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Monday, October 26, 2015

How can we start coming up with new therapies that actually save money?

In the United States, biomedical research, including basic science and clinical studies, is paid for mainly by companies that expect to make money off of new discoveries. The government, through the National Institute of Health (NIH) funds a little over a quarter of it, but most of the money comes from drug and device manufacturers.

This means that interesting research that might result in breakthroughs that save patients money is unlikely to find funding. This is terrible. If gummy bears cured cancer, we might never find out about it. If anything that is easy to come by, from various sources, were to show promise therapeutically, we as US citizens would not be likely to find out about it through our own research.

Some examples:

1. Red yeast rice, a dietary supplement made of rice fermented with the fungus Monascus purpureus in a centuries old process, contains a widely marketed cholesterol medication (lovastatin) that is naturally produced by Monascus. The doses are high enough to reduce cholesterol significantly. The best study of this product was done in China, with an extract of the yeast rice, and showed that it reduced bad heart outcomes more than did lovastatin in clinical trials here. The FDA has banned red yeast rice periodically (though it is now easy to find online) saying that it could be dangerous. For awhile, the only red yeast rice products that could be sold in the US were ones which either didn't mention how much active ingredient they contained, or contained little to none of it. Now that we can buy it again, it is unclear which brands actually work to reduce cholesterol.

2. Aspirin, which was first widely adopted for treatment of pain and fever in the late 1800s, was found in the 1970's to be very effective for treating and preventing disorders due to blood clots, particularly heart attack and stroke. I wondered how, since this drug was widely available at a very low price, research had been done in the US to show how effective it was. It turns out that the groundbreaking work was done in Britain, where most research is funded by the government (which would stand to gain, along with patients, from discovering an inexpensive approach to a common problem.) To be fair, in the 1970's research in the US was much more often paid for by the government, so the aspirin research probably could have been done here.

3. Corticosteroids (prednisone and others) are widely available and inexpensive medications which reduce inflammation. They have various side effects and so are used sparingly in most situations. It turns out that, when used along with antibiotics in severe community acquired pneumonia, they make people improve faster and die less frequently. A review of 13 randomized controlled trials came out in the Annals of Internal Medicine earlier this month. Dr. Reed Siemieniuk was the first author. He and his coauthors are from Canada and Europe and the vast majority of the articles reviewed were done in Europe. Studies like this don't happen in the US because drug companies have no incentive to fund them. Full color, full page ads or TV infomercials will not tout the importance of this discovery, so it will be a little more difficult than it might be to change the habits of US physicians to incorporate this life and money saving approach.

4. Nicotinamide, also known as vitamin B3, a derivative of niacin, was just reported to reduce pre-cancerous skin spots, known as actinic keratoses. These are the little scaly spots that happen on the arms, heads and faces of aging people who have spent time in the sun. It also appears that topical nicotinamide may do the same thing, as well as reducing wrinkles and other signs of aging. This vitamin is available widely and costs pennies a pill. How could such research have been done, since this discovery will likely decrease the amount of money spent on other expensive treatments and prescription potions for this problem? It was done in Australia, funded by the National Health and Medical Research Council. Nicotinamide, though it is related to Niacin, does not cause flushing and does not reduce cholesterol levels, though it has reversed symptoms of Alzheimer's disease in an experimental mouse model.

What can we do in the US to re-purpose our considerable intellectual resources and vast research machinery away from increasingly complex and costly new technology and toward elegant and ingenious cost-saving approaches? In the big picture, we could figure out a way to move money that will likely be spent on useless or overly expensive healthcare toward research that leads to lower consumption of resources. The NIH in the US is the organization that can fund non-biased research, and is perfectly suited to doing so. Money spent on cost-saving technology will pay for itself many times over.

Drs. Arthur Kellermann and Nihar Desai, from Bethesda and Yale respectively, discuss in a recent JAMA article several specific recommendations from RAND health, a think-tank charged with improving global health and reducing costs. These include creating a public-interest investment group to fund good projects, giving cash prizes to inventors, buying out patents to allow reasonable pricing and reducing unnecessary regulatory hurdles. They conclude:
"Realigning incentives to encourage inventors and their investors to develop cost-lowering products could transform technology, which is currently one of the most potent drivers of health care spending in the United States, into a powerful creator of value. Once that is done, ingenuity will take care of the rest."

Sunday, October 18, 2015

Repatha and Praluent: VERY expensive drugs to lower cholesterol which may not actually work to prevent heart attacks (then again, perhaps they will.)

In July of 2015 the US Food and Drug Administration (FDA) approved an injectable monoclonal antibody alirocumab (Praluent) which lowers the LDL or "bad cholesterol". The drug is produced by Regeneron, given by injection once every 2 weeks, and will cost $14,600 wholesale per year. In August, evolocumab (Repatha) was FDA approved. It, too, is a monoclonal antibody and will cost $14,100 wholesale when it is finally released. It was developed and will be marketed by Amgen.

These drugs are antibodies, produced in hamster ovary cells in vats, which, when injected, bind to proprotein convertase subtilisin/kexin type 9 (PCSK9), making it less active. PCSK9 normally reduces the liver's ability to remove low density lipoprotein (LDL) from the blood. The main drug class that we have now which reduces LDL is the statins, also known as HMG CoA reductase inhibitors, which reduce the production of cholesterol. A couple of common statins are atorvastatin (Lipitor) and simvastatin (zocor.) I have ranted about them copiously in the past.

The reason we worry about LDL is that high levels of it seem to be associated with heart attacks and strokes, and people with a genetic defect that raises their LDL to very high levels often die young of heart attacks. There are many drugs which can lower the LDL levels, but the statins work best and also have been shown to reduce the risk of heart attacks and strokes in high risk patients. The studies are less clear about their benefits for lower risk people. Many drugs which lower the LDL do not reduce the risk of strokes or heart attacks, and it may be that statins have positive effects due to their reduction of inflammation or some other positive effect on blood vessels.

In 2013, recommendations from the American Heart Association and the American College of Cardiology changed from recommending using medications to lower cholesterol below certain levels, depending on level of risk, using diet and medications, to simply using statins for everyone at elevated risk of vascular disease, such as heart attack or stroke. Statins don't appeal to everyone, primarily due to side effects of muscle pain and weakness, also sometimes problems with thinking and memory, so this approach is not universally applicable. But with statins now mostly generic, this approach costs only about $150 per year and is pretty effective.

There is another problem with this approach (besides the fact that it puts huge numbers of people who might never have trouble with vascular disease on a statin drug with unclear long term side effects). There is no room in these statin-based recommendations for non-statin drugs, especially absurdly expensive ones that were finally released after more than 10 years of research by powerful drug companies.

The PCSK9 drugs have been approved for use in patients with familial high cholesterol syndromes and those with known disease of the coronary arteries whose cholesterol remains high despite statins. Insurance companies and anyone else with concerns about rising medical costs are concerned that doctors will start prescribing these drugs with gay abandon to everyone whose cholesterol worries them, with a multi-billion dollar impact on health care costs. The drug companies promise to provide the drugs for less money to patients who can't afford them and to cut deals with insurance companies, but the costs may still be staggering.

In the last two days I saw two articles suggesting that we start to obsess about cholesterol levels again, shifting away from the recently accepted approach of simply treating everyone at high risk of heart disease with statins. The first, in JAMA, was authored by 3 physicians employed by the healthcare company CVS, saying that if we don't start checking LDL levels and targeting higher ones for treatment, anyone with very high risk will be put on PCSK9 injections. CVS, as a pharmacy benefit management company, stands to lose money if patients' drug bills go up astronomically. Then again, they might pass the costs on to consumers and manage to make money. Plus CVS sells point of care cholesterol blood tests, so I'm not sure where their interests lie.

The second was an "educational activity" presented by Medscape, featuring a discussion by 3 physicians with academic affiliations (two from Harvard Medical School) who would all like to go back to checking LDL levels and using medications to get the LDL as low as possible so as to reduce the risk of heart attacks. The activity was financed by Regeneron and Sanofi, who make the new injectable super expensive cholesterol drug, and all of the experts have been on the payrolls of one or both of the companies that produce these drugs. They are very excited about how well these new drugs lower the LDL, and they expect that when studies come out looking at reducing risk of heart attacks they will actually have some clinical benefit. They talk about how many patients might be "candidates" for this therapy, as if it's some kind of a sought after political office. That part is just plain creepy.

There are so many problems with all of this. First and most importantly, we don't know if these super expensive drugs actually reduce the risk of heart attacks. We won't know until 2017, when the first of the many studies which are ongoing will be available. It doesn't matter at all if they lower LDL levels, since high LDL levels aren't actually a sickness. The excitement about this new drug will again focus us away from the fact that lifestyle changes such as quitting smoking and becoming at least moderately active are even more effective in reducing risk for all kinds of vascular disease and other miseries than any medication we have produced. It's very likely that patients who continue to smoke and abuse their bodies in other ways will be put on these drugs, because those are the patients who are at highest risk of heart disease. Do we really want to be directing resources in this direction?

And what about the cost? Why $14,600 per year? What a crazy number. Probably we should just shelve it until we know if it works, then, if it does, figure out who actually needs it.

Friday, October 2, 2015

Medical bills: why are these completely inscrutable and full of mistakes?

Within the last two days I received a bill for my glasses and read a post by a friend ranting about medical billing mistakes. This is a huge problem that is so common that it could be considered the norm. It is ridiculously expensive and could probably be fixed.

My exposure to medical bills has been through patients who show them to me, hoping I can make sense of them, my occasional foray into the world of being a healthcare consumer and the woes of friends and family. I can say, with confidence, that I have never read a medical bill that I understood. When I do choose to dig a bit deeper, overcharging and errors are more common than not.

It is very hard to get good statistics on this, but the lower end of what I'm seeing suggests that one in 10 bills contain errors. It's probably higher than that.

Common billing errors include being billed for procedures that were cancelled, being billed twice for the same thing, under different names, being billed for a more complex version of what was actually done and being billed for more time than was actually spent. How do these happen? In general the errors aren't deliberate fraud. Frequently staff in the billing office do not talk to doctors but produce bills based on what the doctors write. Doctors don't document what happened right away if they are busy and so by the time they do make a note, details are often fuzzy. In the case of billing for canceled procedures, the only paper trail available to billers may be the order for the test, and the cancellation may have been communicated by voice, on the fly. When doctors do bill for themselves, it may be difficult to find the correct code, so, in a hurry, we just settle on the first one that resembles what we did. Most of us are not interested in getting better at billing because we hate it. We weren't trained to do it and it takes us away from patient care.

Patients often (but certainly not always) know what did happen. Their bills, though, are written in some long forgotten Martian dialect which makes it really difficult to correct the errors.

My bill for glasses, which turns out to have been correct (after two phone calls) is a good example of what is wrong with medical bills. I apparently owed $137 for "lens sphcyl bifocal 4.00d/0.1, and $155 for "progressive lens per lens" and also more money for "lens polycar or equal" (which I would have assumed was my lens sphcyl, but I guess not), also the anti reflective coating and a miscellaneous vision service and a miscellaneous product which apparently meant that they charged to drill a hole in the lens and polish it. Sales tax I could figure out on my own. Also the bill didn't say anything about insurance, which does pay some portion, and the biller was not planning to submit it. A separate bill has arrived detailing the cost for my exam, also written in some language that I don't speak. The bills are dated a week apart, for unclear reasons. Theoretically I should be pretty well positioned to understand this sort of thing, after 3 decades in the medical field. I'm guessing others, who might be less educated, sicker, more fatigued or less assertive would simply give up and not check the bill at all.

My friend's issue was being billed for copays that he actually paid at the time of service, then getting notices that he was delinquent for not paying them, having to call the billing office multiple times and eventually having to appear in person in order to get it fixed.

Because billing in excess of services usually leads to making more money, there is no real economic incentive to do this right. A responsive and intelligent problem solver in the billing office may actually lose the practice money, if he or she uses the relevant skills to solve customer complaints. The only economic reason to reduce inadvertent overbilling is to avoid being caught and penalized by insurance companies. There are definitely medical billing specialists who delight in doing their jobs accurately, but there is no cash reward for this sort of behavior.

The most effective first step toward taking care of the problem would be a requirement (it could even be a law) that medical bills be descriptive enough that regular people can actually understand them. The affordable care act made health insurance companies describe their services in ways that average people could know what they were buying. If people could actually read and understand their bills, they could see if they were correct. We could even tack on to the law a time limit for resolution of a query. Wouldn't it be sweet if a billing question would be fielded in 24 hours and resolved in a week? That doesn't sound too difficult.

The whole issue of medical billing is, of course, wrong in a very big way, since its existence is based on fee for service. As long as providers can make more money for doing more things and more complex and difficult things, their will be economic pressure to do more intense medicine on more people, thus creating more people who have been medicalized into being sick. We do, though, have fee for service medicine at present, so it's time to support the (not yet written) "Medical Bill
Clarity Act of 2015."

Sunday, September 13, 2015

Marketing medicine and the treatment of high blood pressure

I just read a disturbing article about a recently completed study on treating high blood pressure. The SPRINT (systolic blood pressure intervention) trial was conducted at around 100 locations in the US and Puerto Rico, comparing treating blood pressure intensively to usual care. According to recently adopted guidelines, we now treat blood pressure with the goal of reducing the top number, the systolic blood pressure, to below 140 for adults younger than 60 and below 150 for those 60 an over. The goal for the bottom number, the diastolic blood pressure, is below 90. We recommend lifestyle changes, encouraging exercise, weight loss and reduction in salt intake, and use medications when the blood pressure stays too high. In the SPRINT trial, a comparison group was treated with blood pressure medications, sometimes 3 or more different types, to lower the systolic blood pressure below 120. The patients in the comparison group (more intensive treatment) apparently did better, with a 30% reduction in heart attacks, heart failure and stroke, and 25% reduction in risk of death.

The SPRINT study only looked at patients 50 years of age or older with other risk factors for cardiovascular disease, including heart disease, kidney disease and a calculated risk of cardiovascular events of greater than 15% in the next 10 years. The data still hasn't been released in a way that we can really understand it, and there may be important caveats, such as subgroups who have particularly better or worse outcomes with intensive management, and other beneficial or terrible effects of the interventions. The news so far is just in the form of a press release, with an actual scientific article eventually to be published.

What bothers me is that now a whole group of people who think they are actually well will be encouraged to take medicine, with associated significant side effects, and will identify themselves as vaguely sick and needing medical attention. Also those patients who already are treated for hypertension and have "good control" will be started on yet more medications with drug interactions, high costs and potentially dangerous side effects. It will be difficult to lower the blood pressure below a systolic of 120 without causing symptoms of dizziness and fainting in some patients, and there will be an increase in the number of doctors "failing" to treat high blood pressure adequately and patients "failing" medications.

Already, at our present definition of high blood pressure (hypertension) one in three adults has it. Three out of 4 patients 75 years of age or older has hypertension. The CDC (Centers for Disease Conrol) estimates that treating hypertension costs over $46 billion per year. According to data from various randomized trials, at least 100 people must take blood pressure medications for 5 years to avoid 1 heart attack. This number varies significantly depending on a person's age and overall risk for heart disease, so more than 500 fifty year old women must be treated for 5 years with anti-hypertensive medications to avoid a heart attack, whereas 65 year old men can expect more of a benefit, with a "number needed to treat" of 101. If we lower the target blood pressure to 120, essentially every adult, with a few exceptions, will be on pills for their blood pressure, and the vast majority of them will see no benefit.

The side effects of treating high blood pressure, besides the cost of medications and doctor visits, which aren't trivial, include life threatening electrolyte imbalances, kidney failure and facial swelling as well as annoying dizziness, swelling of the feet and a cough. A sizable portion of the people who are treated with blood pressure medications, or would be, will experience side effects and no actual benefits.

Treating everyone with an elevated blood pressure with medications and defining them as having a medical condition was a huge expansion of the scope of medical care. The first effective anti-hypertensive medications were released in about 1958 and now there are hundreds of them, varying in mechanism, price and effectiveness. Hypertension was really the first symptom-free condition to be widely treated and marked a transition in doctors' roles to include more care that was focused on preventing actual disease than treating it. Most of us like the sound of that, but it means that one in three adults "needs" a doctor for their hypertension, and if hypertension is redefined at a lower number, virtually everyone will be under medical care.

There is a complex interplay of values going on here, and it is strongly influenced by the fact that medicine, as an economic entity, successfully markets itself and expands its markets by identifying conditions that increase risk for actual misery. These conditions then become targets for treatment, which increases doctor visits and medications prescribed. Treating high blood pressure has been perfect in this regard because the need is real in many cases and the outcomes have often been gratifying. People with significantly elevated blood pressure, especially those in whom it is persistent, do develop devastating strokes, heart attacks and kidney failure and treatment to lower the blood pressure, if taken regularly and over long periods of time, really does reduce their risk. Still, vast numbers of people are treated for high blood pressure who experience high costs, significant side effects and medicalization with no benefits, at huge costs to society in general.

Research shows that the vast majority of blood pressure measurements are taken in such a way that blood pressures may be artificially elevated. One way to narrow the scope of treatment would be to measure blood pressure more accurately--either by actually having patients rest for 5 minutes before taking blood pressures or by using ambulatory monitors which take blood pressure throughout the day during a person's regular activities. Both of these methods would serve to focus our efforts on people who might actually benefit from them.

What would be a good direction to move with treatment of hypertension that would help reduce overtreatment and increase benefits of treatment? Research focused on truly identifying who needs antihypertensive medication would be great. If 500 people like me need to be treated for 5 years to avoid one heart attack, that means that too many people are being treated. Research could help determine which of those 500 people actually need treatment, if it was designed to answer that question. The SPRINT trial was designed in such a way that it will likely increase both the number of patients in treatment and the number of drugs prescribed. That is not what most of us want. It is, however, the kind of research that grows medicine's market share.

If the treatment of hypertension was focused on patients who would truly benefit, and the intensity of treatment was proportionally higher for those with the greatest need, quite a bit of the tens of billions of dollars spent on hypertension might be liberated. The money not spent on medications and doctor visits could go to other interventions that would reduce cardiovascular disease. The amount of money that goes into overtreatment of hypertension could buy cooking classes and exercise rooms, swimming pools and dance classes. Unlike doctor visits and medications, this type of preventive medicine also makes us happier and helps make our lives richer.

Monday, August 17, 2015

Medicare Part D--the insurance plan to cover medication for seniors: has it helped?

In 2003 the Medicare Modernization Act added a prescription drug plan to the benefits available to seniors and disabled adults. The act did a few other things, including introducing health savings accounts and defining Medicare Advantage Plans. The prescription drug plan rolled out in 2006, after which time seniors who bought the extra coverage had some help paying for their ever more expensive drugs. Today the government pays about $70 billion per year to provide this service, 11% of the total cost of Medicare.

The purpose of Medicare Part D was to allow seniors, often the most financially vulnerable of our patients, to be able to afford to pay for medications without impoverishing themselves. Since medications are such an important part of treating the diseases of aging, the government hoped that seniors who were able to pay for necessary medications would be healthier, requiring fewer hospitalizations and emergency room visits. This improvement seemed likely to, at least partially, offset the costs of the program.

Medicare Part D is a private insurance plan which costs the insured, on average, $30 a month and pays some or all of the costs of prescription drugs, depending on how expensive they are. Different plans are different, but most stop paying after having paid out $2970, but will pay all but a small amount once the patient's out of pocket costs exceed $4750. The period of time during which the patient must pay all of their drug costs is called, euphemistically,  the "donut hole." Since the total cost of medications is not covered by the premiums people pay, Medicare subsidizes the difference.

In June, the Annals of Internal Medicine published an article which looked at the health benefits experienced by patients on Medicare due to Part D. They were unable to detect any improvement in health or utilization of hospital or emergency room services in Medicare recipients after the initiation of part D in 2006. They did find, however, a 14% increase in the use of prescription drugs. The study certainly would not be able to detect the fact that some seniors certainly did benefit by being able to afford life-saving medications, but on the level of the total population of patients on Medicare, there was no evidence that Part D improved health.

In some ways, Part D coverage is wonderful, despite this study's results. It is definitely less common, since its inception in 2006, to see older people stopping their medications because they can't pay for them. It is also less common for patients to have to choose between having money for food or doctors' appointments and paying for prescriptions. Sometimes I find that, because of the occasionally wonderful oddities of insurance, Medicare insured patients can actually afford the newest and best drug that truly has a positive impact on their lives.The ability to take a drug with a more convenient dosing schedule or with fewer side effects may not keep a patient out of the hospital but it can surely improve their quality of life. Having to stop a medication because of the "donut hole" coverage gap can lead to emergency room visits or hospitalizations, however. A much more expensive Part D without a "donut hole" might have a more impressive outcome.

On the other hand, however, prescription drug coverage that leads to a 14% higher utilization of medications might very well lead to worse health outcomes, which could help explain the findings of this study. In the years since Part D was rolled out, there has been a huge increase in the amounts of opiate pain medications prescribed, and many of the patients who use these are seniors. The epidemic of chronic prescription opiate use and abuse often reduces older peoples' ability to get around and increases falls. Other prescription drugs, even those felt to be pretty much harmless, often have interactions that are much more prominent in bodies that are aging. Side effects are also more common as we age, and can be devastating. Being able to afford more drugs undoubtedly can increase the risk of hospitalization, emergency room visits and disability in a significant subset of patients on Medicare.

When Medicare Part D was adopted it was clear that it benefited the pharmaceutical industry. It was expected, however, to be a win/win situation, with newly insured patients healthier as a result of their improved access to medications. The bill included the requirement that the government not be able to negotiate drug prices with drug companies, which the Veteran's Administration is allowed to do. This results in considerably higher costs for drugs for Medicare recipients than for VA insured patients. So Part D is expensive, and is probably considerably more expensive than it needs to be. People do like being able to get any medication prescribed or recommended by their physician, which is a limitation in a system like the VA's where there is a pretty set and pretty narrow formulary of drugs available. But formularies don't define which medication a patient can take, only which one will be provided at low cost by the dispenser. Negotiating prices within Medicare Part D, with an associated formulary could still allow choice and probably save lots of money.

Does Medicare Part D prescription drug coverage help? It depends on the patient. It clearly does help the person on a fixed budget who finds him or herself in need of  several medications which might add up to a few hundred dollars a month or more. A healthy but not wealthy 70 year old might have a sudden heart attack and find that he has diabetes which he had known nothing about having not visited a doctor for years. That patient might well be discharged from the hospital on 6 new medications which would throw his budget into an uproar, but might well keep him in good health for years. For patients with fewer needs or more abundant income, prescription drug coverage may do no good at all. For some patients whose ability to afford medications means that they will take ones which adversely affect their health, Part D is a hazard. Certainly 70 billion dollars a year and 11% of the healthcare budget is pretty pricey. The Medicare drug benefit probably needs a major overhaul in light of the data that it does not appear to have a significant or cost saving health impact on the population.

Saturday, August 15, 2015

Another rant about how drug companies are not acting for the common good

A few weeks ago I was feeling angry and disappointed when I noticed that many of the articles I was reading in my favorite medical journal were funded by companies who made the products those articles evaluated (that blog here). This is nothing new, but it looks to me like there are increasingly more of these articles which celebrate products and fewer interesting articles about the science of medicine. The other thing that is particularly irritating about this trend, if it is a trend, is that the drugs and devices that are being sold are increasingly more expensive and benefit fewer and fewer people. The reason they benefit fewer people is that they are designed for very specific, and often pretty rare, diseases. Also, since they are so expensive, only a subset of these few people can afford them. They must be very expensive because they benefit fewer and fewer people, so in order to make the money to pay for the research to come up with these drugs and devices, the companies charge small fortunes, which are paid, usually by insurance companies for those who have insurance, and those costs are handed on to everyone who buys insurance or pays taxes.

So drugs and devices are getting more expensive and less useful. But why is this true? Apparently the low hanging fruit of drugs has been picked. We have more drugs for high blood pressure, high cholesterol, infections, diabetes, seizure disorders, depression and lung disease than you can shake a stick at. What's left is rare conditions or subsets of what people commonly get, like like cancers with specific genetic profiles. Also treating diseases that have millions of sufferers is fraught with trouble. If a company produces a drug or device that helps many people who are likely to live a long time in basically good health, any side effect, even a rare one, will eventually become evident, with terrible consequences including lawsuits and even withdrawal of a blockbuster from the market. If a company produces a drug that gives a few people with terrible diseases a few more months or even years of life, not only are those patients often willing to spend a fortune on the drug, but they are very unlikely to notice a rare side effect or be able to connect it with the drug.

So what we are getting now from the pharmaceutical industry (with occasional exceptions) is wickedly expensive drugs of limited scope, whose safety and effectiveness is never studied adequately. These cost so much that they will likely increase the already unsustainable price of medical care. We all share the burden of those costs. The only non-regulated way to fix this problem is to quit agreeing to pay these high costs for miracle (or not so miracle) drugs. I'm not sure that, in our culture, we are willing to make that choice.

Saturday, July 18, 2015

Drug company funded research in the New England Journal of Medicine: this feels like a conflict of interest

Today I thought I'd read the New England Journal of Medicine (NEJM) and learn something deeply meaningful. I usually love the New England Journal (Wikipedia says it is "among the most prestigious peer-reviewed medical journals and the oldest continuously published one") because I feel like it has such a strong history of academic excellence that whatever they print will have value. This is probably not true.

The New England Journal
In 2009, Marcia Angell MD, a senior lecturer at Harvard University and the former Editor in Chief of the NEJM wrote an article entitled "Drug Companies and Doctors, a Tale of Corruption" in the New York Review about the way drug companies skew research to encourage increasing and inappropriate use of medications. It was based on what she had seen published in the New England Journal and others. This might have been a hint that there was something amiss in the contents of my favorite professional publication.

In 2012, the Washington Post published an article about a diabetes drug, Avandia (rosiglitazone), which has proved to increase the risk of heart attacks and heart failure. The New England Journal decided to publish articles which reported results of studies funded by GlaxoSmithKline, the company which produced the drug. These articles concealed information that showed that the drug was harmful. Editorial decisions were made which, at least in hindsight, were bad. The Washington Post article discussed the many ways in which a drug company which funds research for a medication can manipulate the presentation of the data and get that version published in a prestigious journal which doctors like me tend to believe.

The New England Journal has several sections, but the Original Articles is the one I like best. This is the section where new research is reported. There is also the Perspective section, which has gotten more prominent in recent years, and consists of articles by people who are in the thick of something, maybe mass casualty situations, maybe health policy, big picture articles. There are also editorials, usually about the original articles, and there are letters and image challenges and case presentations and educational updates about specific topics.

Articles this week: not great
This week's Original Articles were primarily about new drugs, and were mostly funded by the drug companies that will or do make money off of those drugs. Oh yeah, and one about a new diagnostic test, funded by the company that will make money off of that diagnostic test. There was one article not funded by industry which looked at the causes of pneumonia in patients who were admitted to the hospital with it, reporting that the majority were caused by viruses.

The first article was funded by Pfizer and reported a new chemotherapy drug for breast cancer that, combined with another chemotherapy drug which costs over $10,000 per month results in longer survival. The new drug's is not yet marketed and so a price has not yet been decided.

The second was funded by a Boston company, Vertex, for their new product that can reduce the lung problems that go along with cystic fibrosis, a genetic disease that causes pneumonia and problems with breathing. If the cost of other drugs for cystic fibrosis is a guide, its cost will be sky high.

The third article is funded by Merck Sharp and Dohme, and studies their drug sitagliptan (Januvia), one of the many drugs that reduce blood sugar in patients with type 2 (generally adult onset) diabetes. The study was primarily to see if their drug caused heart problems, because people thought that it might. They studied more than 14,000 patients for about 2 years and found that their drug did not cause heart problems at least over the course of those two years. It also didn't work very well to reduce blood sugar, but not much was made of this in the conclusions. The drug, which helps reduce blood sugars by just a smidgen, costs $3000 a year or thereabouts, far more than generic medications which work better.

The fourth article evaluated a test that could be done to more accurately determine if a person has lung cancer at the time of a bronchoscopy. Since the test can simply be ordered at the time of the bronchoscopy it will probably be ordered nearly all of the time this test is done, and, I'm just guessing, may just about double the cost of the procedure. The first noted funding source for this study was Allegro Diagnostics, which will be marketing the product.

Then came the pneumonia article (yay, information I can sink my teeth into.) If viruses cause most cases of severe pneumonia, there may actually be some argument for not putting everyone we see with pneumonia on antibiotics.

The final article which was funded by GlaxoSmithKline looked at the ability of an antibody to clear amyloid from the liver in a very rare condition called systemic amyloidosis, which mainly causes death and disability through deposits of a protein in various tissues, of which the liver is one. If this is released it will be very very very expensive and will probably serve only to palliate a very rare disease.

Not to put down miracle drugs, because they are pretty cool, but perhaps the Original Articles section should be renamed Articles Funded by Drug Companies Supporting the use of Very Expensive Medications.

Drugs and Doctors
Doctors are increasingly prescribing more and more expensive drugs for just about any complaint. Even the Onion has noticed (read this brief article and chuckle.) This is in no small part because we believe that drugs are the answer, because the research tells us so. The research that tells us so is funded by the companies that make the medications, because they have the money to fund expensive studies. There is much less money in research on cool stuff like what causes severe pneumonia. According to the Washington Post article, the NEJM had published 60 articles about new drugs that were funded by drug companies in the year prior to the report in 2012. Since it publishes 54 times a year, that's just a touch over 1 article per issue. This week's issue had 4 such articles plus the one about the lung cancer test. It seems like they may be escalating.

But why does the New England Journal publish this stuff?  I think this may be a big part of it: we all love magic potions--it's in our basic makeup as people. Even societies nearly untouched by pharmaceutical companies delight in miracle cures. Doctors and chemists love to dabble in potion making and testing, hoping for that amazing discovery that abolishes misery and old age. They have even been successful--look at penicillin and many others. But when big money backs these endeavors to the exclusion of other good science, we tend to focus on them, and our professional publications will reflect that in what they publish. Unfortunately the economic forces at work favor creating potions that sell, and not necessarily ones which work. Even though I think I understand the rationale, it's pretty disappointing that one of the "oldest and most prestigious peer reviewed journals" is filling its pages with research that is funded by the companies that financially benefit from positive results and therefore is likely to be skewed and misleading.

Tuesday, July 7, 2015

Ultrasound in Tanzania--the gift that keeps giving

Another great trip! I have gotten to go with University of California at Irvine medical students to Tanzania for three years as their supervising MD. They do all of the work, pretty much, preparing lesson plans to teach clinical officer students basic ultrasound as well as designing study protocols, getting institutional review board approvals, and carrying ultrasound machines on fatigued shoulders through multiple airports. I get to teach them a bit about clinical medicine, field questions that they couldn't possibly answer and flaunt the MD on my nametag.

Ten students, just done with a pretty grueling first year, came to Mwanza, Tanzania this year and worked like dogs for a month teaching and doing research. Each year the project is a little bit different, with different research protocols along with improved and adjusted curricula. Their primary project is to teach a large group of students (this year about 100) who are in school to become clinical officers, roughly the equivalent of nurse practitioners. These students will go on to practice medicine in a country which has only 1 doctor per 125,000 people, the worst ratio in the world (Germany has one doctor for every 263 people, per the Economist 2015 World in Figures.) UC Irvine teaches their medical students, starting in the beginning of the first year, how to do ultrasound at the bedside, which cements their knowledge of living anatomy and gradually expands during their 4 years to competence in recognizing all kinds of diseases which have ultrasound findings. This group of students is comfortable teaching basic ultrasound to their African counterparts, who are amazingly knowledgeable in anatomy and physiology. The African students get 3 weeks of lectures and daily hands-on sessions, learning how to get good ultrasound views of the heart, lungs, abdomen and even the womb in pregnancy. Having a cadaver to dissect is apparently a luxury not available to these students, so ultrasound is their first opportunity to actually see inside a human body. Unfortunately 3 weeks is not nearly enough training to become competent in performing and interpreting ultrasounds, but these students will never be afraid to take the steps necessary to learn more, and they will never forget how the heart looks when it beats and how the liver, spleen and kidneys nestle close to each other at the peritoneal reflections.

There are ultrasound machines in Tanzania, and few people who know how to use them. There are not enough ultrasound machines in Tanzania, at least not ones that work, but as the technology gets cheaper, the older machines will be even cheaper, and if there are people who understand how powerful the technology is, they will buy them. The teaching project will not create radiologists, but it will make general practitioners push medical practice in the direction of including more bedside ultrasound. In my experience, this will save lives and reduce suffering.

Beside improving their understanding of anatomy, after 3 weeks most of the clinical officer students who were in the ultrasound class had skills which could have profound clinical impact. If provided with a functional ultrasound machine, they could determine the age of a fetus, the position of the placenta and the head, and determine the fetal heartbeat, an important indicator of fetal health. This information could result in appropriate referral for caesarian section, potentially saving the lives of both the infant and the mother. They could identify a pneumothorax (collapsed lung) in a patient with a traumatic chest injury, which would be easily treatable if found in time and maybe fatal if missed. They could identify bleeding into the abdomen or chest in patients who presented after motor vehicle crashes, which are terrifyingly common. They will be able to look at an ultrasound picture and see more than a bunch of blurry gray, black and white shapes.

This project is cool in so many ways. I love that students teach students. The process is very gratifying and makes the material even more exciting. The UC Irvine med students are now completely awesome at basic ultrasound, and they were only just good when we started. The teaching goes both ways--the African students have an accelerated curriculum so they teach the UC Irvine students things they don't know, as well as asking questions that make all of us think harder. I have done overseas projects which directly help people in need, which is wonderful in its way, but this project potentially has legs. Teaching medical practitioners to be better at their jobs is really powerful and has the ability to affect the lives of many patients. In teaching what they have just learned themselves, while they are still excited about it, the US medical students show the Tanzanian ones how to be teachers of each other and to love learning, which could end up being as important as what they actually teach. In Tanzania, medical students work incredibly hard for the opportunity to continue to work incredibly hard in overcrowded hospitals and clinics with inadequate resources. It feels like this project may make them just a little more effective and a little bit happier in the process.

Thursday, May 28, 2015

Actinic Keratoses and Carac (fluorouracil) cream: why is this so expensive?

First, a disclaimer: I don't know why Carac (0.5% flourouracil cream) is so expensive. I will speculate, though, at the very end of this blog.

Sun and the skin: what happens
If a person reaches a certain age, has very little pigment in her skin, and has spent lots of time in the sun, bad stuff happens. The ultraviolet radiation of the sun does all kinds of great things: it makes us happy, causes us to synthesize vitamin D which strengthens our bones and it gives us this healthy glow until we get old and wrinkled and leathery. And even that can be charming. The skin cells put up with this remarkably well for a long time, partly aided by melanin pigment which absorbs the radiation, which is why we tan and freckle, if we are fair skinned. Eventually, though, we absorb enough radiation that it injures the skin and produces cells which multiply oddly. It also damages the skin's elasticity which creates wrinkles.

The cells which reproduce in odd ways peel, creating dry skin or dry spots, or warty growths or even small hard horns. The scaly spots are called "actinic keratoses" which just means sun induced scaly spots. Sometimes the skin cells become cancerous and lump up and create non-healing sores. This is when we regret going out without a hat or sunscreen, but, of course, it is too late.

Topical chemotherapy: good idea or great idea?
In 1957 scientists published a paper showing that flourouracil, a flourine attached to a nucleotide (RNA building block), inhibited liver cancer cells. This became one of our early chemotherapy drugs, and is still an important drug in treating colon cancer. When mixed up in a skin cream, it can kill the abnormal skin cells which grow on our sun exposed skin, allowing the normal ones to take their place.

The way fluorouracil cream was initially used was awesome and terrible. It was applied daily for 4-6 weeks to the affected area and the skin became a war zone. The abnormal cells died, leaving red swollen places where sun damage was most severe. Generally people using it looked pretty bad for weeks or longer. Eventually they healed and got rid of their scaly spots. Many people still use it this way, to good effect. We also found that we could treat just small areas at a time, and even just the scaly spots themselves, and that we could use the cream for shorter courses and avoid the intense inflammation. This was a major advance in therapy since our other main option was to freeze the spots with liquid nitrogen, which was a painful, expensive and seemingly never ending process, and which left little white scars.

A slight catch was that the fluorouracil cream was expensive. It was over $100 for a 30 gram tube. Maybe insurance would pay, but it was top tier, and at least some of the cost made its way to the consumer.

Several years ago my husband was prescribed Carac, one of the first fluorouracil creams. It was expensive, so we have made it last, far longer than the expiration date. It is a prized possession, that tube. We have both spent far too much time in the sun without protection, loving every minute of it, and regretting it now in hindsight. When the scaly spots become too annoying, we use the cream until they go away. But the tube is almost empty. Time to buy some more.

Pretty pricey
I looked online to find out how much it would cost if I bought it internationally. I found a product from India that was not too expensive. It was 5% flourouracil rather than the 0.5%, but that is the percentage in the brand name Efudex which is one of the alternatives in the US, so it seemed reasonable. I got the cream in the mail and tried it and it was slightly granular and didn't work. The effect of the Carac was dramatic. The effect of the Indian cream was essentially nothing. "You get what you pay for," I thought. I asked a compounding pharmacist acquaintance to make me some. I respect this pharmacist. He mixed up flourouracil in a skin cream base at a concentration of 5%. The cream was also grainy and didn't work. It seemed to do a little better than the Indian cream, but nothing like the Carac. Finally I decided to just get the Carac. I asked my friendly neighborhood pharmacist what it would cost. She told me that a tube of Carac, 30 grams, costs around $2000. NO! I will not do that! The amount of active chemical in that little tube, the fluorouracil that is used as intravenous chemotherapy, would cost about $40 retail. It is possible to get generic or brand name 5% fluororuacil creams for prices ranging from $170-$500 for a tube, but that is still horribly expensive, and if they didn't work, that would be an annoying next chapter in this tale of woe. Looking a bit harder I found that there is now a 2% solution which is a little less pricey, though there is nothing that I've read that tells me how or if this works. Maybe I should just make some, but playing around with chemotherapy drugs sounds like a bad idea.

Other options
What, then, should someone do with their actinic keratoses? It is just not reasonable to pay $2000 for a tube of cream. Uptodate, which is an online resource used by many physicians to keep abreast of expert management of diseases, says that the treatment of actinic keratoses, besides 0.5% fluorouracil cream, includes use of sunscreen to prevent further appearances of the little spots, dermabrasion to remove the affected skin (ouch)and that the use of topical retinoids (vitamin A derivatives) can help. They also mention that ingenol mebutate and imiquimod creams (both horribly expensive) are better than placebo as is chemical sensitization plus light therapy (I can only imagine what that costs.)

I have decided to use a retinol preparation which is pretty darn cheap and calls itself "wrinkle cream." It is in the cosmetic section of my local drugstore. Retinol is one of several retinoids that are approved for use on the skin, and also treat acne. I will also wear sunscreen and a hat. So far the retinol, when applied to the whole sun-damaged area (for me, the forehead) is helping reduce my sun induced roughness and scaling. Retinoids appear also to reduce the risk of developing squamous cell cancer, a common malignancy in sun exposed skin. For now, at least, my path is clear.

Mysteries persist
But there remain mysteries which I have been unable to solve using books and the interwebs. Why is 0.5% flurouracil 10 times more expensive than 5% fluorouracil, even though the latter is theoretically 10 times stronger? Why do they even make 5% flourouracil cream if the 0.5% stuff works just as well? Is it in some way very difficult to mix flourouracil into a cream? Why does Uptodate recommend 0.5% flourouracil and not 5%? I have no idea. I can speculate a bit about the costs, though.  It's possible that the cost of the 0.5% flourouracil is made to be as high as the newer creams, like imiquimod, which were priced that high because they were relatively new, and are still not generic. All of these creams are still financially viable because they were cheaper and more acceptable than going in to the doctor every few weeks to have him or her freeze a bunch of spots, resulting in what looked like a mild case of chicken pox which healed to make white scars. It's still really hard to believe that anyone would pay $2000 for a little tube of skin cream and that we, as physicians would regularly recommend that they do so.

Addendum 10/26/2015:
There is another treatment for skin aging and actinic keratoses, which also works for acne! Apparently Nicotinamide, vitamin B3, reduces signs of skin aging when used topically and reduces AK's significantly when taken orally at a dose of 500 mg twice daily. This article, out of Australia, also showed some reduction in non-melanoma skin cancers with it. Both topical and oral versions of Nicotinamide are available without a prescription.

Wednesday, May 27, 2015

More on the epidemic of prescription opiate use and abuse

 Facts (from the Centers for Disease Control Health report, 2013) :
  1. The consumption of opioid pain medications (like morphine, hydrocodone an oxycodone) increased 300% between 1999 and 2010.
  2. The death rates from poisoning by opioid pain medications more than tripled during that time.
  3. The greatest increases in deaths from opioids were seen in non-Hispanic whites and American Indian/Alaskan native populations, who showed a 4 fold increase in deaths.
I have written several blogs on this, most recently talking about the experience of working with a large group of outpatients who are habituated to these drugs and are experiencing side effects, including addiction, along with small improvements in pain that are clearly not worth the devastating consequences of taking these drugs long term.

"What is so devastating?" you may ask.

Here are some stories* (names and details changed for privacy):

  • Crystal is 43 years old. She was diagnosed with fibromyalgia, a painful condition of muscles without a clear cause, 20 years ago. She was started on pain pills 15 years ago and has been on them ever since. The doses have gradually increased and she is no longer able to work because of the sleepiness and confusion that goes along with the pain pills. She has been started on laxatives to treat the constipation and muscle relaxants which make her mouth drier than it already was with the pain pills, and takes an anti-anxiety pill to sleep and to calm down during the day. She still feels terrible and can barely get out of bed, so she has gained 40 pounds. She lives on disability. People ask her if she will sell them her drugs when she comes out of the pharmacy. She has had her car broken into on several occasions by people looking for pills. She can barely afford rent and food and doctor bills on her disability check.
  • John is 50 years old. He hurt both of his shoulders doing drywall installation 10 years ago. He found it difficult to sleep and so they gave him pain pills to take at night. He had his right shoulder operated on by an orthopedic surgeon but it still hurts, as does the left one. He now takes the pain pills all the time so he can do a little work around home. He has been disabled for work for several years. He has gained a lot of weight from being inactive and he feels useless and depressed. His weight has caused him to have knee arthritis and so it hurts when he tries to go out for a walk. He's hoping he can get a knee replacement so maybe he can be more active and lose the weight. His chronic opiate use means that his chance of a successful outcome from knee replacement is substantially poorer.
  • Bill fell off a horse when he was young and has had a tricky back ever since. He used to get prescriptions for pain pills every so often when it acted up, but since it was acting up so often he has started to get a prescription every month, for 240 hydrocodone pills, so he can take 2 of them 4 times a day. He tells the doctor he has to take them all the time or else the back is so bad he can hardly stand it. He has been selling or bartering most of his hydrocodone for several years. Sometimes he takes it for pain, sometimes recreationally and with his girlfriend. If he gets caught, this is a felony. It is also his main income.
  • Nancy has multiple sclerosis. She uses crutches and has back and arm pain. She is on muscle relaxants and pain pills. It is clear to any doctor why she would need these medications, so they are refilled monthly. She lives with her boyfriend and his grown kids. She doesn't take the pills herself. Her boyfriend and his kids use them or sell them. She is vulnerable due to her disability and they threaten to kick her out if she doesn't bring home the pills.
What seems to be happening here is that people get injured or sick, physicians put them on controlled substances in the mistaken thought that it will make them better, and because of the addictive potential and side effects of the medications, they continue to take them and become progressively poor and marginalized. They find relief only in the drugs and end up unable to perform at work, which results in either job loss or being unable to excel and rise in status and income. They get depressed and anxious, often, and are put on more medications. The pain pills can actually make them depressed, but this is rarely obvious to the patient because of the little bit of euphoria that often comes with each dose. They are hassled for their pills. Sometimes they sell them because they are poor, and then they are outside of the law and have a secret that further separates them from people who might help them, such as their doctors. They often smoke, and sometimes drink. The smoking gives them lung disease which puts them at increased risk of death from the respiratory depressant effects of their pain medications. Combining their medications with alcohol can kill them. They get put on medications which lead to obesity and this increases their pain, disability and lack of self confidence.

Turning this process around is going to be hard, but so very worth it. Patients are addicted, but so are we, that is the whole healthcare system. Drug companies make lots of money on these medicines and the medicines used to treat the side effects of the medicines. Doctors get to provide a quick fix and make patients (temporarily) happy just by writing a prescription. Return visits for these patients keep clinics busy. Eventually, though, increasing demands for controlled substances crowds out our ability to see other patients and to provide care that might actually reduce disability. Our opiate using patients burn physicians out because, with rare exceptions, they will never get well. Not writing these prescriptions in the first place or developing alternative strategies that get patients off of them is important work. It will help build healthy communities by reducing the supply of illegal substances. It may even help bring these people back to a place where they can move beyond their identity as chronic pain patients and get on with their lives.

*I am not presently telling the stories of the few patients for whom chronic opiate therapy is a good thing. They do exist, but they are uncommon. They are also usually on low doses and don't take them all the time. I am also not talking about patients with acute pain from injuries, illnesses or surgeries that will resolve. They, too, can have terrible consequences of opiates, but can also benefit a great deal from using them cautiously.

Friday, May 8, 2015

Doctors of tomorrow: please forgive us for thinking that it was a great idea to prescribe sedatives, opiates and stimulants to just about everybody

Lately I've had the opportunity to work in an outpatient clinic where the regular doctor is out sick for a prolonged period of time. It is a breathtakingly beautiful little community, with green hills and a crystal clear river. It is also troubled by methamphetamine and prescription drug abuse.

The little clinic in town is unwittingly a partner in this crime. Like the US itself, this small community clinic has been generous with prescribing controlled substances for those who appear to need them. Sedatives in the benzodiazepine (Valium, Ativan and Xanax are brand name examples) family are prescribed for those with anxiety. Opiates, from the family that includes morphine, are prescribed for patients with back pain and knee pain and a host of other long lasting pains, and continue to be prescribed monthly for round the clock use, sometimes at increasing doses, since these long term pains rarely go away, even on medications. Every young person these days seems to have attention deficit disorder, and many of them have found that they can study better if they take stimulant medications. These medications have been around for years, though there are newer formulations, and used to be called "speed." In moderate doses they make pretty much everybody able to study better. They have become extremely common on college campuses at exam time, since they also allow a person to go without sleep and sometimes without much food. One person with a regular prescription for this kind of medication can supply his or her friends with drugs as needed. Side effects can include heart rhythm disturbances and erratic behavior, especially in higher doses, as are sometimes used recreationally. Some of the patients in this little clinic get ADD drugs so they can work or study, sedatives so they aren't anxious and opiate pain killers for their bad backs or other maladies. Sometimes they take them, sometimes they sell them or give them away, and often they do both.

There is no good evidence that these medications are either safe or effective when used long term. In fact there is good evidence that they are NOT safe, and quite a bit of circumstantial evidence that they are not effective. We prescribe many times the number of controlled substances now than we did a decade ago, and overall Americans are not less anxious or less in pain or better able to concentrate than they were before. Those of us who prescribe opiates to patients with chronic pain very rarely see the pain become significantly more manageable though we do see the patients become less active and more likely to ask us for ever increasing amounts of the medications which don't work very well.

We have known for years that opiates cause constipation, nausea and vomiting, sleepiness and confusion and can cause people to stop breathing at high doses. We are also recognizing that they cause low testosterone levels which results not only in sexual dysfunction but weakness and mood alterations and bone thinning. In some patients overall tolerance to pain or anxiety is decreased. Combining them with sedatives increases the risk that patients taking these medications will stop breathing and die. Most of the patients who die of these medications do so while taking the medications as prescribed though many overdose deaths also occur in people taking the medications recreationally.

I, as a cutting edge physician of my generation, prescribed these drugs with enthusiasm, glad to be able to lessen the burden of anxiety, pain or distraction in my patients. Eventually I noticed that these patients were having real problems, including emergency room visits for confusion or for increased pain, worsening of their pre-existing breathing problems, severe constipation requiring hospitalization, one died by deliberately overdosing. Others' deaths were probably hastened. More subtle has been the increasing number of people who are becoming inactive, apathetic and stuck in poverty who appear to live mostly for their prescription medications. This group of people are not being identified at all by statistics on overdose.

I have been away from regular primary care practice for years now, so have not been writing long term opiate or sedative or stimulant prescription for patients. I have also been in the hospital more and have seen more desperately ill patients whose main problem were prescriptions for controlled substances.

Now I get to be on the receiving end of what goes around which apparently comes around. There are a bunch of patients on controlled substances which will likely kill them (unless they are selling them to people, including school children, who will take them and maybe die) for whom I am asked to write for refills. HELP. Can't do it, can't not do it. Patients can have serious withdrawal syndromes if they run out of their opiates or sedatives suddenly. (Stimulants are usually not an issue, though.) If I do prescribe these medications there is a reasonable chance that I will be responsible for some bad and preventable medical tragedy. If I don't, these patients will be shocked and betrayed, since they really think they need these drugs to be happy.

If this was just my (and their) problem it wouldn't be that interesting. What is interesting is that this is just a tiny microcosm of what is happening in the whole US. Physicians are discovering that these controlled substances are not safe and that their patients are mostly not doing better on them than they were off of them. A small number of patients are doing better, but it's infinitely hard to figure out who those are. Stimulants may have benefit in children with attention deficit disorder, but this is rarely relevant for me as an internist who doesn't see kids. Adults appear to be overusing them in an epidemic manner. The  medical community of the United States needs to make an abrupt about face while showing compassion for the patients who have been taking these medications and probably deteriorating because of them for years. In our opiate dependent patients, we need to re-assess their pain and the causes of it and research the options that might be helpful. We have to do all this while tapering these patients off of the medications which they think they love. We have to realize that many of the things we might do to improve our patients' pain, such as exercise, meditation, non-opiate type drugs, may not be truly effective until the patients are actually off of opiates.

In my experience in trying to deal with this situation, I have found some unexpected allies: the patients themselves. In every patient who I talk to about tapering off of controlled substances I expect anger and resistance. But this is not always the case. I have met patients who seemed like they had just been waiting for someone to help them get off of these meds. It's not even all that uncommon. People don't actually like to be passive and helpless and weak and sleepy and constipated, and some of them are willing to risk experiencing pain or other discomforts in trade for not being on drugs. I see patients on the other end of the process, too. They say that after their injury or operation they were heavily dependent on drugs and that they eventually got fed up and, with the help of a good doctor or nurse or family, got off of them and intend never to take them regularly again.

Opiate pain medications and benzodiazepines are some of the most miraculous drugs physicians can prescribe, and I am not in any way averse to using them when they are needed. The opium poppy and its derivatives can abruptly change the outlook of a person who has the acute pain of a broken bone, a toothache or a recent surgery. They can make the final weeks, days or hours of a person's life be more tolerable. Benzodiazepines can immediately relax a person whose anxiety is running away with them. These drugs are amazing. They just shouldn't be used on a regular basis except in extremely unusual cases.

I'm not positive that adult attention problems should be treated with medications. The rise in use of stimulants may be just an indication that our society expects everyone who intends to achieve financial independence to be able to focus on tasks or studies which are mostly irrelevant to them. As we've moved away from hunting and farming and manufacturing there are many round pegs attempting to pound themselves into square holes. Stimulants, with their known significant side effects and their unknown long term effects, should not be used to make people do things that bore them silly. On the other hand, the rare person who has narcolepsy (a disorder which is characterized by sleep attacks) has my whole hearted support in using stimulants on a regular basis. I will even sign the prescription.

Wednesday, May 6, 2015

Reducing variability in healthcare delivery--maybe not such a great idea

I just got back from the annual meeting of the American College of Physicians, an organization of internal medicine physicians with about 140,000 members. In the annual meetings organizational things take place, such as recognition of particularly hard working members and a kind of graduation ceremony in which members who have achieved a certain level of accomplishment are advanced to fellowship. Mostly, though, the tens of thousands who attend are there to go to lectures and discussions by doctors who know things that we all want to know.

It is possible when attending these meetings to get a general idea of what the leadership in internal medicine thinks is important or acceptable. This year one of the themes seemed to be "reduction of variability." Only one talk actually used those words, but many of the speakers mentioned that they were encouraged to present the "party line" meaning published guidelines by specialty organizations within the ACP. Guidelines are carefully built recommendations for managing various conditions, from diabetes to urinary tract infections, and are extremely helpful in swaying our practice away from things that don't work and toward things that do. They were never intended to be the last and final word.

The one talk that actually used the verbiage "reducing variability" was also addressing the Choosing Wisely campaign. A few years ago the American Board of Internal Medicine championed an initiative to reduce the number of wasteful and useless things physicians did in caring for patients. The idea was that specialty groups would point out the tests or treatments that were being done that really didn't make sense. There are lists now of what not to do (like a head CT scan for a fainting spell or an x-ray for uncomplicated back pain without "red flag" symptoms or antibiotics for the common cold). These lists will help doctors to feel supported when practicing good medicine. They are also an attempt to reduce variability by presenting a unified approach to common problems. I would have liked to see the talk about Choosing Wisely and reducing variability, but for some reason it required an advanced reservation.

I am actually a big fan of Choosing Wisely, since I think that many physicians do more testing and treatment than really makes sense, thus wasting their patients' time and money and cluttering their consciousness with useless and excessive data. But I am not entirely on board with reducing variability.

When I go to a lecture at the ACP meeting, what I hope for is to hear a physician speak who has immense experience in the practice of medicine and who will tell me what he or she does that works well. Sometimes there are controlled trials to support their practice but sometimes their subtle and individualized approaches are not amenable to controlled trials. This is as it should be: much of medicine is an art, and amazing and committed physicians are among us and we can learn a great deal from them. Sometimes different great teachers practice differently from one another. Doing things differently often means that thinking and innovation is going on and that people are not simply acting like sheep.

I heard one speaker, who seemed quite good at what she did, speak of the research regarding her field. She presented data to show that a certain medication worked no better than placebo for treating the condition in question. She said that when her patients asked about using the medication, she told them that they could try it but that it would work no better than a placebo. But she was wrong. The study showed that on average, for a group of patients the medication worked no better than placebo. But for some patients it, of course, worked significantly better than placebo and for some it worked less well. In saying this she made the assumption that there was no variability among patients and that her patient would have the same results as the average patient in the study. Because of this interpretation, those patients of hers who might have benefited from the treatment were probably unlikely to try it.

Because our patients are individuals and not groups of average subjects there should be some variability in how we practice. Because there are more ways than one of doing a job well, we should continue to rejoice in our variability, while striving not to do things that are clearly stupid. It is right that what we do as physicians should be informed by clinical trials and controlled studies, but we should not be convinced by them to ignore the individuality of both physiology and goals of the patient who sits in front of us.

Wednesday, April 22, 2015

Preventive Medicine: on being a "bad patient" (Readers beware: this is the rant of a curmudgeon. Take with at least one grain of salt.)

I am, or will be, a "bad patient." The "good patient" accepts advice gracefully. The "bad patient" may not be a bad person, but does not play the part of the patient well. The word patient comes from the Latin word root pati, to suffer. The "good patient" suffers well, and accepts help from a physician,who Merriam Webster defines as someone skilled in the art of healing. This relationship is one in which the roles are well defined. When the patient is not actually suffering and is even more confusingly "skilled in the art of healing" the roles get really wonky. I will be this kind of "bad patient."

One way in which I do not play the part of the patient well regards preventive medicine. I am getting to an age at which various things are recommended in order to reduce my risk of developing some dread disease. When it comes to these recommendations, I find that I have become quite the picky consumer. I would dearly love not to get a preventable disease, but after more than 2 decades of practicing primary care medicine, I have seen too many undesirable consequences of perfectly benign sounding medical tests.

Breast Cancer Screening:
I don't avail myself of mammograms. I did once, and that was fine. Starting age 50 I was supposed to get mammogams every other year, according to the US Preventive Services Task Force (USPSTF). Maybe I'll get another one sometime if the data gets better. A Canadian study showed no significant effect of regular mammography on breast cancer mortality in average risk patients, though women who get regular screening do get more treatment for breast cancers, including mastectomies and radiation therapy.

Colon Cancer Screening:
I haven't had a colonoscopy. In this test, a fiberoptic scope would be introduced into my lower intestine by way of the rectum and the whole colon would be visualized with the expectation of finding and removing polyps before they become cancers, or seeing cancers before they become incurable. USPSTF said I should have started those at age 50, but the data for women without suggestive family histories of colon cancer is not convincing and the potential for something to go wrong definitely exists. An inadequately sterilized colonoscope could introduce some unfriendly bacterium into my gut. I think I like my flora as it is, thank you. The procedure to clean out my gut, drinking a half gallon of polyethylene glycol solution until my bowels run clear, which is required before the procedure, may be fine, but I'm not entirely sure that a day of rapid intestinal transit is good for me. Intravenous sedation, which is usually given in order to make this procedure tolerable, has a small risk of killing me and will make me goofy, though possibly in a pleasant way. I will watch for updates, but I'm thinking I may have this procedure when I'm 60. Maybe. I prefer to reduce my risk of colon cancer by maintaining a healthy weight and eating a diet rich in fruits and vegetables.

Cervical Cancer Screening:
Pap smears. The recommendations have changed and the schedule is less onerous, but since I had regular yearly pap smears until several years after becoming monogamous, my chance of having a new human papillomavirus infection is vanishingly small, and it is that infection that leads to cervical cancer, which is the only cancer that a pap smear reliably detects. I think I may be done with pap smears.

Blood pressure screening is another story. Detection of hypertension and treatment of high blood pressure saves lives, prevents strokes, heart attacks and kidney failure. I can do it myself, and if my blood pressure is persistently high, I will actually see a doctor and start medications. Let that not happen, because I will not submit gracefully to someone else's opinion on which medication I should take. Unless, of course, they are right. Often I see patients started on some medication which just came out and is available in the doctors free sample cabinet. That one I don't want. It will be expensive to refill and we will know very little about how well it works in the long run. Don't I sound annoying?

Bone density testing. There are machines that will shoot photons at my bones and tell me if I am developing osteoporosis. I should get this done at age 65. Mostly I should avoid breaking bones, though, since that is the real problem. It matters not a bit if my bones are as fragile as dry corn stalks so long as they never break. Staying strong and agile is the best way to avoid falls and fractures. If I find out that my bones are thinning, the main option for bone strenthening are the bisphosphonates, such as alendronate (Fosamax). These are medications which, if they don't get caught in the esophagus and cause a terrible ulcer, which they are known to do, and they don't get entirely eliminated, unabsorbed, due to having taken food with them to avoid getting the esophageal ulcer, will enter my bones to reduce the natural breakdown of bone by my osteoclasts, thus messing up the delicate balance of osteoblasts and osteoclasts that creates normal bone architecture. This will reduce my risk of breaking a hip or vertebra if I fall, but will put me at risk for a rare but horrific breakdown of bone in the jaw called osteonecrosis. So I will work hard on my strength and balance, eat a good diet and encourage the effects of gravity on my bones via weight bearing exercise. Luckily I am not yet 65, so I can decide on this test later. I'm leaning toward not.

But what about taking estrogen for my bones? It is primarily the loss of natural estrogen at menopause that will lead to osteoporosis. Will I take estrogen, then, since I am in menopause? The drawbacks are a slight increase in breast cancer, but without a convincing increase in breast cancer deaths, so this is a wash as far as I'm concerned. There is a slight increased risk of developing blood clots to the legs and lungs, but I didn't get those when I made estrogen with my natural ovaries so I doubt I'll get them with a small dose of exogenous estrogen. There is a slight risk of developing endometrial cancer when taking estrogen if progesterone is not taken as well to maintain a thin endometrium. Birth control pills, which are about 6 times the estrogen dose of a standard estrogen replacement pill, have a progesterone agent in them, and that may well be adequate to maintain a thin and healthy endometrium. I can also check my endometrium regularly with a quick transabdominal bedside ultrasound and make sure everything is looking hunky dory. Will I get a stroke or heart attack with estrogen? The results from the Women's Health Initiative suggested that this might be a risk, but further study has suggested that it may have been the relatively high dose of medroxyprogesterone that caused that problem, and there was no actual survival disadvantage in long term estrogen users. Will estrogen help me avoid hot flashes and vaginal dryness? Yes, it will. Perhaps I shall take one sixth of a birth control pill daily, since that is cheap and generic and will avoid wallet toxicity.

What about vaccinations? Yes, with no hesitation. Yearly flu shots, though I recognize my potential benefit from these is low, pneumonia shots when the time comes, tetanus and acellular pertussis, yes, and appropriate travel vaccinations with the possible exception of yellow fever. (There is a longer discussion of that here.)

How about obsessing about my cholesterol? The present recommendations about cholesterol lowering are to treat patients with a 10 year risk of cardiovascular events of 7.5% or higher. The calculator for this has recently been shown to overestimate this risk, but I have always been in the vanishingly unlikely range, which means that I need not know my numbers. I have checked them occasionally and they are not pristine, but it is not clear to me what intervention would be most likely to lower my already low risk of cardiovascular disease. Certainly there is no indication for medications. I might become primarily vegetarian and eat fish when I can get it, embracing the Mediterranean diet. There is no good data to tell me which fats I should eat, but it seems wise to be moderate and avoid trans-fats which don't naturally occur in the foods I love anyway. 

Moving my body:
How about exercise? Exercise seems to play an important part in preventing all kinds of things I don't want, from diabetes to dementia. It will control my weight, which will help me avoid hypertension and cancer. It will improve my balance so I will avoid falling and breaking bones. I will be more likely to be nimble enough to jump out of the way of an oncoming bus or bicycle. Yes to exercise. Long walks in the woods, cross country skiing, visits to the gym, bicycling, swimming, canoeing. 

The yearly physical:
How about a regular physical exam? Not sure. So far it's been no for me, but yes for my patients. A physical exam is no longer really recommended, though there are many pieces of the physical exam that are part of what we recommend to patients as prevention. I think a physical exam is actually a good idea, but more as a prolonged discussion of preventive testing recommendations and to develop shared goals. Examining the body is not a bad idea, either. As we age, our bodies do weird things. A toe will point in the wrong direction, there will be a lump or a pain or a vague dysfunction, none of them severe enough to warrant a visit to the doctor, but each one deserving attention and maybe explanation. In total, these little irritations may paint a picture of a whole organism which needs some kind of intervention in order to be as healthy and vital as possible. If this kind of an evaluation and discussion is a physical, then yes, definitely, and I might even want one. 

So am I actually a bad patient? Since I am not a patient, it is still a moot point. They say doctors make terrible patients. We will just have to see, when the time comes.

Tuesday, April 7, 2015

Crazy idea: take blood pressure like the pros, and teach patients to meditate.

I recently read a discussion by 3 hypertension specialists, Drs. Jan Basile, Dominic Sica and David Kountz, on how to treat "resistant hypertension." Resistant hypertension is blood pressure that remains above goal despite treatment with 3 drugs, from different classes, one of which must be a diuretic. 10-15% of patients with high blood pressure will have resistant hypertension. These are the people who always seem to have blood pressure at levels that are concerning despite using medications that should be working. We wonder if they are actually taking the medications, but they assure us they are. It's almost like they are just taking sugar pills.

Often patients such as these have extensive testing to see why their blood pressures are so high. They get put on even more medications which then have side effects, and eventually we may just give up and decide that they are as good as they are going to get. Giving up helps to avoid still more medication side effects, but patients with resistant hypertension continue to have significantly increased risk of strokes, heart attacks and kidney failure, which presumably could be reduced by controlling their blood pressure.

So what do the experts do first? They take the blood pressure right. Their scrupulous method of checking the blood pressure is to have the patient abstain from caffeine or excitement for 30 minutes prior to having the blood pressure measured. They then sit in the exam room quietly for 5 minutes and the blood pressure is taken automatically 3 times, at 1 minute intervals, and the results are averaged. Adequately measuring blood pressure in the clinic setting requires that the patient be sitting, back supported, feet on the ground, not talking.

This is almost NEVER the way we do it. Five minutes sitting quietly? When does that ever happen? This would mean just sitting, not messing around with a phone watching cute animal videos, not reading about which movie stars are splitting up, not yelling at one's kids who are wandering around the examining room trying to stick forks in the electric sockets.

As far as I can picture this, the only way to actually get a person to sit quietly for 5 minutes, unless they already know how to meditate, is to teach them to meditate. The easiest instruction is to count each breath up to 10 and repeat. When thoughts happen, which they inevitably do, the patient is instructed to notice them and go on with counting. Mindfulness based stress reduction, which was just demonstrated in an article in this week's JAMA to be effective in treating insomnia in the elderly, also includes muscle relaxation and instruction on acceptance of emotions and sensations. But breath counting is a very basic meditation technique and can be taught in about 30 seconds. The nurse could do it, then go away for 5 minutes, come back and take the blood pressure. In silence. And then the patient has meditated, possibly for the first time ever.

So then you have taken the blood pressure correctly, and it is probably lower than it would have been with our standard techniques. This will likely reduce the number and dose level of medications patients have to take, and they have learned to meditate. They can do it again. It will help them sleep. Perhaps they will learn to like it, do it regularly, and it will reduce their levels of inflammatory cytokines. Then they will have fewer heart attacks.

I can hear the grumpy voices already saying that patients will never do this. I kind of think they will, though, if we advertise it properly. It is the ONLY way to get an accurate blood pressure, which will undoubtedly be lower than if we take the blood pressure the standard way. It will require a little bit of work flow rearrangement, but it is a great idea. I think I will try it first with patients who have resistant hypertension or those who I am thinking about putting on blood pressure medications for the first time. These are the situations in which both the patient and staff will be most motivated to try something new. I will also not necessarily tell them that they are meditating.

Wednesday, April 1, 2015

American Board of Internal Medicine Maintenance of Certification firestorm: what more to say?

About 2 years ago I finished the process of recertifying for the American Board of Internal Medicine. I had last done this in 1990 and had a time unlimited certification, but had heard that recertification, which included doing a certain amount of studying and then taking a long test, was a good idea. Specifically, one internal medicine physician had written an article about the process, which sounded a little like a medieval quest, complete with hardship and mortification. That sounded perversely attractive.

The process was expensive, about $1500 (now $1940) to sign up for the whole deal, which involved keeping track of the educational modules on the ABIM site, access to some educational material and completion of a Practice Improvement Module which was more disruptive than the rest of the process. I had several options, but chose to evaluate how well I was doing on preventive medicine, things like getting my patients to do mammograms and colonoscopies and screening blood tests and that sort of thing. There were before and after questionnaires for my patients to fill out which were tallied and available for me to see on the website. These told me how I was doing before and after instituting certain changes. I've always disliked being evaluated with a numerical scale in a disconnected manner, but it wasn't too awful and I did learn quite a bit about the current recommendations for preventive practice and the evidence behind them. I then took the long test, which was another fee, about half of the original fee, and waited maybe a month before being notified that I passed. In order to feel confident in my ability to pass the test, I attended a several day long preparatory set of lectures at a major medical school, which cost a few thousand dollars and took a couple of weeks off from work to prepare. I didn't resent it, because it felt like the process had fully updated my operating systems, but the cost ended up being somewhere between $10,000 and $20,000.

About a year later I learned that, in order to maintain my certification, the ABIM was asking that I complete ongoing approved Maintenance of Certification (MOC) activities, including the practice assessment modules which would be due every 2 years. This was a change, since the prior requirements were assessed every 10 years, culminating in the exam. I thought that I would go ahead and do this, since I had learned a good deal the previous go round. In my present practice as an itinerant hospitalist and sometime rural primary care physician, the practice assessment piece is really tricky, so I haven't gotten around to that yet. The requirement to do this is presently on hold by the ABIM.

Since the change in requirements for MOC, internists have been rebelling. Many of them have practice responsibilities that are more demanding than mine, so they really don't have time to do all of this. The scope of practice for internists is very diverse and many find that what they learn in the process is not that useful. The price is painfully high. Newsweek picked up the smell of blood in the water and wrote a nice inflammatory article that simplified the issues and opened them up to general scrutiny. The ABIM responded testily. Fur is flying everywhere. Much has been said by knowledgeable people on the many sides of the argument, and I will not attempt to cover their points. I have a few thoughts, though, that don't stand out in what I've read and have some bearing.

1. There is at least one other way to get certification as an internist. The American Board of Physician Specialties offers certification in Internal Medicine and various other specialties. It was initially started as a certifying agency for Osteopathic Physicians, but now includes MD's. The cost of certification is about the same as for the American Board of Medical Specialties, the parent organization for ABIM, and their recertification occurs at 8 year intervals. They do not require ongoing maintenance of certification activities, other than demonstrating involvement in continuing medical education for 50 hours a year. This might be a viable way to opt out of ABIM's requirements.

2. The concept of "Maintenance of Certification" didn't come from ABIM, but was adopted by the parent organization, the American Board of Medical Specialties in the year 2000. This board includes doctors of pretty much all varieties, including surgeons, anesthesiologists, radiologists and everyone I can think of. There are 24 member boards. I checked the boards of Family Medicine, Pediatrics and Emergency Medicine and all of them have MOC requirements that are ongoing in order to continue to have a board certification. There are at least a few of these doctors who write about their specific requirements, and it looks like they also find them onerous and of dubious value. The physicians who find the process to be just fine probably don't write about it. Most of those who are unhappy about the process are likely too busy to write about it and probably just growl quietly to anybody who asks.

3. It is very hard after finishing medical school and residency to keep up with the huge body of internal medicine, with its very active ongoing research on the pathogenesis of diseases and what therapies work and don't work. Having a process such as board certification and recertification that can provide a framework for relearning that body of knowledge as it changes is very important. Just achieving 50 hours of continuing medical education in the fields that most interest us is not enough to maintain competency. The process of learning what I needed to know to pass the ABIM test was valuable and I am a better physician for having done it.

4. Doctors don't want to be attached at the hip to their certifying boards. That goes for pediatricians, family practitioners, emergency physicians (and so on times 24) as well as internists. We already have to prove competency for maintenance of privileges at hospitals, state licensing agencies and even with insurance companies. Something about this recent MOC change was the last straw.