Category Archives: Research

Improving the Evidence

All good physicians want to do the right thing. They want to recommend effective therapies to their patients that will improve outcomes or alleviate symptoms. It is widely accepted that the best way to discover new effective therapies is through the use of clinical trials. Among clinical trials, the reference standard is the randomized, double-blinded, placebo-controlled trial, which is designed to minimize bias in the selection of therapies or the interpretation of results.

I have written before about the limitations of clinical research in advancing medical practice. As I have said, it is literally impossible to study every clinically relevant question, and it is also impossible even in theory to use randomized controlled trials as the methodology for many of the questions that can be studied.

A recent article in the New York Times highlighted another challenge to the paradigm of clinical trials as the engine for improving medical practice. The piece was about a change in policy at the National Institutes of Health, being implemented by Michael Lauer, the “newly appointed deputy director for extramural research.” In the interest of full disclosure, I have known Mike for many years (we were cardiology fellows in the same program at Boston’s Beth Israel Hospital in the late 1980’s) and you would be hard-pressed to find a nicer, smarter or more upstanding guy.
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The New Paradigm

A recent FDA advisory panel recommended the approval of 2 new agents in a novel class of cholesterol lowering drugs known as PCSK-9 inhibitors. What makes this remarkable is that these drugs illustrate all the promise and pitfalls of modern pharmaceutical development.

First, a little science. The target of the new drugs – a protein named proprotein convertase subtilisin/kexin type 9 (PCSK-9) – was discovered in 2001. Two years later, investigators reported that “gain-of-function” mutations in the gene that codes for PCSK-9 were associated with familial hypercholesterolemia and high rates of atherosclerotic vascular disease. Mutations of the gene that led to reductions in the function of PCSK-9 were associated with low LDL-cholesterol levels, and a lower incidence of vascular disease. That made the compelling case that PCSK-9 had a counter-regulatory function in LDL-cholesterol metabolism, so that interfering with its function would lead to lower cholesterol levels.

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Department of Really Cool Ideas

Every so often I come across a research paper that leaves me feeling as if I am glimpsing the future. I had that experience when I came across the work of Cingolani and colleagues in the December 23 issue of the Journal of the American College of Cardiology (volume 64, no. 24). The paper, entitled “Engineered electrical conduction tract restores conduction in complete heart block: from in vitro to in vivo proof of concept” details a new approach to an old problem.

Here’s the problem. Many people develop serious disturbances of the heart rhythm based on deterioration or destruction of specialized “conduction tissue” within the heart. This tissue is responsible for transmitting the electrical impulses that govern the beating of the heart. In the case of the dysfunction of conduction tissue between the atria and ventricles, the chambers become electrically and mechanically dissociated – a condition termed complete heart block, and generally treated with an implanted pacemaker.

Continue reading Department of Really Cool Ideas

Looking for the Pony

There is an old gag about an intensely optimistic child whose bright outlook on life is so irrepressible that when he is presented with a room full of manure for Christmas, he screams with delight, convinced that there “must be pony in there someplace.” Continue reading Looking for the Pony

Images in Medicine

Several medical journals that I receive (if not read) regularly have a section devoted to interesting images. The New England Journal has “Images in clinical medicine,” Circulation has “Images in cardiovascular medicine,” and the Journal of the American College of Cardiology has “Images in cardiology.” Each generally contains a short case description, along with one or more images – photographs of patients, histologic sections, radiographs, MRI images, and the like. Continue reading Images in Medicine

Stress and Health

There was a really interesting article in the business section of the New York Times recently entitled “The mental strain of making do with less.” In it, Sundhil Mullainathan shares some insights from his new book, “Scarcity: why having too little means so much.”

The basic premise is that each of us has only so much “mental bandwidth,” and that coping with psychological stress – in particular the stress associated with poverty – leaves the poor with less mental energy or capacity to deal with everyday life. It is a fascinating and profound proposition. As Mullainathan points out, looking at the world this way could turn a lot of stereotypes on their heads: what if “poor people make bad choices in life” is really a reflection of “being poor makes you less able to make good choices”?
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Practice Guideline Overload

I think I am like many practicing physicians in my “love-hate” relationship with clinical practice guidelines. On the one hand, it is often helpful to look up a set of evidence-based recommendations on a particular clinical issue, and I feel particularly fortunate that the American College of Cardiology and the American Heart Association have collaborated to produce high quality guidelines on a wide-range of subjects relevant to my practice. On the other hand, I am well aware of the shortcomings of practice guidelines, including the limitations of the underlying evidence base, the challenge of synthesizing the available evidence into guidelines, and the often limited applicability of recommendations to clinical practice. Continue reading Practice Guideline Overload

How Reliable is the “Evidence Base”?

Physicians are encouraged, in ways large and small, to practice “evidence-based” medicine, or EBM. The Centre for Evidence Based Medicine at the University of Oxford defines EBM as “the conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients.”

EBM is the basis for developing practice guidelines, and efforts to assess and improve the quality of care are now framed almost exclusively in terms of adherence to evidence-based practice. Continue reading How Reliable is the “Evidence Base”?