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The need for reappraisal of AIDS score weight of Charlson comorbidity index
Journal of Clinical Epidemiology 60 (2007) 867e868
COMMENTARY
The need for reappraisal of AIDS score weight of Charlson comorbidity index Alexandre Prehn Zavascki*, Sandra Costa Fuchs Medical Sciences Post-graduate Program, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil Accepted 7 November 2006
Abstract Objective: To discuss the need for reappraisal of AIDS score weight of the Charlson comorbidity index. Study Design and Setting: This article is a comment on Charlson comorbidity index. Results: This article shows that the weight assigned for AIDS in the original cohort of Charlson score may be higher considering the dramatic improvement in the prognosis of such patients after the advent of highly active antiretroviral therapy. Only a few exceptions among HIV-related diseases are still strongly associated with high mortality rates within 1 year. This might lead to an inaccurate measurement of the impact of Charlson score on mortality rate, particularly in cohorts with high relative number of AIDS patients. Conclusion: Charlson comorbidity index should be reassessed in cohorts with higher proportions of AIDS patients, taking into account the current prognosis of the disease. A stratification of AIDS-related category may be required to improve Charlson score accuracy in predicting mortality or adjusting for confounding. Ó 2007 Elsevier Inc. All rights reserved. Keywords: Charlson comorbidity index; AIDS; Mortality; Highly active antiretroviral therapy; Risk adjustment; Cohort studies
Comorbidity adjustment is an essential component of any longitudinal study that aims to evaluate clinical outcomes. The Charlson comorbidity index, which was developed in 1987 by Charlson et al. [1], is one of the most widely used and validated comorbidity scoring systems, and it has been a useful tool for health researchers in their effort to measure comorbidity disease status or case mix in health care databases [2]. The Charlson score consists of 19 different disease comorbidity categories, each allocated a weight of 1e6 based on the adjusted relative risk of 1year mortality and summed to provide a total score, which is an indicator of disease burden and a strong estimator of mortality. This scoring system has been adapted for use with administrative databases using diagnostic codes from the International Classification of Diseases, 9th and 10th revisions, and it has been validated in different populations [2,3]. However, the overall impact of the score on mortality rates for diseases, which current medical care and treatment
* Corresponding author. Hospital Sa˜o Lucas da Pontifı´cia Universidade Cato´lica do Rio Grande do Sul, Servic¸o de Infectologia, 6690 Ipiranga Avenue, 90610-000 Porto Alegre e RS, Brazil. Tel.:/fax: þ55 51 33621850. E-mail address: [email protected] (A.P. Zavascki). 0895-4356/07/$ e see front matter Ó 2007 Elsevier Inc. All rights reserved. doi: 10.1016/j.jclinepi.2006.11.004
have improved since the score was developed, has not been assessed. For example, the prognosis of patients with HIV infection has dramatically changed with introduction of highly active antiretroviral therapy (HAART), which decreased the rates of opportunistic infections, progression to AIDS, and the overall mortality [4]. AIDS along with metastatic cancer has the highest comorbidity weight (6) in the Charlson score [1]. Because weights for each disease have arisen from the adjusted relative risk for 1-year mortality, and it was extremely high for AIDS patients in the original cohort, AIDS has received the highest value. In fact, the original cohort enrolled patients in 1984, when there was no effective treatment for HIV/AIDS [1]. The 1-year mortality of the 17 patients with AIDS in such a cohort was 82% [1], a rate that surely does not represent current rates of AIDS-patients’ mortality [4]. For instance, in the United States, HAART has prolonged life by an estimated period of 13 years [5]. This benefit is applied even to patients with extremely low T cells CD4 counts [5]. Thus, the weight 6 for AIDS might lead to an inaccurate measurement of the impact of Charlson score on mortality rate, because a high score is assigned to a disease that has no longer such impact. According to recent data [4,5], the relative risk for 1-year mortality of patients with AIDS and consequently its adjusted weights would be similar to, or even lower than, diseases
868
A.P. Zavascki, S.C. Fuchs / Journal of Clinical Epidemiology 60 (2007) 867e868
such as myocardial infarct, congestive heart failure, dementia, and diabetes, which were assigned weight 1 [1]. Only a few exceptions among HIV-related diseases, such as primary central nervous system nonHodking lymphoma [6] and progressive multifocal leukoencephalopathy [7], are still strongly associated with high mortality rates within 1 year, although significant improvement has been reached for the former [6]. Another exception is those multifailed patients with low CD4 cells counts [4,5]. Thus, it is likely that, the weight 6 would be only applicable to both these conditions. Among cohorts of AIDS patients, with small number of participants, this potential bias might not be perceived. However, the Charlson weight is likely to generate more inaccurate results as the proportion of AIDS cases increases. A specific threshold for the number of AIDS patients in which the Charlson score would lead to doubtful estimations could not be easily determined. However, it would be particularly problematic if the score was used to control for confounding comorbidities between groups with different number of AIDS patients, but with similar risk of death for other conditions. In this case, Charlson score would lead to inaccurate estimates because the group with higher proportion of AIDS patients would have higher weight mean, but not higher mortality. For example, in a recent cohort of patients with nosocomial infections [8], the median Charlson score was significantly higher among nonsurvivors than survivors in the univariate analysis (4, interquartile range [IQR] 2e6 vs. 3, IQR 1e5, respectively; P 5 0.002). Nine (8.2%) of the 112 nonsurvivors and 10 (5.4%) of the 186 survivors had HIV/AIDS (P 5 0.51). Hypothetically, if there were 20 more HIV patients or AIDS patients with controlled disease among survivors (30 of 186, 16.1%, P 5 0.07) the median Charlson score of this group would be 4 (IQR 2e6), and there would not be statistically significant difference between survivors and nonsurvivors (P 5 0.24). The specific adjusted relative risk for 1-year mortality for AIDS and AIDS-related diseases should be recalculated. Because AIDS mortality is strongly associated with the immunological status and its potential for recovery with HAART, the ability of the Charlson to risk adjust in analyses relating to HIV/AIDS will require different weights for specific conditions of this disease. A weight of 1 would likely be more suitable for HIV patients with high CD4 counts and 2 for AIDS patients receiving HAART, whereas the weight 6 would likely be applicable to the few conditions cited above. The weights of Charlson comorbidity index related to HIV/AIDS should be reassessed in large cohorts with higher proportions of AIDS patients. However,
such a reappraisal should not be performed in a cohort including only HIV/AIDS patients to keep the overall generalizability of the score. Further research should follow previous successful attempts to develop a new comorbidity index by assigning study-specific data-derived weights to the original Charlson comorbidity variables [9]. In summary, Charlson score is a useful instrument, which has been broadly used across a wide variety of chronic disease populations to control systematic error due to confounding. As the original paper cautioned, the index should not be viewed as the final, definitive study because the number of patients with any given level of seriousness of a comorbid disease was relatively small [1]. Treatment strategies and survival for several of the conditions, particularly AIDS, have changed over the past two decades, when the instrument was originally published, and a reassessment of the weights of AIDS, and maybe of other diseases, is required to ensure the ability of this comorbidity index scoring system to reach its ultimate purpose.
References [1] Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987;40:373e83. [2] Sundararajan V, Henderson T, Perry C, Muggivan A, Quan H, Ghali WA. New ICD-10 version of the Charlson comorbidity index predicted in-hospital mortality. J Clin Epidemiol 2004;57:1288e94. [3] D’Hoore W, Bouckaert A, Tilquin C. Practical considerations on the use of the Charlson comorbidity index with administrative data bases. J Clin Epidemiol 1996;49:1429e33. [4] Mocroft A, Ledergerber B, Katlama C, Kirk O, Reiss P, d’Arminio Monforte A, et al, EuroSIDA study group. Decline in the AIDS and death rates in the EuroSIDA study: an observational study. Lancet 2003;362:22e9. [5] Walensky RP, Paltiel AD, Losina E, Mercincavage LM, Schackman BR, Sax PE, et al. The survival benefits of AIDS treatment in the United States. J Infect Dis 2006;194:11e9. [6] Diamond C, Taylor TH, Im T, Miradi M, Wallace M, Anton-Culver H. Highly active antiretroviral therapy is associated with improved survival among patients with AIDS-related primary central nervous system non-Hodgkin’s lymphoma. Curr HIV Res 2006;4:375e8. [7] Wyen C, Lehmann C, Fatkenheuer G, Hoffmann C. AIDS-related progressive multifocal leukoencephalopathy in the era of HAART: report of two cases and review of the literature. AIDS Patient Care STDS 2005;19:486e94. [8] Zavascki AP, Barth AL, Goncalves AL, Moro AL, Fernandes JF, Martins AF, et al. The influence of metallo-beta-lactamase production on mortality in nosocomial Pseudomonas aeruginosa infections. J Antimicrob Chemother 2006;58:387e92. [9] Ghali WA, Hall RE, Rosen AK, Ash AS, Moskowitz MA. Searching for an improved clinical comorbidity index for use with ICD-9-CM administrative data. J Clin Epidemiol 1996;49:273e8.
COMMENTARY
The need for reappraisal of AIDS score weight of Charlson comorbidity index Alexandre Prehn Zavascki*, Sandra Costa Fuchs Medical Sciences Post-graduate Program, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil Accepted 7 November 2006
Abstract Objective: To discuss the need for reappraisal of AIDS score weight of the Charlson comorbidity index. Study Design and Setting: This article is a comment on Charlson comorbidity index. Results: This article shows that the weight assigned for AIDS in the original cohort of Charlson score may be higher considering the dramatic improvement in the prognosis of such patients after the advent of highly active antiretroviral therapy. Only a few exceptions among HIV-related diseases are still strongly associated with high mortality rates within 1 year. This might lead to an inaccurate measurement of the impact of Charlson score on mortality rate, particularly in cohorts with high relative number of AIDS patients. Conclusion: Charlson comorbidity index should be reassessed in cohorts with higher proportions of AIDS patients, taking into account the current prognosis of the disease. A stratification of AIDS-related category may be required to improve Charlson score accuracy in predicting mortality or adjusting for confounding. Ó 2007 Elsevier Inc. All rights reserved. Keywords: Charlson comorbidity index; AIDS; Mortality; Highly active antiretroviral therapy; Risk adjustment; Cohort studies
Comorbidity adjustment is an essential component of any longitudinal study that aims to evaluate clinical outcomes. The Charlson comorbidity index, which was developed in 1987 by Charlson et al. [1], is one of the most widely used and validated comorbidity scoring systems, and it has been a useful tool for health researchers in their effort to measure comorbidity disease status or case mix in health care databases [2]. The Charlson score consists of 19 different disease comorbidity categories, each allocated a weight of 1e6 based on the adjusted relative risk of 1year mortality and summed to provide a total score, which is an indicator of disease burden and a strong estimator of mortality. This scoring system has been adapted for use with administrative databases using diagnostic codes from the International Classification of Diseases, 9th and 10th revisions, and it has been validated in different populations [2,3]. However, the overall impact of the score on mortality rates for diseases, which current medical care and treatment
* Corresponding author. Hospital Sa˜o Lucas da Pontifı´cia Universidade Cato´lica do Rio Grande do Sul, Servic¸o de Infectologia, 6690 Ipiranga Avenue, 90610-000 Porto Alegre e RS, Brazil. Tel.:/fax: þ55 51 33621850. E-mail address: [email protected] (A.P. Zavascki). 0895-4356/07/$ e see front matter Ó 2007 Elsevier Inc. All rights reserved. doi: 10.1016/j.jclinepi.2006.11.004
have improved since the score was developed, has not been assessed. For example, the prognosis of patients with HIV infection has dramatically changed with introduction of highly active antiretroviral therapy (HAART), which decreased the rates of opportunistic infections, progression to AIDS, and the overall mortality [4]. AIDS along with metastatic cancer has the highest comorbidity weight (6) in the Charlson score [1]. Because weights for each disease have arisen from the adjusted relative risk for 1-year mortality, and it was extremely high for AIDS patients in the original cohort, AIDS has received the highest value. In fact, the original cohort enrolled patients in 1984, when there was no effective treatment for HIV/AIDS [1]. The 1-year mortality of the 17 patients with AIDS in such a cohort was 82% [1], a rate that surely does not represent current rates of AIDS-patients’ mortality [4]. For instance, in the United States, HAART has prolonged life by an estimated period of 13 years [5]. This benefit is applied even to patients with extremely low T cells CD4 counts [5]. Thus, the weight 6 for AIDS might lead to an inaccurate measurement of the impact of Charlson score on mortality rate, because a high score is assigned to a disease that has no longer such impact. According to recent data [4,5], the relative risk for 1-year mortality of patients with AIDS and consequently its adjusted weights would be similar to, or even lower than, diseases
868
A.P. Zavascki, S.C. Fuchs / Journal of Clinical Epidemiology 60 (2007) 867e868
such as myocardial infarct, congestive heart failure, dementia, and diabetes, which were assigned weight 1 [1]. Only a few exceptions among HIV-related diseases, such as primary central nervous system nonHodking lymphoma [6] and progressive multifocal leukoencephalopathy [7], are still strongly associated with high mortality rates within 1 year, although significant improvement has been reached for the former [6]. Another exception is those multifailed patients with low CD4 cells counts [4,5]. Thus, it is likely that, the weight 6 would be only applicable to both these conditions. Among cohorts of AIDS patients, with small number of participants, this potential bias might not be perceived. However, the Charlson weight is likely to generate more inaccurate results as the proportion of AIDS cases increases. A specific threshold for the number of AIDS patients in which the Charlson score would lead to doubtful estimations could not be easily determined. However, it would be particularly problematic if the score was used to control for confounding comorbidities between groups with different number of AIDS patients, but with similar risk of death for other conditions. In this case, Charlson score would lead to inaccurate estimates because the group with higher proportion of AIDS patients would have higher weight mean, but not higher mortality. For example, in a recent cohort of patients with nosocomial infections [8], the median Charlson score was significantly higher among nonsurvivors than survivors in the univariate analysis (4, interquartile range [IQR] 2e6 vs. 3, IQR 1e5, respectively; P 5 0.002). Nine (8.2%) of the 112 nonsurvivors and 10 (5.4%) of the 186 survivors had HIV/AIDS (P 5 0.51). Hypothetically, if there were 20 more HIV patients or AIDS patients with controlled disease among survivors (30 of 186, 16.1%, P 5 0.07) the median Charlson score of this group would be 4 (IQR 2e6), and there would not be statistically significant difference between survivors and nonsurvivors (P 5 0.24). The specific adjusted relative risk for 1-year mortality for AIDS and AIDS-related diseases should be recalculated. Because AIDS mortality is strongly associated with the immunological status and its potential for recovery with HAART, the ability of the Charlson to risk adjust in analyses relating to HIV/AIDS will require different weights for specific conditions of this disease. A weight of 1 would likely be more suitable for HIV patients with high CD4 counts and 2 for AIDS patients receiving HAART, whereas the weight 6 would likely be applicable to the few conditions cited above. The weights of Charlson comorbidity index related to HIV/AIDS should be reassessed in large cohorts with higher proportions of AIDS patients. However,
such a reappraisal should not be performed in a cohort including only HIV/AIDS patients to keep the overall generalizability of the score. Further research should follow previous successful attempts to develop a new comorbidity index by assigning study-specific data-derived weights to the original Charlson comorbidity variables [9]. In summary, Charlson score is a useful instrument, which has been broadly used across a wide variety of chronic disease populations to control systematic error due to confounding. As the original paper cautioned, the index should not be viewed as the final, definitive study because the number of patients with any given level of seriousness of a comorbid disease was relatively small [1]. Treatment strategies and survival for several of the conditions, particularly AIDS, have changed over the past two decades, when the instrument was originally published, and a reassessment of the weights of AIDS, and maybe of other diseases, is required to ensure the ability of this comorbidity index scoring system to reach its ultimate purpose.
References [1] Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987;40:373e83. [2] Sundararajan V, Henderson T, Perry C, Muggivan A, Quan H, Ghali WA. New ICD-10 version of the Charlson comorbidity index predicted in-hospital mortality. J Clin Epidemiol 2004;57:1288e94. [3] D’Hoore W, Bouckaert A, Tilquin C. Practical considerations on the use of the Charlson comorbidity index with administrative data bases. J Clin Epidemiol 1996;49:1429e33. [4] Mocroft A, Ledergerber B, Katlama C, Kirk O, Reiss P, d’Arminio Monforte A, et al, EuroSIDA study group. Decline in the AIDS and death rates in the EuroSIDA study: an observational study. Lancet 2003;362:22e9. [5] Walensky RP, Paltiel AD, Losina E, Mercincavage LM, Schackman BR, Sax PE, et al. The survival benefits of AIDS treatment in the United States. J Infect Dis 2006;194:11e9. [6] Diamond C, Taylor TH, Im T, Miradi M, Wallace M, Anton-Culver H. Highly active antiretroviral therapy is associated with improved survival among patients with AIDS-related primary central nervous system non-Hodgkin’s lymphoma. Curr HIV Res 2006;4:375e8. [7] Wyen C, Lehmann C, Fatkenheuer G, Hoffmann C. AIDS-related progressive multifocal leukoencephalopathy in the era of HAART: report of two cases and review of the literature. AIDS Patient Care STDS 2005;19:486e94. [8] Zavascki AP, Barth AL, Goncalves AL, Moro AL, Fernandes JF, Martins AF, et al. The influence of metallo-beta-lactamase production on mortality in nosocomial Pseudomonas aeruginosa infections. J Antimicrob Chemother 2006;58:387e92. [9] Ghali WA, Hall RE, Rosen AK, Ash AS, Moskowitz MA. Searching for an improved clinical comorbidity index for use with ICD-9-CM administrative data. J Clin Epidemiol 1996;49:273e8.