My goal in Tech Medicine will be to explore the intersection of medicine, new technologies, and the Internet. This is a purposefully broad topic. Several times weekly I will post focused reviews of issues interesting to health professionals and nonprofessionals alike. Posts may include examinations of medical devices, pharmaceuticals, scientific advances, internet services, and other technologies involving health care and the practice of medicine. Mirroring as it does the nature of the Internet and the sometimes surprising nature of new technologies, the content may also include topics that are wonderful, unusual, hilarious, or strange.
I'm trained as a nephrologist (a kidney and blood pressure specialist). For the last two years I've written Kidney Notes, a blog designed to filter and process medical news. Most recently, Kidney Notes has become a collection of links, commentary, and scraps of information -- a reference database of interesting things with the help of a popular social bookmarking service called del.icio.us. While I will continue posting to Kidney Notes, several friends have asked me to write longer posts of original content -- and this is what I will be writing on Tech Medicine.
There are many topics I plan to cover, but I'm also open to suggestions and tips. Please email them to techmedicine@gmail.com.
The Risks of MRI Contrast in Patients with Kidney Disease: Gadolinium and Nephrogenic Systemic Fibrosis (NSF)
Sunday, May 27, 2007
Joshua Schwimmer, MD, FACP, FASN
Gadolinium is a type of intravenous contrast given during MRIs to help radiologists visualize blood vessels. Recently, the FDA has warned that this type of contrast, in patients with decreased kidney function, has been associated with a new type of potentially fatal skin disease called "nephrogenic systemic fibrosis" (NSF).
First, some background. Patients with kidney disease very frequently have narrowing of the blood vessels due to atherosclerosis. This narrowing takes place in different parts of the body -- in blood vessels in the head, neck, legs, heart, and the arteries supplying the kidneys.
There are several methods of visualizing blood vessels to detect abnormal narrowings. One method is an angiogram, typically performed by cardiologists, radiologists, or vascular surgeons. This involves placing a catheter directly in the blood vessel and injecting dye (usually iodine-based). There are two disadvantages to angiograms. One, this is a relatively invasive procedure. Two, the iodine-based dye can sometime cause decreased kidney function or acute renal failure, a condition called "contrast nephropathy."
A second method is a CT scan (or CAT scan). While less invasive than an angiogram, CT scans to visualize blood vessels usually require the administration of larger amounts of iodine-based dye than angiograms. As mentioned in the last paragraph, this type of dye can lead to contrast nephropathy and acute renal failure.
A third method for visualizing blood vessels is an MRI or MRA (magnetic reasonance angiogram). In this procedure, the dye used is gadolinium. MRAs have the advantage of being less invasive than an angiogram with a catheter and the use of gadolinium avoids the use of iodine-based dyes, which can cause contrast nephropathy/acute renal failure, so in the past, gadolinium has been preferred for patients with kidney disease. Consequently, patients with kidney disease have often received MRAs with gadolinium to visualize their blood vessels.
All this has changed. Over the last year, an increasing numbers of cases of NSF have been identified and a strong link to gadolinium has been made. NSF is a condition which is similar to scleroderma, in which abnormal fibrous tissue accumulates in the skin, muscle, and internal organs. Eventually, NSF can lead to severe disability or death.
The FDA has added a "black box" warning to the labels of gadolinium-based contrast agents to emphasize the risk of NSF. The risk appears to be greatest for patients with severe decreased kidney function (glomerular filtration rate <30>2). For patients with severe kidney disease, gadolinium-based contrast agents should be used only when absolutely necessary. In some situations, physicians may choose to perform an angiogram or CT scan with iodine-based contrast rather than perform an MRI with gadolinium.
The full text of the FDA's information for health care professionals is here.
Avandia (rosiglitazone) is a commonly used medication to treat type 2 diabetes. In a study published in the New England Journal of Medicine released online yesterday, Dr. Steven E. Nissen and Kathy Wolski from the Cleveland Clinic analyzed 42 previously performed trials of rosiglitazone. They found that the use of this medication was associated with a 42% increase in the risk of myocardial infarction (heart attack) compared with placebo or other medications used to treat diabetes. The authors caution that this data is preliminary and has many limitations, but it does point to the potential for increased cardiovascular risk from rosiglitazone as compared with other medications used to treat diabetes.
"FDA remains committed to assuring that doctors and patients have the latest information available to make treatment and medication use decisions. In this case, FDA is carefully weighing several complex sources of data, some of which show conflicting results, related to the risk of heart attack and heart-related deaths in patients treated with Avandia," said Steven Galson, M.D., M.P.H., director of FDA's Center for Drug Evaluation and Research. "We will complete our analyses and make the results available as soon as possible. FDA will take the issue of cardiovascular risk associated with Avandia and other drugs in this class to an Advisory Committee as soon as one can be convened."
Rather than removing Avandia from the market, the FDA has decided to further study the data. They caution that patients shouldn't stop Avandia on their own without first speaking with their doctor. They also say that is an open question whether the other medication in the same class as Avandia, Actos (pioglitazone), has the same cardiac risks.
Interestingly, in his paper Dr. Nissan suggests that he believes that Actos may have fewer cardiac risks than Avandia. He points to the PROACTIVE trial, which actually show lower cardiac risks with Actos:
The question as to whether the observed risks of rosiglitazone represent a "class effect" of thiazolidinediones must also be considered. Pioglitazone is a related agent also widely used to treat type 2 diabetes mellitus. However, unlike rosiglitazone, pioglitazone has been studied in a prospective, randomized trial of cardiovascular outcomes, called Prospective Pioglitazone Clinical Trial in Macrovascular Events (PROACTIVE). The primary end point, a broad composite that included coronary and peripheral vascular events, showed a trend toward benefit from pioglitazone (hazard ratio, 0.90; P=0.095). A secondary end point consisting of myocardial infarction, stroke, and death from any cause showed a significant effect favoring pioglitazone (hazard ratio, 0.84; P=0.027). Notably, pioglitazone appears to have more favorable effects on lipids, particularly triglycerides, than does rosiglitazone.
Patients taking Avandia and the physicians caring for them have three choices.
Continue Avandia.
Stop Avandia and use a diabetes medication in a different class instead.
Stop Avandia and substitute Actos, which is the same class of medication but which may be safer.
I predict that many physicians and patients with choose option 3, as long as no significant cardiac risks from Actos are identified.
An interview with Dr. Steven Nissen from the Wall Street Journal is below.
The naturalist E.O. Wilson, who coined the term "biodiversity," was an award winner at the 2007 Technology Entertainment Design conference (which I have previously written about here). In his acceptance speech, posted above, he proposed the creation of an "Encyclopedia of Life." This is one of these ideas that, once proposed, seems so self-evidently important, interesting, and plausibly constructable that it gathers an overwhelming amount of support.
The Encyclopedia of Life (www.eol.org) is an effort to create an online catalog of the 1.8 million known species of animals, plants, and other forms of life on Earth. Initial supporters have included the Field Museum of Natural History, Harvard University, the Marine Biological Laboratory, the Smithsonian, and the Biodiversity Heritage Library. Financial support has been provided by the John D. and Catherine T. MacArthur Foundation and the Sloan Foundation.
"The Encyclopedia of Life will be a vital tool for scientists, researchers, and educators across the globe, providing easy access to the latest and best information on all known species," said Jonathan F. Fanton, President of the John D. and Catherine T. MacArthur Foundation. "Technology is allowing science to grasp the immense complexity of life on this planet. Sharing what we know, we can protect Earth's biodiversity and better conserve our natural heritage."
An example page of Amanita phalloides, the death cap mushroom, is featured below:
It's easy to image how an online database of biological diversity, modifiable by scientists and amateurs alike, could be a useful and inspiring resource, much like Wikipedia. The Encyclopedia of Life is still in its early stages, but the video below show a hint of its potential:
Grand Rounds, this week's best posts of the medical blogosphere, is up at the Medical Humanities Blog. Thanks for including my post on Tekturna (Aliskiren), the first direct renin inhibitor.
This Week's Interesting Links: Creating Medical Blogs, the FDA and Anemia Drugs, Governor Corzine's Doctors, & Angioplasty isn't like Plumbing
Monday, May 14, 2007
Joshua Schwimmer, MD, FACP, FASN
Here are some links that caught my eye over the last week:
Clinical Cases and Images, an outstanding medical blog by Dr. Ves Dimov at the Cleveland Clinic, has a post on "How to start a medical blog in 2 minutes." It points to a video on YouTube by Google showing how to create a new blog with Blogger, a free service. Also described are ways of working with medical RSS feeds to create your own webpage of medical journals.
I spoke about the controversies over anemia drugs in a previous post. Over at the Wall Street Journal Health blog -- an interesting source of information about current health and business issues -- they're following the FDA hearings on the use of drugs like Aranesp, Procrit, and Epogen by oncologists. A sample question by an FDA doctor: "What data do you have to assure me that this is not Miracle-Gro for cancer?"
Finally, Slate, a sharp and well-written online magazine, explores the implications of recent medical studies on angioplasties in Plumber's Butt? The Right and Wrong Way to Think about Heart Attacks. The piece argues that the idea that interventional cardiology is like plumbing is wrong; that not every clogged artery needs to be opened; and that opening up narrowed blood vessels does nothing to prevent future heart attacks. It also features an entertaining look at the history of cardiac catheterization:
Before angioplasty became widespread, the only emergency treatment for heart attacks was to infuse clot-busting drugs like streptokinase into a patient's whole body. This was like running concentrated Drano through a city's water supply to fix a stopped-up sink. It wasn't very effective and also caused side effects like bleeding. In 1929, a budding German crackpot named Werner Forssmann took the first tentative steps to directly unclog blocked vessels, by inserting a urinary catheter deep into his own arm. (A nurse tried to stop him, but he tied her to an operating table.) Forssmann walked up a flight of stairs and took an X-ray showing that the catheter had entered his heart—a feat that earned him the Nobel Prize.
The lead story in yesterday's New York Times had this first paragraph:
Two of the world’s largest drug companies are paying hundreds of millions of dollars to doctors every year in return for giving their patients anemia medicines, which regulators now say may be unsafe at commonly used doses.
To summarize: the article not only implies that medications like Epogen, Procrit, and Aranesp -- used to increase the blood count to treat anemia -- are given needlessly, but that doctors and others have strong financial incentives to prescribe these medications and have disregarded the safety of patients.
One physician I know, a nephrologist, was furious at this article. Prior to the advent of Epogen (erythropoetin) and other erythropoiesis-stimulating agents (ESAs), he said, patients with kidney disease on dialysis were routinely dependent on blood transfusions. (Anemia is a common side effect of kidney disease.) They routinely felt awful. In fact, it wasn't until the widespread correction of anemia with Epogen that physicians realized that it wasn't the kidney disease itself that was making dialysis patients feel awful -- it was often the accompanying anemia. The article in the New York Times, he complained, failed to stress this important benefit of Epogen and other drugs.
Previous studies looking at qualify of life of kidney disease patients have suggested that the optimal hemoglobin is 11 - 12 g/dL, and for many years, this range has been the target for therapy. Some physicians assumed that higher hemoglobin levels were likely to be better for certain patients. But recently, studies in kidney disease and cancer patients have noted an increase in heart attacks, blood clots, and other complications when ESAs are given to maintain a hemoglobin of above 12 - 13 g/dL.
Patients currently using or considering the use of an ESA should know the following:
A higher chance of death and an increased rate of tumor growth were reported in patients with advanced head and neck cancer receiving radiation therapy and in patients with metastatic breast cancer receiving chemotherapy, when ESAs were given to maintain hemoglobin levels of more than 12 g/dL.
A higher chance of death was reported and no fewer blood transfusions were received when ESAs were given to patients with cancer and anemia not receiving chemotherapy.
A higher chance of death was reported and an increased number of blood clots, strokes, heart failure, and heart attacks was reported in patients with chronic kidney failure when ESAs were given to maintain hemoglobin levels of more than 12 g/dL.
A higher chance of blood clots was reported in patients who were scheduled for major surgery and given ESAs.
ESAs are not approved for treatment of the symptoms of anemia, such as fatigue in patients with cancer, surgical patients and patients with HIV.
If you have any questions you should talk with your health care provider.
Important study results include the following:
Patients with chronic kidney failure had an increased number of deaths and of non-fatal heart attacks, strokes, heart failure, and blood clots when ESAs were adjusted to maintain higher red blood cell levels (hemoglobin more than 12 g/dL).
Patients with head and neck cancer receiving radiation therapy had faster tumor growth when ESAs were adjusted to maintain hemoglobin levels higher than 12 g/dL.
Patients with cancer not receiving chemotherapy died sooner and had no fewer blood transfusions when ESAs were given according to the dosing recommendations for cancer patients receiving chemotherapy.
Patients scheduled for orthopedic surgery who received ESAs to reduce blood transfusions during and after surgery had more blood clots than those not given an ESA.
Physicians who prescribe ESAs should consider the important study results above and:
Understand that ESAs are given to decrease the need for red blood cell transfusions;
Consider both the risks of transfusions and those of ESAs when deciding to prescribe an ESA;
Adjust the dose of ESA to maintain the lowest hemoglobin level necessary to avoid the need for transfusions.
Monitor patients’ hemoglobin levels to ensure they do not exceed 12 g/dL;
Understand that ESAs have not been shown to improve the outcomes of chemotherapy treatment (e.g., better tumor shrinkage, delay in tumor growth or longer time for survival); and
Understand that in patients with cancer whose anemia is caused by chemotherapy and in patients with HIV whose anemia is caused by AZT (zidovudine), there are no data to support claims of improvement in health-related quality of life, including effects on fatigue, energy or strength.
In light of new information from recent studies, the FDA and major medical societies are reviewing their guidelines and are expected to issue revised guidelines on the use of medications to treat anemia in the next few months.
Diethylene glycol is an industrial solvent and is a major ingredient in antifreeze. Unfortunately, it is also a deadly poison, and it has caused over 300 deaths in the last year when counterfeiters substituted diethylene glycol for glycerin in cough syrups. Most of the deaths occurred in Panama, and an article in the New York Times recently traced the source of the poisonings to a manufacturer in China. From the NYT:
The kidneys fail first. Then the central nervous system begins to misfire. Paralysis spreads, making breathing difficult, then often impossible without assistance. In the end, most victims die.
The identification and treatment of ethylene glycol intoxication -- which presents identically to diethylene glycol poisoning -- is one of the classic poisonings taught to medical students. (Fortunately, most doctors never see it.) Patients appear intoxicated despite a normal blood alcohol level (unless alcohol was consumed at the same time). The blood is acidic, sometimes fatally so. Kidney failure is common. Dialysis, a way of cleaning the blood, is often used as a treatment for both kidney failure and to remove the poison and its byproducts.
Previously, intravenous infusions of ethyl alcohol were also used to treat ethylene glycol poisonings. The downsides were many, including difficulties with dosing and sedative effects. More recently, the medication fomepizole has taken the place of ethyl alcohol. With early treatment, most patients survive.
Lastly, diethylene glycol intoxication has historical importance -- it led to the creation of the Food and Drug Administration (FDA). In 1937, a preparation of Elixir Sulfanilamide used diethylene glycol as a solvent. (The manufacturer never tested it for toxicity.) 105 people died. This tragedy led directly to the passage of the 1938 Food, Drug and Cosmetic Act and the creation of the FDA.
In part 1, I introduced aliskiren and discussed the renin-angiontensin-aldosterone system. As I mentioned, there are innumerable medications already available that effect this system, leading to the question: what's so special about aliskiren?
Aliskiren is a direct renin inhibitor. Currently, all other agents that inhibit the renin-angiotensin-aldsterone system (like ACE inhbitors and angiotensin receptor blockers) increase the levels of renin (through feedback mechanisms). This increased renin can potentially reduce the effectiveness of theese medications. Aliskiren, in contrast, reduces the activity of renin and has the potential to blunt the effects of the increased renin levels caused by other agents.
For lowering blood pressure, aliskiren is indicated as a single agent and in combination with other agents that affect the renin-angiontensin-aldosterone system. The blood pressure reductions with the combination of aliskiren and other medications, in some studies, are greater than the reductions with either agent alone.
In addition, medications that block the renin-angiotensin-aldosterone system are particularly important in patients with kidney disease and heart failure. For patients with kidney disease and protein in the urine, medications like ACE inhibitors and angiotensin receptor blockers have been shown to protect the kidneys and prevent or delay progression of kidney disease. For patients with heart failure, these medications can improve symptoms and reduce mortality.
Whether aliskiren alone or added to other medications is effective and may provide additional protection is unknown.
It's coming! 24 Hours of Flickr: A global Flickr community event
What happens around the world in one day? In a word – life. Here on Flickr, our members are sharing the world that they see: snapping daily moments, recording history, telling stories, capturing beauty.
To celebrate this global community, we invite you to join us in 24 Hours of Flickr, a day-long global photo project. On May 5 2007, grab your camera and whatever else you need, and chronicle your day in pictures.
Join the 24 Hours of Flickr group to get ready for the big day. After the big day, post your best photo to the group. We'd love to see the group photos on a map as well, so make sure you add your photos to the map using the Organizr.
Remember! We want the photos here to illustrate one day in the life of the Flickr community — May 5, 2007 — so, you can only submit a photo taken on May 5. (You'll have until May 21 to add your photo.)
The event will be commemorated by a companion 24 Hours of Flickr book, which will contain a selection of photographs chosen from the group. Additionally, the group's photos will be featured at Flickr events around the world this summer.
Books will be sold at cost (the amount will be available in the near future) with Flickr donating $1 for each book sold to Médecins Sans Frontières up to a total of $10,000 USD.
By adding your photo to this group, you understand that it may be selected for publication in the 24 Hours of Flickr commemorative book and/or displayed at a Flickr-sponsored event this summer.
As a cardiologist, clinical researcher and vascular biologist, I am salivating at the arrival of this new medication.
The effects that renin inhibition has with regard to long term treatment of ACE intolerant subjects with regard to nephropathy, heart failure and endothelial function will be an interesting investigational opportunity...
Here are a few quick facts about Tekturna:
It is the first new type of blood pressure medication in over a decade.
It was initially called Rasilez. (Perhaps as a reference to the Renin Angiotension System.) The name change to Tekturna caught many drug representatives off guard.
It's produced by the Swiss pharmaceutical maker Novartis.
It works by blocking the enzyme renin. (Tekturna is a "renin inhibitor.")
The name (and logo) are probably references to the "turning" of the feedback cycle of the renin-angiotensin-aldosterone system.
The renin-angiotensin-aldosterone system is a complex, interlocking system of hormones and enzymes critical for regulating blood pressure in the body. Briefly, renin is an enzyme produced by the kidney, which leads to a cascade of events (outlined above) which eventually produces angiotensin II, a powerful constrictor of blood vessels -- and angiotensin II raises blood pressure.
Many drugs already exist that block this system at different sites. Physicians use these medications routinely to control blood pressure (and to treat congestive heart failure and kidney disease -- more on that later). Some of these medications include angiotensin converting enzyme inhibitors, like lisinopril and ramipril (Altace), which prevent the formation of angiotensin II from angiotensin I; angiotensin receptor blockers like losartan (Cozaar) and irbesartan (Avapro), which block the blood vessel-constricting effect of angiotensin II; and aldosterone blockers like spironolactone and eplerenone (Inspra).
So why are physicians and researchers (like the cardiologist quoted above) excited about Aliskiren? This is the first medication that actually blocks renin, which is the critical first agent acting on the entire renin-angiotensin-aldosterone system.
More on the potential benefits of Tekturna in part 2.
The Healthline Site, its content, such as text, graphics, images, search
results, HealthMaps, Trust Marks, and other material contained on the
Healthline Site ("Content"), its services, and any information or material
posted on the Healthline Site by third parties are provided for informational
purposes only. None of the foregoing is a substitute for professional medical
advice, examination, diagnosis, or treatment. Always seek the advice of a
physician or other qualified healthcare provider with any questions you may
have regarding a medical condition. Never disregard professional medical advice
or delay in seeking it because of something you have read on the Healthline
Site. If you think you may have a medical emergency, call your doctor or 911
immediately. Please read the Terms of Service for more information regarding
use of the Healthline Site.
