s also a basic humanitarian concern for people so much less fortunate.
The resources, the training, the publicity — they’re welcome and badly needed. Experts worry, though. Charitable efforts can be counterproductive, competing with each other or, worse, with local governments. Too many disease-specific programs can balkanize health care. Interest could fade and money dry up once global health no longer seems quite so fashionable, but the problems will remain.
6. Putting out the fire
When it’s under control, inflammation is a normal part of our immune response. But when it gets out of control, inflammation causes disease and pain, and fanning the flames is a protein called tumor necrosis factor-alpha (TNF-alpha).
In the 1990s, researchers genetically engineered a protein that blocks TNF-alpha. The FDA approved the fruits of this labor, etanercept (Enbrel), in 1998.
Now two others — infliximab (Remicade) and adalimumab (Humira) — are on the market, and a third — certolizumab — is waiting in the wings.
The TNF-alpha blockers have serious drawbacks: they’re expensive ($10,000 to $25,000 annually per patient), can result in serious infections, and have been linked to cancer, particularly lymphoma. But by tackling inflammation at its roots, they may be paving the way for a new approach to treating many diseases. In 2007, National Institutes of Health researchers proposed using TNF-alpha inhibition to treat brain diseases with an inflammatory component, such as Alzheimer’s and Parkinson’s disease.
7. Covering the uninsured
“Are we there yet?” children ask on car rides long before the trip is over. Asking about progress toward universal health insurance coverage in the United States can seem just as premature — and headache-inducing.
Roughly 47 million people in the country — or about one in every six — don’t have health insurance. Fewer employers are offering coverage to their employees (60% in 2006, down from 69% in 2000). Cost is a major factor: since 2002, the price of health insurance premiums has risen over 4½ times faster than the inflation rate (78% vs. 17%).
Are we there yet? Sometimes it seems like we’re headed in the opposite direction.
But lawmakers are cobbling together solutions. Massachusetts started implementing its groundbreaking plan in 2007 which includes a requirement that all adults buy health insurance, subsidies for those who can’t afford premiums, and insurance regulatory reforms. California and other states may follow suit with similar schemes. The All Kids program in Illinois, paid for entirely with state funds, offers coverage to all uninsured children, with premiums priced on a sliding scale based on family income. As of April 2007, 50,000 children were enrolled. Medicare Part D has its problems, but it has been successful in extending insurance coverage for prescription drugs. Now less than one in every 10 seniors lacks drug coverage, compared with one in three a few years ago.
The 2008 presidential election will undoubtedly politicize many health care issues, including how to cover the uninsured (look what happened to the vetoed State Children’s Health Insurance Program in 2007). But, as with long trips and many difficult problems, progress is being made a step at a time.
8. Doing the right thing — and getting paid for it
2007 saw some progress toward rewarding doctors and hospitals for the quality of the care they deliver, not just the quantity. Medicare started paying doctors a bonus for reporting certain quality measures, such as the percentage of their diabetic patients with controlled blood pressure. The Geisinger Health System in Pennsylvania grabbed headlines with its program, which promises to meet 40 quality-of-care benchmarks in the care of heart bypass patients — and by putting real money on the line by agreeing not to charge for care related to complications that occur within 90 days of surgery. Geisinger’s math: Quality pays for itself, and then some, by reducing complications. That’s also the calculation behind a new Medicare payment system scheduled to go into effect in the fall of 2008 that won’t pay hospitals for treating several secondary conditions, such as bedsores, considered to be preventable complications.
Drug companies are venturing into uncharted pay-for-performance waters. When British health officials refused to cover the cost of bortezomib (Velcade), an expensive cancer drug, the manufacturer, Johnson & Johnson, offered not to charge for the medication unless it produced a response. Devils lurk in the details, most notably in defining what constitutes a response, but performance-based payment could help rein in drug costs.
The worry: we’ll get a superficial, “cookbook” version of medicine, not real quality. In addition, some fear that doctors and hospitals will have a new, perverse incentive to avoid patients who are difficult to treat because they might drag down marks on a quality-of-care report card.
9. A better mammogram?
For most women, mammograms do a good job of finding breast cancer early. But no screening test is perfect, and the x-ray images of the traditional mammogram miss some cancers.
The American Cancer Society revised its screening recommendations to say that women at high risk for breast cancer should get a breast MRI every year, in addition to a regular mammogram. This high-risk group includes women who have a BRCA1 or BRCA2 breast cancer gene mutation or whose first-degree relatives (parents, siblings, children) do. The cancer society guidelines are part of a long-term trend of increasingly complicated screening protocols, tiered by risk group.
MRI scans won’t replace conventional mammography any time soon. Cost and access are major obstacles. In addition, the current technology would generate too many false positives — finding lumps that turn out not to be cancer and increasing the number of unnecessary biopsies. The technology will probably improve, though. Over the next few years, MRIs may become a major part of breast screening programs, particularly for women with dense breast tissue.
10. Peeking into the brain
When doctors diagnose Alzheimer’s disease, depression, and many other conditions related to the brain, they have only symptoms to go by. But with advances in imaging technology, researchers are getting the brain to give up its secrets, and more direct tests may soon be possible.
Functional magnetic resonance imaging (fMRI) scans are allowing researchers to measure minute changes in brain activity. Voltage-sensitive dyes can isolate specific brain circuits. Positron emission tomography (PET) scans use radioactive tracers and CT scanners to generate exquisitely detailed images of brain metabolism.
University of Pittsburgh researchers have developed a PET tracer — dubbed PIB, short for Pittsburgh Compound B — that labels beta amyloid, the protein fragment that many Alzheimer’s researchers believe is the main cause of the disease.
Researchers are heralding PIB testing as a breakthrough. It could — at last — provide a way to detect Alzheimer’s disease before symptoms appear. Treatments directed at reducing beta amyloid are under development. If beta amyloid plaque could be found with PIB testing, these medications might be given early in the disease, before symptoms occur.
To catch a thief may stop a heart
Devices to nab shoplifters can interfere with the functioning of pacemakers and implantable cardioverter-defibrillators.
The exits of most stores these days are guarded even when there’s no security guard in sight. Doors are monitored by “electronic article surveillance” systems that use radio or electromagnetic waves to detect whether tiny sensors affixed to the merchandise have been deactivated. If they haven’t, an alarm goes off. Often these systems are in plain view: two pedestals — one serving as a transmitter, the other as the receiver — form a little checkpoint that you walk through as you leave the store. They’re so common now that we hardly notice them.
People with pacemakers and implantable cardioverter-defibrillators (ICDs) — which shock the heart back into a regular rhythm if it starts to beat erratically — are warned not to lean on, or linger near, the pedestals because they could interfere with the electronics of the cardiac devices. Metal detectors at airports pose a similar risk, which is why people with cardiac devices are usually excused from going through them and searched with a handheld wand instead.
Nothing to worry about?
For the most part, the risk has been viewed as remote. In 2007, Italian researchers reported that over a 16-year period, the ICDs of seven of 336 patients delivered a shock when the heart didn’t need it because of electromagnetic interference from an outside source (an improperly grounded stove, gardening equipment, a sprinkler system, etc.). But there were no misfirings reported because of airport metal detectors or electronic antitheft systems.
German researchers set up an airport metal detector gate and tested its effect on 348 cardiac device patients — 200 with pacemakers, 148 with ICDs. They wanted to create the worst-case scenario, so they had patients stand in the gates for 20 seconds and press their chests as closely as possible to the transmitting side of the gate. None of the devices malfunctioned, and electrocardiograms didn’t show any change in heart rhythm.
Two incidents in Knoxville
Mayo Clinic Proceedings described two cases in the Knoxville, Tenn., area in which cardiac devices malfunctioned, apparently because of electronic article surveillance systems in stores.
In one, a 71-year-old man with an ICD was shopping in the automotive section of a large retail store. When he stepped away from the counter, which brought him closer to the pedestal of the antitheft system, his ICD discharged twice before he staggered and apparently fell out of range of the electromagnetic waves. The man was seen in an emergency room but didn’t suffer any injuries.
The second case is a good deal more frightening. A 76-year-old woman with a pacemaker was getting help loading up her car after shopping at a large commercial store when she suddenly collapsed while standing between the pedestals of the antitheft system. After she regained consciousness, an employee who was trying to be helpful leaned her up against one of the pedestals. She lost and regained consciousness several more times before she was finally moved away from the antitheft equipment. She was taken to an emergency room and recovered.
The electrogram recorded by her pacemaker showed a normal heartbeat followed by high-frequency “noise,” suggestive of outside interference that prevented her pacemaker from working. When the pacemaker stopped, her heart temporarily stopped as well, which is why she collapsed.
Dr. J. Rod Gimbel, coauthor of the report, believes these two cases indicate that antitheft systems interfere with cardiac devices more often than is reported. Moreover, as his article points out, there are now other kinds of implanted electronic medical devices, such as deep brain stimulators, that might be affected.
Don’t lean and linger
We’ve all seen the signs at the airport steering people with pacemakers away from the metal detectors. (The signs should also mention ICDs.) But the antitheft systems in stores usually don’t have clear signs to alert patients to their presence, and in some cases they’re camouflaged. Many stores wrap the pedestals in advertising. Upscale merchants sometimes conceal their antitheft systems in doorways so their customers (and presumably, most shoplifters) are totally unaware of the electronic scrutiny — and possible danger.
People with cardiac devices have enough to worry about these days with malfunctions and recalls. Chances that the next shopping excursion is going to end in a trip to an emergency room because of an antitheft device are low. Still, it might be time to start taking that don’t-lean-and-linger advice seriously.
Store owners, too, should take precautions. At the very least, they shouldn’t put display racks near the antitheft systems. They should also tell employees that if a customer collapses near an exit the person should be moved away from it as quickly as possible.
Screening to prevent stroke
Some companies are pushing ultrasound carotid artery scans, but reducing primary risk factors is where the emphasis should be.
Mobile screening for stroke seems to be everywhere — at a YMCA in Newton, Iowa; an American Legion Post in Vienna, Va.; a community college in Tempe, Ariz. One of the largest mobile screening companies, Cleveland-based Life Line Screening, currently operates in 48 states. It and other companies measure stroke risk with ultrasound scans of the carotid arteries in the neck.
These companies typically promise that the test can give you “peace of mind.” Compared with hospital testing, the mobile services may be more convenient and accessible, and the price is modest — about $50. Some companies offer package deals with other screening tests.
But ultrasound carotid screening remains controversial. Groups like the American Stroke Association don’t endorse mass screening. Some professional organizations are more receptive but would restrict screening to older people with several risk factors for stroke.
If you’re trying to decide for yourself, there are several questions you might want to consider. Is carotid ultrasound the best way to screen for stroke? If the test finds something, what’s next? And if it doesn’t, are you in the clear?
Often unheralded
There are two major types of stroke: ischemic and hemorrhagic. Ischemic strokes, which account for over 80% of strokes, occur when a clot cuts off the blood supply to the brain. Hemorrhagic strokes are caused by a blood vessel bursting open. Transient ischemic attacks (TIAs), sometimes called ministrokes, are similar to ischemic strokes, although by definition the obstruction is temporary.
The mortality rate from strokes has been declining for decades, but the incidence — the number of people having them each year — may be going up, and stroke is a leading cause of disability. Part of the argument for screening is that strokes often seem to strike people out of the blue. Over 70% are “first events,” although some people may miss early warning signs or fail to recognize the symptoms of a TIA or mild stroke.
Clogged supply lines
You have two common carotid arteries, one running up each side of the front of your neck. If you check your pulse in your neck, you’re feeling blood coursing through the carotid arteries. Near the jaw, the common carotids split into the external carotid artery, which supplies the face and other parts of the head, and the internal carotid artery, which supplies the brain.
Plaque in the carotid artery can mean big trouble. It may rupture so a blood clot forms, blocking the artery and blood flow to the brain. The blood clots may break off and block arteries further “downstream.” There’s also a chance that the plaque will break up, shedding pieces of fatty gunk that go on to plug up smaller vessels in the brain.
Here’s another way to think about it: most strokes are not related to carotid stenosis. One study found that less than 10% of first-time stroke patients have carotid atherosclerosis. So screening for clogged carotids lets a lot of people at risk for stroke fall through the cracks.
Ultrasound scans of the carotid arteries
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Cleaning out the carotid
For years, carotid endarterectomy (pronounced end-ar-ter-EK-toe-me) has been the main way of treating carotid stenosis, and about 100,000 of these operations are performed each year in the United States. A surgeon makes a small incision in the neck and carotid and, in effect, reopens the blocked artery by scooping out the atherosclerotic plaque. The procedure has been dogged by concerns that it may cause the problem it’s meant to prevent by setting loose the bits of plaque and tiny blood clots that are capable of causing a stroke during the procedure, or perhaps contributing to one later.
It’s been shown, though, that getting a carotid endarterectomy does, in fact, reduce the risk of future stroke for people with severe carotid stenosis and a history of symptoms (which can include a TIA). It’s a hard call if the stenosis is less severe. And it’s an even harder one for people with carotid stenosis but no history of symptoms or TIAs — the very people that a carotid screening program might identify. Large studies in highly specialized hospitals have shown that the benefits may outweigh the risks, but those calculations are based on low complication rates, and the rates are likely to be higher in most hospitals.
The American Stroke Association came out in favor of carotid endarterectomy for asymptomatic stenosis in 2007, but limited the recommendation to highly selected patients. The guidelines also say that only surgeons with low morbidity and mortality rates should perform the procedure.
Carotid narrowing doesn’t need to be treated with a scalpel or a stent. Aspirin will reduce the risk of blood clots forming. For people who also have high blood pressure, any medication that ratchets it down will bring down stroke risk, too. Studies are showing that for people in high-risk groups — those who have high blood pressure, or a history of heart problems — statins (Lipitor, Zocor, other brands) cut stroke risk, perhaps by stabilizing atherosclerotic plaque instead of by lowering “bad” LDL cholesterol levels. The stroke association’s guidelines recommend that anyone with known carotid narrowing should take a statin.
Stick to the basics
Ultrasound scans are already being used to screen for cardiovascular disease. Medicare now covers a one-time ultrasound screening test for abdominal aortic aneurysms for high-risk individuals (people with a family history or men ages 65 to 75 who have smoked).
But does ultrasound scanning of the carotids for stroke make sense, particularly by “scan-in-a-van” mobile screening programs?
The ads are right: it’s fast and painless. A technician moves a transducer back and forth over your neck for a few minutes, and a computer converts the reflected sound signals into a picture of the artery. The scans probably will identify people with carotid stenosis.
But when we contacted Dr. Farzaneh Sorond, a stroke specialist at Harvard-affiliated Brigham and Women’s Hospital in Boston, she ticked off the drawbacks:
- Ultrasound scans may find carotid stenosis, but among asymptomatic individuals, the benefits of interventions like carotid endarterectomy are not clear.
- Results vary by operator. Depending on the quality of the scanners, some tests might lead to unnecessary procedures or, at the very least, follow-up tests.
- Even if a scan showed that your carotid arteries are “clean,” that doesn’t mean you’re safe from stroke. There are lots of other risk factors.
“The use of carotid ultrasound for stroke screening is more about financial gains for companies than health benefits for patients,” she says.
Dr. Sorond concedes that carotid scans might identify some cases of treatable stenosis before symptoms start, but the chances are slim — too slim to endorse mass screening. In the future, researchers may identify a subset of asymptomatic people who should be scanned, but there’s no agreement on who they are or how they should be identified.
Rather than screen for carotid stenosis, it would be more effective, as Dr. Sorond points out, to focus on conditions that cause or contribute to the stenosis: diabetes, high cholesterol, hypertension, obesity. The next step is getting those risk factors under control. Often that means a combination of medication — particularly blood pressure–lowering medications and now, increasingly, statins — and all those familiar lifestyle changes, like getting more exercise, that are easier said than done. It’s conservative advice, but sometimes conservative is the way to go.
By the way, doctor
Should I get a partial knee replacement?
Q. I am 55 and have a bad right knee from playing lots of sports. I am interested in getting a partial knee replacement. I’ve heard that the recovery is shorter and the result is better than a total replacement. What do you think?
A. The first decision that you and your orthopedic surgeon need to make is whether or not you need an operation. Joint replacement works to relieve pain and will help the knee to function better. If your knee pain prevents you from performing daily activities — walking, climbing stairs, light yard work — a replacement should be considered.
But a lot of flags go up if you are thinking that a replacement will let you return to playing vigorous sports. No knee replacement, whether full or partial, should be subjected to impact loading — the pounding that occurs when you run or jump. The replacement joint will loosen up, and parts of it will wear out faster, so it will almost certainly not last as long. Knee replacements really aren’t the answer for people with arthritic knees who want to go back to the days when they could run for miles or play a hard game of pick-up basketball.
The term “knee replacement” may conjure up notions that the entire joint is replaced. In fact, the operation might best be thought of as a major resurfacing that replaces cartilage, which in a healthy knee allows the femur (thighbone), patella (kneecap), and tibia (shinbone) to move smoothly against one another without pain.
In a total knee replacement, the portions of the femur and tibia that meet to form the joint are cut away and covered with prostheses to restore smooth movement. In a partial replacement, used when arthritic degeneration of the cartilage is more localized, smaller parts of the femur and tibia are cut away and resurfaced.
Knee replacement
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As you said, the recovery from a partial replacement is shorter and range of motion afterward is better. But there’s a lot of controversy about who should get one. They aren’t well suited for people with very bowed or knocked knees. And they’re a good choice only if the knee still contains a fair amount of healthy cartilage.
For someone your age, one important thing to think about is how long a knee replacement will last. Most studies show that total knee replacements last longer than partials because the components that attach the prostheses to the bone are less likely to loosen up. Another problem: the cartilage that wasn’t replaced initially because it was in good shape may become diseased and arthritic later on, so people end up with the knee pain that the replacement was supposed to get rid of.
It’s true that when a replacement fails, you can have it redone — a procedure orthopedic surgeons call a revision. Of course, there are many reasons you’d want to avoid a revision; it’s major surgery, after all. But one big drawback is that the second set of prostheses usually won’t last as long as the first. When the first set loosens up, the bone tissue gets damaged, so the new set often can’t be anchored quite as securely to the bone. As a result, a revision doesn’t last as long and may not provide as much pain relief as the initial replacement.
You should, of course, weigh the pros and cons of a knee replacement with your doctor. And it’s always a good idea to get a second opinion for something as major as knee replacement.
But I think a partial replacement in a young patient who wants to return to vigorous sports is probably a setup for a new knee that won’t last long — and not a good idea.
— Donald T. Reilly, M.D.
Harvard Health Letter Editorial Board
New England Baptist Hospital, Boston
