1. Population

Table 1. Demographics features
Characteristic	Overall, N = 70¹	Classic, N = 25¹	Cognitive, N = 19¹	Heidenhain, N = 15¹	Oppenheimer, N = 6¹	Undefined, N = 5¹	p-value²
Sex	39 (56%)	15 (60%)	12 (63%)	7 (47%)	3 (50%)	2 (40%)	0.8
Age of onset	63 (57, 71)	63 (57, 71)	63 (56, 72)	66 (60, 70)	61 (52, 67)	62 (53, 63)	0.7
MoCA	16 (13, 21)	17 (15, 22)	13 (7, 15)	13 (2, 14)	25 (21, 27)	14 (14, 15)	0.003
Unknown	37	14	10	10	0	3
Cognitive symptoms	60 (86%)	20 (80%)	18 (95%)	14 (93%)	3 (50%)	5 (100%)	0.072
Motor features	12 (17%)	6 (24%)	1 (5.3%)	2 (13%)	0 (0%)	3 (60%)	0.049
Sensitive symptoms	2 (2.9%)	0 (0%)	1 (5.3%)	0 (0%)	1 (17%)	0 (0%)	0.2
Seizures	9 (13%)	6 (24%)	0 (0%)	1 (6.7%)	0 (0%)	2 (40%)	0.031
Dysarthria	22 (31%)	9 (36%)	5 (26%)	4 (27%)	2 (33%)	2 (40%)	>0.9
Visual symptoms	24 (34%)	4 (16%)	5 (26%)	12 (80%)	2 (33%)	1 (20%)	<0.001
Behavioral changes	32 (46%)	11 (44%)	8 (42%)	8 (53%)	1 (17%)	4 (80%)	0.3
Psychiatric symptoms	32 (46%)	13 (52%)	7 (37%)	7 (47%)	1 (17%)	4 (80%)	0.3
Insomnia	27 (39%)	9 (36%)	7 (37%)	4 (27%)	3 (50%)	4 (80%)	0.3
Muscle tone alterations	32 (46%)	12 (48%)	8 (42%)	7 (47%)	2 (33%)	3 (60%)	>0.9
Ataxia	44 (63%)	14 (56%)	10 (53%)	13 (87%)	5 (83%)	2 (40%)	0.12
Cranial nerves dysruption	14 (20%)	4 (16%)	2 (11%)	4 (27%)	2 (33%)	2 (40%)	0.4
Myoclonus	49 (70%)	19 (76%)	10 (53%)	11 (73%)	5 (83%)	4 (80%)	0.5
Gait impairment	55 (79%)	22 (88%)	11 (58%)	12 (80%)	6 (100%)	4 (80%)	0.12
Stratle	13 (19%)	4 (16%)	3 (16%)	4 (27%)	1 (17%)	1 (20%)	>0.9
Hyperekplexia	9 (13%)	3 (12%)	3 (16%)	1 (6.7%)	0 (0%)	2 (40%)	0.4
Extrapiramidalism	20 (29%)	10 (40%)	6 (32%)	0 (0%)	3 (50%)	1 (20%)	0.021
¹ n (%); Median (IQR)
² Fisher's exact test; Kruskal-Wallis rank sum test

2. Time

La siguiente tabla tiene las medias sólo de sujetos que fallecieron, no es el mejor uso ni el mejor calculo y deberiamos hacerlo con la curva de Kaplan Meier

Table 2. Diagnosis delay and evolution times
Characteristic	Overall, N = 29¹	Classic, N = 10¹	Cognitive, N = 7¹	Heidenhain, N = 5¹	Oppenheimer, N = 4¹	Undefined, N = 3¹	p-value²
time_to_first_consultation	16 (13)	15 (12)	25 (16)	6 (4)	18 (13)	15 (16)	0.13
time_to_dx	18 (13)	16 (12)	27 (16)	9 (5)	20 (11)	16 (15)	0.13
time_to_dementia	17 (15)	18 (13)	22 (18)	5 (5)	26 (14)	13 (17)	0.071
time_to_death	52 (52)	40 (28)	82 (65)	13 (7)	96 (75)	30 (32)	0.035
¹ Mean (SD)
² Kruskal-Wallis rank sum test

El siguiente grafico es modo ilustrativo, lo vamos a hacer despues con los datos de kaplan Meier que son mas fidedignos

3. Time to first consultation (Kaplan Meier)

General delay to consultation (weeks)

## Warning: `select_()` was deprecated in dplyr 0.7.0.
## Please use `select()` instead.
## This warning is displayed once every 8 hours.
## Call `lifecycle::last_lifecycle_warnings()` to see where this warning was generated.

##   strata median lower upper
## 1    All     13    11    19

Delay to consultation by variants (weeks)

##                strata median lower upper
## 1     Variant=Classic   13.0    11    24
## 2   Variant=Cognitive   24.0    13    51
## 3  Variant=Heidenhain   10.0     6    21
## 4 Variant=Oppenheimer   13.5    10    NA
## 5   Variant=Undefined   33.0     6    NA

## Call:
## coxph(formula = Surv(data$time_to_first_consultation, data$diagnosis) ~ 
##     Variant, data = data)
## 
##   n= 70, number of events= 70 
## 
##                       coef exp(coef) se(coef)      z Pr(>|z|)  
## VariantCognitive   -0.6150    0.5406   0.3232 -1.903   0.0571 .
## VariantHeidenhain   0.4633    1.5894   0.3315  1.398   0.1622  
## VariantOppenheimer  0.0172    1.0173   0.4566  0.038   0.9700  
## VariantUndefined   -0.8092    0.4452   0.5123 -1.579   0.1142  
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## 
##                    exp(coef) exp(-coef) lower .95 upper .95
## VariantCognitive      0.5406     1.8497    0.2869     1.019
## VariantHeidenhain     1.5894     0.6292    0.8299     3.044
## VariantOppenheimer    1.0173     0.9830    0.4157     2.490
## VariantUndefined      0.4452     2.2461    0.1631     1.215
## 
## Concordance= 0.601  (se = 0.042 )
## Likelihood ratio test= 10.46  on 4 df,   p=0.03
## Wald test            = 10.18  on 4 df,   p=0.04
## Score (logrank) test = 10.77  on 4 df,   p=0.03

Characteristic	log(HR)¹	95% CI¹	p-value
Clinical variant
Classic	—	—
Cognitive	-0.62	-1.2, 0.02	0.057
Heidenhain	0.46	-0.19, 1.1	0.2
Oppenheimer	0.02	-0.88, 0.91	>0.9
Undefined	-0.81	-1.8, 0.19	0.11
¹ HR = Hazard Ratio, CI = Confidence Interval

4. Time to diagnosis (Kaplan Meier)

General delay to diagnosis (weeks)

##   strata   median lower upper
## 1    All 13.42857    12    23

Delay to diagnosis by variants (weeks)

##                strata median lower upper
## 1     Variant=Classic   13.0    11    24
## 2   Variant=Cognitive   24.0    13    51
## 3  Variant=Heidenhain   12.0     7    22
## 4 Variant=Oppenheimer   12.5    11    NA
## 5   Variant=Undefined   33.0     7    NA

## Call:
## coxph(formula = Surv(data$time_to_dx, data$diagnosis) ~ Variant, 
##     data = data)
## 
##   n= 70, number of events= 70 
## 
##                       coef exp(coef) se(coef)      z Pr(>|z|)  
## VariantCognitive   -0.5968    0.5505   0.3263 -1.829   0.0673 .
## VariantHeidenhain   0.4710    1.6016   0.3312  1.422   0.1550  
## VariantOppenheimer  0.1575    1.1706   0.4568  0.345   0.7302  
## VariantUndefined   -0.9122    0.4016   0.5219 -1.748   0.0805 .
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## 
##                    exp(coef) exp(-coef) lower .95 upper .95
## VariantCognitive      0.5505     1.8164    0.2905     1.044
## VariantHeidenhain     1.6016     0.6244    0.8368     3.065
## VariantOppenheimer    1.1706     0.8543    0.4782     2.866
## VariantUndefined      0.4016     2.4898    0.1444     1.117
## 
## Concordance= 0.601  (se = 0.042 )
## Likelihood ratio test= 10.97  on 4 df,   p=0.03
## Wald test            = 10.48  on 4 df,   p=0.03
## Score (logrank) test = 11.11  on 4 df,   p=0.03

Characteristic	log(HR)¹	95% CI¹	p-value
Clinical variant
Classic	—	—
Cognitive	-0.60	-1.2, 0.04	0.067
Heidenhain	0.47	-0.18, 1.1	0.2
Oppenheimer	0.16	-0.74, 1.1	0.7
Undefined	-0.91	-1.9, 0.11	0.080
¹ HR = Hazard Ratio, CI = Confidence Interval

5. Time to death (Kaplan Meier)

General survival time (weeks)

##   strata median lower upper
## 1    All     67    44   150

Survival times by variant

##                strata median lower upper
## 1     Variant=Classic     60    28    NA
## 2   Variant=Cognitive     85    67    NA
## 3  Variant=Heidenhain     23    17    NA
## 4 Variant=Oppenheimer    150    44    NA
## 5   Variant=Undefined     67    13    NA

## Call:
## coxph(formula = Surv(data$time_to_death, data$death) ~ Variant, 
##     data = data)
## 
##   n= 70, number of events= 29 
## 
##                        coef exp(coef) se(coef)      z Pr(>|z|)
## VariantCognitive   -0.70696   0.49314  0.52962 -1.335    0.182
## VariantHeidenhain   0.88135   2.41416  0.58200  1.514    0.130
## VariantOppenheimer -0.61086   0.54289  0.62772 -0.973    0.330
## VariantUndefined    0.04563   1.04669  0.67616  0.067    0.946
## 
##                    exp(coef) exp(-coef) lower .95 upper .95
## VariantCognitive      0.4931     2.0278    0.1746     1.392
## VariantHeidenhain     2.4142     0.4142    0.7715     7.554
## VariantOppenheimer    0.5429     1.8420    0.1586     1.858
## VariantUndefined      1.0467     0.9554    0.2781     3.939
## 
## Concordance= 0.668  (se = 0.058 )
## Likelihood ratio test= 6.13  on 4 df,   p=0.2
## Wald test            = 6.32  on 4 df,   p=0.2
## Score (logrank) test = 6.98  on 4 df,   p=0.1

Characteristic	log(HR)¹	95% CI¹	p-value
Clinical variant
Classic	—	—
Cognitive	-0.71	-1.7, 0.33	0.2
Heidenhain	0.88	-0.26, 2.0	0.13
Oppenheimer	-0.61	-1.8, 0.62	0.3
Undefined	0.05	-1.3, 1.4	>0.9
¹ HR = Hazard Ratio, CI = Confidence Interval

CJD_survival

Ismael calandri

2022-05-23