• 沒有找到結果。

Structure and bioactivity of the polysaccharides in medicinal plant Dendrobium huoshanense

N/A
N/A
Protected

Academic year: 2021

Share "Structure and bioactivity of the polysaccharides in medicinal plant Dendrobium huoshanense"

Copied!
6
0
0

加載中.... (立即查看全文)

全文

(1)

I

ntroductIon

End-stage renal disease (ESRD) has been recognized as an emerging clinical problem all over the world. In Tai-wan, the incidence rate increased from 375 per million population (PMP) in 2004 to 404 PMP in 2005, whereas the prevalence rate increased from 1,706 PMP in 2004 to 1,830 PMP in 2005 (1). Under the new policy of cost containment of the National Health Insurance of Taiwan, peritoneal dialysis (PD) has been promoted mainly due to its lower expenditure compared with hemodialysis (HD). PD may also be superior to HD in other aspects. PD pre-serves residual renal function better (2-4) and is associ-ated with higher scores for quality of life (5, 6). In terms of survival, however, the results seem inconsistent. Some studies suggested a survival advantage of PD over HD (7, 8), but others reported that HD patients lived longer than PD patients (9, 10). Similarity in survival was seen in some investigations (11, 12); yet another analysis showed that PD survival was better only at an earlier stage of the dialysis course (13). Although there was a previous study with a big sample size conducted in Taiwan (14), neither that study nor the above-mentioned ones were random-ized clinical trials. As choice of renal replacement therapy often depends on the decision of both patients and medi-cal staff, and thus involves an unavoidable selection bias, more outcome studies with longer follow-up periods are needed to draw any conclusion.

Prevention over treatment is not generally practiced. For example, despite the evidence of health benefit from early referral of chronic kidney disease patients to neph-rologist care (15), such practice is limited. As the lifelong costs of renal replacement therapy for ESRD patients are

A

bstrAct

Background: Expected years of life lost (EYLL) in dialy-sis patients are rarely discussed. This study compared life expectancy, EYLL and survival between hemodi-alysis (HD) and peritoneal dihemodi-alysis (PD) patients. Methods: Adults who underwent maintenance dialysis at National Taiwan University Hospital from 1995 to 2006 were followed up until December 2007. Kaplan-Meier analysis and a constant excess hazard model were used to estimate and project long-term survival. EYLL was calculated by subtracting the life expectancy of patients from that of age- and sex-matched referents. HD pa-tients were then matched with PD papa-tients on age, sex and diabetes mellitus (DM). Life expectancy, EYLL and survival between the 2 groups were compared. Mortality risks were determined by the Cox model.

Results: Before matching, the 305 HD patients were older than the 428 PD patients (62.4 ± 13.7 vs. 53.1 ± 16.7 years; p<0.0001). More HD patients had DM (HD vs. PD, 29.2% vs. 20.6%; p=0.0072). Life expectancy and EYLL of HD patients were 8.8 and 11.5 years, compared with those of PD patients (19.9 and 7.4 years). After matching, life expectancy (p=0.790) and EYLL (p=0.793) of both groups (236 patients each) were similar. Age (adjusted hazard ratio [AHR] = 1.07; 95% confidence in-terval [95% CI], 1.05-1.09) and DM (AHR=3.81; 95% CI, 2.28-6.36) were independent mortality predictors. For diabetic patients who underwent HD, a better survival rate was observed (AHR=0.24; 95% CI, 0.11-0.53). Conclusions: After matching, HD and PD patients had similar life expectancy and EYLL. Survival was better for diabetic patients if they received HD.

Key words: Hemodialysis, Life expectancy, Peritoneal dialysis, Survival

1 Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei - Taiwan

2 Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University College of Public Health, Taipei - Taiwan

3 Department of Environmental and Occupational Medicine, National Taiwan University Hospital, Taipei - Taiwan

Tze-Wah Kao 1, 2, Jenq-Wen Huang 1, Kuan-Yu Hung 1,

Yu-Yin Chang 2, Pau-Chung Chen 2, 3, Chung-Jen Yen 1,

Yung-Ming Chen 1, Tzong-Shinn Chu 1, Ming-Shiou Wu 1,

Tun-Jun Tsai 1, Kwan-Dun Wu 1, Jung-Der Wang 1, 2, 3

Life expectancy, expected years of life lost

and survival of hemodialysis and peritoneal

dialysis patients

(2)

tremendous (16), the estimation of expected years of life lost (EYLL), which is useful for the quantification of po-tential health benefits gained by prevention, becomes of utmost importance. Moreover, the data of EYLL can be integrated into the cost-effectiveness analysis of both proactive and reactive preventions of ESRD. The pur-pose of this study was to determine the life expectancy, EYLL and survival between HD and PD patients treated at a tertiary medical center where, theoretically, the best medical care has been given to ESRD patients.

s

ubjects Andmethods

ESRD patients registered at the National Taiwan Univer-sity Hospital from 1995 to 2006 were included. Patients who were younger than 18 years of age or had received dialysis for fewer than 3 months were excluded. Basic demographic characteristics were identified. All patients were followed up until the end of 2007 and linked to the National Mortality Database. In the analysis of patient sur-vival, only death was considered as a final event. Patients who dropped out due to other reasons were censored. Baseline characteristics between HD and PD patients were compared using the independent t-test for continu-ous variables and the chi-square test for categorical vari-ables. A 2-sided p of 0.05 was the cutoff value for

statisti-cal significance. The follow-up data were analyzed by the Kaplan-Meier method (17) to yield the estimated survival functions for both HD and PD patients. A constant excess hazard model was used to project the long-term survival of these patients via a newly developed semiparametric method of linear extrapolation from a logit-transformed curve of the survival ratio between HD/PD patients and their age- and sex-matched reference populations. The survival functions of the reference populations generated by the Monte Carlo method (18) were based on the 2005 Life Table of Taiwanese Population (19). Life expectancy was estimated by extrapolating the survival curves to 50 years after the initiation of dialysis, while EYLL was cal-culated by subtracting the life expectancies of PD/HD patients from those of their corresponding age- and sex-matched general populations. The methodological details have been described previously (20), and the computer software can be freely downloaded (21).

We then matched our HD patients with PD patients on age (±2 years), sex and diabetic status. Life expectancy, EYLL and survival of the 2 groups were re-compared after match-ing. Cox model analysis and log-rank test were performed to determine the predictors of mortality.

All analyses were conducted using the SAS system, version 9.1 (SAS Institute, Inc., Cary, NC, USA), and the study was approved by the institutional review board of the hospital.

TABLE I

DEMOGRAPHIC CHARACTERISTICS OF STUDY SUBJECTS ON MAINTENANCE HEMODIALYSIS (HD) OR PERITONEAL DIALYSIS (PD), BEFORE AND AFTER MATCHING FOR AGE, SEX AND COMORBID DIABETES MELLITUS (DM)

Characteristics HD PD p Value

Part A. Before matching

Number 305 428

Age, years, mean ± SD 62.4 ± 13.7 53.1 ± 16.7 <0.001

Male sex (%) 161 (52.8%) 200 (46.7%) 0.11

Cause of renal failure, number (%) Non-DM DM 216 (70.8%) 89 (29.2%) 340 (79.4%) 88 (20.6%) <0.01

Part B. After matching

Number 236 236

Age, years, mean ± SD 60.0 ± 13.8 60.0 ± 13.9 0.9

Male sex (%) 111 (48.3%) 111 (48.3%) 1.0

Cause of renal failure, number (%) Non-DM DM 171 (72.5%) 65 (27.5%) 171 (72.5%) 65 (27.5%) 1.0

(3)

Fig. 1 - Comparison of lifetime sur-vival curves between cohorts of hemodialysis (HD) and peritoneal di-alysis (PD) and their respective refer-ence populations before matching.

r

esults

The underlying demographic characteristics of all eligible patients before matching are summarized in Table I (part A). There were 305 HD patients and 428 PD patients. All HD patients received conventional hemodialysis, and most PD patients (around 90%) received continuous am-bulatory peritoneal dialysis. The HD patients (mean age 62.4 ± 13.7 years) were older than the PD patients (mean age 53.1 ± 16.7 years) (p<0.001); and more of the HD pa-tients had diabetes mellitus (DM) (29.2% of HD papa-tients vs. 20.6% of PD patients, p<0.01). The 2 groups had simi-lar sex distributions, were in general adequately dialyzed and had mean hemoglobin levels more than 9.5 g/dL.

Before matching, as shown in Table II (part A), the life expectancy of HD patients was shorter than that of PD patients (8.8 ± 0.8 years vs. 19.9 ± 2.7 years, p<0.001), while a similar EYLL was found in the 2 groups (HD vs. PD: 11.5 years vs. 7.4 years, p=0.21). Life expectancies of both HD and PD patients were markedly shorter than their age- and sex-matched referents. As shown by the Kaplan-Meier curves in Figure 1, the long-term survival of HD patients was demonstrated to be worse than that of PD patients before matching.

After matching, 236 pairs of HD and PD patients were generated (Tab. I, part B). No statistical difference in life expectancy (HD vs. PD: 9.9 ± 2.1 years vs. 10.9 ± 2.6 years, p=0.79) or in EYLL (HD vs. PD: 12.0 years vs. 11.1 years, p=0.79) was found between the 2 groups (Tab. II, TABLE II

COMPARISON OF LIFE EXPECTANCY AND EXPECTED YEARS OF LIFE LOST (EYLL) BETWEEN PATIENTS ON MAINTE-NANCE HEMODIALYSIS (HD) AND THOSE ON PERITONEAL DIALYSIS (PD), BEFORE AND AFTER MATCHING

HD PD p Value

Part A. Before matching

Number 305 428

Life expectancy (years) 8.8 ± 0.8 19.9 ± 2.7 <0.001

Life expectancy of referents (years) 20.3 ± 0.05 27.3 ± 0.05

Expected years of life lost (EYLL) 11.5 7.4 0.21

Part B. After matching

Number 236 236

Life expectancy (years) 9.9 ± 2.1 10.9 ± 2.6 0.79

Life expectancy of referents (years) 22.0 ± 0.05 22.0 ± 0.046

(4)

TABLE III

IMPACT OF AGE, SEX, DIABETES MELLITUS (DM) AND DIALYSIS MODALITY ON SURVIVAL OF OUR DIALYSIS PATIENTS Adjusted hazard ratio (95% CI) p Value

Age 1.07 (1.05-1.09) <0.001

Sex, male/female 0.81 (0.56-1.17) 0.26

Cause of renal failure

DM versus no DM 3.81(2.28-6.36) <0.001

HD versus PD 0.73 (0.45-1.17) 0.19

Interaction

HD*DM 0.24 (0.11-0.53) <0.001

HD = hemodialysis; PD = peritoneal dialysis.

Fig. 2 - Comparison of lifetime survival curves between co-horts of hemodialysis (HD) and peritoneal dialysis (PD) pa-tients and their respective reference populations after match-ing for age, sex and comorbid diabetes mellitus (DM) in all patients studied (A), and between only those patients without DM (B) and only those with DM (C).

A B

C part B). The Kaplan-Meier survival curves for both HD and PD patients after matching are illustrated in Figure 2A. These 2 curves crossed each other at the time point of 120 months. There was an initial survival advantage of HD patients over PD patients (p<0.01) before the crossing point, whereas PD patients showed better survival after that point. When long-term survivals up to 600 months extrapolated by the Monte Carlo method were compared, no statistical difference was observed between HD and PD patients. Similarly, when only those patients without DM were compared, there was no survival difference

be-tween the 2 groups (Fig. 2B). However, if the patients had DM, those treated with HD exhibited better survival than those with PD (Fig. 2C). As expected, both HD and PD patients had worse survival than their respective referents before (Fig. 1) and after matching (Fig. 2).

(5)

modality on survival of our dialysis patients. Age (adjusted hazard ratio [AHR] = 1.07; 95% confidence interval [95% CI], 1.05-1.09) and DM (AHR=3.81; 95% CI, 2.28-6.36) were significant predictors of mortality. For patients with DM, survival was better if they received HD rather than PD (AHR=0.24; 95% CI, 0.11-0.53).

d

IscussIon

As dialysis imposes a financial burden, policy makers must be informed about the cost-effectiveness of PD versus HD, especially when universal coverage is sought (22). Wheth-er HD or PD is bettWheth-er in tWheth-erms of patient survival has long been under debate because all previous results were not produced from large randomized clinical trials. Different combinations of potential confounders that influence the validity of comparison were also questioned. It is difficult to conduct long-term randomized controlled studies because the choice of dialysis modality depends not only on the wish of the patients, but also on the preference of the caretakers, the expertise of the attending physicians, the accessibility of the dialysis centers and the policy of the government. In this study, we initially demonstrated that the life expectancy of PD patients was statistically longer than that of HD patients. The difference disappeared when we limited the compari-son to 236 matched pairs of patients. That indicated that the initial difference was related to confounding factors, es-pecially age and DM.

To solve the aforementioned problems, we utilized the methods of matching and extrapolation and accomplished a 13-year follow-up. First of all, the patients were matched on age, sex and DM, as these factors significantly affect the survival of dialysis patients (23-25). Secondly, the Monte Carlo method of EYLL estimation incorporated real mortal-ity data of the general population based on vital statistics, instead of assuming an arbitrarily chosen potential limit of life such as 65 years, to ensure more accurate estimates (26). Thirdly, this semiparametric method employed has been proven to give more robust extrapolations than, for example, the Weibull model (27). As our follow-up period was longer than that of previous investigations (7-14), and the comparison was performed with controls for major con-founding factors, the results of our study are valid and reli-able. We concluded that life expectancy and EYLL for HD and PD patients were not significantly different in Taiwan. Ways to further prolong life expectancy of dialysis patients should be sought in the future, but screening for solid organ cancers in those patients with a life expectancy of 10 years or longer is suggested (28).

This study first provides evidence for life-years gained from

successful prevention of ESRD through a long-term follow-up plus a novel extrapolation method. The outcome fac-tually indicates that compared with his/her age- and sex-matched referents, a patient on maintenance dialysis will lose 11-12 life-years on average. Future studies can focus on the exact costs for the prevention of ESRD. Comparison of costs per life-year or quality-adjusted life-year of these patients may also be performed.

By using the Cox model and Kaplan-Meier curves, we dem-onstrated that for DM patients, HD was superior to PD in terms of survival benefit. There were 2 possible reasons. Firstly, control of DM was more difficult for PD patients due to the elevation of blood sugar caused by peritoneal glucose absorption from glucose-based dialysate (29). That was especially true in previous years when icodextrin dialysate was seldom used in our hospital. Secondly, as HD patients receive dialysis treatment 3 times a week, they usually get more intensive medical care than PD patients. More patient education and earlier correction of other medical problems in diabetic HD patients probably contributed to their longer survival (30, 31). Future improvements in care of diabetic PD patients might reduce such a gap.

Our study had some limitations. As other studies, ours was not a randomized clinical trial, and its control of confounding was limited to prognostic factors that were known previous-ly. Moreover, our patient number might not be large enough. To avoid potential confounding, we treated any switch of renal replacement therapy as censored, which limited the proportion of study patients. A larger cohort is indicated to corroborate our findings in the future.

In conclusion, life expectancy and EYLL were similar between matched HD and PD patients in Taiwan. Age and DM were predictors of mortality. For patients with DM, survival was bet-ter if they received HD. On average, 11-12 life-years could be gained from successful prevention of a case of ESRD. Financial support: Financial support for this study was received from the Ta-Tung Kidney Research Foundation and Mrs. Hsiu-Chin Lee Kidney Research Fund.

Conflict of interest statement: None declared.

Address for correspondence: Prof. Jung-Der Wang

Institute of Occupational Medicine and Industrial Hygiene College of Public Health

National Taiwan University No. 17, Shiujou Road Taipei 100, Taiwan jdwang@ntu.edu.tw

(6)

r

eferences

1. Taiwan Society of Nephrology. Available at: http://www.tsn. org.tw/index2.html. Accessed January 27, 2009.

2. Lysaght MJ, Vonesh EF, Gotch F, et al. The influence of di-alysis treatment modality on the decline of remaining renal function. ASAIO Trans. 1991;37:598-604.

3. Berlanga JR, Marrón B, Reyero A, Caramelo C, Ortiz A. Peri-toneal dialysis retardation of progression of advanced renal failure. Perit Dial Int. 2002;22:239-242.

4. Van Biesen W, Lameire N, Verbeke F, Vanholder R. Residual renal function and volume status in peritoneal dialysis pa-tients: a conflict of interest? J Nephrol. 2008;21:299-304. 5. Gokal R, Figueras M, Ollé A, Rovira J, Badia X. Outcomes in

peritoneal dialysis and hemodialysis: a comparative assess-ment of survival and quality of life. Nephrol Dial Transplant. 1999;14(Suppl 6):S24-S30.

6. Tessari G, Dalle Vedove C, Loschiavo C, et al. The impact of pruritus on the quality of life of patients undergoing dialysis: a single centre cohort study. J Nephrol. 2009;22:241-248. 7. Uchida K, Shoda J, Sugahara S, et al. Comparison and

sur-vival of patients receiving hemodialysis and peritoneal dialy-sis in a single center. Adv Perit Dial. 2007;23:144-149. 8. Teerawattananon Y, Mugford M, Tangcharoensathien V.

Eco-nomic evaluation of palliative management versus perito-neal dialysis and hemodialysis for end-stage renal disease: evidence for coverage decisions in Thailand. Value Health. 2007;10:61-72.

9. Couchoud C, Moranne O, Frimat L, Labeeuw M, Allot V, Stengel B. Associations between comorbidities, treatment choice and outcome in the elderly with end-stage renal dis-ease. Nephrol Dial Transplant. 2007;22:3246-3254.

10. Enriquez J, Bastidas M, Mosquera M, et al. Survival on chronic dialysis: 10 years’ experience of a single Colombian center. Adv Perit Dial. 2005;21:164-167.

11. Inrig JK, Sun JL, Yang Q, Briley LP, Szczech LA. Mortality by dialysis modality among patients who have end-stage renal disease and are awaiting renal transplantation. Clin J Am Soc Nephrol. 2006;1:774-779.

12. Harris SA, Lamping DL, Brown EA, Constantinovici N; North Thames Dialysis Study (NTDS) Group. Clinical outcomes and quality of life in elderly patients on peritoneal dialysis versus hemodialysis. Perit Dial Int. 2002;22:463-470.

13. Song YS, Jung H, Shim J, Oh C, Shin GT, Kim H. Survival analysis of Korean end-stage renal disease patients accord-ing to renal replacement therapy in a saccord-ingle center. J Korean Med Sci. 2007;22:81-88.

14. Huang CC, Cheng KF, Wu HD. Survival analysis: comparing peritoneal dialysis and hemodialysis in Taiwan. Perit Dial Int. 2008;28(Suppl 3):S15-S20.

15. Chen SC, Chang JM, Chou MC, et al. Slowing renal function

decline in chronic kidney disease patients after nephrology referral. Nephrology (Carlton). 2008;13:730-736.

16. Kontodimopoulos N, Niakas D. An estimate of lifelong costs and QALYs in renal replacement therapy based on patients’ life expectancy. Health Policy. 2008;86:85-96.

17. Lee ET, Go OT. Survival analysis in public health research. Annu Rev Public Health. 1997;18:105-134.

18. Hwang JS, Wang JD. Monte Carlo estimation of extrapola-tion of quality-adjusted survival for follow-up studies. Stat Med. 1999;18:1627-1640.

19. Life Table of Taiwanese Population. Available at: http://www. moi.gov.tw/W3/stat. Accessed January 27, 2009.

20. Ho JJ, Hwang JS, Wang JD. Life expectancy estimations and the determinants of survival after 15 years of follow-up on 81,249 workers with permanent occupational disabilities. Scand J Work Environ Health. 2006;32:91-98.

21. Jing-Shiang Hwang. Software: ISQoL Package. Available at: http://www.stat.sinica.edu.tw/jshwang. Accessed April 7, 2010.

22. Obama B. Modern health care for all Americans. N Engl J Med. 2008;359:1537-1541.

23. Villar E, Remontet L, Labeeuw M, Ecochard R. Effect of age, gender, and diabetes on excess death in end-stage renal fail-ure. J Am Soc Nephrol. 2007;18:2125-2134.

24. Lorenzo V, Sanchez E, Vega N, Hernandez D. Renal replace-ment therapy in the Canary Islands: demographic and sur-vival analysis. J Nephrol. 2006;19:97-103.

25. Bradbury BD, Fissell RB, Albert JM, et al. Predictors of early mortality among incident US hemodialysis patients in the Di-alysis Outcomes and Practice Patterns Study (DOPPS). Clin J Am Soc Nephrol. 2007;2:89-99.

26. Murray CJ, Mathers CD, Salomon JA, et al. Health gaps: an overview and critical appraisal. In: Murray CJ, Salomon JA, Mathers CD, et al, eds. Summary measures of population health: concepts, ethics, measurement and applications. Geneva: World Health Organization; 2002.

27. Fang CT, Chang YY, Hsu HM, et al. Life expectancy of pa-tients with newly-diagnosed HIV infection in the era of highly active antiretroviral therapy. QJM. 2007;100:97-105.

28. Mandayam S, Shahinian VB. Are chronic dialysis patients at increased risk for cancer? J Nephrol. 2008;21:166-174. 29. Huang CC. Treatment targets for diabetic patients on

peri-toneal dialysis: any evidence? Perit Dial Int. 2007;27(Suppl 2):S176-S179.

30. Schatz SR. Diabetes, dialysis, and nutrition care interaction. Nephrol Nurs J. 2008;35:403-405.

31. Garber AJ. Cardiovascular complications of diabetes: pre-vention and management. Clin Cornerstone. 2003;5:22-37.

Received: June 19, 2009 Revised: November 25, 2009 Accepted: November 27, 2009

數據

Fig. 1 - Comparison of lifetime sur- sur-vival  curves  between  cohorts  of  hemodialysis (HD) and peritoneal  di-alysis (PD) and their respective  refer-ence populations before matching.
Table  III  shows  the  impact  of  age,  sex,  DM  and  dialysis

參考文獻

相關文件

In order to apply for a permit to employ Class B Foreign Worker(s), an Employer shall provide reasonable employment terms and register for such employment demands with local

Should an employer find it necessary to continue the employment of the Class A Foreign Worker(s), the employer shall, within four (4) months prior to the expiration of the

• To enhance teachers’ knowledge and understanding about the learning and teaching of grammar in context through the use of various e-learning resources in the primary

Teachers may encourage students to approach the poem as an unseen text to practise the steps of analysis and annotation, instead of relying on secondary

vs Functional grammar (i.e. organising grammar items according to the communicative functions) at the discourse level2. “…a bridge between

In order to facilitate the schools using integrated or mixed mode of curriculum organization to adopt the modules of Life and Society (S1-3) for improving their

Wang, Solving pseudomonotone variational inequalities and pseudocon- vex optimization problems using the projection neural network, IEEE Transactions on Neural Networks 17

Define instead the imaginary.. potential, magnetic field, lattice…) Dirac-BdG Hamiltonian:. with small, and matrix