The conclusions about the current finding are:
1. Active detection method through a community-based survey and screening is able to
detect around two times the PD cases in comparison with passive method.
2. Temporal natural history of H-Y stage between the SD and the CD was model by using
data from a community-based survey, which provide available information on disease
progression of PD in the absence of intervention.
3. Our study shows that screen for PD with different screening intervals is cost-effective
than no screen at all.
108
Figure 3-1 Simulated randomized controlled trial study design
Simulated cohort
Random assignment
` Screening
Regime 1:
Annual Starting at 60
Screening Regime 2:
Biennial Starting at 60
Screening Regime 3:
Triennial Starting at 60
….. Control group
109
Figure 3-2-1 Decision tree of Parkinson’s disease screening
110
Figure 3-2-2 Decision tree of Parkinson’s disease screening (continue)
111
Figure 3-2-3 Decision tree of Parkinson’s disease screening (continue)
112
Figure 5-1-1 Study Flow Chart
KCIS 2001 N=20,951
Active method N=11,332
Passive method N=9,619
PD case N=58
Non-PD case in 2001 survey
N=11,186
PD case after survey 2001 N=34 2002 N=42 2003 N=27 2004 N=31 Total=134
Random selection KCIS 2001
88 PD cases diagnosed
before 2001 59 PD cases
diagnosed before 2001
N=9,560
PD case in follow-up
2001 N=16
2002 N=29
2003 N=17
2004 N=27
Total=89
113
Figure 5-1 2 Cumulative detection rate of two methods of detecting Parkinson’s disease.
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ŢŤŵŪŷŦġŮŦŵũŰť űŢŴŴŪŷŦġŮŦŵũŰť
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114
Figure 5-2-1 Study flow chart include participants age 60 and older for analysis.
KCIS 2001 N=9,970
Active method N=5,327
Passive method N=4,623
Screening detected PD case
N=75
Non-PD case in 2001 survey
N=5,170
Clinical detected PD cases before the end
of 2004 N=103
KCIS 200182 PD cases diagnosed
before 2001 59 PD cases
diagnosed before 2001
N=4,584
Clinical detected PD cases before the end
of 2004 N=85
anaaaaalylylylylysisisisisis.s.s.s..
115
Figure 5-2-2 Cumulative risk for the SD and CD from free of PD in three-state model
0.0%
0.2%
0.4%
0.6%
0.8%
1.0%
1.2%
1.4%
1.6%
1.8%
2.0%
0 1 2 3 4 5
Cumulative risk
Time (year)
FPD to SD FPD to CD
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116
Figure 5-2-3 Cumulative risk of surfacing to the CD from the SD in three-state model
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5
Cumulative risk
Time (year)
Median time to the CD=1 year
ree-stststststatatatatateeeee mommmmmm dededededeelllll
117
Figure 5-2-4 Cumulative risk for the SD and CD from free of PD in three-state model (sampling fraction)
0.0%
0.2%
0.4%
0.6%
0.8%
1.0%
1.2%
1.4%
1.6%
1.8%
2.0%
0 1 2 3 4 5
Cumulative risk
Time (year)
FPD to SD FPD to CD
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118
Figure 5-2-5 Cumulative risk of surfacing to the CD from the SD in three-state model (sampling fraction)
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5
Cumulative risk
Time (year)
Median time to the CD= 1.2 year
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119
Figure 5-2-6 Predict 20-year risk of being early and advanced H-Y stage
0.0%
1.0%
2.0%
3.0%
4.0%
5.0%
6.0%
7.0%
8.0%
9.0%
10.0%
0 5 10 15 20
Cumulative risk
Time (year) H-Y I&II (SD+CD)
H-Y III-V (SD+CD)
ge
120
Figure 5-2-7 The predicted 20-year risk of PD by Hoehn-Yahr stage
0%
1%
2%
3%
4%
5%
6%
7%
0 5 10 15 20
Cumulative risk
Time (year) SD, H-Y I&II
SD, H-Y III-V CD, H-Y I&II CD, H-Y III-V
121
Figure 5-3-1 Scattered incremental cost-effectiveness analysis for 1-year vs. no screening
Figure 5-3-2 Scattered incremental cost-effectiveness analysis for 2-year vs. no screening.
78.4%
71.4%
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122
Figure 5-3-3 Scattered incremental cost-effectiveness analysis for 3-year vs. no screening.
Figure 5-3-4 Acceptability curve for cost-effectiveness analysis for various inter-screening intervals
0.784 0.714 0.673
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1
0 5000 10000 15000 20000 25000 30000 35000 40000
Probability of being cost-effective
Willingness-to-pay ($) for per life-year qained
Cost- effectiveness acceptability curves of screening for Parkinson's disease
1-year 2-year 3-year
67.3%
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123
Figure 5-3-5 Scattered incremental cost-effectiveness analysis for 1-year with 100%
attendance rate vs. no screening.
Figure 5-3-6 Scattered incremental cost-effectiveness analysis for 2-year with 100%
attendance rate vs. no screening.
79.2%
75.8%
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124
Figure 5-3-7 Scattered incremental cost-effectiveness analysis for 3-year with 100%
attendance rate vs. no screening.
Figure 5-3-8 Acceptability curve for cost-effectiveness analysis for various inter-screening intervals with 100% attendance rate.
0.792 0.758
0.69
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1
0 5000 10000 15000 20000 25000 30000 35000 40000
Probability of being cost-effective
Willingness-to-pay ($) for per life-year qained
Cost-effectiveness acceptability curves of screening for Parkinson's disease (100% attendance)
1-year 2-year 3-year
69.0%
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125
Figure 5-3-9 Scattered incremental cost-effectiveness analysis for 1-year with 60%
attendance rate vs. no screening.
Figure 5-3-10 Scattered incremental cost-effectiveness analysis for 2-year with 60%
attendance rate vs. no screening.
74.4%
64.9%
ar wiwiwiwiwiththththth666660%00%0%000
126
Figure 5-3-11 Scattered incremental cost-effectiveness analysis for 3-year with 60%
attendance rate vs. no screening.
Figure 5-3-12 Acceptability curve for cost-effectiveness analysis for various inter-screening intervals with 60% attendance rate.
0.744 0.649 0.644
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1
0 5000 10000 15000 20000 25000 30000 35000 40000
Probability of being cost-effective
Willingness-to-pay ($) for per life-year qained
Cost-effectiveness acceptability curves of screening for Parkinson's disease (60% attendance)
1-year 2-year 3-year
64.4%
ear wiwiwiwiwiththththth66666660%0%0%%%
127
Figure 5-3-13 Scattered incremental cost-utility analysis for 1-year vs. no screening.
Figure 5-3-14 Scattered incremental cost-utility analysis for 2-year vs. no screening.
68.8%
62.6%
n n n n
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128
Figure 5-3-15 Scattered incremental cost-utility analysis for 3-year vs. no screening.
Figure 5-3-16 Acceptability curve for cost-utility analysis for various inter-screening intervals
0.688 0.626 0.59
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1
0 5000 10000 15000 20000 25000 30000 35000 40000
Probability of being cost-effective
Willingness-to-pay ($) for per QALY qained
Cost-utility acceptability curves of screening for Parkinson's disease
1-year 2-year 3-year
59.0%
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129
Figure 5-3-17 Scattered incremental cost-utility analysis for 1-year with 100% attendance rate vs. no screening.
Figure 5-3-18 Scattered incremental cost-utility analysis for 2-year with 100% attendance rate vs. no screening.
70.2%
66.3%
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130
Figure 5-3-19 Scattered incremental cost-utility analysis for 3-year with 100% attendance rate vs. no screening.
Figure 5-3-20 Acceptability curve for cost-utility analysis for various inter-screening intervals with 100% attendance rate.
0.702
0.663 0.626
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1
0 5000 10000 15000 20000 25000 30000 35000 40000
Probability of being cost-effective
Willingness-to-pay ($) for per QALY qained
Cost-utility acceptability curves of screening for Parkinson's disease (100% attendance)
1-year 2-year 3-year
62.6%
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131
Figure 5-3-21 Scattered incremental cost-utility analysis for 1-year with 60% attendance rate vs. no screening.
Figure 5-3-22 Scattered incremental cost-utility analysis for 2-year with 60% attendance rate vs. no screening.
62.6%
61.0%
h
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132
Figure 5-3-23 Scattered incremental cost-utility analysis for 3-year with 60% attendance rate vs. no screening.
Figure 5-3-24 Acceptability curve for cost-utility analysis for various inter-screening intervals with 60% attendance rate.
0.626 0.61
0.582
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1
0 5000 10000 15000 20000 25000 30000 35000 40000
Probability of being cost-effective
Willingness-to-pay ($) for per QALY qained
Cost-utility acceptability curves of screening for Parkinson's disease (60% attendance)
1-year 2-year 3-year
58.2%
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133
Figure 6-2-1 The predicted 20-year risk of PD by Hoehn-Yahr stage assuming Weibull distribution for transitions
* The transitions from free of PD to SD H-Y I/II, from SD H-Y I/II to SD H-Y III+, from
SD H-Y I/II to CD H-Y I/II and from SD H-Y III+ to CD H-Y III+ were assume to follow
four Weibull distributions, Weibull(0.004, 1.2), Weibull(0.08, 1.08), Weibull(0.3982, 0.8),
and Weibull(2.1227, 1.08), respectively.
0%
1%
2%
3%
4%
5%
6%
7%
0 5 10 15
SD, H-Y I&II SD, H-Y III-IV CD, H-Y I&II CD, H-Y III-V
Time (year)
Cumulative risk
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134
Table 4-6-1 Estimate and distribution of parameters
Item Estimate (Range) Distribution References
Prevalence of each state (normal, SD early, SD late)
Dirichlet(9697, 118, 14) KCIS
Transition rate (per year) KCIS
Normal→ SD early 0.0078 Gamma(86, 11014)
SD early→ SD late 0.2489 Gamma(20.6, 82.5)
SD early→ CD early 0.3981 Gamma(30.3, 76.2)
SD late→ CD late 2.1227 Gamma(6.66, 3.14)
All-cause mortality Life table (2001)
Mortality after treatment( per year) Liou et al., 200918
Stage I 0.0102
Stage II 0.0485
Stage III 0.0797
Stage IV+ 0.1989
Annual transition rate after treatment (per year) Zhao et al., 2010102
Stage IÆII 0.5988
Screen cost 8 Triangular (6,8,10) Expert’s opinion
Annual outpatient cost KCIS,NHI
135
Item Estimate (Range) Distribution References
Prevalence of each state (normal, SD early, SD late)
Dirichlet(9697, 118, 14) KCIS
H-Y Stage IV+ 4352 Triangular(3269,4352,5444)
Admission rate Hassan et al, 201392
H-Y Stage III 40.9% Beta (356, 515)
H-Y Stage IV+ 55.5% Beta (152,122)
Home care, per month 667 Market price
Discount, % 3 uniform(0,6)
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136
Table 5-1-1 Annual Incidence of PD in Active Detection Group
ġ Age(y) 40-49 50-59 60-69 70-79 80+ Total
2001
Population 3,514 2,482 2,724 2,054 412 11,186
Person Year 1,847.39 1,360.93 1,495.64 1,122.76 225.2621 6,051.98
PD 2 1 6 17 8 34
Incidence 108.2607 73.47927 401.1657 1514.13 3551.418 561.7995
2002
Population 3,512 2,481 2,718 2,037 404 11,152
Person Year 3,499.53 2,472.90 2,707.89 2,030.69 402.8556 11,113.86
PD 2 2 9 19 10 42
Incidence 57.15055 80.87677 332.3624 935.6445 2482.279 377.9066
2003
Population 3,510 2,479 2,709 2,018 394 11,110
Person Year 3,497.99 2,472.08 2,705.69 2,027.84 398.809 11,102
PD 0 2 4 16 5 27
Incidence 0 80.90337 147.8365 789.0164 1253.733 243.1903
2004
Population 3,510 2,477 2,705 2,002 389 11,083
Person Year 3,509.85 2,477.11 2,715.65 2,041.67 394.4011 11,139
PD 1 1 6 20 3 31
Incidence 28.49126 40.36964 220.9418 979.5902 760.647 278.3096 8
137
Table 5-1-2 Annual Incidence of PD in Passive Detection Group
ġ Age(y) 40-49 50-59 60-69 70-79 80+ Total
2001
Population 2,868 2,108 2,391 1,802 391 9,560
Person Year 1,268.84 925.62 1,019.90 727.08 152.345 4,093.79
PD 0 1 4 6 5 16
Incidence 0 108.0353 392.1958 825.2155 3282.025 390.8361
2002
Population 2,868 2,107 2,387 1,796 386 9,544
Person Year 2,858.18 2,099.74 2,378.27 1,789.92 383.0226 9,509.14
PD 0 1 9 15 4 29
Incidence 0 47.62488 378.426 838.0266 1044.325 304.9697
2003
Population 2,868 2,106 2,378 1,781 382 9,515
Person Year 2,858.18 2,100.54 2,376.30 1,784.13 381.8042 9,501
PD 0 1 6 8 2 17
Incidence 0 47.6067 252.493 448.3988 523.8286 178.9292
2004
Population 2,868 2,105 2,372 1,773 380 9,498
Person Year 2,866.04 2,105.49 2,384.47 1,795.95 388.742 9,541
PD 0 1 8 13 5 27
Incidence 0 47.49483 335.5046 723.8506 1286.2 282.9984 80
138
Table 5-1-3 Baseline characteristics of two groups of those with idiopathic Parkinson’s disease by detection method.
Active method
n= 11,244
Passive method
n= 9,560
p value
Age (years) 58.36±12.25 58.78±12.30 0.01
Height (cm) 157.30±8.24 157.10±8.25 0.15
Weight (kg) 62.05±10.81 61.48±10.73 <0.01
Waist Circumference (cm) 80.91±10.22 80.57±10.11 0.02
Hip Circumference (cm) 95.71±7.77 95.72±7.70 0.93
SBP (mmHg) 128.10±21.11 129.10±21.36 0.002
DBP (mmHg) 79.95±11.36 80.34±11.73 0.01
Male (%) 4312 (38.35%) 3588 (37.53%) 0.23
Current smoker (%) 2094 (18.64%) 1783 (18.89%) 0.65
Current drinker (%) 1922 (17.13%) 1662 (17.63%) 0.35
Current betelnut use (%) 234 (2.09%) 195 (2.07%) 0.93
SBP: systolic blood pressure
DBP: diastolic blood pressure
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139
Table 5-1-4 Distribution of Hoehn-Yahr (H-Y) stage for cases of idiopathic Parkinson’s disease (IPD) detected by the active or passive method.
H-Y stage Active method
in 2001
IPD case N(%)
Active method
group
IPD case N (%)
Passive method
group
IPD case N (%)
I 13 (22.4) 14 (14.4) 1 (3.8 )
II 41 (70.7) 64 (66.0) 15 (57.7)
III+ 4 (6.9) 19 (19.6) 10 (38.5)
Total 58 (100) 97 (100) 26 (100)
Risk ratio of being stage III+ 0.18 0.51 1.00
*stage III+ (95% CI) (0.06-0.52) (0.27-0.96)
*active method versus passive method
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140
Table 5-1-5 Crude and adjusted relative risk for active and passive detection methods for Parkinson’s disease.
ġ relative risk (95%CI) p value
Crude Estimate
active vs passive method 1.82 (1.42-2.34) <0.0001
Adjusted Estimate
active vs passive method 1.95 (1.51-2.52) <0.0001
age 1.18 (1.16-1.20) <0.0001
weight 1.00 (0.98-1.02) 0.95
waist circumference 1.01 (0.99-1.03) 0.18
systolic blood pressure 0.99 (0.98-1.00) 0.05
diastolic blood pressure 1.01 (1.00-1.02) 0.14
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141
Table 5-2-1 H-Y stage distribution in screen-detective case and clinical-detective case
H-Y stage Active detection Passive detection
SD case CD case CD case
IPD case N (%) IPD case N (%) IPD case N (%)
I+II 57 (76.0) 18 (17.5) 16 (18.8)
III+ 7 (9.3) 11 (10.7) 8 (9.4)
unknown 11(14.7) 74 (71.8) 61 (71.8)
Total 75 (100) 103 (100) 85 (100)
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142
Table 5-2-2 Estimated transition rates with three-state model
ġ Transitions/MST Estimate 95%CI
Normal-> SD (λ1) 0.0076 0.0067 - 0.0086
SD->CD (λ2) 0.6776 0.5303 - 0.8429
MST staying in SD (year) 1.48 1.212 - 1.886
MST: mean sojourn time
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143
Table 5-2-3 Estimated transition rates with a three-state model using a case-cohort design sampling fraction
ġ Transitions Estimate 95%CI
Normal-> SD (λ1) 0.0082 0.0064 - 0.0100
SD->CD (λ2) 0.5935 0.4330 - 0.7541
MST staying in SD (year) 1.68 1.326 - 2.309
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144
Table 5-2-4 Estimated transition rates with a five-state model using a case-cohort sampling fraction design
ġ Transitions Estimate 95%CI
Normal-> SD (λ1) with H-Y I/II 0.0078 0.0062 - 0.0095
SD with H-Y I/II -> SD H-Y III+ (λ2) 0.2498 0.1420 - 0.3576
SD with H-Y I/II -> CD with H-Y I/II+ (λ3) 0.3982 0.2564 - 0.5399
SD with H-Y III+ -> CD with H-Y III+ (λ4) 2.1227 0.5109 - 3.7346
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145
Table 5-2-5 Distribution of characteristics of subjects ġ Covariate
ġ
Level Non-PD ġ PD Total p-value
n % ġ n % ġ
Gender ġ
Female 5282 97.7% 124 2.3% 5406 0.0095
Male 4284 96.9% 139 3.1% 4423
Age group
60-69 5063 98.8% 61 1.2% 5124 <0.0001
70-79 3742 96.3% 144 3.7% 3886
80-89 718 93.2% 52 6.8% 770
90+ 43 87.8% 6 12.2% 49
Education level
<=6 years 7616 97.3% 210 2.7% 7826 0.9264
>6 years 1950 97.4% 53 2.6% 2003
BMI
>=22 7659 97.5% 199 2.5% 7858 0.7877
<22 1907 96.8% 64 3.2% 1971
Ever smokers ġ
No 6847 97.5% 177 2.5% 7024 0.1594
Yes 2656 97.0% 83 3.0% 2739
Ever drinker ġ
Never 7551 97.4% 203 2.6% 7754 0.575
Ever 1947 97.2% 57 2.8% 2004
Serum uric acid, mg/dl
>=5.5 5381 97.6% 132 2.4% 5513 0.0518
<5.5 3749 96.9% 118 3.1% 3867
Less meat intake ġ
No 5498 97.6% 137 2.4% 5635 0.0887
Yes 3985 97.0% 123 3.0% 4108
Less fruit intake ġ
No 7755 97.5% 202 2.5% 7957 0.0983
Yes 1735 96.8% 58 3.2% 1793
Less vegetable intake
No 7383 97.4% 200 2.6% 7583 0.7475
Yes 2111 97.2% 60 2.8% 2171
Less coffee intake ġ
No 9367 97.4% 254 2.6% 9621 0.2495
ġ Yes 109 95.6% ġ 5 4.4% 114
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146
Table 5-2-6 Relative risk on transition rate of normal to SD early phase of five-state Markov model of Parkinson’s disease
Variable Regression
SD RR 95% CI
coefficient
Gender (Male vs. female) 0.46 0.19 1.58 1.10 - 2.28
Age , per 10 years increased 0.63 0.13 1.88 1.47 - 1.47
BMI<22 vs. 22+ 0.71 0.20 2.02 1.38 - 2.97
Low uric acid (<5.5 vs. 5.5+ mg/dl) 0.43 0.19 1.54 1.07 - 2.22 Educated >6 vs. <=6 year) -0.22 0.24 0.80 0.50 - 1.30
Ever smoker 0.42 0.19 1.52 1.05 - 2.22
Ever alcohol drinker 0.37 0.21 1.45 0.96 - 2.18
Less meat intake 0.38 0.18 1.46 1.02 - 2.09
Less fruit intake 0.36 0.22 1.44 0.94 - 2.19
Less vegetable intake 0.21 0.21 1.23 0.81 - 1.86
Less coffee intake 0.41 0.28 1.51 0.88 - 2.59
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147
Table 5-2-7 Relative risk on transition rate of SD early to SD late phase of five-state Markov model of Parkinson’s disease
Variable Regression
SD RR 95% CI
coefficient
Gender (Male vs. female) 0.13 0.43 1.14 0.49 - 2.65
Age , per 10 years increased 0.81 0.43 2.25 0.97 - 5.21
BMI<22 vs. 22+ -0.43 0.46 0.65 0.27 - 1.58
Low uric acid (<5.5 vs. 5.5+ mg/dl) -0.96 0.43 0.38 0.17 - 0.89
Educated >6 vs. <=6 year) 1.81 0.50 6.09 2.28 - 16.26
Ever smoker 0.01 0.43 1.01 0.43 - 2.35
Ever alcohol drinker 0.09 0.46 1.10 0.44 - 2.72
Less meat intake -0.69 0.41 0.50 0.22 - 1.12
Less fruit intake 0.45 0.46 1.58 0.64 - 3.90
Less vegetable intake -0.39 0.49 0.68 0.26 - 1.77
Less coffee intake -1.12 0.52 0.33 0.12 - 0.90
e offfffffiviviviviveeeee-s-s-s-ssssstattt teteeeee
95 95555555% % % % %% % % % CICICICIII 0
0 0
04949494949 - 2 659
148
Table 5-2-8 Relative risk on transition rate of SD early to CD early phase of five-state Markov model of Parkinson’s disease
Variable Regression
SD RR 95% CI
coefficient
Gender (Male vs. female) -0.79 0.33 0.45 0.24 - 0.87
Age , per 10 years increased -1.01 0.27 0.36 0.21 - 0.62
BMI<22 vs. 22+ -0.87 0.37 0.42 0.20 - 0.87
Low uric acid (<5.5 vs. 5.5+ mg/dl) 0.16 0.35 1.17 0.59 - 2.31 Educated >6 vs. <=6 year) -0.07 0.43 0.94 0.41 - 2.16
Ever smoker -0.72 0.36 0.49 0.24 - 0.99
Ever alcohol drinker -0.03 0.38 0.97 0.46 - 2.03
Less meat intake -0.45 0.32 0.64 0.34 - 1.20
Less fruit intake -0.07 0.40 0.93 0.43 - 2.03
Less vegetable intake -0.50 0.40 0.61 0.28 - 1.32
Less coffee intake -0.59 0.45 0.55 0.23 - 1.33
95 95 95 95 95 95 955 95%%%%%%%%%CICICICICICICICIC se ofofofofoffffffivivivivive-e-e-ee-ee sttatatatatatteeee
149
Table 5-2-9 Relative risk on transition rate of SD late to CD late phase of five-state Markov model of Parkinson’s disease
Variable Regression
SD RR 95% CI
coefficient
Gender (Male vs. female) -1.80 1.05 0.17 0.02 - 1.31
Age , per 10 years increased -1.34 0.54 0.26 0.09 - 0.76
BMI<22 vs. 22+ -0.84 0.74 0.43 0.10 - 1.85
Low uric acid (<5.5 vs. 5.5+ mg/dl) 0.21 0.86 1.24 0.23 - 6.68 Educated >6 vs. <=6 year) -1.18 0.75 0.31 0.07 - 1.33
Ever smoker -1.03 0.75 0.36 0.08 - 1.56
Ever alcohol drinker -0.31 0.83 0.73 0.14 - 3.72
Less meat intake -0.09 0.75 0.91 0.21 - 3.97
Less fruit intake -0.41 0.84 0.66 0.13 - 3.41
Less vegetable intake 0.25 1.08 1.28 0.15 - 10.55
Less coffee intake 0.37 0.82 1.45 0.29 - 7.28
of fffffivivivivive-e-e-e-e-stststststataaaaaaee
95 95 95 95 95 95 95 95 95%%%% % %%%CICICICCCCC 0 022222 -11111313131311
150
Table 5-2-10 Multivariate analysis on transition rate of normal to SD early phase Variable Regression coefficient Relative risk
estimate SD estimate 95% CI
Age , per 10 years increased 0.59 0.13 1.80 1.40 - 2.32
Gender (Male vs. female) 0.27 0.22 1.31 0.86 - 2.00
BMI<22 vs. 22+ 0.56 0.20 1.75 1.19 - 2.59
Ever smoker 0.21 0.22 1.23 0.80 - 1.90
Age , per 10 years increased 0.59 0.13 1.81 1.41 - 2.33
Gender (Male vs. female) 0.28 0.21 1.33 0.88 - 1.99
BMI<22 vs. 22+ 0.57 0.20 1.77 1.20 - 2.62
Ever alcohol drinker 0.24 0.23 1.27 0.81 - 1.98
Age , per 10 years increased 0.55 0.13 1.74 1.35 - 2.23
Gender (Male vs. female) 0.42 0.19 1.52 1.04 - 2.22
BMI<22 vs. 22+ 0.57 0.20 1.77 1.21 - 2.61
Educated >6 vs. <=6 year) -0.40 0.25 0.67 0.41 - 1.11
Age , per 10 years increased 0.56 0.13 1.75 1.35 - 2.27
Gender (Male vs. female) 0.46 0.19 1.58 1.08 - 2.31
BMI<22 vs. 22+ 0.49 0.20 1.64 1.10 - 2.45
Low uric acid (<5.5 vs. 5.5+ mg/dl) 0.53 0.19 1.70 1.16 - 2.49
Age , per 10 years increased 0.58 0.13 1.78 1.38 - 2.28
Gender (Male vs. female) 0.35 0.19 1.42 0.98 - 2.05
BMI<22 vs. 22+ 0.54 0.20 1.72 1.17 - 2.55
Less fruit intake 0.31 0.21 1.36 0.89 - 2.07
Age , per 10 years increased 0.57 0.13 1.77 1.38 - 2.27
Gender (Male vs. female) 0.34 0.19 1.41 0.98 - 2.03
BMI<22 vs. 22+ 0.56 0.20 1.76 1.19 - 2.59
Less vegetable intake 0.13 0.21 1.13 0.75 - 1.71
Age , per 10 years increased 0.55 0.13 1.73 1.35 - 2.23
Gender (Male vs. female) 0.38 0.19 1.46 1.01 - 2.11
BMI<22 vs. 22+ 0.56 0.20 1.75 1.18 - 2.58
Less meat intake 0.32 0.19 1.38 0.96 - 1.99
2.
151
Multivariate analysis on transition rate of normal to SD early phase (continued) Variable Regression coefficient Relative risk
estimate SD estimate 95% CI
Age , per 10 years increased 0.57 0.13 1.76 1.37 - 2.27
Gender (Male vs. female) 0.34 0.19 1.41 0.97 - 2.04
BMI<22 vs. 22+ 0.57 0.20 1.77 1.19 - 2.61
Less coffee intake -15.67 77.31 0.00 0.00 -
-0.
152
Table 5-2-11 Multivariate analysis on transition rate of SD early phase to SD late phase Variable Regression coefficient Relative risk
estimate SD estimate 95% CI
Age , per 10 years increased 0.71 0.44 2.03 0.86 - 4.82
Gender (Male vs. female) 0.08 0.55 1.09 0.37 - 3.22
BMI<22 vs. 22+ -0.32 0.49 0.72 0.28 - 1.90
Ever smoker 0.01 0.53 1.01 0.35 - 2.88
Age , per 10 years increased 0.82 0.47 2.27 0.91 - 5.66
Gender (Male vs. female) -0.04 0.51 0.96 0.36 - 2.59
BMI<22 vs. 22+ -0.31 0.50 0.74 0.28 - 1.95
Ever alcohol drinker 0.42 0.56 1.53 0.51 - 4.57
Age , per 10 years increased 1.02 0.47 2.78 1.11 - 6.96
Gender (Male vs. female) -0.51 0.55 0.60 0.21 - 1.76
BMI<22 vs. 22+ 0.04 0.55 1.04 0.36 - 3.03
Educated >6 vs. <=6 year) 2.32 0.63 10.15 2.94 - 35.02
Age , per 10 years increased 0.76 0.47 2.14 0.85 - 5.43
Gender (Male vs. female) -0.18 0.48 0.83 0.33 - 2.11
BMI<22 vs. 22+ -0.42 0.51 0.66 0.24 - 1.79
Low uric acid (<5.5 vs. 5.5+ mg/dl) -1.07 0.48 0.34 0.13 - 0.87
Age , per 10 years increased 0.80 0.45 2.22 0.92 - 5.35
Gender (Male vs. female) 0.07 0.48 1.07 0.42 - 2.73
BMI<22 vs. 22+ -0.43 0.51 0.65 0.24 - 1.75
Less fruit intake 0.67 0.52 1.95 0.71 - 5.37
Age , per 10 years increased 0.69 0.44 1.99 0.84 - 4.70
Gender (Male vs. female) 0.19 0.48 1.21 0.47 - 3.12
BMI<22 vs. 22+ -0.32 0.49 0.72 0.28 - 1.90
Less vegetable intake -0.36 0.54 0.70 0.24 - 2.01
Age , per 10 years increased 0.90 0.45 2.47 1.01 - 6.00
Gender (Male vs. female) -0.10 0.48 0.90 0.35 - 2.32
BMI<22 vs. 22+ -0.13 0.50 0.88 0.33 - 2.34
Less meat intake -0.97 0.50 0.38 0.14 - 1.00
0.
153
Table 5-2-12 Multivariate analysis on transition rate of SD early phase to CD early phase Variable Regression coefficient Relative risk
estimate SD estimate 95% CI
Age , per 10 years increased -0.93 0.27 0.39 0.23 - 0.68
Gender (Male vs. female) -0.49 0.40 0.62 0.28 - 1.35
BMI<22 vs. 22+ -0.82 0.39 0.44 0.20 - 0.95
Ever smoker -0.22 0.43 0.80 0.35 - 1.85
Age , per 10 years increased -0.91 0.28 0.40 0.23 - 0.69
Gender (Male vs. female) -0.65 0.37 0.52 0.25 - 1.09
BMI<22 vs. 22+ -0.85 0.40 0.43 0.20 - 0.93
Ever alcohol drinker 0.13 0.43 1.14 0.49 - 2.67
Age , per 10 years increased -0.91 0.27 0.40 0.24 - 0.68
Gender (Male vs. female) -0.61 0.35 0.54 0.27 - 1.08
BMI<22 vs. 22+ -0.77 0.39 0.46 0.22 - 0.99
Educated >6 vs. <=6 year) 0.16 0.46 1.18 0.48 - 2.90
Age , per 10 years increased -0.90 0.29 0.41 0.23 - 0.72
Gender (Male vs. female) -0.62 0.35 0.54 0.27 - 1.07
BMI<22 vs. 22+ -0.86 0.40 0.42 0.19 - 0.94
Low uric acid (<5.5 vs. 5.5+ mg/dl) -0.08 0.36 0.92 0.46 - 1.86
Age , per 10 years increased -0.91 0.27 0.40 0.23 - 0.69
Gender (Male vs. female) -0.57 0.34 0.56 0.29 - 1.09
BMI<22 vs. 22+ -0.85 0.40 0.43 0.20 - 0.94
Less fruit intake 0.19 0.41 1.21 0.54 - 2.71
Age , per 10 years increased -0.92 0.27 0.40 0.23 - 0.68
Gender (Male vs. female) -0.50 0.34 0.60 0.31 - 1.17
BMI<22 vs. 22+ -0.82 0.39 0.44 0.20 - 0.95
Less vegetable intake -0.44 0.40 0.65 0.30 - 1.41
Age , per 10 years increased -0.85 0.27 0.43 0.25 - 0.72
Gender (Male vs. female) -0.63 0.34 0.54 0.27 - 1.04
BMI<22 vs. 22+ -0.78 0.39 0.46 0.21 - 0.99
Less meat intake -0.35 0.34 0.70 0.36 - 1.38
0.
154
Multivariate analysis on transition rate of SD early phase to CD early phase (continued) Variable Regression coefficient Relative risk
estimate SD estimate 95% CI
Age , per 10 years increased -0.94 0.28 0.39 0.23 - 0.67
Gender (Male vs. female) -0.61 0.34 0.55 0.28 - 1.06
BMI<22 vs. 22+ -0.78 0.40 0.46 0.21 - 1.00
Less coffee intake 9.44 93.80 12629.72 0.00 -
-0
155
Table 5-2-13 Multivariate analysis on transition rate of SD late phase to CD late phase Variable Regression coefficient Relative risk
estimate SD estimate 95% CI
Age , per 10 years increased -1.31 0.57 0.27 0.09 - 0.82
Gender (Male vs. female) -1.88 1.09 0.15 0.02 - 1.30
BMI<22 vs. 22+ -0.90 0.80 0.41 0.09 - 1.93
Ever smoker -0.10 0.80 0.91 0.19 - 4.37
Age , per 10 years increased -1.29 0.57 0.28 0.09 - 0.84
Gender (Male vs. female) -2.06 1.11 0.13 0.01 - 1.12
BMI<22 vs. 22+ -0.91 0.78 0.40 0.09 - 1.84
Ever alcohol drinker 0.46 0.91 1.58 0.27 - 9.40
Age , per 10 years increased -1.37 0.57 0.25 0.08 - 0.77
Gender (Male vs. female) -1.54 1.14 0.21 0.02 - 2.02
BMI<22 vs. 22+ -0.87 0.81 0.42 0.08 - 2.06
Educated >6 vs. <=6 year) -0.78 0.87 0.46 0.08 - 2.53
Age , per 10 years increased -1.22 0.63 0.30 0.09 - 1.02
Gender (Male vs. female) -1.67 1.22 0.19 0.02 - 2.04
BMI<22 vs. 22+ -1.30 0.89 0.27 0.05 - 1.55
Low uric acid (<5.5 vs. 5.5+ mg/dl) 0.27 1.00 1.31 0.18 - 9.33
Age , per 10 years increased -1.34 0.59 0.26 0.08 - 0.83
Gender (Male vs. female) -1.87 1.14 0.15 0.02 - 1.45
BMI<22 vs. 22+ -0.87 0.80 0.42 0.09 - 2.03
Less fruit intake -0.24 0.92 0.78 0.13 - 4.79
Age , per 10 years increased -1.33 0.55 0.27 0.09 - 0.79
Gender (Male vs. female) -2.03 1.12 0.13 0.01 - 1.18
BMI<22 vs. 22+ -1.01 0.79 0.36 0.08 - 1.72
Less vegetable intake 0.89 1.18 2.44 0.24 - 24.78
Age , per 10 years increased -1.30 0.60 0.27 0.08 - 0.88
Gender (Male vs. female) -1.96 1.22 0.14 0.01 - 1.55
BMI<22 vs. 22+ -0.84 0.80 0.43 0.09 - 2.07
Less meat intake -0.33 0.79 0.72 0.15 - 3.38
1
156
Multivariate analysis on transition rate of SD late phase to CD late phase (continued) Variable Regression coefficient Relative risk
estimate SD estimate 95% CI
Age , per 10 years increased -1.31 0.57 0.27 0.09 - 0.82
Gender (Male vs. female) -1.92 1.06 0.15 0.02 - 1.18
BMI<22 vs. 22+ -0.89 0.79 0.41 0.09 - 1.94
Less coffee intake 8.05 82.75 3135.27 0.00 -
-1
157
Table 5-2-14Covariate in transition of five state model with hypothesis testing CovariateġNormal to SD early (ɉଵ) SD early to SD late (ɉଶ) SD early to CD early (ɉଷ) SD late to CD late (ɉସ)
Net force coefficient (NFC)
p value Gender (male vs. female)estimate0.340.22-0.44-1.28-0.610.61 RR1.401.250.640.28 95% CI0.92-2.150.52-3.020.31-1.320.04-1.92 Age, per 10 years increasedestimate0.610.99-0.52-0.451.060.15 RR1.842.690.590.64 95% CI1.38-2.451.30-5.580.34-1.040.22-1.82 BMI<22 vs. 22+estimate0.57-0.21-0.39-0.40-0.210.85 RR1.760.810.680.67 95% CI1.11-2.790.32-2.030.31-1.470.14-3.20 Low UA <5.5 vs. 5.5+ (mg/dl)estimate0.48-0.670.530.05-1.140.35 RR1.610.511.701.05 95% CI1.04-2.480.21-1.270.79-3.640.17-6.47 Education >6 vs. <= 6 yearsestimate-0.061.740.14-0.810.800.48 RR0.945.711.150.45 95% CI0.55-1.611.90-17.200.33-4.060.10-2.06
DDDDDlalatetetetettetetetNNNNNNNNetetetetetetetetffffffffororororororororccecececeececee cocooooooeefefeefififififififificiciciciciciciciieneneeneeeet t tt t t ((NNN(N(N(NNFCFCFCFCFCF))))))
158
CovariateġNormal to SD early (ɉଵ) SD early to SD late (ɉଶ) SD early to CD early (ɉଷ)
SD late to CD late (ɉସ)NFCp value Ever smokeestimate0.310.11-0.41-0.61-0.090.94 RR1.361.110.660.55 95% CI0.87-2.120.47-2.670.30-1.450.12-2.55 Ever alcohol useestimate0.480.350.32-0.040.001.00 RR1.621.431.370.96 95% CI1.01-2.580.55-3.720.61-3.100.19-5.01 Less meat intakeestimate0.25-0.55-0.270.01-0.270.79 RR1.280.580.771.01 95% CI0.83-1.960.24-1.390.37-1.570.23-4.43 Less fruit intakeestimate0.520.740.360.000.380.74 RR1.682.101.431.00 95% CI1.04-2.710.79-5.580.59-3.450.18-5.40 Less vegetable intakeestimate0.06-0.30-0.460.420.580.69 RR1.060.740.631.52 95% CI0.64-1.760.27-2.010.27-1.480.17-13.74 Less coffee intakeestimate0.19-1.15-0.700.44-0.010.99 ġRR1.21ġ0.32ġ0.49ġ1.55ġġġ 95% CI0.67-2.200.09-1.080.15-1.660.31-7.74
NFNFNFNFNFCCCCC --0.0.0.0.0.0.0.0.09090909909090909 5555555555 00000000000
159
Table 5-2-15Multivariate analysis for the multiple transition in thefive-state Markov model CovariateġNormal to SD earlySD early to SD late SD early to CD earlySD late to CD late Age, per 10 years increasedestimate0.5841.626-0.454-0.347 RR1.795.080.630.71 95% CI1.32-2.441.94-13.290.35-1.150.22-2.27 Gender (male vs. female)estimate0.338-0.736-0.362 RR1.400.480.70 95% CI0.90-2.190.15-1.540.35-1.40 Low UA <5.5 vs. 5.5+ (mg/dl)estimate0.431-0.933 RR1.540.39 95% CI1.04-2.280.13-1.19 BMI<22 vs. 22+estimate0.359-0.501 RR1.430.61 95% CI0.90-2.270.28-1.31 Education >6 vs. <= 6 yearsestimate2.685 RR14.65 ġ95% CIġġ3.94-54.53ġġġġ llllaaaaateeeeeee ettotototCCCCCCCCD DD D D DD D Dlalalalalalalalatetetetetetetete ---0.0.00.0.0000343433333377777777 0.0.0.0.0717177
160
Table 5-2-16Multivariate analysis for the multiple transition in the five-state Markov model with further adjustment of vegetable and fruit intake CovariateġNormal to SD earlySD early to SD late SD early to CD earlySD late to CD late Age, per 10 years increasedestimate0.6031.642-0.425-0.419 RR1.835.160.650.66 95% CI1.34-2.501.94-13.760.35-1.210.16-2.74 Gender (male vs. female)estimate0.355-0.693-0.350 RR1.430.500.70 95% CI0.91-2.240.15-1.700.34-1.45 Low UA <5.5 vs. 5.5+ (mg/dl)estimate0.426-0.917 RR1.530.40 95% CI1.03-2.280.13-1.23 BMI<22 vs. 22+estimate0.330-0.545 RR1.390.58 95% CI0.87-2.230.26-1.29 Education >6 vs. <= 6 yearsestimate2.725 RR15.26 95% CI3.96-58.76 etaaablblblblbleeee e anannnnnnnd d dd d ddd dfrfrfrfrfrfrfrfrfruiuiuiuiuiuiuiuiuit ttt ttttininntatatatatakekkkk SSDSDSDSDSDSDSDSDlllllllatatatatatatatate e ee totototototototoCCCCCCCCD DDDD DDDDlalalaalattttet ---0.0.0.0.0.0.0.0.4444144144499999 0.00.0.0.0.0.0.0.666666666 00.161616161161----22.27
161
Multivariate analysis for the multiple transition in the five-state Markov model with further adjustment of vegetable and fruit intake(continued) CovariateġNormal to SD earlySD early to SD late SD early to CD earlySD late to CD late Less vegetable intakeestimate-0.619-0.480 RR0.540.62 95% CI0.16-1.800.30-1.28 Less fruit intakeestimate0.4370.415 RR1.551.51 ġ95% CIġġ0.48-4.96ġġ0.67-3.42 it ininininintatatatatakekeeeeeee(c(c(c(c(c(c(c(c(cononononononononontititititititititnunuuededededed))))) SSDSDSDSDSDSDSDSDlllllllatatatatatatatate e ee totototototototoCCCCCCCCD DDDD DDDDlalalaalattttet ---0.0.0.0.0.0.0.0.0.8484844888000000 0.0.0.0.0.6266262626
162
Table 5-3-1 The simulated results of PD cases by HY stage at diagnosis with 1-, 2-, 3-, 4-, and 6-yearly screening in 12 years for a hypothetical cohort of 9829 elderly people aged
Table 5-3-1 The simulated results of PD cases by HY stage at diagnosis with 1-, 2-, 3-, 4-, and 6-yearly screening in 12 years for a hypothetical cohort of 9829 elderly people aged