ACP Internist Blog

Monday, June 18, 2018

Who should get the liver transplant?

People with liver failure and cirrhosis die every year because there are not enough livers available. Who should receive the treasured life-saving organ? There is an organ allocation system in place, which has evolved over time, which ranks patients who need liver transplants. Without such a system, there would be confusion and chaos. How can we fairly determine who should receive the next available liver? What criteria should move a candidate toward the head of the line? Age? Medical diagnoses? Insurance coverage? Employment status? Worth to society? Criminal record?

Consider the following 6 hypothetical examples of patients who need a liver transplant to survive. How would you rank them? Would those toward the bottom of your list agree with your determination?
• A 50-year-old unemployed poet is an alcoholic. He has been sober for 1 year. His physicians believe he will not survive another year without a transplant.
• A 62-year-old prisoner has end stage liver disease from hepatitis C, contracted from prior intravenous drug use. He has been showing serious medical deterioration and his physician is concerned that his demise approaches unless he undergoes a liver transplant. He will be incarcerated for life. He is taking college classes pursuing an undergraduate degree.
• A 45-year-old piano teacher has a malignant liver lesion. Her physicians have advised a liver transplant. Although the survival rate for a liver cancer transplant is reasonable, it is lower than for sober alcoholics or hepatitis C. There are no other effective treatments available. Her prognosis with standard medical treatment is dismal.
• A 40-year-old has end stage liver disease of unclear cause. Liver transplant would likely save his life. He is self-employed and has no medical insurance.
• A 60-year-old hedge fund operator needs a new liver to survive. He is concerned that according to medical criteria, he will not be given a liver soon enough. In exchange for a liver, he offers to donate $5 million to the medical institution to fund cutting edge research in treating liver disease. This research has the potential improve the lives of thousands of individuals.
• A 55-year-old is trying to get a liver transplant for his child. In exchange for preferential treatment, he will stipulate that several family members will agree to donate various organs upon death.

How should the ranking decision made? What factors should be weighed? Ability to pay? Worth to society, assuming this could be calculated? Probability of long term survival?

Every one of these 6 individuals has a right to receive a new liver, but some of them will be left aside because others will be judged to have a greater right to a transplant. When any decision is made that creates winners and losers, the system will be challenged and attacked by those who decry what they believe to be an unfair process and outcome. It is for this reason that transplant policy be made primarily by those who are as free as possible from agonizing conflicts of interest.

A conflict of interest understandably taints our views. For example, we may be against paying ransom for kidnapped hostages, until our kid is taken hostage.

This post by Michael Kirsch, MD, FACP, appeared at MD Whistleblower. Dr. Kirsch is a full time practicing physician and writer who addresses the joys and challenges of medical practice, including controversies in the doctor-patient relationship, medical ethics and measuring medical quality. When he's not writing, he's performing colonoscopies.
Friday, June 15, 2018

Ode to olive oil

As lovingly and lavishly revealed in her own photo-essay on the topic, my wife and I are recently back from co-hosting an Oldways sponsored culinary travel adventure through Sicily. We ate, we drank, we toured, we made friends, we saw the dual beauties of nature and ancient civilization, and then, inevitably, we ate and drank some more!

The trip and the cuisine were both memorable in many particulars, but I will focus here on one: olive oil. We experienced olive oil as only the true artisans of the craft can make it. For the masters of this culinary art, “olive oil” as a generic reference means little more than, say, “wine.” With wine, there is bad and mediocre and good and stunningly great; wine made from these grapes, or those. So, too, for olive oil.

As a wine enthusiast, I have always appreciated the profound importance of just such considerations to the enjoyment issuing from my glass. I confess I never really paused to think much about the variety of olive making its specific, unctuous contribution to the quality of a meal, but of course that matters.

I did not become anything like an expert during our short time in Sicily, nor on other recent occasions when I learned from experts of the olive oil craft from other parts of the world. I only really learned enough to know what a delight the world's great and diverse olive oils can be, and to share such discoveries – courtesy of, for instance, the Taibi Family and Planeta Vineyards in Sicily; and Boundary Bend in Australia.

From the gustatory perspective, then, I can simply say I recognize great olive oil when I taste it, and I love it. Primarily, that's why I eat it. The right olive oil playing the right role, whether in sauce or sauté, salad dressing or for dipping bread, enhances a meal.

I am, as well, a strong proponent of its nutritional properties, and role in an optimal diet. Olives and olive oil are not merely prototypical of the famously healthful, traditional Mediterranean diet, but formally situated among the key anatomical features of that dietary pattern to which favorable health effects are attributed.

The contributions of olive oil to the good health outcomes that matter most, freedom from chronic disease, vitality, and longevity, warrants some discussion, because there are colleagues I respect, and with whom I agree about much, who differ with me here. Among my friends are some who advocate not only for a plant-exclusive (vegan) diet, but such a diet with no added oil and low in total fat. I have heard them argue that olive oil is “bad” for health, and cite studies to validate the claim.

Olive oil consumption in dietary context is strongly and consistently associated with health benefit. How, then, can any credible expert argue it is harmful? There are isolated studies in which putative harms to endothelial function (a measure of blood vessel behavior and blood flow) were shown with olive oil ingestion, likely because of the dose of oil administered, the nature of the oil used, or both. In general, olive oil intake has been associated with improved endothelial function. To put such conflicting findings in context, exercise is also consistently associated with improved endothelial function, and better cardiovascular health, but isolated studies have shown endothelial dysfunction with exercise, comparably related to “dose” (intensity of exercise), and timing of the measures.

I have other colleagues, again with whom I agree about most things diet-related, who feel so strongly that unsaturated fat is the key to good nutrition that they consider it essential. Well justified enthusiasm for the Mediterranean diet can lead to guidance implying it is the only right way to eat for health, and that olive oil is an essential part of an optimal diet. That's excessive in the other direction. The Tsimane don't consume olive oil, and have perhaps the world's most pristine coronary arteries. The traditional Okinawan diet is low in total fat, and olive oil free, but associated with the same great bounty of years in life, life in years as the Mediterranean diet. So, too, is the low-fat vegan diet among the Seventh Day Adventists.

My view is, predictably perhaps, in between. I am convinced a diet does not require olive oil (or one of the rarefied, rival oils) to be optimal; and equally convinced that an optimal diet certainly allows for good olive oil and may benefit from it. There is, obviously, more than one way to eat badly; there is more than one way to eat well, too. The health effects of virtually any food will depend on its specific preparation; the dose; what it is replacing; and its situation in the balance of the overall diet.

Olive oil in general is exceptionally high in healthful monounsaturated fat (oleic acid), and low in omega-6 linoleic acid (we are prone to a relative excess of omega-6 fats, and there may be potential harms linked to that, at least relative to an optimally balanced diet). The variety that figures in traditional diets, that is widely regarded as most delicious, and to which health benefits are reliably attached is “extra virgin.” This refers to oil pressed from freshly picked olives, under cool temperatures, without the use of any chemicals. Extra virgin olive oil preserves not only the fatty acids native to the olive, but antioxidant nutrients as well.

Heat when cooking can degrade an oil no matter its pristine state when bottled. Olive oil has moderate heat tolerance. It holds up perfectly well for sautéing, but not for deep frying. Peanut oil and avocado oil are among the most healthful choices best able to stand the intense heat of a deep fryer. Such considerations argue for a small portfolio of options rather than relying on any one oil for all dietary duties.

In my view, then, an optimal diet does not require good olive oil, but certainly allows for it, and might be enhanced by it. I happen to love it, particularly the spectacular preparations to which I have been introduced by true experts. I am also a beneficiary of my wife's fabulous cooking, in which well-chosen olive oils, native to her Mediterranean upbringing, feature prominently and often.

Diet is of profound importance to health, leaving all of us who care about the length of our lives and the quality of our health with variants on the theme of wholesome foods, mostly plants, in sensible combinations from which to choose, but no alternative to that basic theme. Diet is also of profound importance to pleasure, leaving us all to choose the dietary variant that lets us love the foods that love us back. Dietary pattern is directly linked to diverse environmental impacts as well, in which context the relative sustainability of olive oil production is another important consideration.

I choose an optimal dietary variant that allows for this time-honored delight because I want pleasure as well as health from food, and fine olive oil contributes to both. In your kitchen, that choice is entirely up to you.

David L. Katz, MD, FACP, MPH, FACPM, is an internationally renowned authority on nutrition, weight management, and the prevention of chronic disease, and an internationally recognized leader in integrative medicine and patient-centered care. He is a board certified specialist in both Internal Medicine, and Preventive Medicine/Public Health, and Associate Professor (adjunct) in Public Health Practice at the Yale University School of Medicine. He is the Director and founder (1998) of Yale University's Prevention Research Center; Director and founder of the Integrative Medicine Center at Griffin Hospital (2000) in Derby, Conn.; founder and president of the non-profit Turn the Tide Foundation; and formerly the Director of Medical Studies in Public Health at the Yale School of Medicine for eight years. This post originally appeared on his Linked In page.

Heart monitors and running toilets

Our most recent water bill was about five times higher than the one for the preceding quarter, so I called the local water authority to see if there had been a mistake. With a few keystrokes, the woman with whom I spoke was able to tell me exactly which days over the previous months appeared to have high usage, and asked if we had a leaky faucet or a running toilet. Well, yes, I explained, we did have a toilet that had been running (which I have since fixed), but I was surprised that it could lead to such an outsized bill. The response was more or less, “Oh yeah, that can do it,” and the more medically resonant “We see this.”

I was disappointed that the bill was real, but also sort of impressed that the water-works was able to pinpoint my usage, so I asked her about the metering. She explained that we have a smart-meter that transmits our usage on a daily basis to the central office. When I heard that, I asked why, if they could tell we had a problem, that they didn't notify us or provide us with access to the data. Turns out they intend to make that information available to users in the near future. Cool.

Of course, it got me thinking about the other continuous monitor that transmits data on a daily basis that is literally near and dear to my heart. I am, of course, talking about my implanted cardiac loop recorder. I still find it stunning (and infuriating) that patients are not provided with access to the data being collected by their cardiac implantable electronic devices, which include loop recorders, pacemakers and implantable defibrillators. Instead, patients have to trust that someone else is diligently monitoring their device, hope that whoever is monitoring will contact them if an abnormality is detected, and forgo the opportunity to make important observations about their own health and well-being.

It is absurd that the municipal water authority has a more enlightened and modern approach to sharing data with customers than medical device companies, but they do.

What do you think?

Ira S. Nash, MD, FACP, is the senior vice president and executive director of Northwell Health Physician Partners, and a professor of cardiology and professor of occupational medicine, epidemiology, and prevention at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell. He is board certified in internal medicine and cardiovascular diseases and was in the private practice of cardiology before joining the full-time faculty of Massachusetts General Hospital. He then held a number of senior positions at Mount Sinai Medical Center prior to joining Northwell Health. He is married with two daughters and enjoys cars, reading biographies, and histories, and following his favorite baseball team, the New York Yankees, when not practicing medicine. This post originally appeared at his blog, Ausculation.
Thursday, June 14, 2018

A monoclonal antibody to prevent migraine

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 1.5 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 $6,000/year for chronic migraine sufferers. The economy loses over $13 billion in lost workdays. Over 44 million people in the U.S. 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 U.S. Several beta blockers, also used to treat high blood pressure, are effective, with the main side effects being change in the heart rate 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 JAMA 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.

Janice Boughton, MD, FACP, practiced in the Seattle area for four years and in rural Idaho for 17 years before deciding to take a few years off to see more places, learn more about medicine and increase her knowledge base and perspective by practicing hospital and primary care medicine as a locum tenens physician. She lives in Idaho when not traveling. Disturbed by various aspects of the practice of medicine that make no sense and concerned about the cost of providing health care to every American, she blogs at Why is American Health Care So Expensive?, where this post originally appeared.