Rheum With a View

California Dreamin’

I just returned home from the ACR annual meeting. I was gratified to hear many kind comments about this “column.” Several colleagues asked about my aging dogs; while I appreciate the solicitous inquiries, I hope readers remember more from my contributions than that Sweedee and Speckles are approaching 100 dog-years (their health remains excellent, I’m happy to relate). Home for me has changed. As suggested in my previous byline, I have left my position as chair and program director in the Department of Medicine at Saint Barnabas Medical Center in Livingston, NJ, after 22 years, to accept a professorship in rheumatology (and medicine) at the Keck School of Medicine of the University of Southern California (USC). I enjoyed my responsibilities at Saint Barnabas but couldn’t resist the opportunity for a new challenge (the average longevities of a medicine department chair or program director are c. 6 years) in the role of a clinical scholar in a exciting fresh academic and geographic setting, with wonderful new colleagues, and the chance to live literally around the block from our only married child, Rachel (married to Will), and our only grandchildren (Lia, 8, and Etan, 5) while they are still young and while my wife, Rena, and I feel young and are reasonably healthy. Indeed, the children all walked over for dinner the other night and Etan asked “Zeide [Yiddish for grandfather; our family tradition], what are mac­rophoges?” Microphone, you mean? “No, Zeide,” he said, “cells that eat the bad B cells that cause disease.” I was stunned; that’s more immunology than I probably learned in medical school. So, my family (including dogs) and I are enjoying this new chapter in my professional and personal life.

It’s quite lovely here in southern California, and particularly appealing in the winter (especially after growing up in Detroit and living 22 years in New Jersey). I love being back at an academic health center with a beautiful campus. Walking from my office to clinic, the consultation center, the hospitals, the library, the bookstore, the nearby park, the Starbucks, or by the volleyball net, and seeing all the students, residents, faculty, and staff in the warm sun is conducive to daydreaming, not unlike the lyrics from the song by The Mamas and the Papas (1965):

All the leaves are brown and the sky is gray.
I’ve been for a walk on a winter’s day.
I’d be safe and warm if I was in LA.
California dreamin’ on such a winter’s day.

But a recent issue of Science would suggest I be careful of my reflections (this was also featured in the November 12 Science Times section of The New York Times and elsewhere in the media).¹ Harvard researchers used the iPhone to periodically interrupt the lives of 2,250 subjects. They found that people’s minds wandered 47% of the time. They reported that those whose minds wandered were less happy than those focused on the task at hand. In nearly two dozen activities reported, subjects’ minds were wandering more than 30% of the time, except for during sex, when people seemed to be focused on what they were doing (90% of the time) and reported being happy. Following sex on the list were exercise, conversation, listening to music, walking, eating, praying and meditating, cooking, shopping, caring for children, and reading; personal grooming, commuting, and working were near the bottom. Overall, people were less happy when their minds drifted than when they were focused on the activity they were doing. Analyses suggested unhappiness did not necessarily lead to daydreaming; rather the opposite. It must have been an interesting subset of subjects, willing to accept the interruptions in their lives, even during sex. I might have considered participating, if asked, but I refuse to use a cell phone, even an iPhone. I always thought reflection was healthy, and there is certainly a robust literature on this; presumably the quality and quantity of “daydreaming”, as well as the context, is relevant. I must confess to feeling quite content, indeed happy, walking and, yes, even letting my mind wander pleasantly in the California sun this winter.

Communication Challenges

“O wad some Power the giftie gie us. To see oursels as ithers see us! …”—To a Louse, Robert Burns

I bet you think, like I do, that you communicate well with your patients. I bet, too, if we collected data that we’d both be chagrined at what patients think and say. A comparison of physicians’ and patients’ perceptions about communication (at a “community teaching hospital,” presumably reflecting reasonably educated patients and physicians not unlike ourselves) was sobering.² Only 26% of patients could identify the physician in charge of their care; only 57% knew their diagnosis; 90% did not recall being told of side effects of new medications; and only 58% thought physician explanations were understandable. Many, if not most of you, have probably heard that we physicians haven’t the patience to listen to patients for more than 13–16 seconds before interrupting, and that if we but let them tell their story, it rarely exceeds a minute or so (on average). I know, from observing my former residents and faculty, how often physicians speak technically and in medical jargon, so I am not really surprised at these data. I interpret this as a reminder to set aside sufficient time at each patient encounter for adequate communication, to not be complacent about what I think my communication skills are, to write down for patients everything that is important, and to query patients and families at the end of the encounter to assure that my perception was their reality.

American Versus Foreign Made

I grew up in medicine with the nonsensical and regrettable prejudice that we were better than anyone else, that “Americans” and American-trained physicians were superior to “foreign medical graduates” (FMGs). I’m embarrassed to recall when, as division chiefs, we disparaged applications from FMGs for fellowship positions and did not even consider them. As a child of immigrants, I should have known better (my parents were surely not intellectually inferior to their American peers). And as a Jew, I surely should have recognized the awful potential implications of racial or ethnic stereotyping.

How medicine has changed! Twenty-six percent of all physicians are now FMGs, as are 58% of primary care doctors, 37% of internists, approximately 45% of medicine residents, and 45% of all physicians in New Jersey (where I was); 51% of rheumatology fellowship positions were filled by non-U.S. graduates in the 2010 match. They are still, however, subject to bias as fellowship candidates; American graduates and even Americans graduated from foreign medical schools are viewed as more desirable than FMGs.

In my previous position, I explicitly addressed this when writing letters of recommendation for my FMG residents, pointing out that, for most of these outstanding, accomplished individuals, it was only an accident of birth that kept them from Harvard, Yale, Johns Hopkins, or USC. Perhaps this helped us achieve success rates for fellowships that exceeded that of even American grads.³ For us, these were people who were selected for medical school by competitive exams from population pools larger than for American medical schools, individuals who were often already trained in medical or other specialties, physicians who successfully passed competitive exams and adapted to a new culture. Would anyone thoughtful really presume to argue that the top few graduates of the medical school in Beijing, for example, which accepts the best 30–40 students each year, by competitive exam, from the most populous countries on the planet, would be less smart or even less well prepared than our medical students?

Therefore, I am not the least bit surprised that the performance of FMGs on the certifying examination of the American Board of Internal Medicine slowly became to equal and even slightly surpass that of American graduates. And I am not the least bit surprised to read that the quality of care (mortality for patients with congestive heart failure and myocardial infarctions, and length of stay in the hospital) provided by FMGs equaled that of American graduates and exceeded that of American graduates of foreign medical schools.⁴ These results may be even more impressive given that FMGs tend to train at less “prestigious” programs than American graduates.

The lessons, I think, are obvious. We should see increasing numbers of FMGs as fellows and future colleagues (until or unless graduate medical education in this country is transformed) and we should certainly welcome them as colleagues. Deana Lazaro at SUNY Downstate, Sharon Kolasinski at the University of Pennsylvania, Rick Brasington at Washington University, Alan Baer at SUNY Buffalo, and Ellen Gravellese at the University of Massachusetts all appreciated this and matched residents from my former program in recent years. After all, we’re all just people—or, in our case, rheumatologists.

Are There Patients With Inflammatory Disease Who Do Not Respond To Prednisone?

Have you ever had a patient you expected to respond to steroids not do so? I have. I first learned this as a fellow at the old Robert Brigham Hospital, seeing a lupus nephritis patient with Peter Schur. Despite “industrial-dose” prednisone, the patient did not improve. We were taught that when such patients did not manifest the anticipated physical and metabolic changes of corticosteroid administration (Cushingoid features, increase in appetite, weight gain, insomnia, leukocytosis, eosinopenia, and lymphopenia) to suspect unusual inability to convert prednisone to prednisolone, its active metabolite (the keto group at position 11 must be converted to a hydroxyl group before any glucocorticoid activity is exhibited). We offer such patients a trial of methylprednisolone therapy when we consider steroid therapy most appropriate for their condition before utilizing other antirheumatic, antiinflammatory, or so-called immunomodulatory/immunosuppressive (“second line”) agents.⁵

This, we think, was first articulated by John Decker, MD, a distinguished and authoritative rheumatologist who was the director of the National Institute of Arthritis and Metabolic Diseases, National Institutes of Health, and president of the American Rheumatology Association (now the ACR). Lack of 11 beta-hydroxysteroid dehydrogenase 1 (11β-HSD1) enzyme activity leads to impaired conversion and poor availability of the active steroid molecule. In such instances, treatment with prednisolone or methylprednisolone, already in an active form, may be effective. Several studies have documented impaired conversion of prednisone to prednisolone in patients with liver disease and suggested that prednisolone be used preferentially in these conditions. Also, there are patients who have deficiency of the 11β-HSD1 enzyme, needed to convert prednisone to prednisolone. This condition, termed acquired cortisone reductase deficiency (ACRD), was recognized as a partial deficiency of 11β-HSD1, which may modulate the levels of both endogenous and exogenous steroids at the tissue level, and it is ubiquitously present in the skin, central nervous system, adipose tissues, and other organs, including synovium, synovial fluid, and bone, that are responsive to endogenous cortisol.⁶

Recently, polymorphisms within the 11β-HSD1 gene and the gene coding for hexose 6 phosphate dehydrogenase (a coenzyme which supplies reducing equivalents to 11β-HSD1) have been identified with a population prevalence of 3% and 4% respectively.⁷ This may have implications both for disease susceptibility and therapy.

Physicians, perhaps especially of the younger generation(s), should be aware of this possible explanation for unexpected prednisone unresponsiveness. I think it is real, has a scientific basis, is not widely appreciated, and is important in optimally caring for our patients with chronic inflammatory diseases.

Dr. Panush is professor of medicine, division of rheumatology, department of medicine, Keck School of Medicine, University of Southern California in Los Angeles.

References

1. Killingsworth MA, Gilbert DT. A wandering mind is an unhappy mind. Science. 2010;330:932.
2. Olson DP, Windish DM. Communication discrepancies between physicians and hospitalized patients. Arch Intern Med. 2010;170:1302-1307.
3. Thirumalaiselvan G, Sapru S, Panush RS. An analysis of resident applications for fellowships from a community hospital, 2001–2006: What predicts success? New Jersey Chapter Scientific Meeting, American College of Physicians, Woodbridge, New Jersey, Feb. 2008.
4. Norcini JJ, Boulet JR, Dauphinee WD, Drantz ID, Anderson ST. Evaluating the quality of care provided by graduates of international medical schools. Health Affairs. 2010;29:1461-1468.
5. Sen D, Rajbhandary R, Carlino A, Anderson R, Schur PH, Panush RS. Are there patients with inflammatory disease who do not respond to prednisone? J Rheumatol. 2010;37:1559-1561.
6. Raza K, Hardy R, Cooper MS. The 11β-hydroxysteroid dehydrogenase enzymes—arbiters of the effects of glucocorticoids in synovium and bone. Rheumatology. 2010;49:2016-2023.
7. Van Oosten M, Dolhain RJEM, Koper JW, et al. Polymorphisms in the glucocorticoid receptor gene that modulate glucocorticoid sensitivity are associated with rheumatoid arthritis. Arthritis Res Ther. 2010;12:R159