Tuesday, November 3, 2009
The Pap Smear: A Symbol for Our Health Care System's Problems
The results of the study are not surprising to me, as I have seen this in clinical practice. The more I thought about why this is occurring, the more I thought about the pap smear as a symbol of our health care system's problems. So why so many pap smears?
1. Pap smears have saved lives. Cervical cancer used to be a major killer of US women. Now it is rare to hear about a women who has died of cervical cancer. Not true in third world countries when screening is not possible. The fact that we have virtually gotten rid of a cancer with early detection is truly amazing. But the danger here is that it has set up the paradigm that this is true for all diseases and cancers. Recently, breast cancer and prostate cancer screening have come under fire for not really saving any lives. However, even with the data, patients and advocacy groups will not likely take a screen only if proven life saving approach. Breast self-examination has absolutely no data to support this practice, and in young women who are likely to find non-cancerous bumps, may actually be harmful. Yet, this practice is routinely recommended for many young women.
2. Women (and many men) want/expect a yearly physical, and most women believe that a pap smear is part of this. Similar to other types of cancer screenings, there is very little evidence that a routine check up is beneficial. This is not to say that you shouldn't visit your doctor regularly. However, many of the things doctors do during a physical have limited to no value. There are some things that have tremendous value, such as checking blood pressure and weight, and talking about diet, exercise, smoking cessation, etc. However, having the doctor check your whole body every year when your feeling just fine is unlikely to be helpful. Yet, the American public expect a full exam every year. After all, their health care premiums are quite high, so they might as well get checked out. This extends to the pap smear. It saves lives (as above), is part of my regular check up, and I am paying a lot of money for this; so therefore I expect my yearly pap.
3. Physicians have little disincentive to refuse to do a pap smear. The pap smear only takes a few minutes. Trying to take the time to explain #1 and #2 above makes little sense for the primary care physician who is not paid by time spent counselling a patient, but by how many patients she can see. In other words, talking a patient out of an unneeded test actually costs the primary care doc money, because that time could be used for seeing another patient. More importantly, if the physician refuses the pap smear, and the patient goes elsewhere to get the pap smear and is found to have cervical cancer; the physician could get sued placing her entire career in jeopardy!
If pap smears save lives, patients expect/demand them, talking a patient out of an unnecessary pap smear only costs me money and not doing the pap could get me sued, why wouldn't I do a pap smear on every women that wanted one?
4. The pap smear rep reminded me to get the test. The drug companies are not really the problem any more. Every day you read about a drug company laying off employees. This is because most drugs are or will soon go generic and there is little in the pipeline. This is not the case for devices and testing. Big labs have reps that come to physician's offices to discuss the latest fancy new test. Like the drug reps, they bring lunch too. The difference: medical devices and testing though FDA approved are not nearly has heavily regulated as the drug companies when it comes to selling to physicians. Drug reps by law are restricted to saying only what is in their label to physicians. It works a little bit differently for the lab and device reps. As newer tests and devices become available, watch for more of a focus on selling these products. Don't be surprised to see direct to consumer advertisements asking patients to ask their doctors about such and such a test.
5. The experts don't agree. It is very hard to keep up with evidence based guidelines in primary care. It's even harder when there are multiple guidelines, and harder still when they don't agree. For prostate cancer, the American Cancer Society and the American Urological Society say that doctors should test for prostate cancer. The US Preventative Health Task Force guidelines say that we shouldn't. Initially, some of the groups recommended more frequent pap smears, but recently decreased the interval due to evidence that less frequent screening was better. However, with all multiple guidelines that often differ, it is not surprising that so few primary care physicians actually knew what all the experts actually did agree upon. Another issue is that reasons behind differing guidelines have to do primary with politics and money. The Urologists want primary care docs to test for prostate cancer because they make money when the test comes back positive. The government doesn't want you to test for prostate cancer, because testing leads to more testing and treatment which costs them (you the taxpayer) more money.
6. Doctor's don't follow guidelines anyway. Even if there was one clear and definitive guideline for docs to follow, they probably wouldn't. There are likely multiple reasons. Our current Continuing Medical Education system (CME) that is supposed to keep docs up to date is horrible and funded by commercial interest. The stimulus package already gave some money for comparative effectiveness research and there will likely be more money for this in any health care reform bill that passes. However, if docs don't know the results of what is best or what actually works, then the data is not all that useful. It is unlikely that a drug company is going to fund a CME program that shows their drug is not useful. So who is going to fund the dissemination of comparative effectiveness findings? There is also no real incentive to follow guidelines. Again, docs get paid for how many patients they see, not by how beneficial their advice was to patients or whether they gave guideline appropriate care.
Since pap smears don't cost a substantial amount of money, it is unlikely that getting rid of all these unnecessary pap smears is going to put a dent in health care spending. However, the underlying reasons behind the many unneeded pap smears is a symbol of what what's right and wrong about our health care system. We should give this study's findings, and more importantly the reasons behind these findings, a critical look.
Monday, October 19, 2009
Parents: Please Keep Your Children in Booster Seats.
Coincidentally, the AAP's journal Pediatrics (not yet available online, but data via Medpage Today) released a study today updating information regarding the use of booster seats in childre 4 to 8 years old. They collected data for over 9 years including 7,151 children in 6,591 crashes. Most kids (70%) were using a seatbelt alone (no booster). The study found that serious injury including concussions, brain injuries, internal organ injuries, spinal cord injuries, and extremity fractures occurred in 1.15% of children; 1.36% of those wearing seatbelts and 0.67% of those in boosters. or double the risk of serious injury with seatbelt alone. Most of the injuries were head injuries and children wearing seatbelts alone had over double the risk of suffering abdominal injuries.
Thus, this study reaffirms the need to keep young children in booster seats until they are tall enough to wear a seat belt alone, which is at 4'9" which occurs sometime between 8 to 12 years of age. It's not that my daughter minds the booster so much. However, she feels like a "baby" when her friends are allowed to ride without a booster. Parents, (especially my children's friends parents) please keep your kids in booster seats until they are 4'9".
Sunday, July 26, 2009
Sick About Singulair
I have no ill will towards Merk. It is an American company that has come up with some products that I find beneficial for patients including Fosamax (which is now generic) and Januvia, and they are the makers of two important vaccines: Gardisil and Zostavax. However, I am concerned about high sales of the asthma drug Singulair, because national guidelines state it should not be used as a first line therapy for asthma.
Facts about asthma
According to the American Lung association, in 2007, it was estimated that 22.9 million Americans currently have asthma. Of these, 12.3 million Americans (3.8 million children under 18) had an asthma attack. In 2005, there were 3,884 deaths attributed to asthma. During 2006, 444,000 hospitalizations and close to 1.7 million emergency room visits were attributed to asthma.
In 2007, the NIH released updated guidelines about asthma. Regarding treatment, the guidelines suggest that all asthmatics with persistent asthma (symptoms or rescue medication use more than twice a week) be initiated on inhaled corticosteroids (ICS). ICS's are considered first line treatment for all asthmatics, from babies to children to adults and to the elderly. The reason is based on solid evidence that these agents work the best in improving lung function and decreasing symptoms. Singulair is listed as an alternative agent. Singulair is an anti-leukotriene. Leukotrienes, like histamines, are substances released in an allergic response that cause the airways to tighten up. Thus, Singulair works in the same way that antihistamines work: by treating the symptoms. ICS's work by blocking inflammation which is what causes the release of leukotrienes in the first place. Singulair is not anti-inflammatory, ICS's are. Singulair treats the symptoms, whereas ICS's treat the problem. This is why study after study proves that ICS's are superior to Singulair, and why guidelines place ICS's as first line treatment and Singulair as alternative.
Does Singulair work?
Of course Singulair works. In order for a drug to be approved by the FDA, the drug company has to show that its product is efficacious. The problem is that it has to show that it is efficacious compared to placebo. Thus, Singulair works better than a sugar pill. However, compared to any other asthma medication, it is not as good. Even when added on to an ICS, it is not as good as other add ons, such as long acting beta agonists (LABA's).
Why do physicians prescribe so much Singulair when is not what the guidelines recommend?
This is an extremely important question. Some may chalk it up to drug company marketing. However, all the ICS and ICS/LABA making companies due their job marketing their product as well. I think the main reason has to do with fear of ICS's. Corticosteroids are different than the kind of steroids athletes take. However, they are not without side effects. Earlier studies on older medications showed some growth delay in children, which is why pediatricians may be so reluctant to use ICS's. However, more recent studies showed that for the newer agents, long term use with mild to moderate doses did NOT cause growth delay. In 2002, the NIH reviewed all the literature and determined that at low to medium doses of ICS's, there are NO SIGNIFICANT SIDE EFFECTS. This is when ICS's became considered first line therapy for ALL asthmatics.
The other issue is the convenience factor of a pill vs. an inhaler. Inhaler use is clearly not as easy as taking a pill (Singulair comes chewable for children).
The thought is probably, "it's a once a day pill that might help my patient, and probably won't hurt them, so why not give it try?" The problem with this approach, is the failure to consider the risks of uncontrolled asthma. Uncontrolled asthma leads to ER visits, hospitalizations, and possible even death. Asthma is a serious disease. For patients who have persistent asthma, following the guideline recommendations of ICS's as first line agents is the right thing to do.
What about allergies?
Singulair is also indicated for allergic rhinitis or allergies. As above, like histamine, leukotrienes play a role in allergic rhinitis, and this is why Singulair is used. I have posted about Singulair and allergic rhinitis previously. Basically, there are several treatments for nasal allergies:Non-sedating antihistamines (Claritin, Zyrtec, Allegra), Leukotriene modifiers (Singulair), inhlaed nasal steroids (Flonase or fluticasone, Rhinocort, Nasacort, Veramyst) and inhaled nasal antihistamines (Astepro). Muliple studies that show that fluticasone (Flonase) is better than Singulair, better than Claritin, and several studies that show that the combination of Singulair and Claritin is not better than either agent alone. However, in one study, though the combination of Singulair and Claritin was better than either agent alone, the individual agents were no better than placebo. An excellent review by Dr. Robert Nathan showed that "leukotriene receptor antagonists (Singulair) are sometimes more effective than placebo, are no more effective than nonsedating antihistamines (Claritin) , and are less effective than intranasal corticosteroids in the treatment of allergic rhinitis." Finally, a recent guideline from World Health Organization suggests that for patients with mild, intermittent allergic rhinitis; treatment with non-sedating antihistamines and leukotriene modifiers were both acceptable forms of treatment, but patients with more chronic or bothersome symptoms, inhaled nasal steroids should be used.
Some would argue that having both allergies and asthma together would be a reason to take Singulair. There is no question that treating allergic rhinitis may help with asthma symptoms. However, the killing two birds in one stone approach simply hasn't been proven to be the case. If you have allergic rhinitis that makes your asthma worse, you should take the most effective agent, which is inhaled nasal steroids.
What if I am taking Singulair for asthma?
Singulair has been proven more effective than placebo, and in some individuals controls their asthma and allergies. However, a recent internet survey revealed that about 55% of asthmatics have uncontrolled asthma, and many of them are on regular medications. Asthma control is the key, according to the new NIH guidelines. If your asthma is well controlled on Singulair, then it is probably OK to take. However, there is a theoretical risk that by taking Singulair (treating the symptoms without treating the underlying inflammation), that though you feel well now, your lung function will be worsening over time. More importantly, if you are taking Singulair and your asthma is not well controlled, then you should definitely switch to at least an inhaled corticosteroid, or possibly an agent combining an ICS with a long acting brochodilator (LABA) such as Advair or Symbicort. There are many ways to determine asthma control, including how much rescue medications you are taking and how asthma affects your daily life. The easiest way to determine your asthma control is by taking the Asthma Control Test
Wednesday, July 22, 2009
Finally! FDA Questions Safety, Quality of Electronic Cigarettes

- In testing 19 products from two manufacturers, investigators found that the majority tested positive for tobacco impurities thought to be harmful to humans.
- In one sample, the FDA’s analyses detected diethylene glycol, a chemical used in antifreeze that is toxic to humans
- Half of the samples appeared to contain known carcinogens
- Some products testing positive for nicotine even though the label said no nicotine was present.
These products are marketed and sold to young people and are readily available online and in shopping malls. In addition, these products do not contain any health warnings comparable to FDA-approved nicotine replacement products or
conventional cigarettes. They are also available in different flavors, such as chocolate and mint, which may appeal to young people
Wednesday, July 8, 2009
Let Google Solve Our EMR problems
Thursday, July 2, 2009
Lantus and Cancer- A Closer Look Is Not Reassuring
The first study was a German study of 127,000 patients, which 20,000 were treated with Lantus. Most of these patients had Type 2 diabetes. Overall, this study found a correlation with all insulins and cancer, but no difference between the analogue insulins. However, because patients on combination analogue and human insulin were excluded in the study, the dose of lantus was much lower than the other analogues. The researchers then adjusted for insulin dose, and they found a dose dependent relationship of cancer and Lantus. The magnitude of this effect was such that 1 cancer might be caused for every 100 patients taking Lantus for a year. One of the limitations of the study was that it was not possible to break the analysis down by types of cancers caused. Given this and other possible limitations, the editors of the journal decided not to publish this study until these results could be replicated in other studies/countries, especially considering the importance of the findings if corroborated.
Since then 3 other studies were performed, and subsequently all four were published together.
The second study was a Swedish study matched a national cancer database and a national diabetes database looking for a connection. This study included over 120,000 patients of which about 6000 were on Lantus. They found no increase in risk for cancer with Lantus when taken with other kinds of insulin. These patients were younger, and more likely to have type 1 diabetes. However, analysis of patients who took Lantus alone, most of whom had type 2 diabetes, showed a doubling of breast cancer, which was highly statistically significant (though no increase in other types of cancers).
A third Scottish study used national database registeries similar to the Swedish study and they found exactly the same thing. The patients who took Lantus with other insulins, who were generally younger type 1 diabetics had no increased risk of cancer with Lantus compared to human insulin (actually had lower rates) but the patients on Lantus without other insulins, mostly older type 2 diabetics had a higher risk of cancer. There was also similarly an increased risk of breast cancer in women taking Lantus alone, which was about the same magnitude as the Swedish study.
The fourth study looked at cancer risks associated with a range of insulins. This retrospective UK study looked at over 62,000 adults that were started on oral agents and/or insulin. Diabetes developed in adulthood, so these were mostly type 2 diabetics. In general, the study found no difference between human insulin and analogue insulins like glargine (Lantus). However, the study did find that metformin use is associated with a lower risk of cancer, and seemed to abolish cancer risk. Also, only 10,000 patients in the study were on insulin, and only 2000 on Lantus. Plus, it was not clear who was taking meformin plus Lantus. Thus, given the very small number of patients on Lantus, some of who may have been taking metformin, this negative finding is not all that reassuring.
Taken together, in my opinion, these 4 studies strongly suggest a link between new cancers in adult type 2 diabetics who are taking Lantus alone. Now, we can't say that Lantus actually causes cancer. In fact, it is unlikely that Lantus actually causes cancer alone, because it takes years to develop most cancers. However, it is more likely that Lantus causes existing cells to grow and divide more rapidly. Usually, the body's own natural cancer fighting abilities take care of these cells. In other words, though Lantus may not cause cancer, adult type 2 diabetics taking Lantus seem to develop clinically apparent cancers at much higher rates (double for breast cancer) then those not on Lantus. Though whether or not Lantus is causative of cancer is an interesting academic discussion. However, from the patient's standpoint if taking Lantus increases the likelihood they will develop cancer, that's all they need to know.
Large observational studies are far from perfect. The can detect differences (i.e. adult type 2 diabetics taking Lantus were more likely to get cancer), but can detect the reasons for these differences. The only way to show actually causation would be a very large, randomized control trial conducted over years. However, this will take years to complete. The Europeans are suggesting meta-analysis of even larger databases to find out sooner.
Until we know for sure, given a possible risk for Lantus increasing the rate of cancer development, I would suggest it would be prudent to stop taking Lantus if you are a type 2 diabetic, especially if you are not taking other kinds of insulin. Detemir insulin (Levemir) is a reasonable alternative. Though it has not been studies as extensively, its effect on the IGF-1 receptor (the purported mechanism of the cancer association) if much, much less than Lantus.
Wednesday, July 1, 2009
Lantus Causes Cancer! Why Doesn't Anyone Seem Care?
I recently posted on the Lantus/cancer connection in my post A New Problem With Insulin: Cancer. The concern was triggered in a press release about a recent European report based on one earlier and three new studies which show a link between Lantus, a long acting insulin, and cancer. As I mentioned, I though it was interesting that more alarm has not been raised, particularly here in the US. Nissen's poorly done Avandia study got major press, and people stopped taking the drug (He was recently proven wrong- see here fore more info). Yet, for Lantus, the report is not about one study, but four studies that show similar findings that Lantus increases rates of cancer. In addition there are some biologically plausible reasons (more later) and a clear dose response. If you look at the criteria for causation, the Lantus/cancer connection seems to ring true. Yet, there seems to be not that much in the press and little public outcry to pull the medication from the market. This may be in part to the fact that the news cycle is now 24/7 Michael Jackson, but other medical stories, like the FDA and Tylenol, seem to be getting some attention, so this can't be the entire reason.
What do the experts say? The Europeans are making "an urgent call for more research". Yet, the US response is much more subdued. The official response from the American Diabetes Association (ADA) stated that findings from these research papers are conflicting and inconclusive, and cautioned against over-reaction until more information is available. A similar response can be found from The American Association Of Clinical Endocrinologists (AACE), the smaller but more academic group of diabetes specialists.
Where is the media attention on this? Where is the warning to patients? Why doesn't anyone seem to care?
MJ aside, here are some reasons:
1. The US experts don't want to say too much because of their ties to the drug companies. Both the ADA and AACE receive huge amounts of money from corporate sponsors, specifically the drug companies. In fact, back in 5/07 the experts issued a joint statement that had similar comments on the Avandia scare (which turned out to be correct). Sanofi-Aventis, the maker of Lantus, gives money to both of the ADA and AACE, and their members are unlikely to bite the hand that feeds them.
2. Though not all endocrinologists think alike, based on national and international diabetes recommendations, the expert guidelines recommend the use of insulin in type 2 diabetes much sooner than I would recommend. I have blogged in the past that I believe the endocrinologist making these recommendations may have a conflict of interest in that they have an incentive to make recommendations that will lead more patients toward insulin is because insulin use in type 2 diabetics is how they make their living. It is possible that the endocrinology experts are cautious about scaring the public about Lantus, because this may cause concern about all insulins, which they believe is the best treatment for diabetes.
3. The reason why Avandia drew more attention is because Dr. Nissen and some Congressmen were the ones making the noise, not the specialty societies. The Nissen meta-analysis on Avandia, from the data analyzed, to the publication, to the media frenzy had political motivations, whereas the Lantus studies do not. (See a timeline of the politics of the Avandia study in my post Diabetes Conspiracy )
What now?
Thanks to a comment on my previous post, I looked into the matter a little more. One of the problems with insulin is that is that it is related to insulin like growth factor (IGF-1) which has been shown to stimulate tumor growth. Regular human insulin has some affinity for the IGF-1 receptor, but Lantus has a much greater affinity, which is the likely reason more cancers were seen. There happens to be another long acting insulin on the market called Levemir that has very little affinity for the IGF-1 receptor (less than even human insulin) and is as effective as Lantus. In 2008, Lantus just missed the top 25 most commonly prescribed branded drugs at #26 with over 10.25 million prescriptions that year. Levemir came in at #170 with only 1.3 million prescriptions. Though I doubt this is public knowledge, I would guess that Novo Nordisk (the company that makes Levemir) is not giving nearly as much to these organizations as Sanofi Aventis (makers of Lantus), but I could be wrong. Since Levemir is a newer drug, is was not included in these studies and one can not rule out potential harm. That said, its low affinity for IGF-1 is reassuring. Thus, upon further reflection, I think that all diabetic patients who are on Lantus should talk to their doctor about insulin use, and if they need it, ask their doctor to consider switching them to Levemir.
Update: Via Med Page today, FDA just announced they were going to look into this. Not sure how much press this will garner. Certainly more valuable use of their time then trying to take down Tylenol.