Oxido Nitrico Inalado Para Tratamento de Infeccao por SARS-CoV2- um
ensaio clinico aberto, paralelo e randomizado
CNPq Processo 403202/2020-5
Coordenador: Marcus Herbert Jones
data preparation
Table: Demographics
## Stratified by grupo
## Control iNO p test
## n 27 27
## Sex = Male (%) 18 (66.7) 19 (70.4) 1.000
## Age (median [IQR]) 53.00 [39.00, 64.50] 57.00 [40.00, 62.50] 0.938 nonnorm
## Weight (median [IQR]) 85.00 [80.00, 100.00] 88.00 [81.00, 96.50] 0.829 nonnorm
## Height (median [IQR]) 167.00 [158.50, 176.00] 174.00 [166.00, 180.50] 0.079 nonnorm
## BMI (median [IQR]) 32.17 [29.02, 33.97] 30.07 [27.07, 32.50] 0.132 nonnorm
## obesity (%) 0.259
## Healthy weight 0 ( 0.0) 2 ( 7.4)
## Obesity 18 (66.7) 14 (51.9)
## Overweight 9 (33.3) 11 (40.7)
## race (%) 0.137
## Black 2 ( 7.4) 5 (18.5)
## Brown 5 (18.5) 1 ( 3.7)
## White 20 (74.1) 21 (77.8)
## Tobacco use = Yes (%) 1 ( 3.7) 1 ( 3.7) 1.000
## Alcohol use = 1 (%) 8 (29.6) 13 (48.1) 0.264
## Symptoms(days) (median [IQR]) 8.00 [7.00, 10.00] 9.00 [8.00, 11.00] 0.383 nonnorm
## Resp Symptoms(days) (median [IQR]) 3.00 [2.00, 5.00] 4.00 [2.00, 5.00] 0.395 nonnorm
## status_vacinal = No COVID vaccine (%) 17 (70.8) 16 (66.7) 1.000
## Antiinflamatorio = Yes (%) 15 (55.6) 15 (55.6) 1.000
## Azitromicina = Yes (%) 15 (55.6) 17 (63.0) 0.782
## Antibioticos = Yes (%) 6 (22.2) 5 (18.5) 1.000
## Hidroxicloroquina = Yes (%) 5 (18.5) 3 (11.1) 0.702
## Corticoide = Yes (%) 15 (55.6) 14 (51.9) 1.000
## Nenhum = Yes (%) 2 ( 7.4) 3 (11.1) 1.000
## Comorbidities = Yes (%) 13 (48.1) 9 (33.3) 0.406
## has = Yes (%) 13 (48.1) 9 (33.3) 0.406
## chf = Yes (%) 1 ( 3.7) 0 ( 0.0) 1.000
## dm1 = Yes (%) 2 ( 7.4) 1 ( 3.7) 1.000
## dm2 = Yes (%) 6 (22.2) 0 ( 0.0) 0.030
## satpo2_ar_ambiente (median [IQR]) 90.00 [89.00, 91.00] 91.00 [89.75, 92.25] 0.159 nonnorm
## C-reactive_protein (median [IQR]) 7.70 [4.75, 21.45] 7.70 [4.30, 22.10] 0.959 nonnorm
## D-dimer (median [IQR]) 601.50 [360.00, 791.25] 783.00 [549.00, 1065.00] 0.040 nonnorm
## CT: pulmonary involvement% (median [IQR]) 50.00 [30.00, 60.00] 50.00 [40.00, 50.00] 0.944 nonnorm
Table 2: Primary and secondary Outcomes Stratified by Treatment
Group
All Subjects
## Stratified by grupo
## Control iNO p
## n 27 27
## Days Free of Vent Support (median [IQR]) 8.00 [2.50, 10.50] 11.00 [8.00, 13.00] 0.043
## Score Day 3 (median [IQR]) 4.00 [4.00, 5.00] 4.00 [3.00, 4.00] 0.010
## Score Day 5 (median [IQR]) 4.00 [3.50, 5.00] 3.00 [2.00, 4.00] 0.032
## Score Day 7 (median [IQR]) 4.00 [2.00, 5.00] 2.00 [1.50, 3.50] 0.081
## worsening = Yes (%) 11 (40.7) 7 (25.9) 0.386
## Supplemental oxygen Day 3 = Supplemental oxygen (%) 26 (96.3) 18 (66.7) 0.014
## Supplemental oxygen Day 5 = Supplemental oxygen (%) 20 (74.1) 13 (48.1) 0.094
## Supplemental oxygen Day 7 = Supplemental oxygen (%) 14 (51.9) 7 (25.9) 0.094
## mech_vent = Yes (%) 5 (18.5) 5 (18.5) 1.000
## Length of Stay (Days) (median [IQR]) 7.00 [6.00, 10.00] 4.50 [3.00, 6.25] 0.004
## Death = Yes (%) 2 ( 7.7) 3 (11.1) 1.000
## Stratified by grupo
## test
## n
## Days Free of Vent Support (median [IQR]) nonnorm
## Score Day 3 (median [IQR]) nonnorm
## Score Day 5 (median [IQR]) nonnorm
## Score Day 7 (median [IQR]) nonnorm
## worsening = Yes (%)
## Supplemental oxygen Day 3 = Supplemental oxygen (%)
## Supplemental oxygen Day 5 = Supplemental oxygen (%)
## Supplemental oxygen Day 7 = Supplemental oxygen (%)
## mech_vent = Yes (%)
## Length of Stay (Days) (median [IQR]) nonnorm
## Death = Yes (%)
wilcox_test clinical score 3 5 7 10 detailed
# load package
library(ggstatsplot)
# plot with statistical results
ggbetweenstats( # independent samples
data = df,
x = grupo,
y = dlo,
plot.type = "box", # for boxplot
type = "nonparametric", # for wilcoxon
centrality.plotting = FALSE # remove median
)
ggbetweenstats( # independent samples
data = df,
x = grupo,
y = do,
plot.type = "box", # for boxplot
type = "nonparametric", # for wilcoxon
centrality.plotting = FALSE # remove median
)
ggbetweenstats( # independent samples
data = df,
x = grupo,
y = los,
plot.type = "box", # for boxplot
type = "nonparametric", # for wilcoxon
centrality.plotting = FALSE # remove median
)
Status Day 5
Status Day 7
Status Day 10
analysis <60
all subjects 3 categories
s3a <- bar3alt + theme(text = element_text(size = 14), legend.position = "none")
s3b <- bar5alt + theme(text = element_text(size = 14), legend.position = "none")
s3c <- bar7alt + theme(text = element_text(size = 14), legend.position = "none")
sup2 <- s3a+s3b+s3c
sup2
s3d <- bar3balt + theme(text = element_text(size = 14), legend.position = "none")
s3e <- bar5balt + theme(text = element_text(size = 14), legend.position = "none")
s3f <- bar7balt + theme(text = element_text(size = 14), legend.position = "none")
sup2a <- s3d+s3e+s3f
sup2a
in subjects <60 years
s4a <- bar360alt + theme(text = element_text(size = 14), legend.position = "none")
s4b <- bar560alt + theme(text = element_text(size = 14), legend.position = "none")
s4c <- bar760alt + theme(text = element_text(size = 14), legend.position = "none")
sup3 <- s4a+s4b+s4c
sup3
s4ab <- bar360balt + theme(text = element_text(size = 14), legend.position = "none")
s4bb <- bar560balt + theme(text = element_text(size = 14), legend.position = "none")
s4cb <- bar760balt + theme(text = element_text(size = 14), legend.position = "none")
sup3b <- s4ab+s4bb+s4cb
sup3b
s360 <- bar360alt + theme(text = element_text(size = 14), legend.position = "none")
s560 <- bar560alt + theme(text = element_text(size = 14), legend.position = "none")
s760 <- bar760alt + theme(text = element_text(size = 14), legend.position = "none")
sup3 <- s360+s560+s760
sup3
Kaplan-Meier Curves
Hazard Ratio & Cox Regression - Days Free of
Oxygen
dloSurv <- Surv(df1$dlo, df1$status1)
dloDiff <- survdiff(dloSurv ~ group, data = df1)
dloDiff
## Call:
## survdiff(formula = dloSurv ~ group, data = df1)
##
## N Observed Expected (O-E)^2/E (O-E)^2/V
## group=Control 27 27 19.9 2.54 5.7
## group=iNO 27 27 34.1 1.48 5.7
##
## Chisq= 5.7 on 1 degrees of freedom, p= 0.02
D1 <- dloDiff$obs[1]
D2 <- dloDiff$obs[2]
E1 <- dloDiff$exp[1]
E2 <- dloDiff$exp[2]
HR <- (D1/D2)/(E1/E2)
HR
## [1] 1.71465
SE_lnHR = sqrt(1/E1 + 1/E2)
SE_lnHR
## [1] 0.282117
L = log(HR)
lower <- exp(L - 1.96*SE_lnHR)
upper <- exp(L + 1.96*SE_lnHR)
ci95 <- c(lower=lower, upper=upper)
ci95
## lower upper
## 0.9863536 2.9806999
z <- coxph(dloSurv ~ group, data = df1)
summary(z)
## Call:
## coxph(formula = dloSurv ~ group, data = df1)
##
## n= 54, number of events= 54
##
## coef exp(coef) se(coef) z Pr(>|z|)
## groupiNO -0.6374 0.5287 0.2838 -2.246 0.0247 *
## ---
## Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
##
## exp(coef) exp(-coef) lower .95 upper .95
## groupiNO 0.5287 1.892 0.3031 0.9221
##
## Concordance= 0.59 (se = 0.042 )
## Likelihood ratio test= 5 on 1 df, p=0.03
## Wald test = 5.04 on 1 df, p=0.02
## Score (logrank) test = 5.19 on 1 df, p=0.02
do
doSurv <- Surv(df1$do, df1$status1)
doDiff <- survdiff(doSurv ~ group, data = df1)
doDiff
## Call:
## survdiff(formula = doSurv ~ group, data = df1)
##
## N Observed Expected (O-E)^2/E (O-E)^2/V
## group=Control 27 27 31.4 0.628 2.21
## group=iNO 27 27 22.6 0.876 2.21
##
## Chisq= 2.2 on 1 degrees of freedom, p= 0.1
D1 <- doDiff$obs[1]
D2 <- doDiff$obs[2]
E1 <- doDiff$exp[1]
E2 <- doDiff$exp[2]
HR <- (D1/D2)/(E1/E2)
HR
## [1] 0.717265
SE_lnHR = sqrt(1/E1 + 1/E2)
SE_lnHR
## [1] 0.2759311
L = log(HR)
lower <- exp(L - 1.96*SE_lnHR)
upper <- exp(L + 1.96*SE_lnHR)
ci95 <- c(lower=lower, upper=upper)
ci95
## lower upper
## 0.4176403 1.2318474
z <- coxph(doSurv ~ group, data = df1)
summary(z)
## Call:
## coxph(formula = doSurv ~ group, data = df1)
##
## n= 54, number of events= 54
##
## coef exp(coef) se(coef) z Pr(>|z|)
## groupiNO 0.3546 1.4257 0.2729 1.299 0.194
##
## exp(coef) exp(-coef) lower .95 upper .95
## groupiNO 1.426 0.7014 0.8351 2.434
##
## Concordance= 0.59 (se = 0.042 )
## Likelihood ratio test= 1.68 on 1 df, p=0.2
## Wald test = 1.69 on 1 df, p=0.2
## Score (logrank) test = 1.71 on 1 df, p=0.2
Hazard Ratio & Cox Regression - Length of Stay
losSurv <- Surv(df1$los, df1$status)
losDiff <- survdiff(losSurv ~ group, data = df1)
losDiff
## Call:
## survdiff(formula = losSurv ~ group, data = df1)
##
## n=49, 5 observations deleted due to missingness.
##
## N Observed Expected (O-E)^2/E (O-E)^2/V
## group=Control 25 20 26.8 1.73 5.77
## group=iNO 24 22 15.2 3.05 5.77
##
## Chisq= 5.8 on 1 degrees of freedom, p= 0.02
D1 <- losDiff$obs[1]
D2 <- losDiff$obs[2]
E1 <- losDiff$exp[1]
E2 <- losDiff$exp[2]
HR <- (D1/D2)/(E1/E2)
HR
## [1] 0.5153699
SE_lnHR = sqrt(1/E1 + 1/E2)
SE_lnHR
## [1] 0.3211165
L = log(HR)
lower <- exp(L - 1.96*SE_lnHR)
upper <- exp(L + 1.96*SE_lnHR)
ci95 <- c(lower=lower, upper=upper)
ci95
## lower upper
## 0.2746497 0.9670723
z <- coxph(losSurv ~ group, data = df1)
summary(z)
## Call:
## coxph(formula = losSurv ~ group, data = df1)
##
## n= 49, number of events= 42
## (5 observations deleted due to missingness)
##
## coef exp(coef) se(coef) z Pr(>|z|)
## groupiNO 0.7105 2.0349 0.3120 2.277 0.0228 *
## ---
## Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
##
## exp(coef) exp(-coef) lower .95 upper .95
## groupiNO 2.035 0.4914 1.104 3.751
##
## Concordance= 0.633 (se = 0.04 )
## Likelihood ratio test= 5.14 on 1 df, p=0.02
## Wald test = 5.19 on 1 df, p=0.02
## Score (logrank) test = 5.39 on 1 df, p=0.02
Subjects < 60 years
## Stratified by grupo
## Control iNO p test
## n 18 16
## Sex = Male (%) 15 (83.3) 12 (75.0) 0.861
## Age (median [IQR]) 43.50 [37.25, 52.75] 40.50 [35.75, 51.75] 0.849 nonnorm
## Weight (median [IQR]) 93.00 [82.25, 106.50] 93.50 [85.00, 100.00] 0.863 nonnorm
## Height (median [IQR]) 170.00 [165.50, 179.75] 180.00 [167.75, 183.00] 0.201 nonnorm
## BMI (median [IQR]) 31.86 [29.42, 33.36] 30.60 [26.71, 33.32] 0.417 nonnorm
## obesity (%) 0.518
## Healthy weight 0 ( 0.0) 1 ( 6.2)
## Obesity 12 (66.7) 9 (56.2)
## Overweight 6 (33.3) 6 (37.5)
## race (%) 0.086
## Black 1 ( 5.6) 3 (18.8)
## Brown 4 (22.2) 0 ( 0.0)
## White 13 (72.2) 13 (81.2)
## Tobacco use = Yes (%) 1 ( 5.6) 1 ( 6.2) 1.000
## Alcohol use = 1 (%) 7 (38.9) 9 (56.2) 0.504
## Symptoms(days) (median [IQR]) 9.00 [8.00, 10.00] 9.00 [8.00, 10.50] 0.807 nonnorm
## Resp Symptoms(days) (median [IQR]) 3.00 [2.00, 5.75] 4.00 [2.75, 6.00] 0.577 nonnorm
## status_vacinal = No COVID vaccine (%) 14 (93.3) 8 (61.5) 0.113
## Antiinflamatorio = Yes (%) 12 (66.7) 9 (56.2) 0.787
## Azitromicina = Yes (%) 13 (72.2) 10 (62.5) 0.812
## Antibioticos = Yes (%) 4 (22.2) 4 (25.0) 1.000
## Hidroxicloroquina = Yes (%) 5 (27.8) 1 ( 6.2) 0.233
## Corticoide = Yes (%) 14 (77.8) 8 (50.0) 0.183
## Nenhum = Yes (%) 0 ( 0.0) 2 (12.5) 0.414
## Comorbidities = Yes (%) 7 (38.9) 5 (31.2) 0.916
## has = Yes (%) 7 (38.9) 5 (31.2) 0.916
## chf = Yes (%) 0 ( 0.0) 0 ( 0.0) NaN
## dm1 = Yes (%) 1 ( 5.6) 1 ( 6.2) 1.000
## dm2 = Yes (%) 3 (16.7) 0 ( 0.0) 0.269
## satpo2_ar_ambiente (median [IQR]) 90.00 [88.50, 91.00] 90.00 [89.00, 92.50] 0.629 nonnorm
## C-reactive_protein (median [IQR]) 8.55 [5.28, 21.53] 8.20 [3.48, 24.48] 0.743 nonnorm
## D-dimer (median [IQR]) 601.50 [320.75, 791.25] 741.00 [482.00, 920.50] 0.301 nonnorm
## CT: pulmonary involvement% (median [IQR]) 50.00 [40.00, 63.75] 42.50 [30.00, 50.00] 0.162 nonnorm
## Stratified by grupo
## Control iNO p test
## n 18 16
## Days Free of Vent Support (median [IQR]) 8.50 [1.25, 10.00] 11.50 [9.00, 13.25] 0.013 nonnorm
## Score Day 3 (median [IQR]) 4.00 [4.00, 5.00] 4.00 [2.75, 4.00] 0.003 nonnorm
## Score Day 5 (median [IQR]) 4.50 [4.00, 5.00] 2.50 [2.00, 4.00] 0.017 nonnorm
## Score Day 7 (median [IQR]) 3.50 [2.25, 5.00] 2.00 [1.75, 3.00] 0.110 nonnorm
## worsening = Yes (%) 9 ( 50.0) 4 (25.0) 0.253
## Supplemental oxygen Day 3 = Supplemental oxygen (%) 18 (100.0) 9 (56.2) 0.006
## Supplemental oxygen Day 5 = Supplemental oxygen (%) 14 ( 77.8) 7 (43.8) 0.092
## Supplemental oxygen Day 7 = Supplemental oxygen (%) 9 ( 50.0) 3 (18.8) 0.123
## mech_vent = Yes (%) 4 ( 22.2) 2 (12.5) 0.771
## Length of Stay (Days) (median [IQR]) 7.00 [6.00, 11.00] 4.00 [2.00, 6.00] 0.004 nonnorm
## Death = Yes (%) 1 ( 5.6) 1 ( 6.2) 1.000
subgroup analysis in patients with 60 years or more
## Stratified by grupo
## Control iNO p test
## n 9 11
## Days Free of Vent Support (median [IQR]) 8.00 [7.00, 12.00] 9.00 [3.50, 11.50] 0.939 nonnorm
## Score Day 3 (median [IQR]) 4.00 [4.00, 4.00] 4.00 [4.00, 4.00] 0.963 nonnorm
## Score Day 5 (median [IQR]) 4.00 [3.00, 4.00] 4.00 [3.00, 4.50] 0.937 nonnorm
## Score Day 7 (median [IQR]) 4.00 [2.00, 4.00] 2.00 [1.50, 4.50] 0.438 nonnorm
## worsening = Yes (%) 2 (22.2) 3 (27.3) 1.000
## Supplemental oxygen Day 3 = Supplemental oxygen (%) 8 (88.9) 9 (81.8) 1.000
## Supplemental oxygen Day 5 = Supplemental oxygen (%) 6 (66.7) 6 (54.5) 0.927
## Supplemental oxygen Day 7 = Supplemental oxygen (%) 5 (55.6) 4 (36.4) 0.684
## mech_vent = Yes (%) 1 (11.1) 3 (27.3) 0.736
## Length of Stay (Days) (median [IQR]) 7.00 [5.50, 7.25] 5.00 [4.00, 7.00] 0.527 nonnorm
## Death = Yes (%) 1 (12.5) 2 (18.2) 1.000
clinical score <60
clinical score >=60 years
Subjects <60 years
Days Free of Respiratory Support
Length of Stay
|
estimate
|
.y.
|
group1
|
group2
|
n1
|
n2
|
statistic
|
p
|
conf.low
|
conf.high
|
method
|
alternative
|
|
-3.000021
|
dlo
|
Control
|
iNO
|
18
|
16
|
73
|
0.0142
|
-6.000013
|
-0.9999679
|
Wilcoxon
|
two.sided
|
|
estimate
|
.y.
|
group1
|
group2
|
n1
|
n2
|
statistic
|
p
|
conf.low
|
conf.high
|
method
|
alternative
|
|
3.999962
|
los
|
Control
|
iNO
|
17
|
15
|
203
|
0.00439
|
1.000032
|
6.000016
|
Wilcoxon
|
two.sided
|
hh <- df %>% select(grupo, do)
ggplot(data = hh, aes(x = do, fill = grupo)) +
geom_histogram(data = subset(hh, grupo == "Control"), binwidth = 1, color="white", position = "identity") +
geom_histogram(data = subset(hh, grupo == "iNO"), binwidth = 1, color="white", position = "identity",
mapping = aes(y = - ..count.. )) +
scale_x_continuous("Days", breaks = c(seq(0, 15, by=1))) +
scale_y_continuous("Groups", breaks = seq(-10, 10, 2), labels = abs) +
scale_fill_discrete(name = "Grupo") +
coord_flip() +
theme_bw()
## Warning: The dot-dot notation (`..count..`) was deprecated in ggplot2 3.4.0.
## ℹ Please use `after_stat(count)` instead.
## This warning is displayed once every 8 hours.
## Call `lifecycle::last_lifecycle_warnings()` to see where this warning was generated.
save(df, file="df.Rdata")
kaplan-meier
library(survival)
library(survminer)
# load("E:/OneDrive - PUCRS - BR/$$-COVID-19/R/df1.Rdata")
load("df1.Rdata")
# do
fit <- survfit(Surv(do, status) ~ group, data = df1)
ggsurvplot(fit, data = df1, pval = TRUE, pval.method = TRUE)
ggsurvplot(fit, data = df1, pval = TRUE, pval.method = TRUE, log.rank.weights = "n", pval.method.coord = c(5, 0.1), pval.method.size = 3)
ggsurvplot(fit, data = df1, pval = TRUE, pval.method = TRUE,
log.rank.weights = "S1", pval.method.coord = c(5, 0.1),
pval.method.size = 3)
ggsurvplot(fit, data = df1, pval = TRUE, pval.method = TRUE,
log.rank.weights = "S2", pval.method.coord = c(5, 0.1),
pval.method.size = 3)
ggsurvplot(fit, data = df1, pval = TRUE, pval.method = TRUE,
log.rank.weights = "sqrtN", pval.method.coord = c(5, 0.1),
pval.method.size = 3)
ggsurvplot(fit, data = df1, pval = TRUE, pval.method = TRUE,
log.rank.weights = "1", pval.method.coord = c(5, 0.1),
pval.method.size = 3)
# los
fit <- survfit(Surv(los, status) ~ group, data = df1)
ggsurvplot(fit, data = df1, pval = TRUE, pval.method = TRUE)
ggsurvplot(fit, data = df1, pval = TRUE, pval.method = TRUE,
log.rank.weights = "n", pval.method.coord = c(5, 0.1),
pval.method.size = 3)
ggsurvplot(fit, data = df1, pval = TRUE, pval.method = TRUE,
log.rank.weights = "S1", pval.method.coord = c(5, 0.1),
pval.method.size = 3)
ggsurvplot(fit, data = df1, pval = TRUE, pval.method = TRUE,
log.rank.weights = "S2", pval.method.coord = c(5, 0.1),
pval.method.size = 3)
ggsurvplot(fit, data = df1, pval = TRUE, pval.method = TRUE,
log.rank.weights = "sqrtN", pval.method.coord = c(5, 0.1),
pval.method.size = 3)
ggsurvplot(fit, data = df1, pval = TRUE, pval.method = TRUE,
log.rank.weights = "1", pval.method.coord = c(5, 0.1),
pval.method.size = 3)
# https://cran.r-project.org/web/packages/survminer/vignettes/Specifiying_weights_in_log-rank_comparisons.html
==========================
analisys in <60 years
==========================
SUBGROUP ANALYSIS: Demographics in <60 years
## Stratified by grupo
## Control iNO p test
## n 18 16
## Sex = Male (%) 15 (83.3) 12 (75.0) 0.861
## Age (median [IQR]) 43.50 [37.25, 52.75] 40.50 [35.75, 51.75] 0.849 nonnorm
## Weight (median [IQR]) 93.00 [82.25, 106.50] 93.50 [85.00, 100.00] 0.863 nonnorm
## Height (median [IQR]) 170.00 [165.50, 179.75] 180.00 [167.75, 183.00] 0.201 nonnorm
## BMI (median [IQR]) 31.86 [29.42, 33.36] 30.60 [26.71, 33.32] 0.417 nonnorm
## obesity (%) 0.518
## Healthy weight 0 ( 0.0) 1 ( 6.2)
## Obesity 12 (66.7) 9 (56.2)
## Overweight 6 (33.3) 6 (37.5)
## race (%) 0.086
## Black 1 ( 5.6) 3 (18.8)
## Brown 4 (22.2) 0 ( 0.0)
## White 13 (72.2) 13 (81.2)
## Tobacco use = Yes (%) 1 ( 5.6) 1 ( 6.2) 1.000
## Alcohol use = 1 (%) 7 (38.9) 9 (56.2) 0.504
## Symptoms(days) (median [IQR]) 9.00 [8.00, 10.00] 9.00 [8.00, 10.50] 0.807 nonnorm
## Resp Symptoms(days) (median [IQR]) 3.00 [2.00, 5.75] 4.00 [2.75, 6.00] 0.577 nonnorm
## status_vacinal = No COVID vaccine (%) 14 (93.3) 8 (61.5) 0.113
## Antiinflamatorio = Yes (%) 12 (66.7) 9 (56.2) 0.787
## Azitromicina = Yes (%) 13 (72.2) 10 (62.5) 0.812
## Antibioticos = Yes (%) 4 (22.2) 4 (25.0) 1.000
## Hidroxicloroquina = Yes (%) 5 (27.8) 1 ( 6.2) 0.233
## Corticoide = Yes (%) 14 (77.8) 8 (50.0) 0.183
## Nenhum = Yes (%) 0 ( 0.0) 2 (12.5) 0.414
## Comorbidities = Yes (%) 7 (38.9) 5 (31.2) 0.916
## has = Yes (%) 7 (38.9) 5 (31.2) 0.916
## chf = Yes (%) 0 ( 0.0) 0 ( 0.0) NaN
## dm1 = Yes (%) 1 ( 5.6) 1 ( 6.2) 1.000
## dm2 = Yes (%) 3 (16.7) 0 ( 0.0) 0.269
## satpo2_ar_ambiente (median [IQR]) 90.00 [88.50, 91.00] 90.00 [89.00, 92.50] 0.629 nonnorm
## C-reactive_protein (median [IQR]) 8.55 [5.28, 21.53] 8.20 [3.48, 24.48] 0.743 nonnorm
## D-dimer (median [IQR]) 601.50 [320.75, 791.25] 741.00 [482.00, 920.50] 0.301 nonnorm
## CT: pulmonary involvement% (median [IQR]) 50.00 [40.00, 63.75] 42.50 [30.00, 50.00] 0.162 nonnorm
Primary and secondary outcomes in <60 years
## Stratified by grupo
## Control iNO p test
## n 18 16
## Days Free of Vent Support (median [IQR]) 8.50 [1.25, 10.00] 11.50 [9.00, 13.25] 0.013 nonnorm
## Score Day 3 (median [IQR]) 4.00 [4.00, 5.00] 4.00 [2.75, 4.00] 0.003 nonnorm
## Score Day 5 (median [IQR]) 4.50 [4.00, 5.00] 2.50 [2.00, 4.00] 0.017 nonnorm
## Score Day 7 (median [IQR]) 3.50 [2.25, 5.00] 2.00 [1.75, 3.00] 0.110 nonnorm
## worsening = Yes (%) 9 ( 50.0) 4 (25.0) 0.253
## Supplemental oxygen Day 3 = Supplemental oxygen (%) 18 (100.0) 9 (56.2) 0.006
## Supplemental oxygen Day 5 = Supplemental oxygen (%) 14 ( 77.8) 7 (43.8) 0.092
## Supplemental oxygen Day 7 = Supplemental oxygen (%) 9 ( 50.0) 3 (18.8) 0.123
## mech_vent = Yes (%) 4 ( 22.2) 2 (12.5) 0.771
## Length of Stay (Days) (median [IQR]) 7.00 [6.00, 11.00] 4.00 [2.00, 6.00] 0.004 nonnorm
## Death = Yes (%) 1 ( 5.6) 1 ( 6.2) 1.000
SUBGROUP ANALYSIS: Demographics in 60 years or more
## Stratified by grupo
## Control iNO p test
## n 9 11
## Sex = Male (%) 3 (33.3) 7 (63.6) 0.369
## Age (median [IQR]) 68.00 [65.00, 73.00] 63.00 [62.00, 73.50] 0.195 nonnorm
## Weight (median [IQR]) 80.00 [78.00, 85.00] 85.00 [79.50, 87.00] 0.446 nonnorm
## Height (median [IQR]) 157.00 [154.00, 167.00] 170.00 [162.50, 173.00] 0.044 nonnorm
## BMI (median [IQR]) 32.44 [28.68, 34.99] 29.41 [27.76, 31.44] 0.271 nonnorm
## obesity (%) 0.495
## Healthy weight 0 ( 0.0) 1 ( 9.1)
## Obesity 6 (66.7) 5 (45.5)
## Overweight 3 (33.3) 5 (45.5)
## race (%) 0.904
## Black 1 (11.1) 2 (18.2)
## Brown 1 (11.1) 1 ( 9.1)
## White 7 (77.8) 8 (72.7)
## Tobacco use = Yes (%) 0 ( 0.0) 0 ( 0.0) NaN
## Alcohol use = 1 (%) 1 (11.1) 4 (36.4) 0.436
## Symptoms(days) (median [IQR]) 8.00 [5.00, 9.00] 10.00 [8.00, 11.00] 0.117 nonnorm
## Resp Symptoms(days) (median [IQR]) 3.00 [2.00, 4.00] 4.00 [2.00, 4.00] 0.482 nonnorm
## status_vacinal = No COVID vaccine (%) 3 (33.3) 8 (72.7) 0.190
## Antiinflamatorio = Yes (%) 3 (33.3) 6 (54.5) 0.619
## Azitromicina = Yes (%) 2 (22.2) 7 (63.6) 0.161
## Antibioticos = Yes (%) 2 (22.2) 1 ( 9.1) 0.850
## Hidroxicloroquina = Yes (%) 0 ( 0.0) 2 (18.2) 0.549
## Corticoide = Yes (%) 1 (11.1) 6 (54.5) 0.120
## Nenhum = Yes (%) 2 (22.2) 1 ( 9.1) 0.850
## Comorbidities = Yes (%) 6 (66.7) 4 (36.4) 0.369
## has = Yes (%) 6 (66.7) 4 (36.4) 0.369
## chf = Yes (%) 1 (11.1) 0 ( 0.0) 0.918
## dm1 = Yes (%) 1 (11.1) 0 ( 0.0) 0.918
## dm2 = Yes (%) 3 (33.3) 0 ( 0.0) 0.148
## satpo2_ar_ambiente (median [IQR]) 90.00 [89.00, 91.00] 91.00 [91.00, 92.00] 0.102 nonnorm
## C-reactive_protein (median [IQR]) 5.60 [3.40, 8.70] 7.60 [6.05, 7.95] 0.342 nonnorm
## D-dimer (median [IQR]) 605.00 [451.50, 701.25] 956.00 [678.25, 2024.25] 0.062 nonnorm
## CT: pulmonary involvement% (median [IQR]) 30.00 [25.00, 45.00] 50.00 [47.50, 55.00] 0.028 nonnorm
subgroup analysis in patients with 60 years or more
## Stratified by grupo
## Control iNO p test
## n 9 11
## Days Free of Vent Support (median [IQR]) 8.00 [7.00, 12.00] 9.00 [3.50, 11.50] 0.939 nonnorm
## Score Day 3 (median [IQR]) 4.00 [4.00, 4.00] 4.00 [4.00, 4.00] 0.963 nonnorm
## Score Day 5 (median [IQR]) 4.00 [3.00, 4.00] 4.00 [3.00, 4.50] 0.937 nonnorm
## Score Day 7 (median [IQR]) 4.00 [2.00, 4.00] 2.00 [1.50, 4.50] 0.438 nonnorm
## worsening = Yes (%) 2 (22.2) 3 (27.3) 1.000
## Supplemental oxygen Day 3 = Supplemental oxygen (%) 8 (88.9) 9 (81.8) 1.000
## Supplemental oxygen Day 5 = Supplemental oxygen (%) 6 (66.7) 6 (54.5) 0.927
## Supplemental oxygen Day 7 = Supplemental oxygen (%) 5 (55.6) 4 (36.4) 0.684
## mech_vent = Yes (%) 1 (11.1) 3 (27.3) 0.736
## Length of Stay (Days) (median [IQR]) 7.00 [5.50, 7.25] 5.00 [4.00, 7.00] 0.527 nonnorm
## Death = Yes (%) 1 (12.5) 2 (18.2) 1.000
clinical score <60
SUBGROUP ANALYSIS
PATIENTS WITH COMORBIDITIES
## Stratified by grupo
## Control iNO p
## n 13 9
## Days Free of Vent Support (median [IQR]) 9.00 [7.00, 11.00] 10.00 [0.00, 13.00] 0.711
## Score Day 3 (median [IQR]) 4.00 [4.00, 5.00] 4.00 [3.00, 4.00] 0.304
## Score Day 5 (median [IQR]) 4.00 [3.00, 5.00] 4.00 [2.00, 5.00] 0.733
## Score Day 7 (median [IQR]) 2.00 [2.00, 4.00] 2.00 [2.00, 5.00] 0.837
## worsening = Yes (%) 4 (30.8) 3 (33.3) 1.000
## Supplemental oxygen Day 3 = Supplemental oxygen (%) 12 (92.3) 6 (66.7) 0.332
## Supplemental oxygen Day 5 = Supplemental oxygen (%) 8 (61.5) 5 (55.6) 1.000
## Supplemental oxygen Day 7 = Supplemental oxygen (%) 6 (46.2) 3 (33.3) 0.873
## mech_vent = Yes (%) 2 (15.4) 3 (33.3) 0.638
## Length of Stay (Days) (median [IQR]) 6.00 [4.50, 7.50] 4.00 [3.00, 6.00] 0.291
## Death = Yes (%) 2 (16.7) 2 (22.2) 1.000
## Stratified by grupo
## test
## n
## Days Free of Vent Support (median [IQR]) nonnorm
## Score Day 3 (median [IQR]) nonnorm
## Score Day 5 (median [IQR]) nonnorm
## Score Day 7 (median [IQR]) nonnorm
## worsening = Yes (%)
## Supplemental oxygen Day 3 = Supplemental oxygen (%)
## Supplemental oxygen Day 5 = Supplemental oxygen (%)
## Supplemental oxygen Day 7 = Supplemental oxygen (%)
## mech_vent = Yes (%)
## Length of Stay (Days) (median [IQR]) nonnorm
## Death = Yes (%)
PATIENTS WITHOUT COMORBIDITIES
## Stratified by grupo
## Control iNO p
## n 14 18
## Days Free of Vent Support (median [IQR]) 8.00 [0.00, 9.75] 11.00 [9.00, 13.00] 0.021
## Score Day 3 (median [IQR]) 4.00 [4.00, 5.00] 4.00 [3.00, 4.00] 0.014
## Score Day 5 (median [IQR]) 4.50 [4.00, 5.00] 3.00 [2.00, 4.00] 0.010
## Score Day 7 (median [IQR]) 4.00 [3.00, 5.00] 2.00 [1.25, 3.00] 0.010
## worsening = Yes (%) 7 ( 50.0) 4 (22.2) 0.205
## Supplemental oxygen Day 3 = Supplemental oxygen (%) 14 (100.0) 12 (66.7) 0.052
## Supplemental oxygen Day 5 = Supplemental oxygen (%) 12 ( 85.7) 8 (44.4) 0.043
## Supplemental oxygen Day 7 = Supplemental oxygen (%) 8 ( 57.1) 4 (22.2) 0.098
## mech_vent = Yes (%) 3 ( 21.4) 2 (11.1) 0.759
## Length of Stay (Days) (median [IQR]) 7.50 [7.00, 18.75] 5.00 [3.00, 7.00] 0.002
## Death = Yes (%) 0 ( 0.0) 1 ( 5.6) 1.000
## Stratified by grupo
## test
## n
## Days Free of Vent Support (median [IQR]) nonnorm
## Score Day 3 (median [IQR]) nonnorm
## Score Day 5 (median [IQR]) nonnorm
## Score Day 7 (median [IQR]) nonnorm
## worsening = Yes (%)
## Supplemental oxygen Day 3 = Supplemental oxygen (%)
## Supplemental oxygen Day 5 = Supplemental oxygen (%)
## Supplemental oxygen Day 7 = Supplemental oxygen (%)
## mech_vent = Yes (%)
## Length of Stay (Days) (median [IQR]) nonnorm
## Death = Yes (%)
##
## Wilcoxon rank sum test with continuity correction
##
## data: df_comorb_n$dlo by df_comorb_n$grupo
## W = 66, p-value = 0.02235
## alternative hypothesis: true location shift is not equal to 0
##
## Wilcoxon rank sum test with continuity correction
##
## data: df_comorb_n$score_dia3 by df_comorb_n$grupo
## W = 183.5, p-value = 0.01464
## alternative hypothesis: true location shift is not equal to 0
##
## Wilcoxon rank sum test with continuity correction
##
## data: df_comorb_n$score_dia5 by df_comorb_n$grupo
## W = 192, p-value = 0.01055
## alternative hypothesis: true location shift is not equal to 0
##
## Wilcoxon rank sum test with continuity correction
##
## data: df_comorb_n$score_dia7 by df_comorb_n$grupo
## W = 193, p-value = 0.0102
## alternative hypothesis: true location shift is not equal to 0
PATIENTS –> MALE
## Stratified by grupo
## Control iNO p
## n 18 19
## Days Free of Vent Support (median [IQR]) 9.00 [1.25, 11.00] 10.00 [5.50, 12.50] 0.289
## Score Day 3 (median [IQR]) 4.00 [4.00, 5.00] 4.00 [3.50, 4.00] 0.083
## Score Day 5 (median [IQR]) 4.00 [3.00, 5.00] 4.00 [2.00, 4.50] 0.279
## Score Day 7 (median [IQR]) 3.00 [2.00, 5.00] 2.00 [2.00, 4.50] 0.642
## worsening = Yes (%) 8 (44.4) 5 (26.3) 0.418
## Supplemental oxygen Day 3 = Supplemental oxygen (%) 17 (94.4) 14 (73.7) 0.205
## Supplemental oxygen Day 5 = Supplemental oxygen (%) 12 (66.7) 10 (52.6) 0.593
## Supplemental oxygen Day 7 = Supplemental oxygen (%) 8 (44.4) 6 (31.6) 0.640
## mech_vent = Yes (%) 3 (16.7) 4 (21.1) 1.000
## Length of Stay (Days) (median [IQR]) 7.00 [5.00, 11.00] 4.50 [2.75, 6.25] 0.050
## Death = Yes (%) 1 ( 5.6) 3 (15.8) 0.637
## Stratified by grupo
## test
## n
## Days Free of Vent Support (median [IQR]) nonnorm
## Score Day 3 (median [IQR]) nonnorm
## Score Day 5 (median [IQR]) nonnorm
## Score Day 7 (median [IQR]) nonnorm
## worsening = Yes (%)
## Supplemental oxygen Day 3 = Supplemental oxygen (%)
## Supplemental oxygen Day 5 = Supplemental oxygen (%)
## Supplemental oxygen Day 7 = Supplemental oxygen (%)
## mech_vent = Yes (%)
## Length of Stay (Days) (median [IQR]) nonnorm
## Death = Yes (%)
PATIENTS –> FEMALE
## Stratified by grupo
## Control iNO p
## n 9 8
## Days Free of Vent Support (median [IQR]) 8.00 [7.00, 9.00] 12.00 [9.00, 13.25] 0.033
## Score Day 3 (median [IQR]) 4.00 [4.00, 5.00] 3.50 [3.00, 4.00] 0.040
## Score Day 5 (median [IQR]) 4.00 [4.00, 5.00] 3.00 [2.00, 4.00] 0.012
## Score Day 7 (median [IQR]) 4.00 [3.00, 4.00] 1.50 [1.00, 2.25] 0.016
## worsening = Yes (%) 3 ( 33.3) 2 (25.0) 1.000
## Supplemental oxygen Day 3 = Supplemental oxygen (%) 9 (100.0) 4 (50.0) 0.064
## Supplemental oxygen Day 5 = Supplemental oxygen (%) 8 ( 88.9) 3 (37.5) 0.088
## Supplemental oxygen Day 7 = Supplemental oxygen (%) 6 ( 66.7) 1 (12.5) 0.076
## mech_vent = Yes (%) 2 ( 22.2) 1 (12.5) 1.000
## Length of Stay (Days) (median [IQR]) 7.00 [7.00, 8.00] 4.50 [3.00, 6.25] 0.022
## Death = Yes (%) 1 ( 12.5) 0 ( 0.0) 1.000
## Stratified by grupo
## test
## n
## Days Free of Vent Support (median [IQR]) nonnorm
## Score Day 3 (median [IQR]) nonnorm
## Score Day 5 (median [IQR]) nonnorm
## Score Day 7 (median [IQR]) nonnorm
## worsening = Yes (%)
## Supplemental oxygen Day 3 = Supplemental oxygen (%)
## Supplemental oxygen Day 5 = Supplemental oxygen (%)
## Supplemental oxygen Day 7 = Supplemental oxygen (%)
## mech_vent = Yes (%)
## Length of Stay (Days) (median [IQR]) nonnorm
## Death = Yes (%)
PATIENTS WITH OBESITY
## Stratified by grupo
## Control iNO p
## n 18 14
## Days Free of Vent Support (median [IQR]) 7.50 [1.25, 9.00] 12.00 [5.25, 13.00] 0.052
## Score Day 3 (median [IQR]) 4.50 [4.00, 5.00] 3.50 [3.00, 4.00] 0.006
## Score Day 5 (median [IQR]) 4.50 [4.00, 5.00] 3.00 [2.00, 4.00] 0.010
## Score Day 7 (median [IQR]) 4.00 [2.25, 5.00] 2.00 [1.25, 4.50] 0.164
## worsening = Yes (%) 9 (50.0) 5 (35.7) 0.653
## Supplemental oxygen Day 3 = Supplemental oxygen (%) 17 (94.4) 7 (50.0) 0.014
## Supplemental oxygen Day 5 = Supplemental oxygen (%) 15 (83.3) 6 (42.9) 0.044
## Supplemental oxygen Day 7 = Supplemental oxygen (%) 12 (66.7) 4 (28.6) 0.075
## mech_vent = Yes (%) 5 (27.8) 3 (21.4) 1.000
## Length of Stay (Days) (median [IQR]) 7.50 [6.00, 10.25] 4.00 [2.00, 6.00] 0.021
## Death = Yes (%) 2 (11.8) 1 ( 7.1) 1.000
## Stratified by grupo
## test
## n
## Days Free of Vent Support (median [IQR]) nonnorm
## Score Day 3 (median [IQR]) nonnorm
## Score Day 5 (median [IQR]) nonnorm
## Score Day 7 (median [IQR]) nonnorm
## worsening = Yes (%)
## Supplemental oxygen Day 3 = Supplemental oxygen (%)
## Supplemental oxygen Day 5 = Supplemental oxygen (%)
## Supplemental oxygen Day 7 = Supplemental oxygen (%)
## mech_vent = Yes (%)
## Length of Stay (Days) (median [IQR]) nonnorm
## Death = Yes (%)
PATIENTS WITHOUT OBESITY
## Stratified by grupo
## Control iNO
## n 9 13
## Days Free of Vent Support (median [IQR]) 10.00 [9.00, 12.00] 10.00 [9.00, 12.00]
## Score Day 3 (median [IQR]) 4.00 [4.00, 4.00] 4.00 [4.00, 4.00]
## Score Day 5 (median [IQR]) 4.00 [2.00, 4.00] 4.00 [3.00, 4.00]
## Score Day 7 (median [IQR]) 3.00 [2.00, 3.00] 2.00 [2.00, 3.00]
## worsening = Yes (%) 2 ( 22.2) 2 (15.4)
## Supplemental oxygen Day 3 = Supplemental oxygen (%) 9 (100.0) 11 (84.6)
## Supplemental oxygen Day 5 = Supplemental oxygen (%) 5 ( 55.6) 7 (53.8)
## Supplemental oxygen Day 7 = Supplemental oxygen (%) 2 ( 22.2) 3 (23.1)
## mech_vent = Yes (%) 0 ( 0.0) 2 (15.4)
## Length of Stay (Days) (median [IQR]) 7.00 [4.00, 7.00] 5.00 [4.00, 6.50]
## Death = Yes (%) 0 ( 0.0) 2 (15.4)
## Stratified by grupo
## p test
## n
## Days Free of Vent Support (median [IQR]) 0.946 nonnorm
## Score Day 3 (median [IQR]) 1.000 nonnorm
## Score Day 5 (median [IQR]) 0.945 nonnorm
## Score Day 7 (median [IQR]) 0.537 nonnorm
## worsening = Yes (%) 1.000
## Supplemental oxygen Day 3 = Supplemental oxygen (%) 0.631
## Supplemental oxygen Day 5 = Supplemental oxygen (%) 1.000
## Supplemental oxygen Day 7 = Supplemental oxygen (%) 1.000
## mech_vent = Yes (%) 0.631
## Length of Stay (Days) (median [IQR]) 0.246 nonnorm
## Death = Yes (%) 0.631
export data for Mario Wagner’s analysis
dfz <- df %>% select(record_id, sexo, grupo, idade, comorb, dlo, los)
dfz$age_group[dfz$idade<60] <- "Young"
## Warning: Unknown or uninitialised column: `age_group`.
dfz$age_group[dfz$idade>=60] <- "Senior"
dfz$age_group <- as.factor(dfz$age_group)
save(dfz, file="dfz.Rdata")
Sys.Date()
## [1] "2024-07-04"
