Volume 7, Number 3, Spring 2001

In This Issue:

Finding Evidence-Based Medicine on the Internet

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For the last decade, the term evidence-based medicine (EBM) has been buzzing around academic centers and community practices, especially in the field of internal medicine. One reason for its popularity is that EBM utilizes resources found on the Internet. More importantly, according to EBM proponents, EBM represents a shift in medical decision-making that may dramatically improve the quality and reproducibility of patient care. If EBM really does offer a unique and beneficial approach in patient care, it also represents a challenge for our generation of medical students to learn. The purpose of this article is to help students see the value of EBM in their education and make some suggestions on how to begin to learn and use the process.

Defining EBM for Medical Students

EBM describes the process of researching and applying information presented in the medical literature to improve patient care. The process involves trained clinicians who transform knowledge deficits into specific clinical questions, research and evaluate the medical literature related to the clinical question, apply the literature to improve patient care, and share new information with their colleagues.

The most important aspects of EBM for medical students to learn are to identify knowledge deficits, determine specific clinical questions, and find relevant articles in the medical literature. One way students can find their hidden knowledge deficits is to keep a notebook in their white coat pockets on the wards. The purpose of the notebook is to record scientific, technical, or ethical topics that come up while discussing a patient. Keeping the notebook on hand reminds the student to record clinical questions as they emerge, rather than letting them slip away.

Devising a Clinical Question

In his book, Evidence-based Medicine: How to Practice and Teach EBM, David Sackett stresses the importance of devising specific, relevant, clinical questions. He says, "To benefit patients and clinicians, such [clinical] questions need to be well built, by which we mean both directly relevant to patients' problems and phrased in ways that direct your search to relevant and precise answers." He goes on to describe how specific, relevant, clinical questions are built from four elements: "1) the patient or problem being addressed; 2) the intervention, whether by nature or by clinical design (a cause, a prognostic factor, a treatment, etc.), being considered; 3) a comparison intervention, when relevant; and 4) the clinical outcome or outcomes of interest" (Ref. 2, p. 26). These four elements form a mnemonic, PICO, that may be helpful to remember: patient, intervention, comparison, and outcome.

The following clinical example will help demonstrate how Sackett et al would transform a knowledge deficit into a clinical question. Mrs. Naggan, a 46-year-old woman, has had ulcerative colitis for 17 years, with extensive involvement of her colon and, at times, severe symptoms. Her colitis is in remission at present. She is loath to have surgery but is concerned about the mounting risk for cancer that she has heard of through the newsletter of your national patient support charity. Her spouse convinced her to find out what the risk might be. (Ref. 2, pp. 43-44).

Using the mnemonic PICO, the key elements of this case are as follows:

P: 46-year-old woman
I: Long-standing ulcerative colitis, now in remission
C: Patients without ulcerative colitis
O: Prevention/control of colon cancer

One possible specific clinical question is, "For a 46-year-old woman with a 17-year history of extensive ulcerative colitis, what is the risk for developing colon cancer?" (Ref. 2, p. 64).

For an alternative example, consider that you have been reading about ulcerative colitis and you wonder if an additional drug, mesalamine, for example, would be helpful in preventing further relapses of Mrs. Naggan's colitis. In that case, the key elements would be:

P: 46-year-old woman with long-standing ulcerative colitis, now in remission
I: Mesalamine
C: Standard therapy
O: Prevention of relapses

Search Strategies

For the purposes of this article, the medical literature search strategies presented here have been limited to MEDLINE. MEDLINE is available at www.nlm.nih.gov/databases/freemedl.html. There are other databases that you may wish to use, such as Best Evidence 5 , the Cochrane Library (www. updateusa.com/clibhome/clib.htm), and Ovid's Evidence-Based Medicine Reviews (www.ovid.com/ products/databases/). Search strategies are similar for the various medical literature databases, but vary slightly. The important concepts for medical students to realize about MEDLINE searches are:

1. Make several broad searches with each of the PICO terms.
2. Experiment with MeSH (Medical Subject Headings) terms and textwords or keywords.
3. When in MEDLINE, use the explode feature to obtain all relevant articles.
4. Include general terms like "risk," "diagnosis," "clinical trial," and "cohort study."
5. Combine the broad searches with the Boolean "AND."
6. When in doubt, reconsider the time span of the database in which the search was performed.

One of the trickiest parts of creating searches to answer clinical questions is to find the appropriate terms to search. Two common ways to search for a topic within the medical literature are to use either textwords or MeSH terms. Textwords represent actual words within the title or abstract of the article; MeSH terms are the topics that form the index in MEDLINE. Searches with MeSH terms in MEDLINE can be limiting because the articles in the literature may be misclassified and fail to fall into appropriate MeSH topics. Supplementing a MeSH search with a textword search can help you avoid overlooking important articles. For example, a search for "asthma" in MEDLINE retrieves 9,208 articles, whereas a search for asthma as a textword ("asthma.tw.") retrieves 10,046 articles. Combining the two searches gives a total of 11,767 different articles.

In addition, because of the way that MeSH terms are mapped in MEDLINE, searching a broad MeSH term with several subheadings fails to retrieve articles classified under the subheadings. For example, searching for "asthma" in MEDLINE retrieves 9,208 articles but excludes 157 articles about "asthma, exercise induced" and 139 articles on "status asthmaticus." The way to avoid missing related articles with different subheadings is to use the MEDLINE feature "explode". For example, using a shortcut by typing "exp asthma" retrieves all 9,422 articles related to asthma, although still fewer articles than retrieved by the textword search.

Next, the search should include some terms that define the type of clinical question being asked. Specifically, the literature and research related to EBM most often falls into four categories: patient prognosis, the value of diagnostic tests, studies of etiology, and the efficacy of treatment. Each of these categories carries with it certain canned terms that filter out articles with poor study design. Thus, the articles you find will be more likely to represent well-designed, valid studies applicable to patient care. In the previous examples, the questions about risk of colon cancer and use of mesalamine are questions of prognosis and therapy, respectively. Please see Table 1 for a list of useful search terms.

Table 1

Type of
Question		 Best Single
Search Term		 Additional
Search Terms
Diagnosis Diagnosis Sensitivity, specificity, diagnostic use
Etiology Risk Cohort studies, odds and ratio, relative and risk, case and control
Prognosis Cohort studies Mortality, survival, follow-up series, prognosis, predict, course
Therapy Clinical trial Randomized, random, drug therapy, therapeutic use

 

Table 2

Mesalamine Therapy

Search Terms Results
Colitis, ulcerative 10,534
Recurrence 82,040
Mesalamine 1,175
1 and 2 and 3 43
and Randomized controlled trial 19

 

Table 3

Risk of Colon Cancer

Search Terms Results
Colitis, ulcerative 10,534
Colonic neoplasms, prevention and control 1,901
Cohort studies 383,766
1 and 2 and 3 8

 

The final step in creating the search strategy is to combine all the broad searches on each of the key elements of the clinical question with the Boolean "AND". Hence, each of the broad searches has retrieved the greatest number of articles on the topic, and ideally the combination of all broad searches should specify the articles most likely to answer the clinical questions. To demonstrate how the searches work, Tables 2 and 3 record two possible MEDLINE searches using the clinical questions we asked about Mrs. Naggan.

The search on mesalamine revealed nineteen viable references. I took the time in the library to skim the articles, copy the ones that seemed most relevant, and then read the articles so that I could discuss them with my attending. The search on the risk of colon cancer retrieved eight articles that were applicable to Mrs. Naggan's condition.

Conclusion

Learning EBM and how to use medical literature databases on the Internet are both complex processes. Nevertheless, learning the concepts behind EBM and how to use it are crucial skills for medical students. To discover the value of EBM, I encourage you to get to know your patients personally, ask yourself how you could better understand their management, find relevant articles to improve your knowledge, and discuss how to interpret and apply the information with your physician mentors.

Christina Charis-Donelson
Council of Student Members Representative, Central Region
University of Iowa College of Medicine, 2001

Life as a Rural General Internist: An Interview with Dr. Michael LaCombe

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Dr. LaCombe was born and raised in upstate New York and received his AB from the University of Rochester. He received his MD from Harvard Medical School, then trained in internal medicine at Strong Memorial Hospital in Rochester, where he also served as chief resident. Dr. LaCombe began his practice as a rural general internist in 1975 at Oxford Hills Internal Medicine (OHIM), a private group practice located in Norway, Maine. While in Norway, he became well known for his pieces of fiction, which were published regularly in the Journal of the American Medical Association (JAMA), the American Journal of Medicine, and the Annals of Internal Medicine. He has done numerous visiting professorships at universities around the nation, and is well known not only for his writing, but also for his work in the fields of medical ethics and physical diagnosis. He has served on the Board of Directors of the American Board of Internal Medicine (ABIM) and on the Board of Regents of the American College of Physicians-American Society of Internal Medicine (ACP-ASIM). He is currently an Associate Editor of the Annals of Internal Medicine, and was recently appointed as a Fellow of the American College of Cardiology. Dr. LaCombe currently works in Augusta, Maine, where he divides his time between serving as the Medical Director of the Division of Cardiology at Maine General Medical Center and continuing to write and publish. I spoke with him at his home in Harrison, Maine.

RS: Just to get us into the atmosphere of rural general internal medicine (GIM), could you describe the layout of an average day at OHIM, the practice in Norway, Maine, in which you worked?

MAL: Sure. You signed in with your partners from 8:00 to 8:30, where you heard about admissions from the night before, talked briefly about the patients in the hospital and any particular problems, any particular puzzling, nettlesome problems that were going on. Then, rounded on the inpatient services, and that might have consisted of anywhere from three to six patients, and if you were up that day for call, you might have done consults. Also, you performed scheduled procedures: one or two treadmills, an endoscopy, if you were so inclined, a permanent pacemaker, a liver biopsy, a bronchoscopy. Then you were at the office by 10:00, saw patients from 10:00 until noon. Noontime was always taken up with some sort of meeting, either a hospital committee meeting or a hospital-driven continuing medical education (CME) course. And then you saw patients from 1:00 until 4:00; walk-ins, that is, unannounced patients from 4:00-5:00; and then went back to the hospital for evening rounds and signed out.

RS: And how, in a very broad sense, do you feel that rural GIM differs from urban GIM?

MAL: Being in a rural area like this affords you the opportunity of practicing the whole gamut of internal medicine, and doing things that you just are not permitted to do in an urban setting, because of the surfeit of subspecialists. General internists even in Portland, Maine, are not permitted to do critical care in intensive care unit (ICU) settings, and in tertiary centers are not permitted to put in pacemakers, either temporary or permanent ones. In many areas they are not permitted to do even standard treadmill testing. At the community hospitals, it's very different. Internists who are trained in these procedures can get credentialed to provide these services, keeping their patients in the community rather than shipping them out. One of the great successes of OHIM has been their ability to do procedures, be it fiberoptics or permanent pacemakers. This not only keeps them abreast of new technology, but also financially helps them a great deal.

RS: If an internist in training wanted to do, for instance, some of procedures you referred to, would that mandate doing an entire cardiology fellowship? How much time beyond residency does one need to invest?

MAL: That's a good question, and one that has actually been answered in a few places already. The UCLA Department of Medicine and the University of Pennsylvania, to my knowledge, are two programs that have instituted fellowships in GIM where, after the usual three years, someone can elect to stay for a year or more and design a program based on what they're interested in. So theoretically, if you had your eye toward rural practice in Maine, and you were a cardiology type, you might spend a year focused on cardiology and specifically on temporary pacemakers. If you were interested in implanting permanent pacemakers, I think these days that would be problematic, but certainly critical care work, or alternatively, learning endoscopy and spending a year doing gastroenterology, could comprise a one-year GIM fellowship.

RS: What other specialties or skills are particularly important in rural GIM?

MAL: Office gynecology is extremely important in rural GIM. Your patients expect you to be able to perform that service and not refer them on to someone else. Interestingly, a lot of rheumatology is seen in rural GIM. But by far the specialties mostly seen have to do with cardiology and pulmonary medicine, and oftentimes, in an elderly group of patients as well.

RS: In terms of the patients that you see in a rural GIM practice, do you feel that you see one demographic group much more than others, in terms of age, socioeconomic status, race, or gender?

MAL: Not really, because when I was with OHIM in Norway, the three of us initially, and then the four and then five of us were really the only medical specialists in town, as opposed to the family practice physicians. So we would often get referrals and self-referrals from all age groups. And it really became a matter of say, drawing the line. For example, at what age were we not going to see kids? Was a 12-year-old asthmatic okay? Was a 16-year-old sport physical or undiagnosed heart murmur okay? In Maine there is a large Medicare population but we really saw all age groups. Because we were identified as the specialists, we saw a lot of business people and a lot of schoolteachers.

RS: Sounds like an incredibly diverse day. I guess it goes without saying that you would never get bored.

MAL: No, it did get boring. Things can get routine. I think the bureaucracy that weighs so heavily on private practitioners can be very frustrating: the endless forms, the endless documentation, now the over-documentation on the inpatient record, all of that is incredibly boring. But the patients were never boring. One particular thing about rural GIM is the thrill of the unknown. When, for instance, a 60-year-old man walks into your office and says, "I'm short of breath," he could have anything from congestive heart failure to a hematocrit of eight. Those are the times when you can't wait for the lab slips to come back, for the x-ray to come out of the dryer. Those are the times it gets really fun. What happens to the rural physician is that you get too busy, you're not able to see new patients, and you lose the fun of being the diagnostician. The internist needs to find ways to keep seeing new patients.

RS: What other things were unique to OHIM, things that set it apart as an excellent rural GIM practice?

MAL: Something I found when I went other places that was really quite unique to OHIM was also very simple: sign-in rounds every morning and sign-out rounds every night. Most groups, incredibly, do not do that. And yet, since 1975, and I assume even to this day, they meet around 8:00 in the morning and they sit down and go over cases that have been admitted, or cases in the hospital that are a problem, and there's brainstorming and sharing of information and knowledge, and even a certain direction in terms of working on the case for diagnosis and treatment. And something as simple as that can make a practice very successful, or, alternatively, make the partners travel in sort of separate spheres and never really communicate, never really share their knowledge. Another key thing that has made OHIM so successful is a premium placed on CME, a premium placed on going away to courses out of state, and then coming back and sharing the knowledge with the other people in the group, which has been a habit since the group was founded in 1975.

RS: Did you set out, either in medical school or residency, with practicing in a rural area in mind?

MAL: No. I set out in medical school to be a pediatrician, and I couldn't take the suffering of really sick children, emotionally. I decided instead that I would go into something that I thought would be more cerebral and more intellectual, so I chose internal medicine and found that I was every bit as much affected by adult illnesses as I was by children's. And then during training and residency, I had intended to go into academic medicine. On an invitation to come to Maine and look at the practice, I came and liked what I saw in terms of the opportunity to practice the whole range of general medicine the way I'd been trained, and that attracted me to come here. I had certainly had some regrets about not doing the teaching that I wanted to do, but in more recent years I've been able to do that as well. But most of my residency training was aimed toward an academic career.

RS: What do you think you missed by not being in urban or academic medicine? Despite the fact that you were practicing the gamut of medicine and applying skills that you might not have been able to in another place, were there particular things that you felt you were sacrificing?

MAL: Practicing in rural areas and even in community hospitals, where I am now in Augusta, almost by definition implies a certain amount of isolation. I have picked that up even in physicians practicing at Maine Medical Center. We are here in a state of a million people, we don't have a university medical center with a medical school, and we don't have high-powered basic research or really competitive urban medical centers like most other states do. That isolationism can breed a certain amount of complacence, the lack of stimulation to learn, to continue to grow, to be challenged, an acceptance of the status quo, and an acceptance that our way of doing things is really the only way. Anyone who's been in academic medicine will tell you that it's exposure to students and housestaff that stimulates you the most.

RS: I know that you have also diversified your professional life by doing visiting professorships. So, in lieu of having housestaff and medical students in your daily practice, did the visiting professorships provide the sort of academic stimulation you were referring to earlier?

MAL: Yes, I think so, to some extent. I do think, though, that visiting professorships are different than having a student or a resident on your service for a month. I did that as well. After 1993, I spent three separate months as a ward attending on three university services, so each of those times I was the visiting attending physician for a month and had a housestaff. That's very different from being in a place for a week as a visiting professor. The week-long visiting professorship is usually focused on you, and they want to please you, you're sort of the visiting big shot. You give grand rounds, you give other talks, and they try like hell to find out what your area of expertise is so they can present patients that are dealing to your strength. Whereas, if you're doing it for a month long, you get to know the students and residents, they get to know you, and you become more of a team, more of a family. I think the communication is much deeper, and there is much more of a chance to affect someone's career. It's very difficult to make a profound effect on a student or a resident when you spend time with them only for a few days or a week.

RS: Do you think the prospect of visiting professorships, of opportunities to teach outside one's practice, might be encouraging to students or residents who might be interested in rural medicine, but fear professional isolation?

MAL: Yes, but I wouldn't want anyone to construe that as being a commonplace opportunity. The invitations to do that came for me because I was a storyteller. Because I wrote pieces of fiction for journals that became very popular, people wanted to meet me and basically invited me to come and read my stories at grand rounds. And I bartered with them: I said if you want me to do this, you've got to give me a piece of the action or I'm not coming. And so it was a quid pro quo with them. I'll give grand rounds, I'll be the court jester, but in turn I would get to take morning report, I would get to round with the students and the residents, and this is the way it's going to be. For the rural internist to think that he or she could go to a small community and then periodically do visiting professorships at major university centers would be a mistake. That's a very uncommon opportunity, and I've been lucky to do it.

RS: Did it become difficult, while you were at the OHIM, to fulfill what you wanted to do as a physician and fulfill what you wanted to do as a writer? Did those two things become mutually exclusive?

MAL: They did. That was my reason for leaving the practice. It was not possible to work out some sort of compromise there such as I have now, where I can have basically about one third of my professional time devoted to writing and two thirds of my time devoted to clinical medicine.

RS: Do you think it would be difficult in any rural practice to split your time in that way?

MAL: No, I don't. I think that it's much easier to do if you set out with that arrangement in mind. If you join a practice with the idea that you're going to devote a significant portion of your time to something else, and it's in the contractual understanding of the practice, it's much easier to do than to change something later on. It's hard for most people, I think, to undergo that kind of change, because there are financial implications, there are implications in terms of patient care load, call responsibilityŃall of those things can become serious impediments. But I have heard about successful practices where a husband and wife with children take one full-time position and each of them split it. So, for the first 15 days of the month, the husband would be in the practice and see the patients, and the wife would be at home doing childcare, and then they'd switch. There was a practice like that in Caribou, Maine. The patients were very accepting of it, as were the partners.

RS: We talked about professional isolation. Do you ever have a sense of social or cultural isolation?

MAL: Oh yes, very much. I think that one of the things that I envy the most about my academic counterparts is their opportunity to have social interaction with disciplines that are very dissimilar to medicine. In rural medicine, you tend to socialize with other doctors, and when doctors get together they tend to talk about medicine. In urban situations, that's very different. Urban academic physicians have friends in economics, history, or languages. A friend of mine at the University of Chicago has lunch every week with a classicist and they are very much fast friends. He is a nephrologist whose specialty is in kidney stones and he lunches every week with this Greek classicist. How I would love to do that! So yes, that kind of social and intellectual isolation is very palpable, and I think that's something you need to work at if you're in a rural setting, in terms of getting season tickets at a symphony, or a theater, or both.

RS: What were your thoughts about raising a family in a rural area? Was that an entirely appealing prospect, or did it have some shortcomings?

MAL: No, it was really very appealing. I think one of the things that tipped the decision in favor of a rural practice versus a large urban academic setting was the quality of life for children.

RS: Was the quality of the public schools a concern?

MAL: Somewhat, but I guess I felt one way or another we could augment that, whether it was through the home environment or through a private school. It really wasn't a big concern.

RS: Now, I know that you had a special kind of rapport with the academic community because of your writing. But did you ever sense that there is a hierarchy among physicians, in which the ones at the major academic centers are closer to the top and rural physicians are closer to the bottom?

MAL: Absolutely. That's actually a very insightful question, and very much to the point. It is as though on the one hand academic medicine extols the virtues of practicing physicians, but on the other hand, demands that the practicing physician know his or her place. I felt when I served on the board of the ABIM and on the Board of Regents for the ACP-ASIM, in both places, perhaps more on the ABIM, that was true. On the one hand, here was this practicing internist, sort of the paragon of the profession, and on the other hand he needed to know his place, and his place was really at the foot of the table. I think that another way of putting it is that I was at a university hospital this fall as a visiting professor and I gave grand rounds, and this was a place where every week grand rounds was usually on basic science, if not clinical science, and was always given by a senior academician. And I was giving this grand rounds, and I was reading stories and reciting poetry, and afterwards the chairman of medicine came up to me with a smile and said he had sat through the whole thing and enjoyed it immensely, but he was amazed that I was "getting away with it."

RS: What does that mean?

MAL: I think that what it means is that this was not the stuff of academic medicine, yet somehow I had pulled it off, even though neither it nor I really belonged there.

RS: I would wonder if that sort of thinking would be prohibitive to some people considering going into rural medicine, that it would be difficult for them to be undervalued even if they were practicing just as good, if not better, medicine than their urban counterparts.

MAL: There are several points to consider here. You will always be a local hero. You will never get national recognition, with just a very few exceptions, and you need to be content with that. There is an immense gratification with that, but if you want to be famous, this is not the way to do it. Also, I think it was Eleanor Roosevelt who said, "The only one who can make you feel inferior is yourself." If you have a strong sense of self and a strong sense of purpose, you should not let what someone else thinks get in the way of your doing what you want to do.

RS: What about the idea of wanting to effect social change? A lot of people go into medicine with the ideal of wanting to help people. Do you think that ideal is less well served, or better served, in a rural setting?

MAL: You affect different lives, but you can affect lives no matter where you are. It's just a matter of what sort of life you affect. In an academic setting, by definition, your "patients" are your students. They are your charge; they are the ones whose lives are in your hands, whose lives you are going to affect. In private practice, especially in a rural area, there is a greater opportunity to do the good thing, to be kind, to be magnanimous, to be generous with your money, to affect lives with that generosity, to get involved locally with students not of medicine but of high school or local colleges, and to make every bit of difference, but you are not going to affect lives as they pertain to medicine. You may affect lives as they pertain to going to law school, for example, or just going to college at all. You'd be giving kids in rural America the idea that there is life beyond high school, they can go to college, that there is life beyond this small town.

RS: Is there still a place in rural America for the comprehensive internist?

MAL: Absolutely.

Rachel Solotaroff
Dartmouth Medical School, 2001

Focus on Subspecialties: Hematology/Oncology

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The discipline of hematology relates to the care of patients with disorders of the blood, bone marrow, and lymphatic systems, including anemias; hematological malignancies and other clonal processes; and congenital and acquired disorders of hemostatis, coagulation, and thrombosis. Medical oncology is the diagnosis and management of benign and malignant neoplasms.

Dual certification in hematology and medical oncology requires three years of full-time combined fellowship training that must include: 1) a minimum of 18 months of full-time clinical training with patient care responsibility; 2) a minimum of 12 months in the diagnosis and management of a broad spectrum of neoplastic diseases including hematological malignancies; and 3) a minimum of six months of training in the diagnosis and management of a broad spectrum of non-neoplastic hematological disorders. During the entire three years, the trainee must attend at least one outpatient clinic for a minimum of one half-day per week and have the responsibility for providing continuous care to a defined cohort of patients being managed for neoplastic and hematological disorders.

The American Board of Internal Medicine offers certification in hematology and oncology. Candidates applying for certification in hematology and oncology must complete all three years of required combined training before being admitted to an examination in either specialty. Those candidates that have completed all three years of required combined training may take the hematology and medical oncology examinations in the same year or in different years.

The following is an interview of a subspecialist trained in hematology, medical oncology, and internal medicine, Tanya L. Repka, MD, FACP. Dr. Repka is an Assistant Professor in the Department of Medicine, Division of Hematology, Oncology, and Transplantation at the University of Minnesota Medical School in Minneapolis, and Governor of the ACP-ASIM Minnesota Chapter. The interview was conducted by Emily Burns, a third-year medical student at University of Colorado School of Medicine.

IMpact: Why did you choose hematology/oncology as a career?

Dr. Repka: During my internal medicine residency, I decided I wanted to pursue a subspecialty. I did my residency in a large county hospital that had quite a bit of critical care exposure and was the Level 1 trauma center for the area. To be honest, several subspecialties were quickly nixed, those that, in my mind, required frequent trips to the hospital in the wee hours of the night, such as pulmonary/critical care, gastroenterology, renal, and cardiology. These are wonderful subspecialties, but I just don't do well with very little sleep! That still left a number of subspecialties. I knew I was doing a chief resident year, so I had extra time to decide which fellowship to pursue. I did my hematology/oncology rotation during my third year and fell in love with the science of hematology and the hematolgy/ oncology patients and their families.

IMpact: What does the training involve?

Dr. Repka: After completion of an internal medicine residency, the hematology/oncology fellowship is typically three to four years, depending on the amount of research one does. There are still a few programs that are split between hematology and medical oncology, but most have merged into one program that allows one to sit for both boards after completion of the fellowship.

IMpact: What are your board certifications?

Dr. Repka: I am certified in internal medicine, hematology, and medical oncology.

IMpact: What kind of patients do you see?

Dr. Repka: I work in both inpatient and outpatient settings. I typically attend four to four and a half months per academic year. In the inpatient setting, I attend on a hospital service, usually on the bone marrow transplant service, but occasionally on the hematology/ oncology service. When I am attending on inpatient service, I work with a hematology/oncology fellow, and housestaff, which usually consists of a resident, an intern, and a medical student. I also attend in the outpatient bone marrow transplant clinic; we call this "Doc of the Month," although we only do it for three weeks at a time. This clinic runs 365 days a year, and recently discharged patients are seen in this clinic, often daily. They receive daily monitoring, which can include such things as blood products, antibiotics, and intravenous fluids and electrolyte replacement. In this clinic during weekdays, there is often a nurse practitioner to help see the patients; on the weekend we alone see the patients.

In the outpatient setting, I have three half-days of clinic per week. I primarily see breast cancer patients and bone marrow transplant patients in my clinics. In clinic I usually work alone, but sometimes one of the nurse practitioners will help with my patients.

IMpact: What is unique to this field as opposed to general internal medicine?

Dr. Repka: We are subspecialists, so we only look at a specific issue or problem, although with my hospice and end-stage patients I am their primary care physician. With my breast cancer patients I insist they also have a primary care physician, preferably an internist! Despite my trying to keep current, I am really not up on the latest anti-hypertensives, lipid screenings, and lipid-lowering drugs. Patients need a physician who will look at their entire health history and needs. We care for patients as they go through what will likely be the most difficult time in their lives for themselves and for their families, the cancer diagnosis and treatment, or bone marrow transplantation.

IMpact: What is your favorite aspect of the field?

Dr. Repka: I have several favorite aspects. Helping patients through a very difficult time period, telling them the truth about their disease in language and stages that they can understand and cope with. Helping patients and their families through the dying process, in essence, helping patients die well, with good pain control and dignity. People, including other physicians and medical students, often ask, "How can you do this day after day?" I think that helping someone die well is a great art and the patient and family greatly appreciate a "good death." Probably my favorite aspect is seeing my patients alive and well years after they have been told they will die. One of my patients is a young man who had Glioblastoma multiforme. I treated him through many cycles of chemotherapy, radiation, and pushed the surgeons to re-resect. It is now about five years after his last treatment and he works as a security guard at the airport. He always gives me a hug when I go through the security checkpoint, and the last time I saw him he told me he was getting married soon.

IMpact: What is your least favorite aspect of the field?

Dr. Repka: Knowing that despite my best efforts and our great medical care of today, not all my patients will survive. I wish we had better treatments (drugs, immunotherapy, etc.) that would cure my patients. Another least favorite is not being able to assure patients, especially my breast cancer patients, that their disease will not return. They live in constant fear of disease recurrence.

IMpact: Do you have any suggestions for a medical student who is interested in the field?

Dr. Repka: Spend some time with a hematology/oncology physician, or several. Make sure some of that time is in the outpatient setting because housestaff get a very skewed picture of what we do and who our patients are. The majority of my oncology patients are never hospitalized. This is a very emotionally draining yet rewarding field that can be immensely satisfying, but it is certainly not for everyone. The science we have is astounding: the gene project, growing stem cells into all the tissues of our body, stem cell/umbilical cord blood transplantation, and immunotherapy. It really comes down to the doctor-patient relationship and what you bring to your profession. I think my field personifies the art of medicine. I want the best and brightest going into this field. After all they may be taking care of me someday!

Review: Palliative Chemotherapy Reduces Death and Progression at 12 Months in Advanced or Metastatic Colorectal Cancer

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ACP Journal Club. 2001 Jan-Feb;134:25.

Colorectal Meta-analysis Collaboration. Palliative chemotherapy for advanced or metastatic colorectal cancer. Cochrane Database Syst Rev. 2000;(2):CD001545 (latest version 16 Nov 1999).

Question: In patients with locally advanced or meta-static colorectal cancer, what are the benefits and harms of palliative chemotherapy?

Data sources: Studies were identified by searching MEDLINE, EMBASE/Excerpta Medica, CancerLit, the Cochrane Controlled Trials Register, CINAHL, HealthSTAR, Science Citation Index, Edina Biosis, NHS Economic Evaluation Database, Index to Scientific and Technical Proceedings, and PASCAL (to October 1998); hand searching conference abstracts; scanning bibliographies of relevant studies; searching sources of unpublished trials; and contacting authors.

Study selection: Studies in any language were selected if they were randomized controlled trials (RCTs) that compared palliative chemotherapy with supportive care alone in patients with advanced or metastatic colorectal cancer.

Data extraction: The quality of studies was assessed by using the Jadad scale. Authors were contacted for individual patient data (baseline patient characteristics, allocated treatment group, date of randomization, tumor response, survival and progression status, and date of death or last follow-up). 2 reviewers extracted data from published studies, and meta-analysis was done by using both published data and individual patient data.

Main results: 13 RCTs (1365 patients) met the selection criteria. Individual patient data were obtained for 7 RCTs (866 patients). Meta-analysis of published data showed that palliative chemotherapy (5-fluorouracil [5-FU], alone or in combination; fluoridine; irinotecan; or tauromustine) led to a reduction in death and progression at 12 months (Table). Statistically significant heterogeneity existed among these RCTs. Studies with individual patient data were not heterogeneous; they also showed a reduction in death (7 RCTs; number needed to treat [NNT] 6, 95% CI 4 to 11) and progression (3 RCTs, NNT 4) at 12 months. The evidence for toxicity, quality of life, and symptom control was inconclusive because of inconsistent reporting and use of poor-quality methods.

Conclusions: In patients with locally advanced or metastatic colorectal cancer, palliative chemotherapy reduces death and progression at 12 months. The evidence on toxicity, symptom control, and quality of life is inconclusive.

Source of funding: NHS National Cancer Research & Development Programme UK.

For correspondence: Dr. L.Y. Best, CRX Wessex Medical Oncology Unit, Southampton General Hospital, Level F (809), Centre Block, Southampton SO16 6YD, England, UK. FAX 44-1703-783839.

Commentary

This well-conducted meta-analysis by the Colorectal Meta-analysis Collaboration supports the view that palliative chemotherapy is beneficial in treating colorectal cancer. Progression-free survival is prolonged, and deaths are reduced at 12 months. The benefits are substantial and clinically important. When studies with individual patient data are analyzed, relative risk reductions of 35% in deaths and 49% in progression at 12 months are shown. This finding translates into a 16% absolute difference in survival and a 25% increase in progression-free survival (increases of 3.7 mo in median survival and 6 mo in median progression-free survival).

This benefit is probably underestimated. An unknown proportion of patients randomly allocated to supportive care received delayed chemotherapy, and 3 trials allowed chemotherapy at the onset.

The issue is not whether to treat but when and how it is best to treat. Other potential modalities that either improve outcome or decrease toxicity include the use of continuous-infusion 5-FU (1), oral 5-FU (2), and combination chemotherapy (3). Future studies that incorporate measures of quality of life will better define the role of palliative chemotherapy in colorectal cancer.

Edmond Chouinard, MD
Hamilton Regional Cancer CentreHamilton, Ontario, Canada

References

1. Meta-analysis Group in Cancer. Efficacy of intravenous continuous infusion of fluorouracil compared with bolus administration in advanced colorectal cancer. J Clin Oncol. 1998;16:301-8.

2. Twelves C, Harper P, Van Cutsem E, et al. A phase III trial (SO14796) of Xeloda™ (capecitabine) in previously untreated advanced/metastatic colorectal cancer [Abstract]. Proc Annu Meet Am Soc Clin Oncol. 1999; 18:A1010.

3. Saltz LB, Douillard J, Pirotta N, et al. Combined analysis of two phase III randomized trials comparing irinotecan (C), fluorouracil (F), leucovorin (L) vs F alone as first-line therapy of previously untreated metastatic colorectal cancer (MCRC) [Abstract]. Proc Annu Meet Am Soc Clin Oncol. 2000;18:A938.

A Simple Clinical Tool That Included Age, Weight, and Estrogen Use Helped to Select Women for Bone Densitometry

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ACP Journal Club. 2001 Jan-Feb;134:37.

Cadarette SM, Jaglal SB, Kreiger N, et al. Development and validation of the Osteoporosis Risk Assessment Instrument to facilitate selection of women for bone densitometry. CMAJ. 2000 May 2;162:1289-94.

Question: Can a simple screening tool accurately identify which women are at increased risk for osteoporosis and should have bone densitometry?

Design: A population-based cohort study, the Canadian Multicentre Osteoporosis Study (CaMos), provided data for the derivation and validation of the screening tool.

Setting: Hamilton, Kingston, and Toronto, Ontario, Canada.

Patients: 1376 women >= 45 years of age (mean age 63 y, 95% white), who had had dual-energy radiographic absorptiometry testing at both the femoral neck and lumbar spine (L1 to L4) and had a Mini-Mental State score > 20. Exclusion criteria were previous diagnosis of osteoporosis or current use of bone-active medications other than ovarian hormones. The derivation cohort comprised 926 randomly selected women, and the validation cohort comprised 450.

Description of prediction guide: Of 6 predictors of low bone-mineral density (BMD) (age, weight, current estrogen use, menopause, physical activity, and previous minimal trauma fracture at >= 45 y of age), 3 were selected for inclusion in the final model, the Osteoporosis Risk Assessment Instrument (ORAI): age (score of 15 if >= 75 y, 9 if 65 to 74 y, 5 if 55 to 64 y, and 0 if 45 to 54 y), weight (score of 9 if weight < 60 kg, 3 if 60 to 69 kg, and 0 if >= 70 kg), and current estrogen use (score of 2 if no and 0 if yes).

Main outcome measure: Low BMD (BMD >= 2 SDs below the mean for young Canadian women at either the femoral neck or lumbar spine).

Main results: A score >= 9 identified 90% of women with a BMD >= 2 SDs below the mean and was therefore chosen as the recommended threshold for BMD testing. This score had moderate specificity but high sensitivity for the diagnosis of low BMD. Similar sensitivities, specificities, and positive and negative likelihood ratios were found for the derivation and validation cohorts (Table).

Conclusion: A simple screening tool that included age, weight, and current estrogen use helped to identify women who were at increased risk for osteoporosis and who should therefore have bone densitometry.

Source of funding: University of Toronto Dean's Fund.

For correspondence: Dr. S.M. Cadarette, Osteoporosis Research Program, Sunnybrook and Women's College Health Sciences Centre, 76 Grenville Street, 10th Floor East, Room 1005, Toronto, Ontario M5S 1B2, Canada. E-mail: s.cadarette@ utoronto.ca.

Commentary

The ORAI was designed to identify women who would benefit from bone densitometry. The objectives of this screening tool are to select a population of women in whom bone densitometry could be avoided without substantially increasing the risk of missing a diagnosis of significant osteopenia or osteoporosis. The ORAI identified many women who were likely to have low BMD, but similar to existing instruments, it failed to reach an appropriate level of specificity. However, the use of such an instrument could potentially reduce the costs of bone densitometry when compared with a program of mass screening. The ORAI provided similar results to those obtained with the Simple Calculated Osteoporosis Risk Estimation (SCORE) instrument (1). The small differences between the 2 instruments could be because of different study populations. It would be interesting to see whether the results vary when other clinically useful diagnostic end points are used: either a T-score < -2.0 with a fracture or a World Health Organization definition of established osteoporosis (i.e., a T-score ¾ -2.5 and >= 1 fracture).

Future studies might consider using 2 thresholds: one to identify women with a very low risk for low BMD osteoporosis who should not have bone densitometry and one for those with a very high risk for osteoporosis who should be treated immediately, regardless of BMD testing. BMD measurements could be done for those with scores between these 2 thresholds. Subsequent economic analyses to evaluate the cost-benefit of such screening strategies should also be considered.

Jean-Yves Reginster, MD, PhD
University of Ličge
Ličge, Belgium
Reference

Reference

1. Lydick E, Cook K, Turpin J, et al. Development and validation of a simple questionnaire to facilitate identification of women likely to have low bone density. Am J Manag Care. 1998;4:37-48.

Test Properties of the Screening Tool (score >= 9) for Derivation and Validation Cohorts for Women Who Had Low Bone-Mineral Density*

Sample Sensitivity Specificity (CI) +LR -LR (95% CI)

Derivation 90% (85 to 94) 45% (41 to 49) 1.6 0.22

Validation 93% (86 to 97) 46% (41 to 52) 1.7 0.14

*LRs defined in Glossary and calculated from data in article.

Internal Medicine Interest Group Activity Ideas

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One important role of internal medicine interest groups is to provide resources for students interested in medical subspecialties. The interest group at the Mount Sinai School of Medicine in New York City recently started biannual meetings to accomplish this goal. Most recently, Dr. Lori Croft, an Instructor of Medicine and a recent graduate of the Mount Sinai Fellowship Training Program, presented information on the subspecialty of cardiology. The presentation included information about the training process in cardiology, employment options within the field, and considerations for medical students who are interested in this career. She concluded with a demonstration of a portable echocardiography machine, using several members of the audience as subjects. This event was informative, educational, and was greatly enjoyed by all. It also resulted in a student research project, studying the use of echocardiography in the emergency department!

MKSAP Question 1

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A 26-year-old man weighing 70 kg (154 lb) completed a course of chemotherapy for acute myelogenous leukemia 2 months ago, and he is presently in remission. During that course of therapy, he developed thrombocytopenia and received multiple platelet transfusions. He is now receiving intensive consolidation chemotherapy, and his platelet count has decreased from a normal level to 12,000/µL and, although he is not hemorrhaging, he is treated with a prophylactic transfusion of one plateletpheresis product.

One hour after transfusion, the platelet count is 15,000/µL. The patient does not have splenomegaly, fever, infection, or disseminated intravascular coagulation.

What is the most probable cause of this patient's poor response to the platelet transfusion?

(A) Inadequate dose of platelets

(B) Antibodies to platelet-specific antigens

(C) Antibodies to HLA antigens

(D) Autoantibodies to platelets

(E) Inadequate time for equilibration

MKSAP Question 2

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Which one of the following detection techniques refers to detection of RNA by labeled DNA?

(A) Southern blot

(B) Western blot

(C) Northern blot

(D) Southwestern blot

MKSAP Question 3

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A 68-year-old woman with psoriasis presents to your office because she has developed dysuria. She is receiving oral methotrexate, 10 mg per week, for treatment of her psoriasis. A urinalysis shows multiple bacteria and 40 to 60 leukocytes per high-power field.

Which of the following drugs is contraindicated for treatment of this patient's urinary tract infection?

(A) Ampicillin

(B) Trimethoprim-sulfamethoxazole

(C) Cephalexin

(D) Ciprofloxacin

(E) Amoxicillin-clavulanate

MKSAP Question 4

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High-dose chemotherapy and radiation therapy followed by stem cell rescue (that is, autologous bone marrow transplantation) has been shown in randomized trials to prolong survival when compared with more conventional treatment in which one of the following conditions?

(A) Multiple myeloma

(B) Chronic myelogenous leukemia

(C) Chronic lymphocytic leukemia

(D) Acute lymphocytic leukemia

Question 1

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Answer: C

Educational Objective: Diagnose refractoriness in a patient who has received random-donor platelet transfusions.

Patients who receive numerous transfusions may become alloimmunized to HLA antigens present on leukocytes that contaminate erythrocytes and platelet products. Such HLA antibodies may cause destruction of subsequently transfused platelets and are the most common immunologic cause of a poor response to a platelet transfusion.

A plateletpheresis product contains the equivalent of about 7 units of platelets. Therefore, the dose of platelets in this patient was 1 U/10 kg of body weight (an appropriate dose) and can be expected to increase the platelet count by about 50,000/µL in a nonrefractory patient.

Antibodies to platelet-specific antigens can cause refractoriness to platelet transfusion, but this mechanism occurs much less commonly than HLA antibodies. In one study, only 2 of 160 evaluable multitransfused patients developed platelet-specific antibodies causing refractoriness to platelet transfusion.

There is no evidence suggesting autoimmune thrombocytopenia in this patient. In particular, the platelet count before the second course of chemotherapy was normal and the clinical setting, including the onset of thrombocytopenia following intensive chemotherapy, strongly suggests a hypoproliferative thrombocytopenia induced by chemotherapy.

A common cause of a poor response to platelet transfusion is the presence of clinical factors that results in a short survival of transfused platelets. Among incriminated clinical factors are sepsis, high fever with temperatures greater than 38.5 °C (101.3 °F), concurrent amphotericin administration, disseminated intravascular coagulation, splenomegaly, and previous bone marrow transplantation.

Because refractoriness to platelet transfusion presents a significant problem in management, it is customary to provide leukocyte-reduced platelets and erythrocytes at the onset of transfusion therapy for patients who can be expected to need long-term platelet support. Most evidence suggests that blood components containing less than 100,000/mL leukocytes per product (accomplished by filtration) delay the onset of primary, but not secondary, alloimmunization. Some plateletpheresis procedures are also capable of producing platelets that are leukocyte-reduced to this level.

References

1. Rintels PB, Kenney RM, Crowley JP. Therapeutic support of the patient with thrombocytopenia. Hematol Oncol Clin North Am. 1994;8:1131-57.

2. Bordin JO, Heddle NM, Blajchman MA. Biologic effects of leukocytes present in transfused cellular blood products. Blood. 1994;84:1703-21.

3. Petz LD. Platelet Transfusions. In: Petz LD, Swisher SN, Kleinman S, Spence RK, Strauss RG, eds. Clinical Practice of Transfusion Medicine. 3rd ed. New York: Churchill Livingstone; 1995:359-412.

4. Doughty HA, Murphy MF, Metcalfe P, Rohatiner AZ, Lister TA, Waters AH. Relative importance of immune and non-immune causes of platelet refractoriness. Vox Sang. 1994;66:200-5.

5. Novotny VM, van Doorn, R, Witvliet MD, Claas FH, Brand A. Occurrence of allogeneic HLA and non-HLA antibodies after transfusion of prestorage filtered platelets and red blood cells: a prospective study. Blood. 1995;85:1736-41.

Question 2

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Answer: C

Educational Objective: Understand the various gels used to document expression of genes or proteins.

Gels are used to separate biologic molecules of interest, primarily based on their size. Detection of different sized RNA molecules can be useful for determining which genes are being expressed in a tumor or cell line.

The Northern blot involves detection of RNA by labeled DNA. Gels made of either agarose (for large molecule fragments) or polyacrylamide (for smaller molecules) separate proteins, DNA, or RNA on the basis of size. For example, RNA isolated from a cell would consist of ribosomal RNA and messenger RNA. Placing the RNA over a column containing oligomers of deoxy-thymidine, allows retention of the messenger RNA species due to the poly-A tail on mature messages in the cytoplasm. If the gene sequence which gave rise to some RNA is known, it can be detected by eluting the RNA from the column, separating on a gel, and then transferring the RNA to a solid support such as nitrocellulose or nylon membranes. Now by using labeled DNA to "probe" the gel, that is, incubate the membrane in a solution of a radioactive labeled specific DNA sequence, the hybridization of A to T(or U) and C to G will allow the uniquely encoded RNA to be detected. A cell culture or tumor NOT expressing the gene would not give rise to a signal, since none of the RNA would be present.

Southern blots involve similar separation techniques and membranes but rely on DNA-DNA hybridization, while Western blots are protein-protein interactions. (for example, a labeled antibody binding to an antigenic protein separated from other proteins based on size and mobility in polyacrylamide gels). Southwestern blots are a way of probing protein-DNA interactions such as might occur when a transcription factor binds to DNA, retarding its mobility in a gel. The terminology all stems from the original use of DNA-DNA detection by Dr. Earl Southern.

References

1. Naber SP. Molecular pathology -- detection of neoplasia. N Engl J Med. 1994;331:1508-10.

2. Rosenthal N. Tools of the trade -- recombinant DNA. N Engl J Med. 1994;331:315-7.

Question 3

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Answer: B

Educational Objective: Recognize drugs that are contraindicated in patients taking methotrexate.

Trimethoprim-sulfamethoxazole inhibits dihydrofolate reductase and has been known to enhance methotrexate toxicity. None of the other drugs are associated with a drug-drug interaction. Patients taking methotrexate should notify their practitioners. Patients should be told to give a complete list of medications they are receiving to other physicians they visit to avoid drug­drug interactions.

Reference

1. al-Awadhi A, Dale P, McKendry RJ. Pancytopenia associated with low dose methotrexate therapy. A regional survey. J Rheumatol. 1993; 20:1121-5.

Question 4

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Answer: A

Educational Objective: Know that autologous ztransplantation has been shown to prolong survival in myeloma.

For autologous bone marrow transplantation to be optimally effective, the burden of tumor cells must be maximally reduced, the residual tumor must remain sensitive to the myeloablative effects of chemotherapy and/or radiation therapy, and the source of the stem cells for hematopoietic rescue (bone marrow or peripheral blood) must be free of the malignant clone. A large randomized trial conducted in Europe has show this management strategy to prolong survival in patients with multiple myeloma. Since the neoplastic clone in patients with chronic myelogenous leukemia (hematopoietic cells containing the "Philadelphia chromosome") can never be fully eradicated with chemotherapy, autologous bone marrow transplantation (in contrast to the highly effective allogeneic bone marrow transplant) does not represent a curative strategy for patients with this disorder. Similarly, the mature lymphocytes in patients with CLL can rarely be fully eradicated and the advanced age of most patients with this condition (many of whom have a quite prolonged prognosis)has precluded the use of this aggressive strategy for patients with this disorder. Data are conflicting regarding the value of autologous transplantation for patients with acute lymphocytic leukemia (or acute myeloid leukemia); the concept has not been subjected to a controlled trial.

Reference

1. Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF, et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. N Engl J Med. 1996;335:91-7.

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