Hypertension Drug Aliskiren Approved

Aliskiren, the first direct renin inhibitor, was approved by the FDA yesterday. The drug will be marketed by Novartis under the trade name Tekturna.

(WSJ) Tekturna is the first in a new class of blood-pressure lowering medicines, called renin inhibitors. It acts within the renin system, which is central to blood-pressure regulation. Renin is an enzyme that controls the formation of a hormone called angiotensin II, the key mediator in the regulation of body-fluid volume and blood pressure.

Minor physiologic correction to the WSJ quote above: renin cleaves the inactive peptid angiotensinogen into Angiotensin I, which is then converted in the lung to Angiotensin II by angiotensin converting enzyme (ACE). As such, the new drug acts to control hypertension earlier in the development of the metabolically active compound, Angiotensin II.

-Wes

Grand Rounds 3.24 Is Up

Medical Blogging Grand Rounds is up over at GruntDoc, the first four-time host of the event. It's all-inclusive - 60 posts - but organized well.

Enjoy!

-Wes

Word Play

As a blogger, you can't help but love words. So if you get a chance, see if you can pick up the small book called Words Fail Me by Teresa Monachino. She finds the inconsistencies and nonsense in the English language. It's quite entertaining. As an example, I like her section on antigrams.

"Whereas anagrams simply transpose the letters in a word to give us a new meaning, antigrams have a more sinister tendency. Rearranging the letters of the words on the left-hand page gives a new word or phrase on the right that opposes or contradicts it."

Some examples:

astronomers	no more stars
funeral	real fun
honestly	on the sly
silent	listen
forty-five	over fifty
medicate	decimate

And my favorite:

elvis

lives

Check it out. It's a fun read and the perfect book for the powder room, if you know what I mean...

-Wes

Dick Cheney's Deep Venous Thrombosis

Look for a pair of these compression stockings on Vice President Dick Cheney's leg soon. He was reportedly diagnosed with a deep venous thrombosis (DVT) today and will likely be treated with low molecular weight heparin (enoxaparin) shots twice daily for several days, followed by warfarin therapy. His family has been understandably tight-lipped about these details of his therapy.

Given his history of a weakened heart muscle from coronary artery disease, multiple vein harvestings to procure conduit for his bypasses (yes, he's had more than one), the repair of a popliteal artery aneurism behind his knee, coupled with his significant travel history, he really was a set-up for this occurence. If he was my patient, I'm not sure I'd just treat this for "a couple of months" with anticoagulants as the article suggests because I doubt his risk factors for DVT will subside. Others agree.

But spokeswoman Lea Anne McBride's statement that "He'll maintain his regular schedule. He feels fine." might not be such bad advice after all, since there have been some studies that have suggested that early ambulation speeds recovery in patients with DVT.

-Wes

Image credit.

Implications of a New Screening Test for Lung Cancer

Lung cancer is a devastating disease. It is one of those diseases, like ovarian cancer, that has often metastasized before it is detected. Certain forms of lung cancer can be particularly lethal, with mortalities of 50% or more within 6 months of diagnosis. That is why early detection is so critical.

Now we learn of a clever way of screening for lung cancer using… are you ready?… genetic profiling.

That’s right. Take 80 or so of the most likely genes from the DNA of the cells lining the patient’s airways and test them for the presence of certain gene sequences implicated in lung cancer to predict their likelihood of having lung cancer.

The authors from Boston University studied 129 patients undergoing bronchoscopy for the diagnosis of lung cancer that had a nearly 50% incidence of the disease in their study population (60 patients were diagnosed with lung cancer). Their test utilized microarray genechips made by Affymetrix for their analysis. The authors acknowledged an 80% sensitivity and 83% specificity with their test – far higher than other tests available to date, but had some important limitations:

In the setting of our study, where disease prevalence was 50%, a negative bronchoscopy and negative biomarker for lung cancer resulted in a 95% negative predictive value, potentially allowing these individuals to be followed nonaggressively with serial imaging studies. For individuals with a negative bronchoscopy and positive gene-expression signature, the positive predictive value was 70%; these individuals would probably require further invasive testing to confirm the presumptive lung cancer diagnosis. However, compared to bronchoscopy alone, the strong negative predictive value of the combined cytopathology and gene-expression biomarker test should substantially reduce the number of individuals requiring further invasive diagnostic testing.

The notion of a cancer-specific airway-wide injury suggests that cancer-specific alterations in gene expression that occur as a result of smoking might precede the development of lung cancer. If this is true, the lag between alterations in gene expression and the appearance of lung cancer could contribute to the biomarker's false-positive rate in our cross-sectional study. A longitudinal study will be needed to assess whether false-positive biomarker diagnoses represent smokers at higher risk for developing lung cancer. If this is the case, our biomarker might be useful as a screening tool for lung cancer among healthy smokers and may have the potential to identify high-risk smokers who would derive the most benefit from chemoprophylaxis.

So What Do These Data Mean?

Well, I’m not sure we’re ready to go the chemoprophylaxis or even the screening of smokers route just yet. To better understand the implications of a test with 80% sensitivity and 83% specificity, one must understand the statistical definitions of these two terms. For sensitivity, it means the probability that a test is positive in the population of people known to have the disease. Specificity, on the other hand, is the probability that a test is negative in the population known not to have the disease.

So how can these numbers be applied here? Doing some back-of-the-envelope calculations from the authors’ data, their test with its 80% sensitivity in 60 people known to have lung cancer means that 48 had a positive test that appropriately detected the cancer while 12 had cancer that the test failed to detect. Likewise, if 69 patients did not have cancer and the test had an 83% sensitivity, then 57 patients who did not have cancer tested appropriately negative for the disease, but 12 tested positive for the disease, even though they did not have cancer.

Now, in this population with a strikingly high incidence of cancer, the reliability of this test is reasonable, but in the population at large (i.e., all smokers) where the prevalence of disease if likely to be much lower, there will be far too many false positive tests (diagnosing cancer in people actually free of disease) and importantly, still a significant false negative rate (thinking a person is free from cancer based on a negative test, when, in fact, they have a cancer).

So there’s still some work to be done before such a test can be applied to the general population. But the study authors should be commended on their clever use of micro-array DNA genomic phenotyping to improve the detection of lung cancer during bronchoscopy over current cytologic (cell analysis) techniques.

Things You Never Want to Hear

Echo Doc sounds off.

I couldn't agree more.

-Wes

The Samaritan

She was 27 years of age, poor, withered, scared, alone. She had grown up in a tough neighborhood. She never knew her father, lost her mother, her job, and earlier had lost her brother when she was six. The father of this pregnancy was uncertain.

She presented in labor at 26 weeks gestation. She delivered her child quickly. Every effort was made to save the child, but two days later, the baby died. She sat quietly in her room, no family visited.

Her obstetrician entered and saw her staring away, a small tear from her eye, exhausted.

“What’s the matter?”

“No one will talk to me. The technician enters the room, takes my blood pressure and leaves. The resident checks if I’m bleeding and leaves. The person drawing the blood does so and leaves. The dining staff brings my tray of food and leaves. No one will talk to me – why is that?”

The obstetrician stopped and sat on her bed. He took a deep breath and said, “Carrie, at the end of each day as I get out of that elevator at the end of the hall, I have to make a decision. Do I turn right and head down the hall to return home for dinner, see my family and hear about their day, or do I turn right and walk down this hall to your room and face your grieving, the sadness, the messiness of the moment? None of us likes to confront the difficult issues of the day, the despondent, the complex, the threatening.” He reached out and held her hand.

She looked at him, eyes blood-shot, seeking, yearning. She squeezed his hand. Time stood still.

“Thank you,” she said, and smiled a half-hearted smile and closed her eyes.

As he left, the obstetrician turned out the lights. And she slept.

Paying To Be A Top Doctor

America’s Top Doctors®. Every doctor wants to be one. The prestige. The glory. The acclaim.

The narcissism.

On the surface this accolade sounds so wonderful, so comforting. Just to know your health care is being delivered by one of The Best®. (I thought I’d trademark that term).

You see, that little ® symbol means that certain corporate gnomes called Castle Connolly Medical Ltd. have paid to protect the term “America’s Top Doctors®.” I guess they're afraid someone might want to steal this term and change it into “My Hospital Paid For Me to be Listed as one of America’s Top Doctors®.”

To really search their database of presumed America’s Top Doctors®, you have to pay these corporate gnomes – that is unless you want to see the doctors from certain centers that have already paid to be sure you see their doctors. Then you can search their database to see those carefully chosen doctors are chosen not only by doctor peers, but by hospital administrators that want their doctors to look good to America.

I guess I can stand patients rating doctors – after all, they’re the consumers of health care. But when companies are paid as fronts for hospital systems to preferentially promote their physicians as “America’s Top Doctors®,” the ethical nature of this practice is suspect at best.

But their data stinks, too. I tried to find an America’s Top Doctor in Illinois who practiced as a Cardiac Electrophysiologist. Guess how many were there?

One.

Amazing. Only one Top American Cardiac Electrophysiologist Doctor® exists in Illinois (I didn’t pay to see if it was me).

But then I saw this press release about how their also providing searches about disciplinary actions against doctors in 46 states. You can click on their website and get the information.

I wonder if they’ve filtered the data the same way they’ve filtered the Top Doctor data as a means of skewing public opinion about a competing health care systems that have not paid to be included in their database.

You see, once they make differential displays of data that are dependent on receiving payments to view their database, the potential for manipulating what is displayed is unlimited and limits credibility of the data displayed.

But then, they don’t care about accuracy. They just care about the money.

-Wes

Boston Scientific Joins the DTC Fray

Like Medtronic, it seems Boston Scientific Corporation has their own version of direct-to-consumer (DTC) advertising going on: now it's Formula One racing as a venue to sell neural stimulators. Will it ever end?

"Chronic pain costs society more than $100 billion annually and is the leading cause of adult disability in the U.S.," said Michael Onuscheck, President of Boston Scientific's Pain Management Business. "While all physicians treat pain, few specialize in pain management. The Race Against Pain campaign will help raise awareness for the under-recognized medical discipline of pain management and help guide chronic pain sufferers to possible solutions."

Most doctors I know don't attend Formula One races, only corporate monkey-monks. And tell me, what's the return on investment for such advertising in the Formula One venue when implanting doctors rarely attend such events?

Now that's a pain.

And it looks like it's chronic alright.

-Wes

The Dyslexic Tatoo Artist

I learned some amazing statistics today about tatoos and body piercings:

Dr. Anne E. Laumann, associate professor of dermatology at the Feinberg School of Medicine, and co-researcher Dr. Amy Derick, of the University of Chicago, found that year of birth was a predictive factor for tattoos: 36 percent of people aged 18 to 29; 24 percent of those aged 30 to 40; and only 15 percent of those aged 40 to 50 had tattoos. Sixteen percent had obtained their first tattoo before age 18.

These percentages seemed awfully high to me. But in light of this, I guess I shouldn't be surprised that there might be a problem placing a tatoo once in a while. And this poor guy demonstrates just how bad it can be:

Michael Duplessis loves Chicago so much that he wanted its nickname tattooed on his chest.

But the idea went terribly awry in a North Side tattoo parlor: He left with the word "CHI-TONW" inked into his skin where "CHI-TOWN" should have been.

Now Duplessis is suing the business and the tattoo artist for monetary damages in the 2005 mess after suffering what he says in his lawsuit was "emotional distress from public ridicule."

"It was so embarrassing," Duplessis, 40, said Thursday from his home on the Northwest Side. "It was on my chest, and it was spelled wrong. I had to deal with all the people teasing me about it."

Nothing worse than a dyslexic tatoo artist.

But it was interesting that the tatoo parlor obtained "informed consent:"

Duplessis signed a release, but the defendants modified it once the error occurred by writing "chi-tonw" across the top of the form, according to the lawsuit.

Somehow, I think I know who might win this suit...

-Wes

More information on dyslexia.

Microsoft Word macro to transpose letters in misspelled words.

Heart Failure Monitor Device Fails with FDA

In a disappointing decision today, the FDA advisory panel failed to approve the Chronicle implantable hemodynamic monitor on the basis that it wasn't effective at helping to manage congestive heart failure:

(AP) — Federal health advisers recommended Thursday that the government not approve a novel implantable device designed to detect worsening heart failure.

The recommendation to the Food and Drug Administration against the Chronicle Implantable Hemodynamic Monitor came on a 9-2 vote. The FDA isn't required to follow its advisory committees' advice, but it does so most of the time.

A study of the device, made by Medtronic Inc., suggested it isn't effective.

This is a significant blow to the company who had visions of placing this pressure sensor on defibrillator leads in patients with congestive heart failure. Additional trials in patients with severe heart failure might be forthcoming, but unless other trials demonstrate that such monitoring can affect care, it is unlikely insurers will pay for the technology, especially in light of the current concerns over health care costs.

Health Care Should Include Dental Care

In the debate for public health care coverage, we should not forget about the importance of dental care.

-Wes

One Heck of a Nice Guy

Boy, I knew I worked at a great institution, but I wish I could do what Dr. Silverman did:

Northwestern University Professor Richard Silverman is donating royalties he receives from the drug Lyrica to help pay for the construction of a new science research building in Evanston.

Silverman developed Lyrica, a drug used to combat epilepsy and neuropathic pain that is sold by Pfizer Inc. University officials did not disclose the amount of Silverman's donation, but they said it would help fund the construction of the $100 million facility.

Now, back to my patent work...

-Wes

Reference: Chicago Tribune, 1 March 2007 (Registration required)

Patient Safety and Physician Regulation

At a symposium yesterday at the University of Denver Sturm College of Law, leaders of the medical and legal professions in Colorado and national and international experts in medical regulation discussed how improvements in medical regulation and medical injury dispute resolution can support patient safety enhancements, with particular attention to the role of state medical boards. Speakers included Dr. Randy Bovbjerg of The Urban Institute, Dr. James Thompson, President and CEO of the Federation of State Medical Boards, David Swankin, President of the Citizen Advocacy Center, and Dr. Marie Bismark, a medical injury compensation expert from New Zealand. The event was coordinated by Common Good Colorado. The overriding theme?

If we could improve the regulatory environment of health care, what would those improvements be, and what would it take for us to achieve them?

A webcast of the proceedings can be seen here (just click on the person's name in the left-hand column to view their presentation - Windows Media player required).

-Wes

Hat tip: Sarah, web editor, Common Good.

Heart Failure Device: Diagnose or Adios?

Tomorrow, the FDA will review the Chronicle – an implantable hemodynamic monitor (measures heart pressures) made by Medtronic, Inc. that is used for long-term measurement of patients with congestive heart failure. The device looks just like a pacemaker (in fact it uses one of their old pacemaker generator cans) but does not pace. Instead, the device measures the time, surface EKG, temperature and right ventricular heart pressures on a continuous basis. Patients can then upload this information via the internet to a central database for their doctor to review in an attempt to facilitate their management.

So why is this such a big deal?

Because it will be the first time the FDA considers an implantable device that has no therapeutic value – only diagnostic. It heralds the beginning of a development cycle for numerous other devices soon to be developed for this and other ailments by Medtronic and their competitors including pressure and chemical sensors. Importantly, it will also provide the FDA with data regarding the utility of these devices to facilitate management of complicated patients with heart failure and avoid hospitalization.

Why might such a device be needed?

Clinicians are keenly aware of their inability to reliably assess fluid status in a number of select patient groups: the obese, those with underlying lung disease, etc. Patients with recurrent admissions for congestive heart failure exacerbations might be good candidates for such a device, provided the company can convince the FDA that the benefits of the diagnostic data can outweigh the risks of implanting the device.

How Does it Work?

The Chronicle system is composed of three parts: the sensor lead, Chronicle device, and an external pressure reference device that the patient wears. The lead is implanted into the patient’s right ventricle, preferably in an area of high blood flow (to assure non-fouling of the sensor), and connected to the Chronicle device planted beneath the skin of the chest just below the collar bone. The patient also wears a device that measures ambient barometric (atmospheric) pressure throughout the day. Every so often, the patient downloads the pressure and temperature information stored on the Chronicle by first placing their external pressure reference in a base station (similar to a wireless phone’s base station) that is plugged into a phone jack and contains a wand. The wand is then placed over the person’s implanted Chronicle device and the information stored in the Chronicle (time, pressure and temperature information) are downloaded. During the download process, the Chronicle’s internal clock is synchronized with the clock on the external pressure reference to permit adjustments to measured heart pressures based on the ambient atmospheric pressure at a given time. The time, pressure, and temperature data are then uploaded via the internet for the physician’s review.

Implications

While it is uncertain where a stand-alone pressure sensor such as the Chronicle will gain approval (but I think it will be at least approved for the sickest of patients), the technology is sure to be incorporated in future devices incorporating pacing and defibrillation in the future – and this might be the best news of all for those suffering with severe heart failure.

-Wes

References: Wall Street Journal (subscription)

Medtronic COMPASS-HF Study Press release summarizing the Chronicle heart failure study data.

Pneumopericardium

Amazing images of a rare case of pneumopericardium (air in the sac that surrounds the heart) from Dr. S. Venkatesan From Madras Medical College in India:



-Wes

Nicotine Wars

It still puzzles me that we use an incredibly addictive drug, nicotine, to help smokers quit their habit. It's like we've given up and decided that Nicorette gum is to the smoking addiction as methadone is to a heroin addiction. To make matters worse, it now seems that the pharmaceutical industry, in its press to promote its products, wants to limit the verbage on the warning label on the smoking cessation drugs.

(WSJ) As evidence mounts that nicotine-laced stop-smoking aids are producing only limited gains, some critics are calling the products over-rated and over-promoted.

But some high-profile public-health experts say the problem may be over-regulation. They say that federal law requires nicotine gums, patches, lozenges and other products to carry so many warnings that smokers are reluctant to use them. Indeed, the warning literature on a package of nicotine gum is about 20 times lengthier than the warning on a package of cigarettes.

So tobacco researchers and policy makers are starting to argue that the federal Food and Drug Administration should tone down the warnings on pharmaceutical nicotine. At a day-long summit last week in Austin, Texas, entitled "The Case for More Flexible Regulatory Policy," public-health experts discussed a number of changes they may seek to current regulations. Among other possibilities, they say they may recommend relaxing the health cautions for pregnant women and eliminating the requirement that teenagers refrain from using over-the-counter nicotine products without the approval of a physician.

"A 17-year-old smoker of 25 cigarettes per day is doing the right thing to use nicotine gum," says Jonathan Foulds, a tobacco researcher at University of Medicine and Dentistry of New Jersey. "Why give him another hurdle to cross to get help?"

Over-regulation as the cause for lack of utilization? How about the methadone/heroin analogy? Maybe the reason people aren't using these meds is because they're expensive and people don't like taking drugs - especially one that is powerfully addictive. And there are even researchers who question the efficacy of these drugs to stop the smoking habit in the first place.

Recent studies of successful quitters have suggested that the significant benefits of nicotine products seen in randomized clinical trials may not apply in real-world conditions. Critics say the public-health experts who favor nicotine medicines are too financially tied to manufacturers to see the products' limitations. And use of nicotine by teens, pregnant women, heart-disease patients and smokers who haven't quit remains controversial.

"The use of nicotine, whose efficacy in treating nicotine addiction is controversial even in adults, must be strictly avoided in pregnancy, breastfeeding, childhood and adolescence," argues an editorial in the current Journal of Health Psychology, written by a group of eight researchers and antismoking advocates.

To think that people actually READ a warning label and that this is the sole cause of the lack of utilization of these smoking cessation drugs belittles any real analysis of human behaviour.

The reality? We have been incredibly successful in the US at educating our population about the effects of smoking and reducing the number of individuals who smoke. Smoking bans have also been remarkably effective. Why make us smoke this lame excuse for "limited gains" of achieving our goals of smoking cessation in the interest of making pharmaceutical companies more money? Maybe, just maybe, the real reason that smoking cessation aides are producing only limited gains (in sales) is because fewer people are smoking.

Personal Health Insurance Claims Adjusters

Online claims adjusters, like the web-based My Medical Control, will soon be commonplace on the American Health Care landscape where individuals will need to control more of their out-of-pocket expenses.

(NYT) Mr. Fontana, a 42-year-old salesman, has a high-deductible health plan coupled to a health savings account. Since he was nowhere near meeting his deductible, he was on the hook for the entire bill.

So he did something that insurance companies routinely do: he forwarded the bill to a claims adjuster, in this case My Medical Control, a Web-based company that reviews doctor and hospital bills for consumers.

After concluding that Mr. Fontana was not getting the best possible price, the company’s representatives called the imaging facility and demanded a lower one, promptly saving him $200 — minus a 35 percent collection fee.

I think this will get filed under "Why didn't I think of that?"

But even more interesting is the company Vimo.com, that estimates nation-wide prices negotiated for by insurers and compares them to list price. Here's the information for a pacemaker and a defibrillator implant. (Where they got 5 days as an average length of stay for these procedures is anybody's guess: our length of stay is under 1 day, but I digress). These guys, too, will negotiate a lower fee on behalf of patients, not to mention permit ratings of hospitals and doctors along the way.

Transparency of sorts is here, it seems. The real question is, will people switch facilities for a lower price? I suspect if they're paying a bigger piece of the pie, they will. But "quality" of care rendered by a cheaper facility is still difficult to gauge, even for those of us in the business. Where the dust will settle with this price/quality war is anyone's guess.

No matter how we slice it, it seems the terrain for health care delivery has forever changed.

-Wes

When More Is Not Enough

I was feeling down that I just haven't been able to get enough done lately. Especially at work. There just hasn't been enough to multi-task, so I became dysphoric and upset. So in an effort to do more and be more, I sought evaluation and discovered that I, too, suffer from dysphoric social attention consumption deficit anxiety disorder (DSACDAD).

I thought this was a terminal condition, until I found the drug that saved me. I'm sure it can save you, too.

If you doubt it, be sure to check out the testimonials under the "resources" tab on their website. I mean, it helped them, didn't it?

-Wes

Hat Tip: Claudius, a faithful reader

Obesity and Government Intervention

In England, it seems the government can take your child if he's gaining too much weight:

Dr Colin Waine, chairman of the National Obesity Forum, said that removing a child from their family could be justified.

"The long-term impacts of this child's gross obesity are frightening.

"He has great risk of diabetes and coronary illness.

"His life expectancy is severely prejudiced. So action is required if his health is to be safeguarded."

A spokeswoman for North Tyneside Council and North Tyneside Primary Care Trust, a spokeswoman said on Sunday: "We share the concerns over the child's health and well-being.

"We have been working with the family over a prolonged period of time and will continue to do so.

"The child's interests are paramount."

It seems his mother feels otherwise:

She said she had seen doctors, but no-one had actually stepped in to offer her help.

She said that taking Connor into care would be "disastrous".

Can anyone say "civil liberties?"

-Wes