- Email: [email protected]
Lung transplantation
CORRESPONDENCE
methods could have provided a superior specificity, but were not a practical alternative. To avoid unnecessary bias, we did not actively seek information on sideeffects, and the few severe reactions were recorded separately from the patients’ medical records. The methods we used for the diagnosis of non-bacteraemic pneumonia are not universally accepted. However, to our knowledge there are no other methods available, and again, the study was double-blind. We do not believe that we overdiagnosed pneumococcal pneumonia in our study. The rate of bacteraemic and non-bacteraemic pneumococcal pneumonia was about 1 and 5–6, respectively, a figure similar to earlier reports. It is unfortunate that the full set of tests was not obtained in all patients. However, since streptococcus is the main pathogen of communityacquired pneumonia, and it is not possible to obtain an aetiological diagnosis in all patients with this infection, the primary endpoint of pneumonia is probably the most important one. The power of our study was less than expected because the incidence of pneumococcal pneumonia in our population was lower than our pretrial calculations. However, the KaplanMeier survival curve clearly spoke against the possibility that the vaccine was efficacious against pneumococcal pneumonia in this population. Further, until recently the only basis for a possible protective efficacy against pneumococcal pneumonia in the elderly has been data obtained from efficacy studies on invasive disease, and not from clinical studies of pneumonia. There is one recent exception (published after our study was submitted) in which elderly high-risk patients had a 59% (95% CI 6 to 82), protective efficacy in the prevention of pneumococcal pneumonia.3 However, this study, conducted more than 10 years ago with the 14-valent vaccine, yielded conflicting results, since nearly the opposite results (although not statistically significant) were observed in low-risk patients, with a protective efficacy of ⫺66% (⫺257 to 23). Finally, our study lends support to earlier findings that the vaccine is effective in the prevention of invasive pneumococcal disease in elderly patients. Unlike Sutton, we believe that this is the indication for using the vaccine. The incidence of invasive pneumococcal disease and of antibiotic-resistant pneumococci is increasing in most parts of the world. These factors, together with
THE LANCET • Vol 351 • April 25, 1998
the safety and low costs associated with the pneumococcal vaccine, make a general vaccination in the elderly advisable.
about the benefits and risks of lung transplantation in the clearest possible terms. *Scott D Ramsey, Eric Larson
*Åkke Örtqvist, Jonas Hedlund, Mats Kalin Department of Infectious Diseases, Karolinska Institute, Danderyd Hospital, S-18288 Danderyd, Sweden 1
2
3
Hedlund JU, Örtqvist BÅ, Kalin Me, ScaliaTomba G, Giesecke J. Risk of pneumonia in patients previously treated in hospital for pneumonia. Lancet 1992; 340: 396–97. Hedlund JU, Kalin ME, Örtqvist BÅ, Henrichsen J. Antibody response to pneumococcal vaccine in middle-aged and elderly patients recently treated for pneumonia. Arch Intern Med 1994; 154: 1961–65. Koivula I, Stén M, Leinonen M, Mäkeä PH. Clinical efficacy of pneumococcal vaccine in the elderly: a randomised, single-blind population-based trial. Am J Med 1997; 103: 281–90.
Lung transplantation Sir—Jeffrey Hosenpud and colleagues (Jan 3, p 24)1 find that survival for most lung-transplant patients does not exceed survival for patients on the waiting list for transplants. With mathematical techniques to project short-term survival statistics, we reported similar findings in our costeffectiveness analysis of lungtransplantation 3 years ago.2 This finding was the primary reason that lung transplantation proved costineffective compared with other organtransplant technologies. Our study was greeted with scepticism and hostility by many in the transplant community.3 Since there are limitations on the resources that can be allocated for health care, policy makers should ask whether expensive new interventions provide good health value for expenditure. So far, the limited supply of donor lungs had not made this an especially important issue—transplant demand will continue to greatly exceed supply for the foreseeable future. At the level of doctor and patient, however, it is most important to provide clear information about the health value of a particular treatment relative to the alternatives. For patients considering lung transplantation, the most relevant question is whether they will be willing to accept the up-front mortality risks (and out-of-pocket expense) for improved quality of life without a high likelihood of longer survival. Economics aside, the data provided by the United Network for Organ Sharing team compel clinicians to speak openly
Center for Cost and Outcomes Research, School of Medicine, School of Public Health and Community Medicine, University of Washington, Box 358853, Seattle, WA 98195, USA 1
2
3
Hosenpud JD, Bennett LE, Keck BM, Edwards EB, Novick RJ. Effect of diagnosis on survival benefit of lung transplantation for end-stage lung disease. Lancet 1998; 35: 24–27. Ramsey SD, Patrick DL, Albert RA, Larson EB, Wood DE, Raghu G. The costeffectiveness of lung-transplantation: a pilot study. Chest 1995; 108: 1594–601. Reassessing the cost-effectiveness of lung transplantation. Chest 1996; 110: 577.
Do Asian HBV carriers differ from non-Asian carriers? Sir—In his Jan 17 commentary, Robert Carithers1 expresses concerns about our report2 of spontaneous rates of seroconversion in hepatitis B virus (HBV) carriers from HBeAg-positive to HBeAg-negative. We compared spontaneous seroconversion rates in a cohort of Asian-American carriers with those reported for carriers treated with interferon-␣ in randomised clinical trials, most of whom were non-Asian.3 As a guide to physicians in advising patients whether to undergo this difficult, expensive, and often unsuccessful treatment, we presented a natural history of spontaneous seroconversion in carriers (aged 5–50 years) with raised serum alanine aminotransferase (ALT) over the average treatment and follow-up period used in clinical trials compared with treatment-associated seroconversion rates. We showed that seroconversions continue to occur at a substantial rate throughout adulthood in carriers, and concluded that treatment therefore results in an average acceleration of seroconversion usually of only 8–18 months. Because studies differ greatly in their initial populations, follow-up methods, and prevalence of raised ALT, there is great variation in published rates of spontaneous seroconversion for both Asian and non-Asian patients. Carithers suggests that our seroconversion rates in people with raised ALT (15–23% in 15 months) are substantially higher than those seen in carriers of European origin who generally acquire infection later in life. He cites an average rate of 9% in 15 months for European carriers on the
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methods could have provided a superior specificity, but were not a practical alternative. To avoid unnecessary bias, we did not actively seek information on sideeffects, and the few severe reactions were recorded separately from the patients’ medical records. The methods we used for the diagnosis of non-bacteraemic pneumonia are not universally accepted. However, to our knowledge there are no other methods available, and again, the study was double-blind. We do not believe that we overdiagnosed pneumococcal pneumonia in our study. The rate of bacteraemic and non-bacteraemic pneumococcal pneumonia was about 1 and 5–6, respectively, a figure similar to earlier reports. It is unfortunate that the full set of tests was not obtained in all patients. However, since streptococcus is the main pathogen of communityacquired pneumonia, and it is not possible to obtain an aetiological diagnosis in all patients with this infection, the primary endpoint of pneumonia is probably the most important one. The power of our study was less than expected because the incidence of pneumococcal pneumonia in our population was lower than our pretrial calculations. However, the KaplanMeier survival curve clearly spoke against the possibility that the vaccine was efficacious against pneumococcal pneumonia in this population. Further, until recently the only basis for a possible protective efficacy against pneumococcal pneumonia in the elderly has been data obtained from efficacy studies on invasive disease, and not from clinical studies of pneumonia. There is one recent exception (published after our study was submitted) in which elderly high-risk patients had a 59% (95% CI 6 to 82), protective efficacy in the prevention of pneumococcal pneumonia.3 However, this study, conducted more than 10 years ago with the 14-valent vaccine, yielded conflicting results, since nearly the opposite results (although not statistically significant) were observed in low-risk patients, with a protective efficacy of ⫺66% (⫺257 to 23). Finally, our study lends support to earlier findings that the vaccine is effective in the prevention of invasive pneumococcal disease in elderly patients. Unlike Sutton, we believe that this is the indication for using the vaccine. The incidence of invasive pneumococcal disease and of antibiotic-resistant pneumococci is increasing in most parts of the world. These factors, together with
THE LANCET • Vol 351 • April 25, 1998
the safety and low costs associated with the pneumococcal vaccine, make a general vaccination in the elderly advisable.
about the benefits and risks of lung transplantation in the clearest possible terms. *Scott D Ramsey, Eric Larson
*Åkke Örtqvist, Jonas Hedlund, Mats Kalin Department of Infectious Diseases, Karolinska Institute, Danderyd Hospital, S-18288 Danderyd, Sweden 1
2
3
Hedlund JU, Örtqvist BÅ, Kalin Me, ScaliaTomba G, Giesecke J. Risk of pneumonia in patients previously treated in hospital for pneumonia. Lancet 1992; 340: 396–97. Hedlund JU, Kalin ME, Örtqvist BÅ, Henrichsen J. Antibody response to pneumococcal vaccine in middle-aged and elderly patients recently treated for pneumonia. Arch Intern Med 1994; 154: 1961–65. Koivula I, Stén M, Leinonen M, Mäkeä PH. Clinical efficacy of pneumococcal vaccine in the elderly: a randomised, single-blind population-based trial. Am J Med 1997; 103: 281–90.
Lung transplantation Sir—Jeffrey Hosenpud and colleagues (Jan 3, p 24)1 find that survival for most lung-transplant patients does not exceed survival for patients on the waiting list for transplants. With mathematical techniques to project short-term survival statistics, we reported similar findings in our costeffectiveness analysis of lungtransplantation 3 years ago.2 This finding was the primary reason that lung transplantation proved costineffective compared with other organtransplant technologies. Our study was greeted with scepticism and hostility by many in the transplant community.3 Since there are limitations on the resources that can be allocated for health care, policy makers should ask whether expensive new interventions provide good health value for expenditure. So far, the limited supply of donor lungs had not made this an especially important issue—transplant demand will continue to greatly exceed supply for the foreseeable future. At the level of doctor and patient, however, it is most important to provide clear information about the health value of a particular treatment relative to the alternatives. For patients considering lung transplantation, the most relevant question is whether they will be willing to accept the up-front mortality risks (and out-of-pocket expense) for improved quality of life without a high likelihood of longer survival. Economics aside, the data provided by the United Network for Organ Sharing team compel clinicians to speak openly
Center for Cost and Outcomes Research, School of Medicine, School of Public Health and Community Medicine, University of Washington, Box 358853, Seattle, WA 98195, USA 1
2
3
Hosenpud JD, Bennett LE, Keck BM, Edwards EB, Novick RJ. Effect of diagnosis on survival benefit of lung transplantation for end-stage lung disease. Lancet 1998; 35: 24–27. Ramsey SD, Patrick DL, Albert RA, Larson EB, Wood DE, Raghu G. The costeffectiveness of lung-transplantation: a pilot study. Chest 1995; 108: 1594–601. Reassessing the cost-effectiveness of lung transplantation. Chest 1996; 110: 577.
Do Asian HBV carriers differ from non-Asian carriers? Sir—In his Jan 17 commentary, Robert Carithers1 expresses concerns about our report2 of spontaneous rates of seroconversion in hepatitis B virus (HBV) carriers from HBeAg-positive to HBeAg-negative. We compared spontaneous seroconversion rates in a cohort of Asian-American carriers with those reported for carriers treated with interferon-␣ in randomised clinical trials, most of whom were non-Asian.3 As a guide to physicians in advising patients whether to undergo this difficult, expensive, and often unsuccessful treatment, we presented a natural history of spontaneous seroconversion in carriers (aged 5–50 years) with raised serum alanine aminotransferase (ALT) over the average treatment and follow-up period used in clinical trials compared with treatment-associated seroconversion rates. We showed that seroconversions continue to occur at a substantial rate throughout adulthood in carriers, and concluded that treatment therefore results in an average acceleration of seroconversion usually of only 8–18 months. Because studies differ greatly in their initial populations, follow-up methods, and prevalence of raised ALT, there is great variation in published rates of spontaneous seroconversion for both Asian and non-Asian patients. Carithers suggests that our seroconversion rates in people with raised ALT (15–23% in 15 months) are substantially higher than those seen in carriers of European origin who generally acquire infection later in life. He cites an average rate of 9% in 15 months for European carriers on the
1285