Doing Global Health--not always the same as doing good

When I went to medical school over 30 years ago I dreamed of working in exotic places, plagued with poverty, where nothing was familiar and where I could be of use. It sounded deeply gratifying. I imagined that I might escape the small fiddly problems of my privileged life by trading them for large, worthy problems. I longed for the feeling of being sure that I was doing the right thing.

Not long after finishing my residency in internal medicine I took a trip to Thailand where, after being a tourist for several days, I visited a leprosy colony run by the Anglican church near the city of Chiang Mai, spending a week there watching and trying to help out. It was profoundly educational. Not only did I learn about the disease but also about all of the creative approaches the hospital there used to manage anything from chronic wounds to physical disability and patients' need to have meaningful work. The patients had illnesses that took years to heal, and they had workshops where they made beautiful wood boxes, prosthetic limbs and a variety of wheeled chairs or carts for getting around. Fishing line was sterilized to be used as suture material. Many things we throw away in the US were sterilized and re-used. Care was excellent and there was mutual respect between doctors and patients. That week was more important to my becoming a real doctor than many months I spent in medical school. My skills at that time were basic and I doubt I was of any real help, but I always hoped to go back when I had more time and more competence to offer.

Decades passed. In the spring of 2010 I began a series of trips to Haiti, Tanzania and South Sudan primarily to educate and be educated in medical programs of various descriptions. This included being involved in projects to do with sanitation and nutrition, teaching bedside ultrasound, helping out with research and occasionally providing direct care to patients. These projects have been wonderful in so many ways. They all have their own blog posts, scattered throughout whyisamericanhealthcaresoexpensive. They have also allowed me to make a myriad of mistakes that I can never undo and learn a great deal about how global health projects can have unexpected bad consequences.

There are a couple of root causes of the badness that comes of trying to do good. The first is ignorance. When we go to places that are exotic and unfamiliar we don't understand their culture or their diseases, how they deal with them, how systems that appear to be chaotic and just plain wrong are actually delicately balanced. We don't know their languages or customs. The second is resource inequity. We are rich and they are poor. This fact and the processes that caused it to be true and perpetuate it have created the need that draws us to help but also sets us up to fail.

We start with hurdles that stand between us and our goals. Sometimes we find that our important gizmos and doohickeys have been stolen because we don't understand the risks of where we stowed them. We then find that there are rules or regulations that govern what we intend to do which we were not aware of before leaving home. Solving those problems puts us in long lines and costs us unexpected fees and delays that were not part of our calculations. We offend people who we expected to work with due to misunderstandings. We find that despite the fact that we spend large amounts of money on our carefully designed plans, everyone seems to want something else, something we don't think we can provide. We become tired, frustrated and sometimes demoralized. Often we are resilient, though, and pop back, ready to face insoluble ethical quandaries.

We face ethical problems in the three main functions that we take on when we are doing global medicine: research, donations and volunteering.

Research:
Scientists in developed countries use the informed consent process as a way to protect our patients from possible harm. The idea is that we will explain what we are doing, why we are doing it, and what harms can arise from our research protocol. Our subjects will listen and judge for themselves if they are willing to take on the risk. This works fine if our subjects really understand what we are saying. In the US, with a population that generally shares our language and values, it's a pretty good strategy. In rural Africa, an informed consent form is nearly useless. A few years ago we did a research project in a small impoverished island in Tanzania. Our consent form informed one of our subjects that we would not be reimbursing her for parking. Since there were no parking lots in her village and she didn't own a car or even know anyone who owned a car, this was hard to understand. The form was pages long and had been painstakingly translated into Swahili, which she spoke far less fluently than her tribal language. She was also used to making decisions based on the judgment of a male leader or relative, so the very concept of giving consent was foreign to her. Our translators were hurried and most likely told her that if she wanted the mzungu (foreigner) to do this thing she should sign her name on the line. Explaining the whole thing would probably have taken an hour or more.

We also do research into techniques or treatments which are impractical or unnecessary. My group researched using ultrasound to diagnose malaria. Although it was definitely interesting to look at the ultrasound findings in patients with malaria, there is a perfectly good fingerstick test for malaria widely available where we were which was much easier to do than an ultrasound. Patients might have seen us doing an ultrasound for malaria and then believed that their own doctors who did not use ultrasound for this were giving them substandard treatment. We may have been unintentionally undermining perfectly adequate care. In helping us with our research, physicians who normally saw 100 patients in a day were slowed by helping us, leaving their patients in the lurch.

These are only our well-meaning mistakes. Sometimes research projects are truly harmful, offering treatments that have unacceptable side effects or comparing active drugs to placebo thus denying sick patients access to proven therapy. Well publicized harms caused by research projects have soured many African countries on any research which involves human subjects.

If we avoid all of these errors, we still take our data home for processing and submission and don't necessarily inform our subjects or local collaborators of the results. We take (from a poor country) and don't give back.

Donations:
I have enjoyed donating medical goods of various description when I travel, but I'm not entirely sure it was the right thing to do. Often we donate what we have, which has for some reason ended up un-used in our hospitals. I've seen specialized bone suture at a hospital in South Sudan, which had taken up space in a transport plane to get all that way so was by no means free. It was completely useless, as were boxes of plastic vaginal specula in a place where speculum exams were almost never done and where metal ones which could be sterilized and re-used were much more useful. We are often asked to donate ultrasound machines, but when we do, the machines are not under warranty and the companies that make them have no obligation to fix them should they fail. The machines we give are often far more expensive than the models African hospitals would normally buy from China and have unfamiliar buttons and knobs. If they had the money we spend on a machine to donate, they could buy several ultrasound machines. When we donate machines, the health authorities don't know which hospitals have functional ultrasound machines and which do not. Our good intentions may be slowing the development of sustainable local health systems.

Often when we donate some piece of equipment we do so with the agreement that the receiving hospital will use it free of charge to patients. This obliges the recipient to budget time to a procedure that gives them no profit. The providers may decide to charge for the procedure after we are gone, limiting its use to those who can afford it. Either of these arrangements can take time away from other obligations.

Volunteering:
Potentially the greatest gift of all that we can give in ourselves. As doctors or nurses we have trained for years in our fields and have added wisdom from our years of practice. Most of the countries where we go to volunteer don't have nearly enough skilled medical practitioners so you would think that they could use our help. Unfortunately it isn't quite that simple.

Often the places we go to volunteer are in disarray. This can be due to some horrendous natural disaster, but more often is caused or exacerbated by bad and corrupt leadership. As humanitarians we may need to help, but we must understand that our support may be propping up a bad regime or allowing a government which does have resources to shirk responsibility for creating a functional health care system.  In less catastrophic times our help may be competing with a new and fragile homegrown capability and may cause it to fail. It seems benign to come to a place a provide free dental care, for instance, but in some of the places we serve there are trained dentists. If we come once or twice a year, patients will wait for us. We have fancier machines and don't charge for our services. Any potential local dentist will be wise to establish his or her practice in a place where volunteers don't visit.

Some projects have been categorized as "drop and run." Specialized surgeries may be unavailable in remote areas and it makes sense to try to deliver this care with a specialized team. This can, however, disrupt regular services if a project is set up to happen at a functioning hospital or clinic. Also there can be complications of our surgeries which fall on already overworked and not-specialty-trained local providers after we leave. Such projects work best if these issues are taken into consideration and if we focus on training local providers to do what we do.

Even training local doctors or nurses to provide specialty services can have unintended consequences. People trained to provide a technically difficult or much-needed procedure will be able to find a higher paying job in a different area, maybe a place that has less need and so is less stressful. Training is a gift to the provider but may place an intolerable strain on the clinic that they leave behind. In Tanzania we introduced a clinical officer with a busy obstetrics practice to ultrasound. He easily learned basic obstetrical ultrasound allowing him to improve his care of mothers and babies. He fell in love with ultrasound, though, and I believe he left the over-stretched health center to pursue a career in radiology.

Working in resource poor communities can be an opportunity to do things that we would never get to do in our own settings. Medical students have found themselves delivering babies or taking the lead in performing some procedure with which they have little familiarity. I do many more procedures in Africa than I do at home, making me more capable when I get back but potentially putting African patients at risk from my lack of expertise. We do these things because we are convinced that we are "better than nothing." Sometimes we are, but sometimes we do things that would much better have been left undone. When we make catastrophic errors, not only do we risk patients' lives but we undermine the trust of the communities we are trying to serve.

And we are so expensive. It costs about $2000 for me to fly in and out of Juba, South Sudan. The small plane that will be chartered to take me to the village will cost someone a fortune, but will also transport supplies. Still, I am part of that cargo and I add a cost. While in Juba I will stay in a safe hotel which will cost $100 a night and there will be a capable person assigned to me to make sure I don't die, since robberies and carjacking are common. If I do get robbed or injured, other costs will pile up quickly. Is there a better way to use those resources?

So am I saying that we just shouldn't go?
No, not at all. There are many good reasons for healthcare providers from wealthy countries to offer their services to places and people in need. We must do research to find out what works and what does not in resource poor countries where diseases and problems are different from our own. Doing global health projects creates bonds of caring and makes us into better people. The vast majority of global health projects succeed in building compassion, empathy and perspective. That, in itself, probably achieves far reaching benefits. It's just that we should pay attention to the details and try to follow Hippocrates' advice to "do no harm." I emphasize "try." It is not possible to do absolutely no harm, but if we're careful we can minimize it.

Advice:

1. Find out about a trip or project before committing to go. Ask lots of questions and make sure you are satisfied with the answers.
2. Partner with local people. Listen to them. Ask them about etiquette and politics. Find out what they think about the impacts of a project.
3. Don't be too set on your own agenda. After all of your good planning ahead of time, you may still find out that what you had planned to do is wrong or needs tweaking.
4. Find out as much as you can about the health systems already in place in the area you plan to visit.
5. Step out of your doctor suit and think about social justice. Figure out how you can contribute to the health of the community you serve rather than just your patients.
6. Forgive yourself for your inevitable mistakes and try not to take yourself too seriously. 

Lewy body dementia and a farewell to my father

When I finished my training I was taught that the vast majority of dementia was Alzheimer's disease, with occasional cases of multi-infarct dementia as well as odd syndromes such as Kreutzfeld-Jacob disease and genetic, traumatic, toxic and tumor related syndromes. Parkinson's disease, we were taught, caused a tremor and freezing up of a person's movements and only very rarely was associated with any kind of memory loss.

These teachings helped us modern doctors leave behind terms such as "senility" or "hardening of the arteries" to explain cognitive loss. We still had no useful tools to change the course of dementia, but we were more scientific in our description of it.

In the last several years, however, neurologists have determined that there is a very common dementia that is associated with Parkinson's disease. Lewy body disease or Lewy body dementia was a condition that I had been taught was not only uncommon but only accurately diagnosed at autopsy or with a brain biopsy. It appears, now, that it is quite common, comprising up to 30% of cases of dementia. It is more common in men than in women, like Parkinson's disease but not like Alzheimer's disease and is more common in people who have higher educational attainment. It is characterized by collections of protein known as Lewy bodies that are found throughout the cerebral cortex, rather than just in the movement centers of the midbrain, as in Parkinson's disease.

There are some medical tests that will help to diagnose Lewy body disease, but they are not commonly performed. It is most commonly diagnosed by the identifying 2 of 4 common clinical features. These are:

1. Fluctuating cognition with varying levels of consciousness and alertness. They will fall deeply asleep and be unarousable or be very slow and confused, lasting hours sometimes, then improve to a more normal baseline, laughing and participating in conversations. Family will sometimes think they have had a stroke or a seizure.
2. Visual hallucinations. These may be quite detailed.
3. REM sleep disorder. Patients will often talk in their sleep or do complex movements, often getting up and walking or performing complex behaviors. This can be disturbing and even dangerous to a bed partner.
4. Motor features of Parkinson's, including pill rolling tremor, slow movements and rigidity. These features almost always follow the development of memory loss.

Patients have other clinical features such as depression, anxiety, apathy and loss of executive function (unable to clean a closet, sort and pay bills or put together a photo album.) They often have autonomic dysfunction, with fainting spells due to drop in blood pressure or inability to tolerate changes in temperature. They become unstable in their walking or standing and fall frequently. They have urinary incontinence. They have delusions that are detailed and hard to shake.

My father had this and I didn't recognize it until about 3 months before his death. He was a very smart man, having graduated in physics from Caltech and then worked with early computers and was an important part of the space program. He worked on developing electric cars and wind power and studied the feasibility of oil shale and tar sands (not feasible and not efficient, he concluded.) He brought a supercomputer to the island of Maui and helped jump start their technology industry. He was funny and engaging and had a knack for encouraging others by being a springboard for their ideas. He was the most compelling conversationalist I have ever known and played a mean game of scrabble.

When he lost his wife to cancer 12 years ago he began to notice some disturbing memory failures. He put those down to the stresses of home hospice and the depression that followed her death. He was capable with his laptop computer and enjoyed the early handheld computing devices, but when he got his first smartphone, the technology became more difficult for him to learn. He could use email, but forgot how it worked and never learned to access it with his iPhone. He took on the position of board president with an academic organization and wasn't able to keep up with what he needed to do. He resigned and felt terrible about that. He tried to take blood pressure medication but would pass out unexpectedly so stopped it. He kept all of his mail and couldn't figure out how to file it, feeling ashamed about the state of his desk. He flailed and talked in his sleep so much that his wife had to go to bed elsewhere. He would wake up at 4 in the morning, inconsolably sure that he needed to catch a plane or teach a class.

He fell frequently and when he walked or stood, would lean to one side, unaware that he was doing it. It was nerve wracking to walk with him because he refused to take an arm and never learned to use a walker or cane. He slept more, often while sitting up, and had periods of unresponsiveness that were alarming. His falls were not minor and he gashed his face and ripped the skin on his arms, broke his hand and hit his head hard enough to spend an agitated night in the hospital. His writing became small, shaky and cramped.

It was clear he had dementia and that it wasn't a normal kind. He saw a neurologist who thought he might have Parkinson's disease and a wonderful gerontologist who diagnosed Alzheimer's disease. His wife, who had been attending a dementia support group, had heard about how common Lewy body dementia was and suggested it might be that. I read the most recent literature and decided she was right. Not only did he have it, so had many of my patients over the years who I had thought had Alzheimer's disease.

The fluctuations. The falls. The detailed hallucinations and delusions. The executive dysfunction. It isn't subtle how different it is from Alzheimer's disease. These are the people who come into the emergency department frequently when they are clearly worse than normal but improve overnight and return home, even though we think that's a bad idea. They do fine until they fluctuate again and then are back. These are the difficult to handle patients with the mean delusions who drive their families or spouses nuts but are unmanageable in nursing homes. If Alzheimer's disease were vanilla ice cream, Lewy body dementia would be rocky road, with real rocks.

My father was a sweet guy but this disease made him critical, unkind and selfish. But only sometimes. Only when we were so deliberately stupid that we didn't understand that his reputation would be ruined if he didn't get to the airport or to the lecture he was supposed to be giving. Only if we tried to help him walk when he could clearly do it better without our pushing him off balance. Only when he woke up scared and didn't understand what was going on. At other times he was kind and appreciative and full of sweetness, humor and wisdom that he could no longer put express with words.

It was possible for him to stay at home with his wife for a long time with the help of caregivers. Eventually, however, the combination of impulsiveness, weakness and sleep disturbance made even 24 hour caregiver support inadequate and he had to be moved to a memory care center. The facilit was really wonderful, catering to the dotty, delirious and demented, many of them with what appeared to be Lewy body dementia. He perked up briefly after moving, but then began to sleep more, sitting up in his wheelchair. He still had up times, explaining the chemical properties of tungsten, listening to a talk I needed to practice and offering good questions. He became weaker, unable to hold a cup or a fork, barely able to lift a cookie. Eventually he didn't wake up at all and two days later died peacefully, in the care of hospice.

Since his diagnosis, I have been much more aware of those demented people who don't have Alzheimer's disease. It helps to know, so we don't compare them unfavorably. They aren't just difficult people with dementia, they are regular people with difficult dementia.

Robin Williams, the gifted actor and comedian, developed a set of disturbing symptoms in the last years of his life that were unexplained but progressive and horrible. He said goodnight to his wife one evening (she slept in a separate room because of his sleep behaviors), went to his bedroom and hung himself. An autopsy showed severe Lewy body dementia. She wrote a letter to the journal Neurology detailing their medical odyssey. It is heartbreaking to read.

We have no useful treatments for Lewy body dementia. Sometimes benzodiazepines help a bit with the sleep disorder, but my experience was that they did nothing. Anti-psychotic medication is not helpful and often can worsen the symptoms significantly. Parkinson's medication can help with the rigidity and tremor, but my experience was that, by the time that was prominent it was more helpful for my father not to have the ability to act out his impulsivity. A wheelchair was much safer. Cholinesterase inhibitors, used in Alzheimer's disease, are recommended but don't help much and can cause sleep problems, nausea and drooling.

I will miss my father. I will think about his voice, his conversation, his smile, his love of math and his scientific contributions. I will remember his smell, his wispy white hair and the way he loved to have his back scratched hard. I will not miss his last 6 months, though, and I resent those nasty Lewy bodies that infested his wonderful brain.

Overachievers on a plane

"If there is a physician on the plane, please press your call light!"

The vast majority of doctors who have flown on airplanes have heard this, and most of us are willing, if not entirely eager, to respond. What follows is usually a far from ideal encounter with inadequate information, too much noise, a cramped space to work in and little knowledge of what is expected or even possible.

My experiences (I think there have been 3) were people who had become dizzy or had passed out. One of them was pretty frail, but none required that we land before our destination airport. What I learned was that:

1. More than one physician usually responds to these calls. As a general internist, I'm usually the most appropriate person to evaluate the patient (winning out over ophthalmologists, dermatologists and obstetricians.)

2. The flight attendants are very grateful, bring me an extra glass of juice and promise some kind of compensation from the airline which may or may not materialize.

3. It's really pretty challenging to do it right, and I end up spending weeks thinking about the ways I could have done it better.

Since the last experience, I have looked up what is in an airplane medical kit. There is a stethoscope, a blood pressure cuff, an IV and some fluid, some IV glucose for hypoglycemic patients, an asthma inhaler, some non-aspirin pain reliever and some actual aspirin for suspected heart attacks, some medication for severe allergic reactions and some stuff that might be useful in a cardiac arrest. All planes must carry an automatic external defibrillator, which is as it should be. There is nothing particularly useful for nausea, severe pain or anxiety.

There is no protocol that I was aware of regarding what needed to be done. There was no obvious way to communicate with the doctor who would take care of that patient after the event in the plane about what had actually happened. There was no way to find out whether the patient did OK after he or she got home that I could use to help guide my next experience.

I just recently had a discussion with a couple of other physician friends (overachievers I guess) about what we do and how to prepare for the inevitable "doctor on a plane" scenario. Despite not knowing whether we had made the right decisions (other than that our patients remained alive and presumably vertical at the end of the flight) we all wanted to do better. We had been good Samaritans, but we wanted to be very good Samaritans.

The first thing we discussed were our tools and tech. My kit includes a small ultrasound (if I'm going somewhere medical, which I usually am), a tiny two lead electrocardiogram which works with my iPhone and fits easily in my purse, my lightweight stethoscope (which actually works, unlike the ones on the plane) and a not-so-basic first aid kit with medication for various random diseases. My friend carries an oximeter (measures blood oxygen level) as well. I always have a downloaded copy of UpToDate, a constantly updated disease and treatment encyclopedia, on my phone.

I try to find out my patient's story, including medical history and what they think is going on. I provide as much compassion and reassurance as such a cramped space will allow. Still. I think I could do better.

The main problem is not that I didn't think to bring the oximeter, but the fact that the process is bad. Airlines know that medical emergencies happen when they are aloft. They should be less random about how they respond. According to Bloomberg, many airlines contract with MedAire, a remotely available medical service that serves aviation and yachts and other situations that require medical advice at unscheduled times. Apparently they must only use this service when they think they need it, because none of my events seemed to use any remote support. But it is available. Why, as the doctor responding to the emergency, did I not know that they were available?

A person who gets sick on a plane is in a bad situation. He or she is often old, sometimes alone and always vulnerable. It is frightening and embarrassing be sick on a plane. Airlines charge lots of money for their services and are at risk for expensive diversions and crushing damage to their reputation if these scenarios go poorly. They should try to get this right.

I would propose:

1. Ask people at the time they schedule a flight whether they are a physician and whether they would be interested in being called upon in an emergency.

2. If we say yes, get a copy of our medical license. If my relative got sick on a plane, it would be awfully nice to know that the physician who responded to the event was actually a physician or an otherwise qualified medical professional.

3. Give us a little information to read on the process, including what is expected of us, what kind of support exists, what is in the medical kit...

4. Have the flight attendants take some kind of medical history from the patient or relatives if possible and enter that data into a simple electronic form. Make it possible for the doctor to enter some information about what happened. Send that to the patient and or his or her primary care provider.

5. Compensate us in some (maybe small) way for volunteering, since it is not necessarily an easy thing to be on call on a plane. Compensate us more generously if we provide a service. Let us know what the compensation will be.

6. Tread gently around Good Samaritan laws so we won't be exposed to liability. From what I read, it looks like preparing for this kind of thing and even being compensated for it wouldn't create a problem.

This isn't just overachieving. Doctors actually want to do a good job whenever we take care of someone. When we respond to the inevitable "is there a doctor on the plane?" we are agreeing to participate in a system that makes it difficult to provide adequate care. That would be acceptable if we were in a refugee camp or disaster situation, but airlines could and should be held to a higher standard..

Dang. Just have to rant about some really expensive drugs: Lucemyra, Trelegy Ellipta and Andexxa.

The price of new drugs just seems to go up. I've stopped being excited about innovative pharmaceuticals that target various hard to treat diseases and conditions, simply because they cost so horribly much. Each of these new developments looks like a classic philosophical dilemma. Do I pull the lever that makes the trolley kill one person instead of 5 or do I save the one and allow the trolley to kill 5? Do I prescribe the new drug that potentially helps my patient but may destine a whole population to lousy health care by making the overall budget unsupportable?

When I was in residency in the 1980's medication that cost a dollar a pill was crazy expensive. Inflation doubles that plus a little more, so think $2.25 and pill in 2018 money. But today's expensive medication costs 10-20 dollars a pill. Or $1000 a pill for the drug to cure hepatitis C. Or, in the case of a now pretty commonly used drug for advanced cancer, $150,000 a year. This is real money. On the lower end, it costs as much as all of one's food. At the higher end, it is enough to live like a rich person. If we insist that everyone have access to some of these new drugs we admit that we will never be able to offer universal health care. It would eat up all of the money we have.

Here are the new, latest and greatest drugs announced in The Medical Letter of Drugs and Therapeutics, a publication published by a non-profit not aligned with any pharmaceutical companies.

1. Lofexidine (Lucemyra) for opioid withdrawal: this is a central alpha receptor agonist, similar to the drug clonidine, which has been available and successfully used for the physical symptoms associated with ceasing to take opioid drugs when one is addicted. It reduces the anxiety, sweating, irritability and diarrhea that characterize withdrawal. It costs $1738.00 for a week supply. It is no more effective than clonidine which costs $1 for a week, though it does cause less reduction in blood pressure. The drug of choice for this situation is buprenorphine which costs $23 for a week.

2. Trelegy Ellipta: inhalers for asthma have been prohibitively expensive for years. People with airway obstruction, classic asthma with wheezing, shortness of breath and cough, usually require inhaled medication to open up the small airways in the lungs and to reduce mucus and inflammation. Originally the only drug for this was epinephrine which eased breathing when injected, taken orally or inhaled, but also sped up the heart and caused the shakiness associated with adrenaline release. Newer drugs worked on the inflammatory response, reduced the cardiac side effects and were longer acting. Inhalers cost less than $20 for a month supply when I graduated from medical school. Now some of the common brand name inhalers, combinations of long acting bronchodilator and a corticosteroid for inflammation, cost $300-$400. Now Trelegy Ellipta has been introduced which costs $530.00 for a month's supply. It includes 3 drugs rather than 2, and if one were to buy those three types of drugs as individual inhalers they would cost more than that. People mostly use a drug like this every day forever, at a cost of $6360 per year. Many of these drugs are not available as a generic, but even generics can be costly. Some of the generic combination inhalers cost less than $100 a month, but different patients respond differently and some have no luck at all with certain drugs or combinations and will end up on branded products.

3. Andexxa (andexanet alpha) will rapidly reverse certain anticoagulants ("blood thinners"). A few years ago the most commonly used anticoagulant, warfarin (coumadin), got some competition. A new drug was approved that reduced clotting by a slightly different mechanism and did not require regular blood tests to monitor it. Now there are at least 3 such drugs commonly used for patients who have a high risk of blood clots. They are considerably more expensive but also a bit safer and quite a bit more convenient. Unlike warfarin, however, which can be reversed by vitamin K or fresh frozen plasma, the new anticoagulants did not have an effective reversal agent. So if a patient on one of these new blood thinners came in having injured themselves, with uncontrolled bleeding, it was very difficult to stop the bleeding. We did discover that prothrombin complex (Kcentra is the brand name) worked pretty well. The hitch was that it cost about $5000 for the usual injection. We still used it, but it definitely put a dent in pharmacy budgets in hospitals. Andexxa was specifically developed to reverse two of these newer anticoagulants, apixaban and rivaroxaban. It can be dosed low or high, depending on the dose of the anticoagulant. One high dose treatment costs...wait for it...think high...YES. $49,500.

Costs of this magnitude are hard to put in context. I have read that there are about 750,000 people on the newer anticoagulants. If one in a hundred of them had a bleeding episode in a year which was treated with Andexxa, that would be nearly 400 million dollars. 400 million dollars is enough money to buy a year's supply of a nice cheap generic blood pressure pill for 10 million people to help prevent the atrial fibrillation which eventually leads to prescription of the anticoagulant. Or enough money to pay for a week's vacation to Hawaii for 10,000 people, which is mostly irrelevant.

What makes me sad here is that these new drugs are being pushed out of the pharmaceutical pipeline and, although they have the potential to reduce misery if used for the conditions they can treat, they will bankrupt either real people or health care budgets or both. The folks who could benefit from them will perhaps achieve better health only to be crushed by debt or unable to afford health insurance.

Something could be done to fix this.

Pharmaceutical companies are motivated to create drugs whose high prices and popularity will result in profits. We can, however, fund drug development in a different way. If academic labs developed drugs through grants from the National Institutes of Health or other government agencies, their costs would not need to be made up by sky high drug prices. In fact, since the government pays the vast majority of health care costs in one way or another, the payoff for these grants for drug development would be through lower pharmacy costs and also improved health and productivity. This kind of payment would favor affordability and efficacy, not just expensive drugs that add very little incremental benefit for patients.

For now, new drugs come from pharmaceutical companies and are priced beyond what a conscientious health care system can pay. Still, these drugs will be advertised and prescribed and health care costs will go up and medical debt will destroy lives. It's really hard to get excited about this most recent batch of wonder drugs.

How did American healthcare get so expensive? Perhaps it was Ronald Reagan's presidency.

The New York Times has pointed out a very interesting coincidence. It was during the presidency of Ronald Reagan that health costs and outcomes began to diverge from the rest of high income countries with which we compare ourselves.

In an article by Austin Frakt, a healthcare economist, physicist and mathematician, he points out that America began to abandon healthcare cost controls, except for Medicare, when Ronald Reagan took the helm from Jimmy Carter, who had steadfastly backed limiting public and private healthcare spending. Deregulation of many institutions followed. Regulation of industries related to health were rolled back and new regulations which helped control spending in Europe were not introduced.

In the early 1980's insurance companies began to change the way they paid hospitals for their services, introducing "DRG's (diagnosis related groups). Hospitals responded to this change in payment methods, being paid according to diagnosis rather than time or intensity of treatment, by increasing their size and leverage and mobilizing other cost centers to bolster their profits and economic viability. To be fair to hospitals, this was a difficult time for them and many failed. Nevertheless, in a successful change in strategy, they did begin eating up more healthcare dollars.

Other developments that came with this conservative sea change included support for medical spending to the exclusion of social spending and the success of big drug companies in marketing their more expensive products to consumers.

These are some very compelling associations and definitely worth exploring further. In addition to helping explain our high healthcare costs,  these observations suggest some remedies that might gain traction in the post-Trump era. The article is short and sweet and I encourage you to read it. I am looking forward to a more detailed look at what actually happened from this or other authors with suggestions for concrete changes in our future direction.

A monoclonal antibody to prevent migraine!

This last week a monoclonal antibody injection for migraine was released, with fanfare and great hopes of becoming a commercial success. Amgen developed Aimovig (erenumab) and published its findings in the New England Journal of Medicine last November. It is an injection that targets calcitonin gene-related protein (CGRP), a chemical released in the brain during migraine which dilates blood vessels. The monoclonal antibody inactivates this protein for a long time, on the order of one and a half months.

Migraine is often involves head pain, nausea, weird neurological symptoms including vision loss and even stroke symptoms. The combination of symptoms is frequently disabling and "migraineurs" suffer not only from their nausea and headache, but also from large financial burdens associated with the condition, on average around $6000/year for chronic migraine sufferers. The economy loses over $13 billion in lost workdays. Over 44 million people in the US have migraines, though this probably underestimates the numbers since many never come to medical attention. Migraine is a worldwide problem. In a rural area in Haiti where I have seen patients, the most common complaint was "tet fe mal, vant fe mal" meaning "my head and my stomach are bad." I was confused because of how nearly universal the complaint was. In retrospect they were describing migraine. I come from a family of migraineurs and can attest to how chronic and episodic migraine affects the rest of us: children with migraine vomiting their Saturday French toast, a mother with migraine spending what seemed like half my childhood in a darkened bedroom, a partner with alarming neurological symptoms. It's enough to give those of us without headaches headaches.

Theories of what causes migraines have evolved over the years and presently I understand that the phenomenon is felt to be a "spreading depression" of brain electrical activity, resulting in hypersensitivity to normal processes including the pulsating of blood vessels. Migraine is hereditary and common, and includes some annoying but tolerable symptoms such as caffeine withdrawal headache, carsickness and ice cream headaches. It can also be a disablingly horrible, usually pulsating, headache with nausea and vomiting, light and sound sensitivity, sometimes preceded by sparkles or blind spots that move across the visual field. It can be brought on by a change in routine, certain foods or drinks, menses and stresses. Home remedies bring mixed results: caffeine helps but can perpetuate headache, as can normal analgesics. Anti-inflammatories including aspirin can be very effective, but daily use can induce migraine and can cause ulcers and intestinal bleeding. Herbal remedies such as feverfew have gained attention from the medical community in the last few years but are not very effective for most people. "Triptans" (including sumatriptan, the first in the class) which can be taken by pill, shot or nasal inhalation, can be quite effective, but not universally so, and are still costly. Many patients, in the throes of a migraine they can't control at home, end up in emergency rooms for intravenous treatments which can leave them or their insurance companies with multi-thousand dollar bills.

Preventing migraines by the use of medication has been an effective approach for decades. When lifestyle approaches such as regular sleep and meal schedules, exercise and management of specific triggers is not effective, drugs in the beta blocker, antidepressant and anticonvulsant categories can be tried. Not all migraine prone people need to take medication to prevent headaches, but if the headaches are severe or frequent or associated with severe neurological symptoms, this is a good approach. One of the earliest drugs used for migraine prevention was methysergide, an ergotamine derivative, which was very effective but caused a frequently fatal side effect of scarring of the internal organs in one in 5000 patients. It is rarely used now, and is not available in the US. Several beta blockers, also used to treat high blood pressure, are effective, with the main side effects being change in the heartrate and feeling cold in the hands or feet. With prolonged use they can lead to weight gain and increase the risk of diabetes. Amitryptilene, an older tricyclic antidepressant, can be effective in migraine and other pain syndromes, but does lead to weight gain and can cause intolerable sleepiness. Valproic acid, a drug originally for epilepsy, can be quite effective, but also causes weight gain, can upset the stomach and cause lethargy. Topiramate, a more recently developed drug for epilepsy, has been remarkably effective, without causing weight gain. In fact it can help with weight loss. It can cause sleepiness and brain fog however. I used to say that these drugs made you fat, stupid and poor, but they are all now generic, so with the exception of topiramate, just fat and stupid. For those who get these side effects, the trade-offs are often unacceptable.

Enter, now, the monoclonal antibodies. There are four of them, with the unpronouncable names of eptinezumab, erenumab, fremanezumab and galcanezumab. Erenumab is the first to have been approved by the FDA. It is given as a subcutaneous injection once a month and, in the study reported in the New England Journal of Medicine last year, at the higher dose tested it reduced the number of headache days by about 50%. The study lasted 6 months and the primary side effect was upper respiratory and sinus infections. There was an excellent editorial in the JAMA (Journal of the AMA) by Elizabeth Loder MD and Matthew Robbins MD which mentions some other concerning information. In clinical trials of fremanezumab and erenumab there have been 3 deaths: one due to suicide, one to chronic obstructive lung disease and another to an arteriosclerotic event. These were probably people thought to be relatively healthy, or they wouldn't have been included in a clinical trial. Also, although these causes of death seem to be far removed from migraine prevention, the target of this monoclonal antibody, the protein CGRP, could definitely have something to do with any of the three. Trials of these drugs have been pretty short, and we don't really know whether there are any long term safety problems. This is a real concern, since migraine is often a lifelong disease that can start in childhood.

The cost of these drugs is a real concern as well. Erenumab has been priced below what was initially predicted, out of concern that a higher price point would invoke the wrath of everyone who is already angry about ridiculous drug costs. Erenumab is considered "affordable" at an estimated cost of $6900 per year. Almost $20 per day. Wow. I sure wouldn't want to deprive a fellow human of a chance to be relieved of pain, but if even 1% of migraine sufferers use this medication for a year, it will add tens of millions of dollars to the healthcare budget. In comparison, a drug like topiramate costs less than a dollar a day and is about as effective. Methysergide, when it was studied, was even more effective.

The bottom line on all of this as I see it: Migraines are terrible and common and the treatments are far from perfect. Prevention is important and the drugs for this are also far from perfect. There is a new option out there which is wickedly expensive and has unknown long term side effects but may work where other drugs do not. We will all pay for it (and its yet to be released cousins) via higher taxes and insurance costs.

How the best of care can be terrible without bedside ultrasound

I just read a "Clinical Problem Solving" case from the New England Journal of Medicine (NEJM). It was entitled Stream of Consciousness and it told the story of a 65 year old man who was a patient at the Brigham and Women's Hospital of Harvard Medical School, arguably one of the finest medical institutions in the world.

These cases are presented in single paragraphs to a clinical expert physician who then comments about his or her thought processes and discusses how he or she would have handled the situation. In this narrative the patient presented to a different hospital in New England with kidney failure and a gradual onset of confusion in the setting of very high blood pressure. He was then transferred to the Brigham and Women's Hospital for further evaluation and treatment. He had lab tests of all color and stripe along with MRI and CT scans of his brain which showed some disconcerting spots. He had a lumbar puncture and his high blood pressure was treated. Eventually, after 2 or 3 days in the hospital (I can't tell from the narrative), an ultrasound was done which showed that his bladder had not been emptying properly, which had caused the kidney failure and probably the high blood pressure. A foley catheter was placed which drained nearly 3 liters(!) of urine after which his blood pressure was much more easily controlled.

The exciting diagnosis was Posterior Reversible Encephalopathic Syndrome (PRES) which was first described in a case series in 1996. It is closely related to eclampsia, a condition of women in labor or directly following labor in which the is injured by high blood pressure leading to seizures and sometimes death. The cause is thought to be leakiness of the blood vessels in the brain related to high blood pressure. It is very important to recognize PRES because prompt treatment to lower the blood pressure can prevent long term brain damage.

This guy had the best of treatment by the best of doctors, but what he really needed was a bedside ultrasound at the first hospital or on arrival at the Brigham. People who read this blog will have noticed that I am a strong proponent (nerd perhaps) of ultrasound performed by a treating physician as part of a physical exam in just about everyone with a significant medical concern. If he had a bedside ultrasound the doctor performing it would have seen that the collecting systems in his kidneys were dilated and that the cause was a massively over-full bladder, likely due to an enlarged prostate. The bladder would have been drained immediately, resulting in correction of his blood pressure and improvement in his kidney function. He might not have needed to be transferred to the larger hospital at all.

Perhaps his physicians at the community hospital did not know how to perform an ultrasound. Still, he would have benefited mightily from prompt point of care ultrasound once he arrived at the Brigham. Head scratching about the cause of his kidney failure might have been curtailed. Blood pressure control would have been more rapidly achieved, benefiting his spotty brain. His very complete and likely very costly evaluation might have been briefer and less expensive. Physicians might have been able to discharge him to home more quickly.

The impact of bedside ultrasound could have been even more profound had it been done even earlier in his course. This fellow's problem emptying his bladder did not happen all of a sudden 3 weeks before he came to the hospital. It is likely that he had mentioned to his primary care doctor some slowness passing urine or a feeling that he hadn't emptied completely. If that physician had performed an ultrasound of the bladder in the office he would have seen that it wasn't emptying properly and would have initiated some kind of treatment before it got to be the size of a large honeydew melon. It is possible, even likely, that this whole near-tragedy could have been prevented.

Bedside ultrasound is not yet the standard of care among internal medicine physicians. It should be, and in the fullness of time, it probably will be.