ACP Internist Blog


Monday, September 18, 2017

Of Research, RxESPECT, And Silver Spoons

Among the predominant themes of modern medicine is a consistent emphasis on high standards of evidence. For purposes of this column, we may forgo consideration of all the implied methodologic minutiae, from randomization to statistical power, confounding to external validity. It suffices here to note there are many subtleties involved in producing high quality evidence as the foundation of something nearing certainty about the effects of X on Y, with many of them well established and universally acclaimed, others more controversial.

There is, however, a considerably larger potential problem than the reliability of any given P value, and that is the matter of parity in what research gets done, how it is reported, and what becomes of the results. From my vantage point, more than 20 years running a clinical research lab, over 25 years of clinical care, I see a very unlevel playing field. I am concerned in particular that lifestyle as medicine gets all too little respect.

Let's start with the most recent case. A study was just published in JAMA comparing a lifestyle intervention comprising both dietary modification and exercise, to standard care relying principally on drugs for blood glucose control in type 2 diabetes. The primary outcome measure was change in glycohemoglobin (HgbA1c), a kind of “weighted average” of blood sugar over time, and the participants were followed for a year.

There was an unusual element in the study design that hints already at the biomedical biases of modern society. Since standard care that relies preferentially on medication is, indeed, “standard,” the researchers designed a “non-inferiority” study, otherwise known as an equivalence study. The statistical techniques were chosen to show that the lifestyle intervention was as good as standard care; most studies are designed to show that treatments differ.

At 12 months, the treatment assignments were not equivalent. HgbA1c had improved more in the lifestyle treatment group than the standard care group, despite what the authors described as a “substantial and parallel reduction in glucose-lowering medication” in that group. In plain words, with the lifestyle intervention, participants had better blood glucose despite taking less medication. In this “lifestyle as medicine” versus “medicine as medicine” contest, lifestyle won, reminding us all of the same result when lifestyle was compared to medication in a much larger, and rather famous study of diabetes prevention.

The new study made the medical news, but that's where things took an odd turn. The headline at MedPage Today, since changed (at my request), was originally: “Exercise Not on Par with Meds for Glucose Control in T2D.” That's true. It was “not on par” because it was better!

The headline in the American College of Physician's JournalWise, a personalized literature updating service available to ACP members and widely distributed to physicians, was: “In adults with type 2 diabetes for < 10 y, a lifestyle intervention was not equivalent to standard care for glycemic control.” Again, that is technically true; it was “not equivalent” … because it was better.

Admittedly the odd reporting in this case had much to do with the investigators' choice of an equivalence design, and with the very tempered language the investigators themselves used in their paper. But still, it's hard to imagine a drug study showing effects greater than the control group being reported as “failure to show equivalence” under any circumstances. There is a ubiquitous bias at play.

As noted, the evidence has long been clear that lifestyle intervention is superior to medication in the prevention of type 2 diabetes in those at high risk (twice as good, in fact). The Diabetes Prevention Program does enjoy wide support now. But still, vastly less money is spent on translating what we know about diabetes prevention with lifestyle into routine practice than is spent on developing and disseminating new medical treatments.

While we generally use the term “standard of care” to imply state of the art, the standard may refer more reliably to the state of the status quo, the nature of which is to defend itself. My friend and colleague, Dr. Dean Ornish, developed a lifestyle intervention that could treat and reverse life-threatening coronary artery disease as effectively as coronary bypass surgery, but without the need to have your chest cracked open. The chest-cracking surgery was, of course, reimbursed by major insurers, including Medicare and Medicaid, as soon as it was established; it took Dr. Ornish, and those running a comparably robust program at the Pritikin Longevity Center, years and even decades to achieve the same for the lifestyle alternative.

Some years back, I was working as the medical director at a boarding school for adolescents with severe obesity. The results achieved were stunning in every way. But the school has since folded, because the kids who most needed the help came from families that could least afford it, and the third party payers who will, as a matter of routine, cover bariatric surgery for a 17-year-old, don't have policies to cover the even better results intensive lifestyle medicine can achieve.

My final illustration of our costly societal bias is a tale I have long been telling. A tiny, brief, and presumably fairly inexpensive study of coenzyme Q10 for heart failure published in 2000 in Annals of Internal Medicine failed to show any benefit. An editorial in the same issue asserted that the “final nail” had been driven into the CoQ10 for heart failure hypothesis. Can you imagine such an editorial accompanying a small, brief study that failed to show some particular effect of a newly patented drug? I cannot either; I have never seen any such thing.

Within a year (2001), results of the much larger, longer, and vastly more expensive CAPRICORN trial were published in The Lancet, showing the therapeutic benefits of the proprietary drug, carvedilol, in heart failure. The predictable ensued: carvedilol has long been incorporated into the standard care of congestive heart failure, whereas CoQ10 has not.

What's the problem? When the money was finally scraped together to run a study of CoQ10 roughly comparable to the CAPRICORN trial, in 2013, this result was reported: “first drug to significantly reduce heart failure mortality in over a decade.” A rather impressive resurrection for a nutrient decisively nailed into its coffin 13 years prior.

Lifestyle as medicine is the best medicine we have, the only one appropriate for universal application, suitable for children and octogenarians and breast-feeding mothers; the only one that can add years to almost everyone's life, add life to almost everyone's years. But lifestyle medicine is undermined by those profiting from the propagation of lifestyle disease, and gets too little respect from those selling the standard remedies of modern medicine.

In other words, those holding the silver spoons may not want you to have the spoon you need to help lifestyle as medicine go down. That just means it's time to invent new spoons.

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 blog at The Huffington Post.
Friday, September 15, 2017

ObiTrio

When I was young, I avoided reading obituaries out of superstition that I or a family member might fall ill or die.

When I was pursuing a medical education, my fear lessened and I became fascinated by obituaries, especially the second paragraph, in which the cause of death is mentioned (or speculated upon).

As I've matured, I now read them because they are a distinct form of writing—succinct, and in telling about the decedent's life, amazing true stories of our time here on earth.

Three recent New York Times obits caught my eye, because each one had an interesting connection to health care. In chronological order of when they died, here they are:

John Sarno was a physical medicine and rehab specialist at New York University for almost 50 years. He was adored by his patients, particularly those for whom he helped achieve relief from back pain. He authored several books on the topic, suggesting that most if not all of it was caused by unresolved anxiety and rage. He coined the term “tension myositis syndrome” as a catch-all for the most common form of back pain, muscular pain that in most cases is episodic or short-lived. The obituary discusses how his ideas were never accepted into the medical mainstream, despite the facts that his books sold millions of copies just by word-of-mouth, and his own skeptical physician colleagues turned to him for help.

Spencer Johnson started his career as a medical doctor, but decided against a career in clinical medicine. As the obituary states, “… while working in a hospital, he grew frustrated at seeing the same patients return with the same ailments, as if they were not trying to better their lives …” He went to work for a medical device company, becoming its director of communication. Learning how to write succinctly for lay audiences led him to his ultimate success, co-authoring the massive bestseller “Who Moved My Cheese,” a parable about pushing ourselves out of our comfort zones. It has since sold nearly 30 million copies worldwide and has been translated into 44 languages.

I love the quote he gave to a newspaper writer: “Most writers write the book they want to write. You're much wiser if you write the book people want to read.”

Keith Conners was a psychologist most known for his work in the world of defining and diagnosing Attention Deficit Hyperactivity Disorder (ADHD). In the first half of the 20th century, hyperactive children with difficulty focusing were said to suffer from “hyperkinesis,” or the lovely moniker “minimal brain disorder.” Conners brought rigor to the field, and created the Conners Rating Scale, a 39-item questionnaire that became the gold standard for diagnosing ADHD. Conners went on to become a critic of what has become a big industry, stating that ADHD is now diagnosed about three times as much as its actual prevalence. (If you are interested further in this topic, you can hear a podcast of my interview with author Alan Schwarz of “ADHD Nation” here.)

These doctor/writers all lived interesting and varied lives. I was simply struck by the proximity of their deaths and the loveliness of their obituaries.

This post by John H. Schumann, MD, FACP, originally appeared at GlassHospital. Dr. Schumann is a general internist. His blog, GlassHospital, seeks to bring transparency to medical practice and to improve the patient experience.
Thursday, September 14, 2017

The heartbreak of psoriasis and guilt by association

I was asked this week for an informal opinion by someone who was advised by his dermatologist to take a biologic medicine for psoriasis. Now, my knowledge of this disorder is barely skin deep, yet knowledge alone will not set you free in the murky world of medicine. Knowingsomething is not as significant as knowing when to do something.

Biologic medicines, which have surpassed in frequency the nearly omnipresent TV ads for erectile dysfunction, are expensive medications that have risks of serious, albeit uncommon, side effects. And, unlike chemotherapy for cancer, which has a finite course, biologic medicines are administered forever, that is, without a clear stopping point.

The individual who questioned me was not suffering from insufferable psoriasis and was satisfied with the conventional topical treatments he has been using for years. His dermatologist offered the biologic in an effort to reduce his risk of heart disease. Let me try to explain.

If you Google psoriasis and heart disease, you will find a surfeit of hits claiming some kind of connection between the two conditions. However, if you Google any two items on any subject, you are likely to hit upon some “connection”. I just randomly Googled guacamole and cancer and sure enough, there is a “connection”! Presumably, the dermatologist accepted the psoriasis-cardiac connection to be one of causality, meaning that psoriais can cause heart disease. Extrapolating beyond this FAKE NEWS, he assumed that treating the psoriasis would mitigate the risk of an adverse cardiac event. It is exactly this false reasoning that so often gets patients into trouble. The logic of the intervention seems sound, but it is entirely specious.

The facts are here that there is no proof that psoriasis causes heart disease. Clearly then, it makes no sense to treat the skin condition hoping to prevent a complication for which there is no proof that psoriasis causes. Psoriasis may be associated with or linked to heart disease, which understandably suggests to an ordinary patient that there is a strong connection where Condition A causes Condition B. I address this fallacy several times each week when I am asked if heartburn medications cause hip fractures or dementia. They are associated with these complications in a statistical sense, but have not been shown to cause the complications.

Say I publish a study showing that tall individuals are associated with high blood pressure. This does not mean that height is responsible or that we should hope that our children remain short.

Do you think that this blog is associated with astute and discerning readers? If so, can I write next week that reading the Whistleblower blog is powerful brain food?

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.

Antibiotic duration is a Goldilocks problem

Antibiotics save lives, but antibiotics can have negative effects. When patients have bacterial infections, we want to treat them to prevent complications of the bacterial infection, but not treat them for an excessive duration. So we have a Goldilocks problem; we want antibiotic duration to be just right—neither too short or too long.

Some clinical conditions have adequate research to define the Goldilocks duration. Community acquired pneumonia only requires 5 days of antibiotics, if the patient is clinically stable at 3 days. We know that 5 days is sufficient, so if we give antibiotics for 7 or 10 days, the patient gets exposed to unnecessary antibiotics.

Unfortunately this example is rather unusual. We have learned antibiotic duration without the teaching (and guidelines) having an evidence base.

So a new movement suggests that we should tell patients to stop the antibiotics when they feel better. The antibiotic course has had its day: “The concept of an antibiotic course ignores the fact that patients may respond differently to the same antibiotic, depending on diverse patient and disease factors. Currently, we largely ignore this fact and instead make indication specific recommendations for antibiotic duration that are based on poor evidence. This situation is changing in hospital practice, where biomarkers of treatment response such as procalcitonin can guide when to stop antibiotic treatment. Outside hospital, where repeated testing may not be feasible, patients might be best advised to stop treatment when they feel better, in direct contradiction of WHO advice. Of note, a recent clinical trial found that using fever resolution to guide stopping antibiotics in community acquired pneumonia halved the average duration of antibiotic treatment without affecting clinical success. Further similar studies are needed.”

So this interesting idea got published in the British Medical Journal. But does subjectivity get us to the Goldilocks duration? So this article argues against the BMJ opinion piece – Why you really should take your full course of antibiotics: “So, knowing what you now know, do you think stopping a course of antibiotics when you feel better as opposed to completing the course is a good idea? It may be the case that your infection is completely clear by day two of your five-day course, but it's equally possible that a small population remains that can grow back and reinfect you. More research and clinical trials (as also noted in the BMJ article) are required in order to fully understand and adjust the lengths of antibiotic courses, but, in my opinion as a microbiologist, the risks of taking an insufficient course significantly outweigh the benefits.”

As you might imagine, I do not think this opinion gets us to the Goldilocks duration.

In 2000, Zwart and colleagues published a study of placebo versus 3 days penicillin versus 7 days penicillin for severe adult pharyngitis (defined as a Centor score of 3 or 4). Their results are instructive: “Patients who took penicillin for seven days showed a permanent resolution of sore throat 1.9 and 1.7 days sooner than those who took penicillin for three days or placebo respectively. During the first three days of treatment, patients in the three day penicillin group showed a similar resolution of symptoms to those in the seven day penicillin group. However, 40% (77 of 194) of the three day penicillin group had a temporary resolution of symptoms, which recurred later that week, against 5% (10 of 190) of the seven day penicillin group. This finding accounts for the difference between the two penicillin groups in the Kaplan-Meier curves during the first three days. Using the definition of permanent resolution of symptoms, patients in the three day group did not recover more rapidly than those in the placebo group. Analgesic use until day 4 was similar in all three groups. From day 1 until day 7, however, the proportion of patients taking analgesics declined from 61% to 5% in the seven day penicillin group, whereas in the two other treatment groups the reduction from day 4 until day 7 was considerably smaller.”

So to reach the Goldilocks duration recommendations, we need more research. We will have more side effects if we encourage patients to take unnecessary long antibiotic courses, but we will have patients relapse if we do not give antibiotics for an adequate duration. Perhaps in the sore throat example, 5 days might be satisfactory, but we do not have the data, so it remains 7 days for now.

Both sides have salient points in this debate, but we cannot judge the debate until we get better duration studies. We must encourage the infectious disease community to expand their work on this question so that we can give antibiotics for the proper duration. Currently, we are really just guessing for most infections.

db is the nickname for Robert M. Centor, MD, FACP. db stands both for Dr. Bob and da boss. He is an academic general internist at the University of Alabama School of Medicine, and is the Regional Associate Dean for the Huntsville Regional Medical Campus of UASOM. He still makes inpatient rounds over 100 days each year. This post originally appeared at his blog, db's Medical Rants.