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Friday, April 22, 2016

How bedside ultrasound was awesome last week

I sometimes do locum tenens assignments as a hospitalist in rural hospitals. It is a good way to find out how other systems work, or don't work, and meet new people and interact with new communities. It's great to be home and also good to go away and come back later.  Besides the usual trappings of doctoring, including stethoscope, otoscope and white coat, I wouldn't be caught dead without my pocket ultrasound.

I just got back from a week of 12 hour shifts in a 48 bed hospital and once again was very happy to have the ultrasound. They do have ultrasonography in the radiology department at this hospital, but echocardiography (ultrasound of the heart) is only available on weekdays from about 8 to 5, and it needs to be scheduled in advance. Also the ultrasonographers don't necessarily look at the things I find interesting, and can't combine imaging with physical exam findings and what the patient tells me in real time. Patients also really enjoy seeing what's going on inside when we both look at the pictures together. Ultrasound has been part of my usual practice for 4 years now, and you might think it would get old or boring, but it hasn't.

These are a few of the cases in which it made a huge difference to a patient that I had access to ultrasound at the bedside as part of the physical exam:

1. A man came in with a history of heart valve surgery and swelling of the legs. It was not clear how well he took his medication at home, but he was known to have congestive heart failure. He had had a large pericardial effusion with tamponade (fluid surrounding the heart causing it to fail) a few months before I saw him. The bedside ultrasound ruled out tamponade and showed that his heart failure was in pretty good control. He improved impressively with just staying on his regular medication and keeping his feet up. Without the reassurance of the ultrasound I might have given him extra diuretic medication and perhaps caused kidney failure. I also might have had to send him to another hospital for a full scale echocardiogram to rule out tamponade, which would have required an emergency intervention.

2. A person with a long history of alcohol abuse came in feeling generally terrible. After treatment for alcohol withdrawal, he developed very low blood pressure and high heart rate with a low grade fever. Ultrasound of the left lung showed a definite pneumonia, though the chest x-ray visualized that area poorly, missing the pneumonia completely. Having this diagnosis helped considerably in diagnosing sepsis and choosing the right antibiotic as well as ruling out a heart problem as the cause of the vital sign abnormalities.

3. A very old man came in from home with a recent history of bleeding from his urinary catheter due to pulling on it. The family was worried about blood clots obstructing the catheter. A very quick ultrasound reassured them that all was working as it should have been. The patient was saved having the catheter unnecessarily removed and replaced.

4. After a motorcycle wreck which caused rib fractures and a pneumothorax (popped lung) a patient had persistently low blood oxygen levels. She was also a smoker so the differential diagnosis included worsening pneumothorax or simply not breathing deeply due to pain. The little ultrasound detected no pneumothorax so treatment was aimed at improving breathing rather than considering placement of a chest tube. There are many other imaging procedures that could have made this determination, but none of them were instantly at hand when I needed the answer.

Bedside ultrasound is gaining popularity as a tool for internal medicine physicians and hospitalists, but is nowhere near being universally or even commonly a part of our practice. It does take training, practice and the little machine in the pocket or easily available on a cart in the clinic or hospital floor. Truly, these are obstacles, but totally worth tackling.

Sunday, March 27, 2016

What's up with people who are in the hospital a very long time?

I just finished reading a very delightful "A Piece of My Mind" essay in JAMA (The Journal of the American Medical Association.) The JAMA is primarily a research journal, filled with new scientific or semi-scientific studies and comments on those, plus reviews of the literature and editorials on science or politics. There are also letters and announcements and educational sections for doctors or patients, even poems, but the part I like to read all the way through is called "A Piece of My Mind." These essays are almost always stories about something that has made a profound impression on the writer. The most recent title was "A Place to Stay," written by Benjamin Clark, an internist at the Yale New Haven Medical Center. He describes a patient who is stuck in the hospital probably for the rest of his life due to a medical condition whose treatment requires management that can't be done anywhere else. It's lovely, and true (even if the details are not, and I'm guessing they aren't) and I won't describe it more fully because it is available in full at the link.

It made me think about the vast diversity of patients I've known who have stayed in the hospital for way too long.

The “Piece of My Mind” story was about a well-educated and deeply lovable person with a bad disease that was in no way his fault. Most of the patients we end up taking care of for very long stretches are not this way. This sometimes makes them less appealing. Still, all of them are people with whom we become intimately familiar, knowing their families and their prospects as well as their everyday quirks, preferences and routines. We fuss and connive about how we might move them out of our hospitals and eventually, for most of them, this happens. They don’t usually die with us. 

During their stays we feel frustration and experience dread as we repeatedly fail to do our job as hospitalists which is to get them better and get them out. As the days pass we adjust medication and perform diagnostic tests, consider and try new approaches and eventually manage expectations.

We feel that these cases are failures because we can’t get the patient well as fast as we think we should. This is partly because of the ways hospitals are paid to take care of people. For decades we have been urged to reduce the number of days patients stay in the hospital. This started decades ago when healthcare costs were first starting to be alarming to payers, especially Medicare. Patients who remained in the hospital for many days often were getting complications, pneumonia, other hospital acquired infections, confusion, and these extra days were costing insurance companies and the government lots of money. Payment models were changed and we were paid flat amounts for a given diagnosis. Because of this, our hospital made more money if a patient was cured more quickly than expected. This can be good all around. Patients don’t usually want to be in hospitals and often get sicker if they stay, and hospitals don’t want to foot bills that are made larger by more days and more tests and treatments. This method of payment gave us financial incentives to cure patients rapidly. They also left us no room in our hearts or minds for the outliers who take a long time to be ready to leave.

Beside the patient in the “A Piece of My Mind” story, who are these patients?

We just discharged a patient who had been in our hospital for over a month. She had been heavy all of her life, but after having children her situation became dire. She had a gastric bypass and lost 100 pounds, which brought her down to a manageable 300 pounds. Job changes resulted in gaining most of that weight back, and then a divorce made her even less active as she turned to alcohol for comfort. She finally sought help when she was 600 pounds, couldn’t get out of bed and was so swollen that half of her skin was oozing, some of it covered with infected wounds. When she got to our emergency department it was difficult to maintain her oxygen level. She could barely breathe and was so heavy and weak that she could only just move her arms. Her chronically low oxygen levels had led to severe pulmonary hypertension and so much of her weight was retained fluid. We began the process of giving her diuretics to remove extra fluid, cleaning and dressing her wounds, using mechanical lifts to be able to lift the skirt of fat and fluid to care for the skin underneath. She was horribly malnourished, since her diet was terrible and her gastric bypass made her unable to absorb nutrients well. She was depressed with horrible self esteem, and was surprised to learn that we thought this was a problem. Over the course of 5 weeks she was able to lose nearly 200 pounds of primarily water weight, with daily attention to replacement of rapidly depleted electrolytes. Physical therapy worked with her daily and by the time of discharge she could climb stairs and walk the halls alone. She will get further rehabilitation which should allow her to cook and bathe and even drive independently. During the 5 weeks we all got to know her well and discussing her success became a high point of all of our day. There was no point during those 5 weeks that she could have successfully left the hospital.

Another patient arrived with high fevers and back pain. He had been in recovery from heroin abuse but had relapsed. He had Staph aureus growing on one of his heart valves and had been throwing little infected blobs to his spine, his spleen and his kidneys. He was treated with the proper antibiotics, but ended up with abscesses in his brain, which made him confused and difficult to handle. He had a long term central intravenous catheter (PICC line) that we placed in hopes that he might be able to get antibiotics as an outpatient, but his parade of misfortunes made it impossible for him to survive outside of an actual hospital and the temptation to inject heroin into his pristine PICC if he were on the outside made it unwise once he stabilized. Nursing homes do not like young drug addicts because they assume that they won’t play well with their primarily ancient clientele. He needed at least 6 weeks of intravenous antibiotics. He was ours. No other options. After he stopped being a complete pain in the rear he was like a family member.

Who pays for all of these hospital days? It varies. In actual fact, we all do. Hospitals eat some of the costs and pass them on to other payers if they are to remain solvent. All of us who work, pay taxes, buy insurance or use medical services pay in some way.

So what do we do about patients like this, ones who can’t go home? We struggle. We stew. We blame ourselves and them. Discharge planners shake their heads and make more telephone calls. We dread our daily visits in which there is nothing much to say that we haven’t all said before. At our best we finally come to peace with the fact that these patients and their epic hospitalizations are part of what is real about our job and not just inconvenient outliers.

Sunday, March 20, 2016

Why most published research findings are false, and why you usually can't read them anyway--the pioneering work of Dr. John Ioannidis

In 2005 Dr. John Ioannidis, a Greek researcher and professor of health policy at Stanford University, best known for his critiques of the science of medicine, published a paper entitled "Why Most Published Research Findings are False." This was not from the point of view of a science denier--actually closer to the opposite. Ioannidis loves good science, but points out that the vast majority of scientific studies today are biased, often asking the wrong questions and making the wrong inferences. In the case of medicine, this often means that claims of the effectiveness of a treatment or diagnostic test are exaggerated and often just plain wrong. This stems partly from the fact that positive and exciting results lead to further funding for the researcher involved and that the sources of this funding are often entities such as drug companies that stand to benefit from a certain outcome.

Recently Dr. Ioannidis published a new article, much more accessible than the first, entitled "Evidence Based Medicine Has Been Hijacked: A Letter to Dr. David Sackett." The first was very much based on math and statistics. He observed that most studies, when repeated, came up with different results. This was particularly true of studies with smaller numbers of subjects and ones where the effect sizes were small. Such studies were more likely to come out of fields in which there was money to be made out of a positive result and ones in which the field of study was particularly hot and there fore several groups were competing to get results.

The second and most recent article is a conversation with one of Ioannidis' most important mentors, a man named David Sackett who was possibly the first person to introduce the concept of evidence-based medicine. By this he meant combining understanding of science and research with clinical judgment and experience. This idea was inspiring to John Ioannidis and his relationship with David Sackett (physician and founder of the Center for Evidence-Based medicine at Oxford University) was profoundly influential in his career. David Sackett died in May of 2015. He was apparently not only a wonderful clinical teacher but a great and appreciative listener. Dr. Ioannidis has been explaining his hopes and frustrations to the David Sackett who remains very much alive in his mind, and in this article Dr. Ioannidis shares with his internal Dr. Sackett his frustration with what has become of evidence based medicine. It is a delightful article and well worth a read. In it he laments the growing body of crappy and biased research upon which much of our advice to patients is now built.

This article is important for all practicing physicians to read and yet, when I tried to find it, the journal in which it was published asked that I part with around $32 to see it. This felt a bit ironic. The article by the man who champions truth and transparency was guarded by trolls who wanted $32 a pop. But then, when I checked it a few days later, it became free, and if you click on the link above, you will be able to read it. I'm not sure there is a moral to this part of the story, but I'm guessing that the irony was noted by Dr. Ioannidis who told the journal editors that they could do whatever they wanted with the rest of the content of their issues, but they could jolly well make his article available for free. Still, in addition to the bias present in medical studies, lack of free access to the original articles further dilutes any truth to be found in them. Any scientific study that is likely to be "click bait"--that is to say interesting enough to readers that they will click on a link to read more about it--is described in the secondary literature by a journalist who strips it of any actual detail and spins it in any way that will engender further clicking behaviors. I venture to say that the vast majority of learning about clinical research by practicing physicians is through articles written about articles. These are produced by companies such as Medpage Today whose entire mission is to make money through advertising based on the number of times we click on their headline news. Their articles on articles appear to us to be a vital service, though, because most research articles are not free to us in their entirety and keeping up on the breadth of medical knowledge by subscribing to a vast number of journals is neither efficient nor affordable.

These are fascinating things to think about. My present distilled words of wisdom are:
1. Read Ioannidis' article while it's still free, before the journal changes its mind.
2. Don't take what passes for science too terribly seriously, especially if the effect is small or it goes against common sense and what you know about human physiology.
3. Really don't base your practice off of news releases about articles you haven't read or thought about.
4. Agitate for free and open access to important scientific research so you can read it critically for yourself.

Tuesday, February 2, 2016

Old Fangak, South Sudan--Bedside Ultrasound and other stuff

I just got back from a couple of weeks in Old Fangak, a community of people living by the Zaraf River in South Sudan. It's normally a small community, with an open market and people who live by raising cows, trading on the river, fishing and gardening. Now there are tens of thousands of people there, still displaced from their homes by the civil war which has gone on intermittently for decades. There are even more people now than there were last year.

There is a hospital in Old Fangak, which is run by Jill Seaman, one of the founders of Sudan Medical relief and a fierce advocate for treatment of various horrible and neglected tropical diseases, along with some very skilled and committed local clinical officers and nurses and a contingent of doctors, nurses and support staff from Medecins Sans Frontieres (Doctors Without Borders, also known as MSF) who have been helping out for a little over a year. The hospital attempts to do a lot with a little, and treats all who present there with whatever is available to combat their myriad ills. There are special programs for children with severe acute malnutrition, for patients with tuberculosis, kidney disease, Kala Azar, including food distribution for a subset of people with chronic illnesses.

I've been to Old Fangak 3 times now, always in the winter (warms my toes for a few weeks) during their dry/cool season. Cool means that it doesn't get much above 100 degrees during the day and cools down to sometimes below 70 at night. My stated purpose in going is to teach Jill and anyone else who wants to learn how to do bedside ultrasound. I love teaching people to do ultrasound and it means that a 2 week trip can actually have some long lasting benefits. I also get to be a general all purpose doctor who can give shots to babies, sew up lacerations, trim down leprous calluses, ponder the etiology of obscure illnesses and cook dinner. I get to see how the staff at the hospital manages to do the loaves and fishes trick with far too many diversely sick people and far too few resources.

They have a work horse of a Sonosite MicroMaxx ultrasound machine which is good for anything from babies to hearts to fractures and abscesses. I got to teach a midwife who has seen other people use ultrasound but hasn't been able to do it herself, an ER doctor who had only previously learned to do ultrasound to identify blood in the abdomen in patients with blunt trauma and a nurse who will likely make international medicine her career and was an awesomely quick study. Jill was already quite good with obstetrical ultrasound but became more confident with hearts and abdomens. Everyone learned how to make gel with glucomannan powder for when the carefully hoarded real ultrasound gel goes mysteriously missing. I brought my Vscan (little pocket ultrasound) for ultrasounding on the fly, and that was really useful as well.

An ultrasound machine paired with a person who can use it makes a big difference to care in the US, but is life-alteringly amazing in a rural hospital in Africa. What, you might ask, was it good for?

  1. An old woman limped in with a hard lump sticking out of the top of her foot. It had been swollen in the past, but now just hurt. It started when she kicked a tree. I can check it out by putting her foot in a tub of water and using the ultrasound transducer to see whether the little lump is a foreign body or a bone. Unfortunately it was a bone, sticking out of the top of her foot. Ouch. Not a lot to be done for that in this situation. 
  2. Babies. So many babies! One night there were two sets of twins delivered in one hour. The ultrasound could confirm the positions of the little tykes and predict the ease of delivery. The first pair were both head down and came out without a hitch. The second pair were smaller, worrisome for prematurity, and after the first one emerged (squalling nicely) the second one was lying in a transverse position. With a little manipulation from the outside, she was able to flip so that the head was down and was delivered without incident. There were slow or obstructed labors and being able to know that the baby was alive and well meant that the mother could be motivated to push hard even though she was really tired. 
  3. Abdominal pain in a person with known hepatitis B: Hepatitis B is unfortunately still quite common, and vaccination is not standard. One relatively young woman had been treated for hepatitis B but was having pain in her abdomen. The ultrasound showed a small nodular liver and ascites, but a small enough amount that removing it might be dangerous and certainly wouldn't make her feel better. Treatment with anti-viral medications was indicated, paracentesis (removing fluid from her belly) was not. 
  4. A pregnant woman was very anemic and also nauseated and unwilling to eat. On ultrasound her baby is still doing OK, but her amniotic fluid level is a bit low. When the transducer peeked around the uterus there were multiple loops of large bowel that are filled with fluid and thickened. In this situation the most common cause of such a finding is giardia, an endemic intestinal parasite. She got intravenous hydration, treatment for her giardia and her nausea magically resolved. She had lain in the hospital for over a week being miserable, but the ultrasound was able to point us towards the right diagnosis. 
  5. Heart disease is common there as it is here, but in Old Fangak it is primarily due to birth defects or rheumatic fever. A man presented to the hospital with swelling of his legs and shortness of breath. He was exhausted. He hadn't been able to lie down to sleep for months. He was treated with diuretic medication and beta blockers to slow the heart and improved quite a bit. The ultrasound showed advanced rheumatic heart disease, with a stenotic mitral valve and a leaky aortic valve. It was nice to know, and perhaps an email to specialists in Khartoum, the nearest city with really high quality medical care could secure him the heart surgery he needs. Probably not, but it's worth a try. There were children with signs of heart failure due to ventricular septal defects and a young woman as well, probably with an atrial septal defect. They could live relatively normal lives with heart surgery, but the Italian group that used to do this for free in Khartoum is no longer providing that service. They will get medicines which will work a little bit and they will probably die young. Stuff like that is hard to watch.
  6. Pus. People come in with swollen hands, fingers, thumbs, feet. There was a guy with a swollen thumb. After the obvious pus was drained there was still pain and swelling. We could see with the ultrasound that there was very little pus left to drain, but that the bone in the last joint of the thumb had broken due to the infection, suggesting a need for amputation of that bone. Another guy had a swollen finger, with pus on both sides of the tendon. This guided the drainage procedure. He didn't have obviously infected bone and might well recover the full use of his index finger. 
  7. People also became desperately ill sometimes, short of breath, low blood pressure, that sort of thing. A woman with a history of heart problems in the past came in unable to catch her breath, with a fever. Ultrasound showed that her heart was doing just fine and that her inferior vena cava was very small supporting a diagnosis of sepsis and pneumonia and leading to successful treatment with fluids and antibiotics. Another woman had known kidney failure and came in with a cough. The ultrasound also showed normal heart function, an abnormal left lung and dehydration in her. She was treated with intravenous antibiotics and fluids. The next day the inferior vena cava was full, meaning that she did not need more fluids, and her bladder was full as well, showing that she did have some residual kidney function. Her overall prognosis is terrible, but she was able to survive another few days at least. 
So bedside ultrasound clearly rocks. Living in South Sudan and being sick does not. 

Saturday, January 16, 2016

Annoying acronyms and miserable mnemonics: AIDET and the H's and T's

Mnemonics can be incredibly cool. When I was in medical school there was just too much stuff to remember and memory aids were so very helpful. Most specifically I refer to the vile and inappropriate one that helped me remember the cranial nerves which I remember to this day and will not share in print. In ancient times orators used memory palaces to memorize long speeches or poems, associating words with familiar and sometimes bizarre images. All this is to say that I have nothing against a good mnemonic. Lately though, as I have struggled to memorize a new acronym which is supposed to be good for me, I've been thinking about what makes a mnemonic good and what makes one annoyingly terrible.

The most irritating mnemonic in recent experience is probably the "H's and T's" from Advanced Cardiac Life Support (ACLS). When a person's heart has ceased to be able to sustain life or blood pressure, we use a memorized sequence of interventions to resuscitate them, the ACLS protocol. Ideally, we would all be fast enough and coolly competent and use our diagnostic skills and knowledge of treatment to rapidly and effectively help the patient recover in short order. The fact is that, for most of us, a cardiac arrest occurs rather infrequently and is associated with enough anxiety that, without a good solid script, shared with a treating team, we might just stand around and flap our hands and mumble. With the script we sometimes are able to restore a functional cardiac rhythm in time to keep from irrevocably damaging the brain. But if we try the usual maneuvers and nothing works, we are encouraged to think of the H's and T's. I have studied this for years and still I find that these letters do not help me much at all. That is because humans are not good at thinking of many things that start with the same letter. That's why the game Scattergories is actually challenging. A mnemonic has to be really good to work in a life and death situation. 

In order to help me maybe remember the H's and T's again, here they are. If a person persists in being dead despite your best efforts they may have: hypoxia, hypovolemia, high hydrogen ion (acidosis), hypothermia, thrombosis of the coronary or pulmonary circulation, tamponade, tension pneumothorax or toxins (poisoning.) And don't you forget it!

The other annoying acronym is AIDET, a communication tool introduced by healthcare consultants the Studer group to help improve patient satisfaction. The Studer Group arose out of the experience of Quint Studer in using a business model to improve patient and employee satisfaction in a failing hospital. Many hospitals could use help and Studer techniques have become very well accepted by management in hospitals, though somewhat less enthusiastically by clinical staff, who right or wrong do not feel like they need a script in order to communicate. AIDET stands for Acknowlege, Introduce, Duration, Explanation and Thank You. As a grammar police person I resent the fact that these are different parts of speech. Two are verbs, two are nouns and the last one is two words that make up a sentence. If one does by some chance memorize the words the problem may reasonably arise that they don't actually tell one what to do. After attending a workshop one might learn that one is supposed to say, "Good morning, Mr. Qwerty. My name is Jkl;. I'll be working with you today in what I hope is your most awesome and joyful healthcare experience ever. In 15 minutes your anesthesiologist, Dr. Asdf will be in to assess you for your surgery scheduled for 2 PM today. You will not be able to eat prior to surgery but we will  be happy to get you a late tray when you return. Thank you for allowing us to work with you today. We know you have many choices and  we are happy you chose X hospital."

AIDET is not entirely bad. Maybe it's not mostly bad. But it is also not great. First the acronym/mnemonic. It doesn't work. That's one reason why hospitals have to get their employees to attend practice sessions to absorb it.  And they do. I have failed to attend a practice session myself and, once I get back from Africa, I will likely need to do remedial work. A good mnemonic is ABC for airway, breathing, circulation, the recently replaced beginning of cardiopulmonary resuscitation (now CAB.) Or "righty tighty, lefty loosey" for opening a valve. Using AIDET to remember to recognize a patient, introduce oneself, explain what will happen and when and express gratitude of some sort is like grabbing for a cement life preserver. Maybe "who, what, when, where, why and hurray for you" or something goofy like that could work. The AIDET acronym is actually copywright protected so maybe that's why they push it--if you use it you have to pay Studer Group. Also the content and the concept is less than great. I accept that doctors and nurses often need to slow down and introduce themselves and explain what's going to happen, also to affirm the worth and dignity of the patient. But we need to do it in our own way, otherwise we lose our own dignity and will fail to notice what this patient needs at this particular moment. Patients will also start to notice that we are talking strangely. 

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.