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Podcast Transcript - September 4, 2007

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Hello, and welcome to this week’s Annals of Internal Medicine audio summary for our September 4, 2007 issue. I’m Michael Berkwits, Deputy Editor at Annals.

We have a fabulous issue for you this week, with articles on the effects of antibiotic-impregnated urinary catheters on reducing antibiotic prescriptions; the diagnostic performance of serologic tests and HLA-DQ typing in patients with celiac disease; electrocardiographic left ventricular hypertrophy and patients’ risk for heart failure; and hyperkyphosis in the elderly.

And, for listeners who were English majors or who love drama and literature, I’ll be talking to the author of our Medical Writings essay this week about her new perspectives on what the play Wit and what the 16th century poet John Donne can tell us about caring for patients in the modern world.

But first an in-depth summary of some of this week’s articles.

Our lead article this week is a randomized trial of nitrofurazone-impregnated urinary catheters in trauma patients. Urinary catheters increase patients’ risk for urinary tract infection. Silver-coated catheters have been shown to reduce the incidence of UTI, but manufacturers also produce antibiotic impregnated catheters, and few if any of these have been evaluated in randomized trials. The authors of this study randomized trauma patients seen in their ED to nitrofurazone-impregnated or standard silicone catheters; nitrofurazone is an antibiotic like nitrofurantoin, a drug commonly used to treat UTI.

The trial has 3 main findings.

First, there were significantly fewer instances of bacteriuria and funguria in patients who received the nitrofurazone-impregnated catheter than in patients who were given the standard silicone catheter, and bacteriuria and funguria took longer to develop in patients with the nitrofurazone catheter.

Second, and perhaps more importantly, the reduction in CABF in patients with the nitrofurazone catheter appeared to lead to a reduction in the need for new antibiotics or for a change in antibiotics

Third, there was no evidence of an increase in resistance to nitrofurantoin among the mostly gram-negative organisms isolated from patients with the impregnated catheters.

So this trial appears to demonstrate that a nitrofurazone-impregnated catheter really works. One of the strengths of this study is that it was able to link the reduction in incidence of bacteriuria in patients with a reduction in antibiotic use; bacteriuria and funguria are standard outcomes in studies like this one but they may represent urinary colonization rather than infection, and not all patients with colonization develop infection. So the data suggest that the effects of antibiotic-impregnated catheters may lie at least as much in health care processes – that is, a reduction of antibiotic overuse for bacteriuria of questionable significance – as in biological processes, such as development of infection. However, the authors acknowledge that more studies of these catheters in other patient populations will need to be conducted, as will cost-effectiveness analyses, before antibiotic-impregnated urinary catheters such as the one in this study can be recommended for routine use.

Our second article this week is a secondary analysis of the Losartan Intervention For Endpoint reduction in hypertension or LIFE trial. The trial was a large industry-funded clinical trial originally published in 2002, that found that 50 mg of losartan significantly reduced the relative risk of major cardiovascular events compared to a 50 mg dose of atenolol in people 55–80 years old with hypertension and ECG signs of left ventricular hypertrophy, or LVH.

In this week’s article, lead author Peter Okin of Cornell University uses data from the trial to see if regression of LVH during treatment was associated with a reduction in hospitalization for new-onset heart failure. Heart failure hospitalization was a secondary endpoint of the trial that was measured but not reported in the original publication.

Their analysis has two main findings

First, 214 patients or 2.5% of the original trial cohort had a first hospitalization for heart failure. Patients who developed heart failure had a statistically significantly higher prevalence of ECG-defined LVH, and mean measures of LVH progressed, or they regressed more slowly, in patients with heart failure compared to those without.

Second, regression in LVH was associated with reductions in the hazard of hospitalization for heart failure independent of blood pressure, medication, and other heart failure risk factors, such as diabetes and history of atrial fibrillation and ischemic heart disease.

The authors note that these findings are significant because, while the association between ECG-defined LVH and new onset heart failure is well-documented, this is the first analysis to demonstrate an association between regression of LVH on antihypertensive treatment and a reduction in incident heart failure hospitalization. They acknowledge that the findings may not be generalizable because the parent trial enrolled patients with LVH at baseline, so the population may be at higher heart failure risk than the general population. They also acknowledge that using heart failure hospitalization rather than the diagnosis of heart failure itself underestimates the true incidence of the disease, AND that the phenomenon of regression to the mean could explain some of their findings.

But the authors conclude that reduction in electrocardiographic signs of LVH with antihypertensive treatment is associated with a decreased in risk for heart failure independent of blood pressure lowering and of other heart failure risk factors, and they make the claim that the data support serial monitoring of ECG for LVH during antihypertensive treatment to monitor the risk for developing heart failure. However, studies of such a strategy, and studies to determine if treatment titrated to reduce LVH beyond attainment of target blood pressure can reduce the incidence of new heart failure in hypertensive patients with LVH, are needed before monitoring for LVH can be recommended, and before clinicians can be advised to routinely pick drugs shown to reduce LVH, such as ACE inhibitors, over those that do not.

Our CME article this week is a narrative review of hyperkyphosis in the elderly. The premise of the review, by lead author Deborah Kado and two colleagues from the David Geffen School of Medicine at the University of California in Los Angeles, is that hyperkyphosis is more than just loss of height and posture from osteoporosis and osteoporotic fractures; those are present in only about a 1/3 of those with the condition. Rather, the authors claim, hyperkyphosis is a distinct geriatric condition with adverse outcomes, and it warrants more serious attention.

Hyperkyphosis is present in an estimated 20 to 40% of elderly people. It has no discrete causes, but is associated with other postural changes, such as cervical and lumbar lordosis; and with degenerative disk disease; and diminished muscle strength. There is a probably a genetic component.

Spinal curves are measured clinically using a goniometer or flexible ruler, or radiologically using spinal radiographs. Kyphosis is defined by the Cobb angle, which is the angle of intersection of lines perpendicular to those drawn from the beginning of the thoracic curve and from the interface of the thoracic and lumbar curves; the article’s Figure 2 provides an illustration much more clear than my description. Normal kyphosis is about 48 to 50 degrees in older women and about 44 degrees in older men. The angle increases with age, but there is no clear threshold that defines hyperkyphosis.

The quality of evidence linking hyperkyphosis to adverse health consequences is low, but there is some evidence that hyperkyphosis may be associated with thoracic fractures due to changes in gravitational load; impaired pulmonary function, specifically reductions in FEV1 and FVC; and diminished physical function, including reduced upper extremity strength and gait speed and more trouble rising from a chair and with movement.

There is no standard treatment, but measures shown to be useful in small studies include back-strengthening and spinal flexibility exercises; spinal orthotics; and vertebroplasty and kyphoplasty for patients with painful vertebral fractures.

The authors acknowledge that the evidence in their review is weak, but they make the case that hyperkyphosis is likely to become more common with aging of the population, and is a sign or cause of adverse health consequence shown to reduce the quality of lives of the elderly. So they end their review with a call for multidisciplinary research into the causes, prognosis, and treatment of the condition.

Subscribers to Annals can receive CME credits by answering 2 quiz questions about this article at cme.annals.org. Just click the “My CME” link, to register or sign in.

We have several other articles in this week’s issue.

We have a prospective cohort study detailing the diagnostic accuracy of serologic testing and HLA typing for diagnosing celiac disease, suggesting that anti-transglutaminase and anti-endomysial antibody testing are highly specific and HLA-DQ typing is highly sensitive for detecting the disease, but that the combination of testing strategies provides the same measures of test performance as either one alone. There’s also a must-read editorial accompanying the article giving clinicians reasoned guidance about when to use which combinations of tests.

We have a subgroup analysis of data from the OASIS trial, originally published in 2006, which found that fondaparinux was noninferior to enoxaparin in the treatment of non-ST segment elevation acute coronary syndrome. This week’s analysis suggests that fondaparinux may lead to less major bleeding than enoxaparin in patients with renal dysfunction, possibly because of differences in renal metabolism of the two drugs.

We have a secondary analysis of data from 3 trials of strategies for implementing depression practice guidelines in primary care settings, suggesting that providers do well at recognizing and monitoring depression, but that they did less well at a number of indicators of depression care quality, such as adjusting treatment in non-responsive patients and assessing suicidual ideation and alcohol use. More importantly, the study suggests that greater adherence to practice guidelines is associated with fewer depressive symptoms.

And we have a Trials That Matter editorial, one of an occasional Annals series that attempts to give readers commentary on important trials they might have overlooked in other journals. This week’s editorial reviews the LOCSS trial, published in May of 2007, which compared twice-daily fluticasone, nighttime fluticasone and salmeterol, and nighttime oral montelukast in the treatment of mild persistent asthma.

And finally, for listeners who were English majors and who love fiction and literature, we have a Medical Writings piece entitled “A Rigorous Mind Meets Her Yielding Body: Intellectual Life and Meaning-Making in Wit,” by Ellen Foster.

Wit is a play originally brought to the stage in 1995 and made into an HBO movie in 2001. It was written by Margaret Edson, who at the age of 30 distilled what she saw and felt as a ward clerk on the oncology/AIDS unit in a Washington D.C. area hospital into the character of Vivian Bearing, a professor of English literature and scholar of the poetry of 16th century poet John Donne. The play portrays the physical and psychological challenges faced by Dr. Bearing as she undergoes treatment for advanced stage ovarian cancer. A standard interpretation of the play sees Dr. Bearing and her physicians as alike in some ways but ultimately very detached from each other, and sees the health care system as overbearing, overwhelming, and perhaps even exploitive of the vulnerable, dying patient. The play has had a long and active life as part of The Wit theatre and film project, a collaborative effort to bring the film to medical students and residents to educate them about the humanistic aspects of caring for dying patients.

This week’s article explores the play from a different perspective. It uses the character Dr. Bearing to examine how a patient who is a scholar and intellectual comes to understand illness and mortality, and how the character comes to accept and illustrate for us the limits of the intellect for finding comfort in that understanding.

In a phone conversation, the author of this week’s piece, Dr. Ellen Foster, an Assistant Professor of English at Clarion University on the Venango campus in Oil City, PA, explained to me the significance of her essay for busy clinicians, and of broader lessons physicians might take from the play.

Q: Dr. Foster, thank you for joining me.

A: Thank you for inviting me.

Q: For listeners unfamiliar with Wit, what story does the play tell?

A: Well, essentially it’s the story of Vivian Bearing, a professor of English, and it focuses on her journey through the diagnosis and then aggressive experimental treatment of a late stage ovarian cancer. She does not survive this cancer. The movie then focuses on her perspective on the process of both living and dying through this treatment, and then trying to come to terms with her approaching death, trying to understand the potential for human redemption or salvation, and most importantly probably realizing her need for human love and kindness.

Q: And what’s different about your perspective. What do you write about in this week’s essay?

A: My interest is on how the professor thinks her way through being ill. Early in the movie she tells us that she knows all about life and death because she is a scholar of John Donne’s poetry. But then she finds out that she is faced with her imminent mortality and she really does have to learn something more. She is trying to find a way to integrate who she is as a thinker, as someone who’s interested in language, in trying to understand the human experience through literature, with her experience of confronting her own mortality.

Q: And is she ultimately successful in the play, in your reading?

A: Ultimately, yes, I do think she is successful, mostly because she learns the limitations of the intellectual. Her abilities as a scholar to tackle very complex questions, and to try to find answers to them or to make assertions about them has worked very well for her up to that point and so when she comes to the point where she realizes that the intellectual is not enough, that’s when she finally learns the lesson that she has been trying to learn unsuccessfully even since the time when she was student and her mentor tells her that rigorous scholarly work and simple human kindness are connected. She’s never really been able to tackle the human element very well, so she avoids it. Ultimately though when she does find that she needs both, then she has essentially found the knowledge that she has been seeking. The very end of the film is a kind of a benediction that she has successfully learned the lessons of life and death, that she has come to learn this totality of human potential.

Q: Do you think the play has lessons for physicians as they become patients?

A: I think that physicians who would take on the patient’s perspective in viewing the film might see how Professor Bearing, like the physician, has a position of authority where she has a great deal of control over the work that she does and the people that she works with or that she teaches, and she is not used to being in a position where she has to submit, and learning that process of submitting to what must be done I think is extraordinarily difficult for anyone who is used to being in control or to being the one to make the decisions. The physician would have to learn, as the Professor does, that she needs to step out of her professional role, to let herself be human and to feel the pain, feel the suffering, to allow herself to be taken care of, which I think probably for a physician would be very difficult.

Q: Does Vivian Bearing have any counterparts in English literature? Are there other literary characterizations of illness and dying that you think might be important for physicians to have as a reference as they care for patients?

A: Well I’m not aware of any exact counterpart, but I would recommend the short story by Alice Munro called Floating Bridge. It details a woman’s reaction to the news that possibly her course of chemotherapy is working, and that therefore her chances of survival have just increased. One would think that a patients’ response to the news that the chemotherapy is working would be nearly exclusively positive, but the character in the story is essentially alarmed by the fact that she might live, because she has been working through a process of accepting that she is going to die. And so when she is delivered what appears to be good news it requires her to essentially rethink her entire perspective. And I think that, because it comes at that experience from a different angle, might be interesting for physicians who might think that they’re delivering excellent news, and how could it not be good.

Q: Can you tell us anything about John Donne? Does he have anything to say to the modern world of medicine and illness?

A: I am not a Donne scholar but I think that John Donne would offer an awful lot to an audience of physicians, or any reader really, in simply the focus that he has on reflecting upon the spiritual or emotional nature of being ill and the contemplation of one’s own mortality, and whether there’s going to be life after death, in very much from a Christian perspective of human salvation. In poetry and in a series that is actually called Meditations he talks about his own physical suffering and the illnesses that he has encountered and his own anxiety and concern about whether or not there is going to be a promise of eternal life. One of the Meditations that I think that people who are encountering a terminal illness, or physicians who are dealing with patients with a terminal illness can think about, is the theme that he often returns to which is the connection among humans. And so the famous line “Ask Not For Whom the Bell Tolls, It Tolls For Thee,” or that “No man is an island;” those kinds of ideas can offer some interesting perspective and insights.

Q: When the play was first published its title was formally spelled W;t rather than Wit. What do you think the playwright was getting at by doing that?

A: I think that she was trying to draw our attention to the conversation between Professor Bearing and her mentor, when Professor Bearing was a student, and the conversation is about a piece of punctuation in one of Donne’s poems, and whether the punctuation was a comma or whether it was a semicolon. And the discussion among literary scholars about a piece of punctuation can literally go on for centuries. And so if it is a comma, which is the argument that her mentor makes, the comma is indicating that there is just a pause between the two ideas, between life and death, whereas the semicolon would almost bring it to a full stop. So I think that she was trying to draw attention to that discussion, and the idea of whether there is a comma between life and death, or whether there is a semicolon.

Q: Any final thoughts about the play, and what physicians might take from it?

A: One perspective that I would like people to think about would be to think of the consequences of a diagnosis for the patient, and to think about illness and particularly terminal illness as a life-altering event but not necessarily a life-defining event. Vivian Bearing’s life is not really defined by her death, but she takes her illness and absorbs it into the totality of her experience. And so her life is altered by it, and she does die from the illness, but it doesn’t define who she is. She tries very hard to remain true to herself.

Q: Dr. Foster, thank you so much for talking to me.

A: It’s been a pleasure.

That was Dr. Ellen Foster from the Venango campus of Clarion University in Oil City, Pennsylvania, talking about the play Wit, and her perspectives on its lessons about medicine, illness, and dying. Listeners interested in the Wit Film project can go to www.growthhouse.org/witfilmproject for more information.

Well that’s it for today. If you liked what you heard, of if you didn’t, tell us about it, at podcast@annals.org.

For full details of all of this week’s articles, please consult your print journal, or go to www.annals.org.

Technical support for this summary was provided by Andrew Langman, Neil Kohl, and Beth Jenkinson.

Special thanks to Kevin Stahl and all our friends at WHYY, public radio and television of Philadelphia, who helped produce this podcast.

Check back in 2 weeks for a complete summary of our regularly scheduled September 18, 2007 issue.

I’m Michael Berkwits, and thanks for listening.

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