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Podcast Transcript - November 20, 2007

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00:37 Clinical outcomes by virologic response in hepatitis C patients and an interview with Dr. Gary Davis, Chief of Hepatology at Baylor University

13:12 The comparative effectiveness of CABG and PCI and an interview with Dr. Stephan Fihn of the VA Puget Sound

27:30 The CDC’s ACIP adult immunization schedule for 2008-2008 and an interview with Dr. Greg Poland of the Mayo Clinic

43:02 Summaries of other articles in this week's issue.

Hello, and welcome to this weeks Annals of Internal Medicine Audio Summary for our November 20, 2007 issue. I’m Michael Berkwits, Deputy Editor at Annals.

We have another outstanding issue for you this week, with articles and interviews on clinical outcomes in patients treated for chronic hepatitis C; the comparative effectiveness of coronary artery bypass grafting and percutaneous coronary intervention in patients with stable angina; I’ll replay my interview last month with Dr. Greg Poland about changes in the recommended vaccine schedule for adults; and I’ll summarize the rest of the articles in this week’s issue.

But first, here’s an in-depth summary of those first articles.

Clinical Outcomes in Patients Treated for Chronic Hepatitis C With Sustained Virological Response (Time: 00:37)

Our lead article this week is a study of long-term clinical outcomes for patients with chronic hepatitis C infection based on their response to treatment.

The efficacy of treatment for chronic hepatitis C is typically measured by its effect on liver enzymes and hepatitis C virus RNA. Many hepatologists treat the disease thinking that improvements in these measures are good surrogates for a reduction in risk of liver failure and cancer, but the connection has not been well established in high quality studies.

In this week’s article, lead author Bart Veldt of Erasmus Medical Center in Rotterdam, The Netherlands, and his coauthors provide such a study. They pooled 479 patients who had advanced fibrosis or cirrhosis and who had received interferon-based therapy at 5 medical centers in Canada, Germany, and Switzerland, and they distinguished the third who had sustained virological response, defined as the absence of detectable hepatitis C RNA 6 months after the completion of treatment, from the 2/3 without sustained response. They then followed the patients in each group to determine the incidence of clinical events, specifically liver failure, liver-related and non-liver-related death, and hepatocellular carcinoma.

Their study had two main findings.

First, patients infected with genotypes other than type 1, those who had never been treated, those who had been treated with ribavirin, and those treated for longer than 35 weeks were more likely to have sustained response to treatment.

Second, 4 patients with sustained response developed a clinical event compared to 83 without sustained response, giving an adjusted relative reduction in the hazard of any of those events of 80%. Patients with sustained response did better across the board, experiencing fewer cases of liver failure, hepatocellular carcinoma, and liver and non-liver-related deaths, but the overall effect was largely driven by the apparent elimination of the risk of liver failure in patients who had a sustained response.

Based on these findings, the authors conclude that sustained virologic response to antiviral therapy reduces complications of liver disease in patients with chronic hepatitis C and advanced fibrosis. They acknowledge that the findings may be affected by selection bias, because theirs was an observational, retrospective cohort study, and patients with more severe cirrhosis who may not have been considered for treatment might have also been excluded from the study sample. They also acknowledge that while they found many clinically significant differences in outcomes between groups, individual clinical events were too few for them to find many statistically significant differences. The authors don’t fully acknowledge that theirs is really the second study to establish this association. A larger study by Italian researchers published in March of this year in the journal Hepatology also demonstrated the association between sustained virologic response and improved clinical outcomes, and it made the additional point, illustrated by data in this week’s article but not emphasized by this week’s authors, that while the risk for hepatocellular carcinoma is reduced, it is not eliminated, so all patients, even those with sustained reponse, need surveillance screening for liver cancer. Still, the editors thought this was something like the hepatitis C article we’ve all been waiting for, and one that could be used as a model for other diseases. This is a study which carefully demonstrates a direct line between treatment, surrogate measures of response, and clinical measures of response.

Because this seemed pretty important, I called Dr. Gary Davis, Chief of the Division of Hepatology at Baylor University in Dallas Texas and the author or co-authore of hundreds of articles on viral hepatitis and the treatment of hepatitis C. I asked him how and if these findings should change the approach to hepatitis C patients, and he was kind enough to share his impressions with me about the article.

Q: Dr. Davis thank you for talking to me.

A: Thank you for asking me.

Q: I’m wondering if we can start with a basic clinical review. Remind us of the treatments now available for hepatitis C

A: Well the standard treatment is pegylated interferon, this is a long-acting form of interferon that’s administered once a week; and ribavirin, which is an oral nucleodise analogue, which augments the effects of the interferon. And those are given together for 6-12 months depending on the genotype olf virus. And sustained response is undetectable virus by sensitive assay 6 months after completion of therapy. If that occurs the chance of the virus coming back is essentially nil; in long-term follow-ups it’s been 1 or 2% and it’s not clear whether those are actually resurgence of the virus or reinfection, since there’s no lasting fixed immunity to this infection. I suspect it’s reinfection, since if we get a sustained virologic response and immune suppress the patient, for example with liver transplant, the virus doesn’t come back. So I think that we ought to consider sustained viral response equivalent to cure, and that’s kind of unique to this infection. It’s the only chronic viral infection where our antivirals are able to cure the infection.

Q: What do we learn from this week’s article that we didn’t know before?

A: There has been some reluctance to accept this therapy without evidence that it really alters the natural history of the disease. And in the last year, the data has really started to come out that we do alter the natural history of the disease. We’ve known for some time that if you get a sustained virologic response, your histology improves, fibrosis regresses, cirrhosis may even disappear. And there was an Italian study published in Hepatology earlier this year that showed that cirrhotic patients who were treated with standard interferon 10 years ago, if they were able to achieve a sustained virologic response, that they had no hepatic decompensation following that, and a much reduced risk of hepatocellular carcinoma. So this article really confirms that, so we have data from two different continents now since Canada participated in this study, and the advantage of this study is it uses a number of patients who were using a more contemporary treatment regimen -- pegylated interferon and ribavirin, that was about 40% of the patients -- whereas the previous study was just standard interferon without ribavirin. And I think the message is clear when you look at the figure in the paper that hepatocellular carcinoma does appear to be less common after sustained virologic response, though it didn’t reach statistical significance. So that in combination with the Bruno paper I think is pretty strong evidence that this does decrease with a good response to interferon. The fact that it doesn’t disappear is an important message too, because that tells us that even though these patients have no chance of going into liver failure, they retain that risk of hepatocellular carcinoma so you have to keep an eye on them, you have to maintain your surveillance for hepatocellular carcinoma.

Q: The authors hint at two different implications of these findings that I wonder if you can comment on. First, they write that the lack of data on long-term outcomes after treatment for hepatitis C has been one of the main reasons that programs to screen people at risk for the infection have not been implemented. What are your impression of that: do you think this study can or should change people’s thinking about hepatitis C screening?

A: I think that there has been a reluctance in some groups of physicians to treat such patients because this had not been shown in a definitive study before. I think those of us who treat a lot of these patients have been aware that this was happening despite the lack of formal data. But this should provide some impetus to perhaps screen these patient more aggressively, there are projections that say that all the patients infected in the ‘60s and ‘70s are now older and their disease is maturing just as their age is, and as that happens we’re going to see more liver failure, so that in itself is a great impetus to find these patients, weed them out of the population and get them treated so that we don’t have to deal with the complications of liver failure and cancer.

Q: And are you proposing that all patients should be screened, or only those at high risk for infection, and can you remind us what risk factors are for hepatitis C virus.

A: Well the major risk factors are use of intravenous drugs in the past, or sharing of needles for any purpose, immigrants from endemic areas, and people who received blood transfusions or blood products prior to about 1990. All of them certainly ought to be screened. Though the recommendations from agencies like the CDC have not gone beyond that, there are epidemiologic studies that show that perhaps we ought to be broader in our screening and perhaps men of certain age ought to be screened more rigorously despite whether they volunteer such a history of a risk factor or not.. There’s no doubt that the hepatitis C virus can be transmitted sexually but it is exceedingly unusual for it to happen, so it is a risk that is real but it’s very small. There was just a paper presented at the recent liver meetings in Boston looking at risk factors for transmission and particularly looking at tattoos, and they found that it did appear to significantly increase the risk that that person would be positive independent of a history of other risk factors such as transfusion or IV drug use. Other large population surveys, for example those done by the CDC, could not find such an association. So I think there probably is a risk there, particularly with home-done tattoos that are not done in tattoo parlors, but what the magnitude of that risk is hard to define.

Q: And the authors of this week’s article also claim that the findings make clear the importance of developing treatment regimens that are simple to adhere to and that maximize the probability of sustained response. What are the prospects for that: are there promising treatments in the pipeline that listeners should be aware of?

A: Well, I don’t think that’s likely to happen in the near future. Treatment right now is fairly complicated to manage because of the side effects and cytopenia that can develop on treatment, so dose reductions are often needed, say in about 1/3 of folks. With the new nucleosides and other small molecules that are being developed now if those prove to be effective and get approved, they’ll be given in combination with current therapy to increase the efficacy and perhaps shorten the duration of therapy, but like the small molecules that are being used for HIV, the protease inhibitors and polymerase inhibitors, these all have their own unique set of side effects, and I suspect that treatment regimens will become more complex rather than less complex.

Q: And so what’s the clinical bottom line as you see it of this article: should these findings change practice?

A: Well it emphasizes that the goal of treatment is sustained virologic response, and it’s not just a laboratory goal, that it really influences longer-term outcome of these patients, it’s going to increase life expectancy, and their quality of life in the long run

Q: So this is an argument to aggressively identify risk factors for hepatitis C virus infection so that patients can screened and then referred for appropriate treatment.

A: Correct. But it’s important to look at a number of factors in a patient and treat the individual rather than just treating everybody or not treating everybody. You need to see where in the course of the disease they are, whether their disease has progressed over a period of time – some patients don’t progress; whether they have comorbid conditions that will cause their mortality before their liver disease would even if you leave it untreated; do they have conditions that would make treatment intolerable and not likely that they’ll get through the course. And all those things need to be considered when you decide about whether it’s appropriate to treat a patient or not.

Q: Dr. Davis, thanks so much for talking to me.

A: You bet. My pleasure.

That was Dr. Gary Davis, Chief of Hepatology at Baylor University in Dallas, discussing this week’s lead article demonstrating the association between sustained virologic response to hepatitis C treatment and improvement in clinical outcomes.

The Comparative Effectiveness of Coronary Artery Bypass Grafting (CABG) and Percutaneous Coronary Intervention (PCI) (Time: 13:12)

Our CME article this week is an Agency for Healthcare Research and Quality-funded systematic review of the comparative effectiveness of percutaneous coronary interventions and coronary artery bypass graft surgery.

Listeners who heard this summary and my interview with the article’s editorialist when it was posted on-line at annals.org last month can go to the next segment of this podcast by advancing their mp3 players to about the 27:35 marker in this audio file.

Randomized trials suggest that coronary artery bypass graft surgery, or CABG, is indicated for patients with left main coronary artery disease and patients with triple-vessel disease with reduced left ventricular function, while percutaneous interventions, or PCI, are technically preferred for single vessel disease. Most patients do not fit neatly into these specific anatomic categories, having proximal left anterior descending rather than left main artery disease, for example, or double-vessel disease, or less extensive triple vessel disease without LV dysfunction.

In this week’s article, lead author Dena Bravata and her colleagues from Stanford University report findings from a systematic review of trials comparing PCI and CABG in these patient groups. They identified 23 trials that met their criteria, including 9 in which the percutaneous intervention was balloon angioplasty. Fourteen compared stents and CABG, all but one of which compared bare metal stents to CABG.

Their review had 4 main findings.

First, overall long-term survival was similar with the two procedures.

Second, participants who underwent CABG were more likely to have relief of their angina than those who underwent PCI, although the proportion of patients whose angina was relieved was high in both groups. Patients who had percutaneous interventions were more likely to require repeat revascularization.

Third, in the 6 trials that reported outcomes separately for patients with diabetes, there was no overall significant difference in survival by procedure.

And finally, there was a slightly higher incidence of stroke after CABG compared to PCI.

Based on these findings, the authors conclude that CABG and PCI confer the same long-term benefits for patients in whom revascularization in clinically indicated and in whom both procedures are technically feasible, but short-term differences exist, such as risk for stroke and need for revascularization, that might drive a preference for one or the other procedure in an individual patient. They acknowledge that only 1 small trial compared the use of newer drug-eluting stents to CABG, but they say that newer PCI devices and procedures have not been shown to reduce mortality or myocardial infarction after PCI, so that these review findings are still relevant to today’s procedures and devices. The authors point out that the findings differ from those of studies using data from clinical registries, which have reported improved survival after CABG, but they attribute the difference to the greater representation in the registries of patients with more extensive coronary artery disease at higher risk for events, a group known to do better with surgery. And, they acknowledge that the finding that CABG was no different from PCI for patients with diabetes differs from the conventional wisdom that patients with diabetes do better with CABG, but they say that observational studies using data from clinical registries have found the same thing. For this reason and others they say, more trials are desperately needed to compare the two procedures in important patient subgroups, including patients with and without diabetes, older and younger age groups, men and women, and patients within strata of left ventricular function.

In an accompanying editorial, co-authors Ray Gibbons of the Mayo Clinic and Stephan Fihn of the University of Washington in Seattle reiterate that the review’s findings of long-term equivalence between the two procedures are most applicable to patients with coronary artery disease of intermediate severity, somewhere between left main coronary artery disease or triple vessel disease, in whom CABG is better, and patients with single vessel coronary artery disease and normal LV function, in whom PCI is better. They make the important point that recent trials comparing PCI to optimal medical therapy suggest that referral for revascularization can safely be deferred for many patients if standards for medical therapy set by those trials, including use of antiplatelet agents, anti-ischemic drugs, and aggressive management of coronary risk factors, are upheld in practice. And they reiterate the call for better trials, pointing out the gross imbalance between patients studied – about 10,000 patients over 40 years in 23 trials – and those revascularized over 900,000 patients in 2005 alone.

To get a better handle on these points and on the review, I called one of the editorial’s co-authors. Dr. Stephan Fihn is the Director of the Health Services Research & Development Center of Excellence at the VA Puget Sound in Seattle, Washington, and is a Professor of Medicine and the Division head of General Medicine at the University of Washington-Seattle. He is also the co-chair of the AHA/ACC/ACP committee on guidelines for stable ischemic heart disease.

B: Dr. Fihn thank you for talking to me.

F: You’re welcome

Q: The authors of the review make clear that all the trials were performed prior to the era of drug-eluting stents. But they say that the findings are still relevant because newer PCI techniques and drugs haven’t really been shown to affect mortality or post-procedure MI which were the outcomes of the trials they reviewed. What’s your impression of that claim? Are the findings relevant today or do we need to wait for trials of contemporary PCI and CABG to really say how the interventions compare?

A: That’s a great question. Obviously, one of the difficulties is that we’re always going to be a bit behind the latest technology with the evidence from studies. I think it’s important however to look at the evidence that has emerged in perspective going back to the initial trials, which really have been remarkably consistent. The early trials did show that there were select subgroups of patients particularly those with left main disease, severe multi-vessel disease and left ventricular impairment, who garnered the optimal benefit from revascularization, and those findings remain true to this day. The question then is for patients outside of these special select subgroups to what extent they benefit. And not only has the technology of CABG and PCI greatly improved over this period of time but our understanding and implementation of medical therapy has improved equally. And so in a sense, yes, you’re right, both medical therapy and revascularization therapy have improved. We’re still faced with an incomplete understanding of the benefit of each head-to-head in modern times. But I don’t think we can ignore all the trial data that have been accrued up to this time and my sense is that these findings are relatively stable and will remain so for the foreseeable future.

Q: The review doesn’t make very clear in which clinical populations the 23 trials were conducted. Do we know enough to say if the review’s findings then come from patients with stable angina or those with unstable angina or ST elevation or non ST elevation, MI, and to say if they apply equally or especially to one or more of those groups?

A: That’s another excellent question. The trials that were reviewed were heterogeneous but all were patients who apparently did not have acute coronary syndrome. Some of the trials in enrolled patients who were more high risk and potentially unstable, the AWESOME trial for example, enrolled some patients who were within 7 days of a myocardial infarction. But in general, this was a population with relatively stable coronary disease that could undergo evaluation on a reasonably elective basis. So that I think these apply to the larger population of patients with stable, or if you will, mildly unstable ischemic heart disease. One of the points that Dr. Gibbons and I try to make in the accompanying editorial is that subgroups to which these revascularization techniques are being applied in real practice actually differ substantially from those that have been enrolled in the trials which include either very high risk or very low risk patients. And it turns out that in practice, as one might expect, the vast majority of patients who seem to undergo these procedures according to the registries which the authors of the review examined tend to be of a more intermediate risk category.

Q: You note in your editorial that the Occluded Artery and the COURAGE trials show that optimal medical therapy is as effective as PCI for preventing death and MI. Given that this review found that survival of PCI and CABG are equivalent for those outcomes, can we say anything about the comparative effectiveness of optimal medical therapy and CABG? Can an indirect comparison be made at least for patients like those in the two trials of medical therapy who resemble patients in the review trials?

A: That’s a great question again. To be strictly guided by the evidence, we don’t have modern trials that directly compare head-to-head current optimal medical therapies, such as that which was employed in the COURAGE trial, with CABG for relevant subsets of patients. We only have that with PCI. I think we can extrapolate for some of the patients with an intermediate severity of disease for CABG by the following logic. What COURAGE demonstrates to us is that patients at medium risk of subsequent cardiovascular events and death appear to do as well with aggressive medical management as with revascularization. Thus I think the practicing physician can be reassured that after doing appropriate re-stratification in a patient with symptomatic coronary artery disease, and show that individual to be of low or to medium risk or subsequent events, they can with a fairly high degree of confidence embark upon a course of aggressive medical therapy, understanding that if the patient is not successfully treated in terms of their cardiovascular symptoms they can be subsequently referred for revascularization. At that point then there needs to be a discussion with the patient and the consideration of the alternatives for revascularization which are largely PCI with stenting versus CABG. And it is for that decision that this review is really quite helpful, I believe, in informing physicians and patients about the relative risks and benefits of those two approaches. What COURAGE again tells us is that for the majority of patients who don’t fit into those high risk subgroups which have been shown to have improved survival with revascularization primarily with CABG based on older trials, then we can with confidence treat those patients with modern aggressive medical therapy.

Q: Can you remind us how the provider risk stratifies somebody into low or higher risk, and makes that decision about the need to refer for possible revascularization?

A: It’s done primarily with a clinical assessment and noninvasive tests, particularly exercise tolerance tests, with or without pharmacologic stressors. And using such things as the Duke treadmill score and other scoring techniques, we have what turn out to be very good prognostic instruments which can give us a fairly accurate estimate of an individual patient’s risk of untoward cardiovascular events over the subsequent five years or so. And again, if that percentage is relatively low we can I think confidently treat those patients medically with a very low likelihood of missing life threatening coronary disease that would require revascularization. One of the concerns that Dr. Gibbons and I raise in the editorial is that it does appear that with the widespread adoption of revascularization techniques, that there are enormous geographic variations in the application of this to patients. And in addition there are data from the National Cardiology Data Registry maintained by the American College of Cardiology Foundation, that a substantial number of patients even as reported by hospitals around the country don’t have strong indications according to current clinical practice guidelines for revascularization. Perhaps some of this is related to practitioners’ uncertainty about whether it’s safe to treat patients with angina medically. Those patients get referred for diagnostic catheterization and then because they have lesions they get instrumented and stented. Again I think that we can apply the results of the COURAGE trial and this review to some extent to reassure ourselves about the safety of medical therapy and perhaps improve the appropriateness and reduce what appears to be the overutilization of revascularization for relatively low risk patients.

B: Dr. Fihn, thank you so much for talking to me.

F: You’re welcome. Thanks very much.

That was Dr. Stephan Fihn, Director of Health Services Research & Development at the VA Puget Sound in Seattle and co-author of an editorial accompanying this week’s article on revascularization.

Adult Immunization Schedule, October 2007-September 2008 (Time: 27:30)

This issue also has the latest immunization schedule for adults. We put this out as a separate podcast feed when it was released early last month, but I’m going to replay it again today because of the importance of immunizations to public health and because we’ve taken on new listeners since it was released last month. Once again, if you heard this summary and my interview with Greg Poland when it was posted last month and can’t stand to hear it again, then keep one hand on the driving wheel or the treadmill and use the other to advance your mp3 player to about the 43:09 marker in this audio file.

For the first time this week, Annals is publishing the Center for Disease Control’s annual Adult Immunization Schedule for October 2007 through September 2008.

As in past years, this year’s schedule provides vaccine recommendations for adults stratified by age group, and by medical conditions that might modify recommendations made for the general population. In an editorial accompanying the schedule, Dr. Greg Poland of the Mayo Clinic in Rochester, Minnesota and Dr. William Schaffner of Vanderbilty University in Nashville, urge physicians to familiarize themselves with the immunization schedule and then ensure that their adult patients receive the appropriate vaccines, either by administering the vaccines themselves or by referring patients to setting where they can get them. They acknowledge this will require hard work on the part of organizations and individuals, but say that it should be considered a patient safety and quality of care issue.

I called Dr. Poland, who is the Director of Mayo Vaccine Research Group at the Mayo Clinic in Rochester and is the liaison between the American College of Physicians and the Advisory Committee of Immunization Practices that issues the guidelines, and I asked him to review this year’s schedule.

B: Dr. Poland thank you for joining me.

P: My pleasure.

Q: What’s new in this year’s schedule?

A: In terms of vaccines there’s been a lot of movement. One is a vaccine now to prevent herpes zoster and the major complication of herpes which is post-herpetic neuralgia; a vaccine to prevent at least the more common serotypes of human papillomavirus that cause cervical cancer and genital warts; a slightly less new, but nonetheless important vaccine against pertussis; and then a variety of new indications or new pushes for older vaccines such as influenza vaccine and, based on the recent outbreaks of mumps we’ve had, mumps vaccine.

Q: So let’s break that out a little bit. What are the recommendations for the zoster vaccine? Who should be getting it?

A: So herpes zoster vaccine is indicated routinely for all immunocompetent adults who are age 60 or older. Being that it’s a live though attenuated vaccine, it’s not one used in immunocompromised individuals. And it’s given one time, at least at this point, in a lifetime. We don’t believe at the current time that booster doses would be needed.

Q: And can you remind listeners about the difference between the varicella and zoster vaccines?

A: The varicella vaccine is given to prevent chickenpox or varicella, and the herpes zoster vaccine is given to people who have already had chickenpox and we’re trying to boost their cellular immunity to prevent reactivation of latent virus. The herpes zoster vaccine has a level of virus in it that is many-fold higher than the varicella vaccine.

Q: So as the young cohort who have been receiving primary varicella series gets older, will they need zoster vaccine?

A: That’s a good question and it’s unclear. In part, with the varicella vaccine\ and we should say with all vaccines, there is a certain level of vaccine failure, so there will be and are some people who have gotten varicella vaccine who nonetheless will develop chickenpox upon exposure. So it’s a little unclear yet as those cohorts mature and become older what we’ll do. I suspect that just like the case with natural virus infection at some level of age in the 50, 60 age group we will need to give something to boost cellular immunity because it’s quite apparent that zoster results from a decrease or a waning of cellular immunity and hence an activation of virus that’s latent and chronic and persistent.

Q: And you mentioned the new human papillomavirus vaccine. What should listeners know about that?

A: A couple of things. It’s a quadrivalent vaccine. That means it includes four of the well over 100 subtypes of HPV but these 4 subtypes cause about 70% of cervical cancers and about 90% of genital warts. At the current time it’s recommended only for women, though studies are being done in men, and it’s indicated for all women age 11 to 26 years of age and certainly that’s an age group that internists do see. It is a 3-dose series at 0, 2, and 6 months. And really the only contraindication other than allergy to a component of the vaccine would be pregnancy.

Q: You mentioned the new pertussis vaccine. Now that’s been grouped with the tetanus and diphtheria vaccine to make the Tdap immunization.

A: Just to be clear, because it is a little confusing, there are two Tdap products but only one, the one called Adacel® that’s made by Sanofi Pasteur and is licensed for use in adults. It’s recommended as a one time, one dose administration to all adults age 64 or younger. Now, for our usual patients we would give it in place of the next Td booster so when the last one was ten years or more ago. But for health care workers and for women who are postpartum or individuals who have a lot of contact with young children and infants, the interval between the last Td booster and this new Tdap booster can be as short as two years.

Q: So if a patient without those qualifying medical conditions has recently received a tetanus-diphtheria booster, how long should they wait to receive the Tdap? Can they wait 10 years?

A: Well they’d wait a minimum of two years from the last booster and we wouldn’t want them to be more than 10 years from that last booster. And one point to particularly make clear is that this is a vaccine recommended for all health care workers who have patient contact. It’s worth emphasizing particularly to internists that adults are the reservoir of infection for children and there have been over the last several years numerous outbreaks of pertussis where a health care worker was the vector and was the index case. So we’re really trying to make a strong push for health care workers getting this vaccine.

Q: And remind us why adults age 65 and older are excluded from the recommendation.

A: Yeah that’s a good question. It has more to do with the fact that it wasn’t studied in people older than that, primarily I think out of convenience but when you think about it certainly people that age are still in practice, for example, if they’re health care workers and probably more importantly are grandparents and have exposure to young children. But it just simply hasn’t been studied and because that data was not available, FDA doesn’t license it for an age group in which it wasn’t studied.

Q: And in your editorial this week you write about new indications for influenza vaccines. Can you review those for us?

A: Yes. You know there are now well over 15 indications for influenza vaccines. But a couple that internists may not be aware of is a new indication to give the vaccine to anyone who has any condition that compromises the handling of respiratory secretions or increases the risk of aspiration. Just because of the increased risk of pneumonias that occur and certainly during influenza season that’s a risk. The other thing is that women who will be or are pregnant any time during influenza season at any stage of their pregnancy should get influenza vaccine. And then to come back to a topic we discussed with pertussis, it’s very clear that health care workers spread influenza to their patients and to their co-workers and health care facilities and now there has been a big push to get health care workers immunized every year, either with trivalent, inactivated, or the live attenuated intranasal spray vaccine. And in fact, the CDC, the American College of Physicians, the Infectious Disease Society of America, and a host of other professional societies have now said this is the standard of care. All health care workers should get this vaccine unless they have a contraindication or sign actively a declination form. And it really relates to physicians and nurses and other health care workers being the vectors of spread to influenza to the patients we see, and when you think about it, it’s the immunocompromised, for pediatricians and family docs the young, the pregnant woman, the people who are likely to have complications or perhaps even die if they get influenza.

Q: What are the updated recommendations for the hepatitis B vaccine?

A: Importantly the ACIP recommendations have been modified a little bit. It used to be that for adults hepatitis B vaccine was given if they met certain occupational or lifestyle circumstances. One of my colleagues likes to put it, you really couldn’t get hep B vaccine unless you admitted to bad behavior. And now the CDC is recommending hepatitis B vaccine for all sexually active persons who are not in a long-term mutually monogamous relationship. And that’s different. So no longer does one have to acknowledge a specific risk factor to meet the criteria for vaccination. It’s really any sexually active adult who’s not in a long-term monogamous relationship.

And I should say too that there are also some new recommendations regarding mumps vaccine. Because there have been some large scale mumps outbreaks within the US the ACIP has recommended a second dose of mumps vaccine for people who fit in specific age groups or who have risk factors. And in particular, the ACIP is recommending a second dose of mumps vaccine for adults who work in any sort of health facility. And immunity to one or more of the MMR components is not a contraindication to receiving mumps vaccine and I mention it because it’s standardly given as an MMR and not just as mumps.

Q: So you don’t split that out to give a second mumps booster, you give the MMR again?

A: Right, there’s no need to, and in fact, I believe mumps vaccine alone is equally, if not more, expensive than MMR vaccine.

Q: Now the recommendations for pneumococcal vaccination remains unchanged. That is, a single vaccination for at risk patients followed by another at age 65.

A: The recommendations are, that if there’s a specific risk factor you’d get it below the age of 65. If you are otherwise healthy, the recommendation is to give it at age 65. There’s only a small subgroup of people whoever get a second one-time dose. And I’ll mention those in a minute but I say it carefully like that because it is a persistent misconception on many internists’ part that pneumococcal vaccine should be repeated every five years or given multiple times. And that is both untrue, incorrect, and potentially harmful. The recommendation is that if you got your first dose below the age of 65 when you are 65, or it’s been 5 or more years, you get a one-time, one-dose, never any more after that. If you’re over the age of 65 when you get your first dose, if somebody is immunocompromised or has a medical condition whereby they rapidly lose antibody, for example in chronic renal failure, they get a one-time dose if its been 5 or more years. So nobody gets more than two doses as an adult in a lifetime. And it’s only a subset who actually ever get that second dose.

Q: And why are multiple doses of the vaccine potentially harmful?

A: For one, there’s the possibility of allergic reactions or hypersensitivity reactions and we see it with Td vaccine too related to having high levels of antibodies against a polysaccharide antigen and then further stimulating. The other side of the coin is there’s some, and this is a little less clear, but some experimental evidence to say that when you give a polysaccharide vaccine like this too frequently you may in fact induce tolerance to that antigen and paradoxically have a decrease in antibody level.

Q: One of the things we commonly encounter in the clinic is an incomplete medical record without knowing whether a patient has had pneumovax or not and the default has always been well if we don’t know if they’ve had it and their at risk let’s give it.

A: And I would agree absolutely with the idea that if it’s unclear as to whether the patient has had pneumococcal vaccine to go ahead and give it. From a public health perspective, that’s a better strategy because the vast majority of those people, it’s unlikely that they’ve had 3, 4, or 5 or more vaccines without knowing it.

B: Dr. Poland thank you so much for talking to me.

A: My pleasure.

That was Dr. Greg Poland, the Director of the Mayo Vaccine Research Group at the Mayo Clinic in Rochester and the author of an editorial this week on the new CDC recommendations.

For more information about ACIP immunization recommendations for specific vaccines and patient subsets, go to www.cdc.gov/vaccines. And if you’re a medical student, a resident, or an attending physician listening to this summary, go out now and get your flu shot and your mumps and Tdap boosters if you haven’t had them already.

Other Articles In This Week’s Issue (Time: 43:02)

Other articles in this week’s issue include a randomized trial of lumbar supports to prevent low back pain in home care workers in the Netherlands, demonstrating that the supports reduced the number of days the workers had pain by about 5 days, but disappointingly, had no effect on work absenteeism.

We have a cross-sectional study from Mount Sinai Medical Center’s geriatrics practice in New York City in which 16 providers documented the amount of time they spent caring for patients outside of office visits, and the group reported spending an estimated mean 112 extra minutes per week – that’s almost 2 hours per provider – or 6 to 7 minutes outside of the scheduled visit for each scheduled half-hour of work. This is a small study, but it seemed to be the first published empirical data on the total amount of unreimbursed work adult primary care providers do to support reimbursed visits, and it leads Tom Bodenheimer from San Francisco General Hospital to call for reimbursement reform in an accompanying editorial.

We have a description of 130 cases of spontaneous tuberculosis associated with the use of infliximab and reported to the FDA through May of 2006, 19 of which were fatal, leading the authors to conclude that clinicians need to be vigilant in screening and monitoring for tuberculosis in patients receiving infliximab.

And finally we have an Update in Hematology, the 8th of 10 updates appearing this year based on presentations given at the American College of Physicians annual Internal Medicine 2007 session held in April in San Diego.

Well that’s it for today. This has been our longest audio summary ever, and I appreciate your sticking with me. You’ve eaten your vegetables for this issue, and now it’s time for dessert. We went out with a song on last issue’s summary and we’ll do it again this week.

For any medical students who may be listening, this song describes some of the symptoms and signs of hepatitis C infection, the sometimes disabling side effects of interferon therapy, and the songwriter’s struggle to deal with his embarrassment at having the infection and the lifestyle choices it implies. In honor of our lead article demonstrating improved clinical outcomes in hepatitis C patients with sustained response to treatment, here’s Zeb Calister from Paragon Indiana outside of Indianopolis, with his 2006 recording of Simple Lies, Ordinary Dreams.

[Music]

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 these podcasts.

Send feedback, suggestions, comments, and criticisms about this summary and the journal to podcast{at}annals.org.

Check back in 2 weeks for a complete summary of our regularly scheduled December 4, 2007 issue.

If you live in the United States have a great Thanksgiving holiday.

I’m Michael Berkwits, and thanks for listening.

[Music]

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