Introductie

Onderzoeksgroep: Vrouwen met RRMS en COVID-19 Symptomen

In dit groepsproject hebben we onderzocht in hoeverre vrouwelijke patiënten met relapsing remitting multiple sclerose (RRMS) die bepaalde medicamenteuze therapieën ondergaan, meer gerapporteerde COVID-19 symptomen ervaren in vergelijking met andere behandelingen.

Hypotheses:
- H₀: Het gebruik van specifieke medicatie heeft geen effect op de kans op het ontwikkelen van bepaalde symptomen.
- Hₐ: Het gebruik van specifieke medicatie heeft wél een effect op de kans op het ontwikkelen van bepaalde symptomen.

Bijkomende onderzoeksvraag:

Zijn er bepaalde COVID-19 symptomen die vaker samen voorkomen?


Objectieven

  1. Het voorkomen van COVID-19 symptomen bij vrouwen met RRMS beschrijven.
  2. Het medicatiegebruik bij vrouwen met RRMS in kaart brengen.
  3. Het verband onderzoeken tussen medicatiegebruik en meer gerapporteerde COVID-19 symptomen, gebruikmakend van de dataset GDSI_OpenDataset_Final.

Groepsleden

  • An-Sofie Verhoeven
  • Dennis Hertoghe
  • Dries Nassen


Methodologie

We hebben gewerkt in verschillende stappen om ons onderzoek systematisch uit te voeren:

1. Inladen van de data

De dataset GDSI_OpenDataset_Final werd geïmporteerd en gecontroleerd op volledigheid.

2. Descriptieve analyse

Het aantal vrouwen met RRMS dat COVID-19 symptomen rapporteerde werd geanalyseerd, inclusief de verdeling van suspected en confirmed gevallen. Daarnaast werd medicatiegebruik in kaart gebracht.

3. Sorteren op enkel vrouwen met RRMS

De dataset werd gefilterd om alleen vrouwen met RRMS te behouden, aangezien deze groep het meest vertegenwoordigd is.

4. Imputatie van missende waarden

Missende antwoorden in de symptoomkolommen werden vervangen door “no” om uniformiteit in de dataset te krijgen.

5. Data voorbereiden voor clusteranalyse

Symptoomkolommen werden binair gemaakt (aanwezig = 1, afwezig = 0) om clustering mogelijk te maken.

6. Hiërarchische clustering

Symptomen werden geclusterd met een hiërarchische methode, resulterend in een dendrogram om de samenhang tussen symptomen te visualiseren.

7. Statistische toetsing

Een Chi-kwadraat test voor goodness of fit werd uitgevoerd om te beoordelen of de clustering van symptomen significant is.

8. Clusterinformatie toevoegen

Een extra kolom werd toegevoegd aan de dataset met de clusterinformatie per patiënt.

9. Logistische regressie

Per symptoom werd een logistische regressie uitgevoerd om te onderzoeken welke factoren de kans op het optreden van een symptoom beïnvloeden.

10. Discussie en interpretatie

De resultaten van de analyses werden geïnterpreteerd en besproken.

Descriptieve Analyse

We hebben de data van vrouwen met RRMS geanalyseerd om inzicht te krijgen in hun COVID-19 symptomen en medicatiegebruik. Hieronder worden de resultaten weergegeven.

Tabellen

Aantal vrouwen met RRMS die COVID-19 symptomen rapporteren.
Symptoomstatus Aantal
7
no 489
yes 243
Verdeling van medicatiegebruik onder vrouwen met RRMS.
Type Medicatie Aantal
82
currently not using any DMT 59
currently on alemtuzumab 8
currently on another drug not listed 117
currently on cladribine 29
currently on dimethyl fumarate 101
currently on fingolimod 90
currently on glatiramer 43
currently on interferon 59
currently on natalizumab 49
currently on ocrelizumab 52
currently on rituximab 8
currently on teriflunomide 42
Aantal vrouwen die ‘Yes’ hebben geantwoord op specifieke COVID-19 symptomen.
Symptoom Aantal ‘Yes’
Droge hoest 139
Rillingen 74
Vermoeidheid 159
Kortademigheid 70
Keelpijn 114
Koorts 95
Verlies van reuk/smaak 60
Pijn 125
Longontsteking 10
Neusverstopping 115

Visualisatie van afstandmatrix

# transpose

symptomen_transposed <- data.table::transpose(as.data.table(vrouwenRRMS_symptomen),keep.names = "col")

# gebruik eerste kolom (omschrijving van het symptoom) als rownames

symptomen_transposed <- data.frame(symptomen_transposed, row.names = 1)

rm(vrouwenRRMS_symptomen)  # tabel niet meer nodig

#afstand berekenen WAAROM binary!!!!
distance_matrix <- dist(symptomen_transposed, method = "binary")

fviz_dist(distance_matrix)

Hierargisch clusteren

#cluster methode  
hclust_result <- hclust(distance_matrix, method = "ward.D")

plot(hclust_result, main = "Dendrogram van Hiërarchische Clustering voor COVID-19 Symptomen",labels = rownames(symptomen_transposed),
     cex=0.7)

Cluster frequenties

Aantal items en proporties per cluster
Cluster Frequency Proportion
1 3 0.3
2 5 0.5
3 1 0.1
4 1 0.1

Histogram cluster frequenties

Statistisch testen van clusters

## Warning in stats::chisq.test(x, y, ...): Chi-squared approximation may be
## incorrect
Resultaten van de Chi-kwadraattoets
Statistiek p.waarde Vrijheidsgraden
X-squared 4.4 0.2213854 3

Logistische regressie

Symptoom rillingen


modelchills <- glm(chills ~ dmt_type_overall + symptoom_cluster1 + symptoom_cluster2 + symptoom_cluster3,  family = "binomial", data = vrouwenRRMS)
## Warning: glm.fit: fitted probabilities numerically 0 or 1 occurred
summary(modelchills)
## 
## Call:
## glm(formula = chills ~ dmt_type_overall + symptoom_cluster1 + 
##     symptoom_cluster2 + symptoom_cluster3, family = "binomial", 
##     data = vrouwenRRMS)
## 
## Coefficients:
##                                                        Estimate Std. Error
## (Intercept)                                            -37.7215  2433.4455
## dmt_type_overallcurrently not using any DMT              0.7388     0.8001
## dmt_type_overallcurrently on alemtuzumab                15.1555 17212.7910
## dmt_type_overallcurrently on another drug not listed     0.1201     0.7571
## dmt_type_overallcurrently on cladribine                  0.6383     1.0806
## dmt_type_overallcurrently on dimethyl fumarate          -0.3634     0.7861
## dmt_type_overallcurrently on fingolimod                 -0.4860     0.7933
## dmt_type_overallcurrently on glatiramer                  0.4678     0.9101
## dmt_type_overallcurrently on interferon                  0.6457     0.9762
## dmt_type_overallcurrently on natalizumab                -0.1613     0.9179
## dmt_type_overallcurrently on ocrelizumab                -1.4340     0.9122
## dmt_type_overallcurrently on rituximab                   0.2442     1.5575
## dmt_type_overallcurrently on teriflunomide               0.1229     0.9582
## symptoom_cluster1                                       20.3459  1681.9380
## symptoom_cluster2                                       17.1315  1758.6197
## symptoom_cluster3                                        1.0268     0.4480
##                                                      z value Pr(>|z|)  
## (Intercept)                                           -0.016   0.9876  
## dmt_type_overallcurrently not using any DMT            0.923   0.3558  
## dmt_type_overallcurrently on alemtuzumab               0.001   0.9993  
## dmt_type_overallcurrently on another drug not listed   0.159   0.8739  
## dmt_type_overallcurrently on cladribine                0.591   0.5548  
## dmt_type_overallcurrently on dimethyl fumarate        -0.462   0.6439  
## dmt_type_overallcurrently on fingolimod               -0.613   0.5401  
## dmt_type_overallcurrently on glatiramer                0.514   0.6073  
## dmt_type_overallcurrently on interferon                0.661   0.5083  
## dmt_type_overallcurrently on natalizumab              -0.176   0.8605  
## dmt_type_overallcurrently on ocrelizumab              -1.572   0.1159  
## dmt_type_overallcurrently on rituximab                 0.157   0.8754  
## dmt_type_overallcurrently on teriflunomide             0.128   0.8980  
## symptoom_cluster1                                      0.012   0.9903  
## symptoom_cluster2                                      0.010   0.9922  
## symptoom_cluster3                                      2.292   0.0219 *
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## 
## (Dispersion parameter for binomial family taken to be 1)
## 
##     Null deviance: 480.91  on 738  degrees of freedom
## Residual deviance: 188.15  on 723  degrees of freedom
## AIC: 220.15
## 
## Number of Fisher Scoring iterations: 21

Symptoom droge hoest

modeldrycough <- glm(dry_cough ~ dmt_type_overall + symptoom_cluster1 + symptoom_cluster2 + symptoom_cluster3,  family = "binomial", data = vrouwenRRMS)
## Warning: glm.fit: fitted probabilities numerically 0 or 1 occurred
summary(modeldrycough)
## 
## Call:
## glm(formula = dry_cough ~ dmt_type_overall + symptoom_cluster1 + 
##     symptoom_cluster2 + symptoom_cluster3, family = "binomial", 
##     data = vrouwenRRMS)
## 
## Coefficients:
##                                                        Estimate Std. Error
## (Intercept)                                            -31.2872  1514.4174
## dmt_type_overallcurrently not using any DMT             -0.3257     0.7053
## dmt_type_overallcurrently on alemtuzumab                 9.7212 10445.5918
## dmt_type_overallcurrently on another drug not listed    -0.4952     0.6388
## dmt_type_overallcurrently on cladribine                 -0.6878     0.9113
## dmt_type_overallcurrently on dimethyl fumarate          -1.1560     0.6827
## dmt_type_overallcurrently on fingolimod                 -0.6944     0.6458
## dmt_type_overallcurrently on glatiramer                  0.7852     0.9360
## dmt_type_overallcurrently on interferon                 -1.5712     0.7414
## dmt_type_overallcurrently on natalizumab                -1.1202     0.6984
## dmt_type_overallcurrently on ocrelizumab                 0.2889     0.7740
## dmt_type_overallcurrently on rituximab                  14.5448  1071.8416
## dmt_type_overallcurrently on teriflunomide              -1.0404     0.7895
## symptoom_cluster1                                        0.4997     0.3069
## symptoom_cluster2                                       31.8901  1514.4174
## symptoom_cluster3                                        0.6295     0.3636
##                                                      z value Pr(>|z|)  
## (Intercept)                                           -0.021   0.9835  
## dmt_type_overallcurrently not using any DMT           -0.462   0.6443  
## dmt_type_overallcurrently on alemtuzumab               0.001   0.9993  
## dmt_type_overallcurrently on another drug not listed  -0.775   0.4382  
## dmt_type_overallcurrently on cladribine               -0.755   0.4504  
## dmt_type_overallcurrently on dimethyl fumarate        -1.693   0.0904 .
## dmt_type_overallcurrently on fingolimod               -1.075   0.2823  
## dmt_type_overallcurrently on glatiramer                0.839   0.4015  
## dmt_type_overallcurrently on interferon               -2.119   0.0341 *
## dmt_type_overallcurrently on natalizumab              -1.604   0.1087  
## dmt_type_overallcurrently on ocrelizumab               0.373   0.7090  
## dmt_type_overallcurrently on rituximab                 0.014   0.9892  
## dmt_type_overallcurrently on teriflunomide            -1.318   0.1875  
## symptoom_cluster1                                      1.628   0.1035  
## symptoom_cluster2                                      0.021   0.9832  
## symptoom_cluster3                                      1.731   0.0834 .
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## 
## (Dispersion parameter for binomial family taken to be 1)
## 
##     Null deviance: 714.53  on 738  degrees of freedom
## Residual deviance: 272.49  on 723  degrees of freedom
## AIC: 304.49
## 
## Number of Fisher Scoring iterations: 20

Symptoom vermoeidheid

modelfatigue <- glm(fatigue ~ dmt_type_overall + symptoom_cluster1 + symptoom_cluster2 + symptoom_cluster3,  family = "binomial", data = vrouwenRRMS)
## Warning: glm.fit: fitted probabilities numerically 0 or 1 occurred
summary(modelfatigue)
## 
## Call:
## glm(formula = fatigue ~ dmt_type_overall + symptoom_cluster1 + 
##     symptoom_cluster2 + symptoom_cluster3, family = "binomial", 
##     data = vrouwenRRMS)
## 
## Coefficients:
##                                                        Estimate Std. Error
## (Intercept)                                          -3.078e+01  1.510e+03
## dmt_type_overallcurrently not using any DMT          -7.616e-01  7.585e-01
## dmt_type_overallcurrently on alemtuzumab              9.217e+00  1.044e+04
## dmt_type_overallcurrently on another drug not listed  2.738e-01  7.443e-01
## dmt_type_overallcurrently on cladribine              -5.066e-01  1.025e+00
## dmt_type_overallcurrently on dimethyl fumarate       -1.031e+00  7.485e-01
## dmt_type_overallcurrently on fingolimod              -9.853e-02  7.320e-01
## dmt_type_overallcurrently on glatiramer              -8.108e-01  8.272e-01
## dmt_type_overallcurrently on interferon               1.532e-01  8.745e-01
## dmt_type_overallcurrently on natalizumab              2.446e-01  8.163e-01
## dmt_type_overallcurrently on ocrelizumab             -2.242e+00  7.747e-01
## dmt_type_overallcurrently on rituximab                1.405e+01  1.069e+03
## dmt_type_overallcurrently on teriflunomide           -1.421e+00  8.377e-01
## symptoom_cluster1                                     9.504e-01  3.386e-01
## symptoom_cluster2                                     3.143e+01  1.510e+03
## symptoom_cluster3                                     8.376e-01  4.132e-01
##                                                      z value Pr(>|z|)   
## (Intercept)                                           -0.020  0.98374   
## dmt_type_overallcurrently not using any DMT           -1.004  0.31532   
## dmt_type_overallcurrently on alemtuzumab               0.001  0.99930   
## dmt_type_overallcurrently on another drug not listed   0.368  0.71303   
## dmt_type_overallcurrently on cladribine               -0.494  0.62116   
## dmt_type_overallcurrently on dimethyl fumarate        -1.378  0.16830   
## dmt_type_overallcurrently on fingolimod               -0.135  0.89292   
## dmt_type_overallcurrently on glatiramer               -0.980  0.32699   
## dmt_type_overallcurrently on interferon                0.175  0.86095   
## dmt_type_overallcurrently on natalizumab               0.300  0.76444   
## dmt_type_overallcurrently on ocrelizumab              -2.894  0.00381 **
## dmt_type_overallcurrently on rituximab                 0.013  0.98951   
## dmt_type_overallcurrently on teriflunomide            -1.697  0.08976 . 
## symptoom_cluster1                                      2.807  0.00500 **
## symptoom_cluster2                                      0.021  0.98340   
## symptoom_cluster3                                      2.027  0.04265 * 
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## 
## (Dispersion parameter for binomial family taken to be 1)
## 
##     Null deviance: 769.61  on 738  degrees of freedom
## Residual deviance: 235.20  on 723  degrees of freedom
## AIC: 267.2
## 
## Number of Fisher Scoring iterations: 20

Symptoom koorts

modelfever <- glm(fever ~ dmt_type_overall + symptoom_cluster1 + symptoom_cluster2 + symptoom_cluster3,  family = "binomial", data = vrouwenRRMS)

summary(modelfever)
## 
## Call:
## glm(formula = fever ~ dmt_type_overall + symptoom_cluster1 + 
##     symptoom_cluster2 + symptoom_cluster3, family = "binomial", 
##     data = vrouwenRRMS)
## 
## Coefficients:
##                                                        Estimate Std. Error
## (Intercept)                                          -2.214e+01  1.191e+03
## dmt_type_overallcurrently not using any DMT           2.734e-01  7.830e-01
## dmt_type_overallcurrently on alemtuzumab              5.695e-01  1.040e+04
## dmt_type_overallcurrently on another drug not listed  1.122e+00  7.983e-01
## dmt_type_overallcurrently on cladribine              -8.273e-02  1.043e+00
## dmt_type_overallcurrently on dimethyl fumarate        3.209e-01  7.939e-01
## dmt_type_overallcurrently on fingolimod               1.028e+00  8.134e-01
## dmt_type_overallcurrently on glatiramer               6.096e-02  9.028e-01
## dmt_type_overallcurrently on interferon               6.628e-01  9.796e-01
## dmt_type_overallcurrently on natalizumab             -9.474e-04  9.026e-01
## dmt_type_overallcurrently on ocrelizumab              1.435e+00  9.999e-01
## dmt_type_overallcurrently on rituximab                2.643e-01  1.560e+00
## dmt_type_overallcurrently on teriflunomide            1.392e-01  9.616e-01
## symptoom_cluster1                                     2.280e+01  1.191e+03
## symptoom_cluster2                                    -9.257e-01  1.247e+00
## symptoom_cluster3                                     1.063e+00  4.698e-01
##                                                      z value Pr(>|z|)  
## (Intercept)                                           -0.019   0.9852  
## dmt_type_overallcurrently not using any DMT            0.349   0.7270  
## dmt_type_overallcurrently on alemtuzumab               0.000   1.0000  
## dmt_type_overallcurrently on another drug not listed   1.405   0.1599  
## dmt_type_overallcurrently on cladribine               -0.079   0.9368  
## dmt_type_overallcurrently on dimethyl fumarate         0.404   0.6860  
## dmt_type_overallcurrently on fingolimod                1.263   0.2064  
## dmt_type_overallcurrently on glatiramer                0.068   0.9462  
## dmt_type_overallcurrently on interferon                0.677   0.4987  
## dmt_type_overallcurrently on natalizumab              -0.001   0.9992  
## dmt_type_overallcurrently on ocrelizumab               1.436   0.1511  
## dmt_type_overallcurrently on rituximab                 0.169   0.8654  
## dmt_type_overallcurrently on teriflunomide             0.145   0.8849  
## symptoom_cluster1                                      0.019   0.9847  
## symptoom_cluster2                                     -0.743   0.4578  
## symptoom_cluster3                                      2.264   0.0236 *
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## 
## (Dispersion parameter for binomial family taken to be 1)
## 
##     Null deviance: 567.00  on 738  degrees of freedom
## Residual deviance: 185.45  on 723  degrees of freedom
## AIC: 217.45
## 
## Number of Fisher Scoring iterations: 20

Symptoom reukverlies

modellossofsmell <- glm(loss_smell_taste ~ dmt_type_overall + symptoom_cluster1 + symptoom_cluster2 + symptoom_cluster3,  family = "binomial", data = vrouwenRRMS)
## Warning: glm.fit: algorithm did not converge
summary(modellossofsmell)
## 
## Call:
## glm(formula = loss_smell_taste ~ dmt_type_overall + symptoom_cluster1 + 
##     symptoom_cluster2 + symptoom_cluster3, family = "binomial", 
##     data = vrouwenRRMS)
## 
## Coefficients:
##                                                        Estimate Std. Error
## (Intercept)                                          -2.657e+01  4.000e+04
## dmt_type_overallcurrently not using any DMT          -3.548e-13  6.110e+04
## dmt_type_overallcurrently on alemtuzumab             -9.917e-13  1.321e+05
## dmt_type_overallcurrently on another drug not listed -7.615e-13  5.140e+04
## dmt_type_overallcurrently on cladribine              -2.463e-12  7.699e+04
## dmt_type_overallcurrently on dimethyl fumarate       -7.915e-13  5.303e+04
## dmt_type_overallcurrently on fingolimod              -1.908e-12  5.457e+04
## dmt_type_overallcurrently on glatiramer              -6.543e-13  6.723e+04
## dmt_type_overallcurrently on interferon              -2.619e-12  6.082e+04
## dmt_type_overallcurrently on natalizumab             -1.856e-12  6.470e+04
## dmt_type_overallcurrently on ocrelizumab              3.301e-13  6.327e+04
## dmt_type_overallcurrently on rituximab               -1.729e-12  1.321e+05
## dmt_type_overallcurrently on teriflunomide           -1.419e-12  6.767e+04
## symptoom_cluster1                                     8.463e-12  4.872e+04
## symptoom_cluster2                                    -5.592e-12  4.425e+04
## symptoom_cluster3                                     5.313e+01  5.358e+04
##                                                      z value Pr(>|z|)
## (Intercept)                                           -0.001    0.999
## dmt_type_overallcurrently not using any DMT            0.000    1.000
## dmt_type_overallcurrently on alemtuzumab               0.000    1.000
## dmt_type_overallcurrently on another drug not listed   0.000    1.000
## dmt_type_overallcurrently on cladribine                0.000    1.000
## dmt_type_overallcurrently on dimethyl fumarate         0.000    1.000
## dmt_type_overallcurrently on fingolimod                0.000    1.000
## dmt_type_overallcurrently on glatiramer                0.000    1.000
## dmt_type_overallcurrently on interferon                0.000    1.000
## dmt_type_overallcurrently on natalizumab               0.000    1.000
## dmt_type_overallcurrently on ocrelizumab               0.000    1.000
## dmt_type_overallcurrently on rituximab                 0.000    1.000
## dmt_type_overallcurrently on teriflunomide             0.000    1.000
## symptoom_cluster1                                      0.000    1.000
## symptoom_cluster2                                      0.000    1.000
## symptoom_cluster3                                      0.001    0.999
## 
## (Dispersion parameter for binomial family taken to be 1)
## 
##     Null deviance: 4.1631e+02  on 738  degrees of freedom
## Residual deviance: 4.2874e-09  on 723  degrees of freedom
## AIC: 32
## 
## Number of Fisher Scoring iterations: 25

Column

Symptoom verstopte neus

modelnasalcongestion <- glm(nasal_congestion ~ dmt_type_overall + symptoom_cluster1 + symptoom_cluster2 + symptoom_cluster3,  family = "binomial", data = vrouwenRRMS)

summary(modelnasalcongestion)
## 
## Call:
## glm(formula = nasal_congestion ~ dmt_type_overall + symptoom_cluster1 + 
##     symptoom_cluster2 + symptoom_cluster3, family = "binomial", 
##     data = vrouwenRRMS)
## 
## Coefficients:
##                                                        Estimate Std. Error
## (Intercept)                                          -2.034e+01  7.782e+02
## dmt_type_overallcurrently not using any DMT          -3.410e-01  6.251e-01
## dmt_type_overallcurrently on alemtuzumab             -2.231e-01  6.317e+03
## dmt_type_overallcurrently on another drug not listed  1.386e-01  5.810e-01
## dmt_type_overallcurrently on cladribine              -9.410e-01  8.636e-01
## dmt_type_overallcurrently on dimethyl fumarate        1.955e-01  6.348e-01
## dmt_type_overallcurrently on fingolimod              -9.843e-01  5.969e-01
## dmt_type_overallcurrently on glatiramer              -6.833e-01  7.139e-01
## dmt_type_overallcurrently on interferon              -6.311e-01  6.817e-01
## dmt_type_overallcurrently on natalizumab             -7.596e-01  6.535e-01
## dmt_type_overallcurrently on ocrelizumab             -2.040e-04  6.466e-01
## dmt_type_overallcurrently on rituximab               -4.257e-01  1.497e+00
## dmt_type_overallcurrently on teriflunomide           -3.898e-01  7.410e-01
## symptoom_cluster1                                     1.687e-01  2.952e-01
## symptoom_cluster2                                     2.060e+01  7.782e+02
## symptoom_cluster3                                     1.218e-01  3.282e-01
##                                                      z value Pr(>|z|)  
## (Intercept)                                           -0.026   0.9791  
## dmt_type_overallcurrently not using any DMT           -0.545   0.5854  
## dmt_type_overallcurrently on alemtuzumab               0.000   1.0000  
## dmt_type_overallcurrently on another drug not listed   0.239   0.8115  
## dmt_type_overallcurrently on cladribine               -1.090   0.2759  
## dmt_type_overallcurrently on dimethyl fumarate         0.308   0.7581  
## dmt_type_overallcurrently on fingolimod               -1.649   0.0991 .
## dmt_type_overallcurrently on glatiramer               -0.957   0.3385  
## dmt_type_overallcurrently on interferon               -0.926   0.3545  
## dmt_type_overallcurrently on natalizumab              -1.162   0.2451  
## dmt_type_overallcurrently on ocrelizumab               0.000   0.9997  
## dmt_type_overallcurrently on rituximab                -0.284   0.7762  
## dmt_type_overallcurrently on teriflunomide            -0.526   0.5989  
## symptoom_cluster1                                      0.572   0.5676  
## symptoom_cluster2                                      0.026   0.9789  
## symptoom_cluster3                                      0.371   0.7105  
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## 
## (Dispersion parameter for binomial family taken to be 1)
## 
##     Null deviance: 638.98  on 738  degrees of freedom
## Residual deviance: 299.38  on 723  degrees of freedom
## AIC: 331.38
## 
## Number of Fisher Scoring iterations: 19

Symptoom pijn

modelpain <- glm(pain ~ dmt_type_overall + symptoom_cluster1 + symptoom_cluster2 + symptoom_cluster3,  family = "binomial", data = vrouwenRRMS)
## Warning: glm.fit: fitted probabilities numerically 0 or 1 occurred
summary(modelpain)
## 
## Call:
## glm(formula = pain ~ dmt_type_overall + symptoom_cluster1 + symptoom_cluster2 + 
##     symptoom_cluster3, family = "binomial", data = vrouwenRRMS)
## 
## Coefficients:
##                                                        Estimate Std. Error
## (Intercept)                                            -32.5505  1526.0814
## dmt_type_overallcurrently not using any DMT              0.7734     0.6429
## dmt_type_overallcurrently on alemtuzumab                10.9844 10447.2893
## dmt_type_overallcurrently on another drug not listed     0.5584     0.5811
## dmt_type_overallcurrently on cladribine                  0.1313     0.8498
## dmt_type_overallcurrently on dimethyl fumarate           0.9632     0.6490
## dmt_type_overallcurrently on fingolimod                  0.6053     0.5941
## dmt_type_overallcurrently on glatiramer                  0.2403     0.7163
## dmt_type_overallcurrently on interferon                 -0.2193     0.6951
## dmt_type_overallcurrently on natalizumab                 1.2438     0.6825
## dmt_type_overallcurrently on ocrelizumab                -0.6662     0.6749
## dmt_type_overallcurrently on rituximab                  15.7930  1080.2646
## dmt_type_overallcurrently on teriflunomide               0.9660     0.7747
## symptoom_cluster1                                        0.5797     0.3009
## symptoom_cluster2                                       31.8408  1526.0813
## symptoom_cluster3                                        0.3805     0.3403
##                                                      z value Pr(>|z|)  
## (Intercept)                                           -0.021   0.9830  
## dmt_type_overallcurrently not using any DMT            1.203   0.2290  
## dmt_type_overallcurrently on alemtuzumab               0.001   0.9992  
## dmt_type_overallcurrently on another drug not listed   0.961   0.3366  
## dmt_type_overallcurrently on cladribine                0.155   0.8772  
## dmt_type_overallcurrently on dimethyl fumarate         1.484   0.1378  
## dmt_type_overallcurrently on fingolimod                1.019   0.3083  
## dmt_type_overallcurrently on glatiramer                0.335   0.7373  
## dmt_type_overallcurrently on interferon               -0.316   0.7523  
## dmt_type_overallcurrently on natalizumab               1.822   0.0684 .
## dmt_type_overallcurrently on ocrelizumab              -0.987   0.3235  
## dmt_type_overallcurrently on rituximab                 0.015   0.9883  
## dmt_type_overallcurrently on teriflunomide             1.247   0.2124  
## symptoom_cluster1                                      1.927   0.0540 .
## symptoom_cluster2                                      0.021   0.9834  
## symptoom_cluster3                                      1.118   0.2635  
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## 
## (Dispersion parameter for binomial family taken to be 1)
## 
##     Null deviance: 671.80  on 738  degrees of freedom
## Residual deviance: 286.04  on 723  degrees of freedom
## AIC: 318.04
## 
## Number of Fisher Scoring iterations: 20

Symptoom pneumonie

modelpneumonia <- glm(pneumonia ~ dmt_type_overall + symptoom_cluster1 + symptoom_cluster2 + symptoom_cluster3,  family = "binomial", data = vrouwenRRMS)
## Warning: glm.fit: fitted probabilities numerically 0 or 1 occurred
summary(modelpneumonia)
## 
## Call:
## glm(formula = pneumonia ~ dmt_type_overall + symptoom_cluster1 + 
##     symptoom_cluster2 + symptoom_cluster3, family = "binomial", 
##     data = vrouwenRRMS)
## 
## Coefficients:
##                                                        Estimate Std. Error
## (Intercept)                                            -36.3295  3840.4430
## dmt_type_overallcurrently not using any DMT            -19.6104  8882.2680
## dmt_type_overallcurrently on alemtuzumab                12.7635 28355.3396
## dmt_type_overallcurrently on another drug not listed     0.6760     1.2577
## dmt_type_overallcurrently on cladribine                -19.1139 12278.3740
## dmt_type_overallcurrently on dimethyl fumarate          -0.3252     1.4721
## dmt_type_overallcurrently on fingolimod                  0.8992     1.2963
## dmt_type_overallcurrently on glatiramer                  0.3834     1.5231
## dmt_type_overallcurrently on interferon                -18.5547  8482.6306
## dmt_type_overallcurrently on natalizumab               -18.9422  9538.3917
## dmt_type_overallcurrently on ocrelizumab               -19.3156  9235.5279
## dmt_type_overallcurrently on rituximab                 -19.1561 23736.6538
## dmt_type_overallcurrently on teriflunomide               0.6742     1.5523
## symptoom_cluster1                                       18.5375  2677.3437
## symptoom_cluster2                                       15.1054  2753.3333
## symptoom_cluster3                                        0.4590     0.8074
##                                                      z value Pr(>|z|)
## (Intercept)                                           -0.009    0.992
## dmt_type_overallcurrently not using any DMT           -0.002    0.998
## dmt_type_overallcurrently on alemtuzumab               0.000    1.000
## dmt_type_overallcurrently on another drug not listed   0.537    0.591
## dmt_type_overallcurrently on cladribine               -0.002    0.999
## dmt_type_overallcurrently on dimethyl fumarate        -0.221    0.825
## dmt_type_overallcurrently on fingolimod                0.694    0.488
## dmt_type_overallcurrently on glatiramer                0.252    0.801
## dmt_type_overallcurrently on interferon               -0.002    0.998
## dmt_type_overallcurrently on natalizumab              -0.002    0.998
## dmt_type_overallcurrently on ocrelizumab              -0.002    0.998
## dmt_type_overallcurrently on rituximab                -0.001    0.999
## dmt_type_overallcurrently on teriflunomide             0.434    0.664
## symptoom_cluster1                                      0.007    0.994
## symptoom_cluster2                                      0.005    0.996
## symptoom_cluster3                                      0.569    0.570
## 
## (Dispersion parameter for binomial family taken to be 1)
## 
##     Null deviance: 105.918  on 738  degrees of freedom
## Residual deviance:  61.428  on 723  degrees of freedom
## AIC: 93.428
## 
## Number of Fisher Scoring iterations: 22

Symptoom keelpijn

modelsorethroat <- glm(sore_throat ~ dmt_type_overall + symptoom_cluster1 + symptoom_cluster2 + symptoom_cluster3,  family = "binomial", data = vrouwenRRMS)
## Warning: glm.fit: fitted probabilities numerically 0 or 1 occurred
summary(modelsorethroat)
## 
## Call:
## glm(formula = sore_throat ~ dmt_type_overall + symptoom_cluster1 + 
##     symptoom_cluster2 + symptoom_cluster3, family = "binomial", 
##     data = vrouwenRRMS)
## 
## Coefficients:
##                                                        Estimate Std. Error
## (Intercept)                                          -3.207e+01  1.520e+03
## dmt_type_overallcurrently not using any DMT           2.374e-02  6.254e-01
## dmt_type_overallcurrently on alemtuzumab              1.050e+01  1.045e+04
## dmt_type_overallcurrently on another drug not listed -3.580e-01  5.722e-01
## dmt_type_overallcurrently on cladribine              -1.308e+00  9.381e-01
## dmt_type_overallcurrently on dimethyl fumarate       -4.385e-01  6.212e-01
## dmt_type_overallcurrently on fingolimod              -1.105e-01  5.858e-01
## dmt_type_overallcurrently on glatiramer              -1.693e-02  7.129e-01
## dmt_type_overallcurrently on interferon              -1.049e+00  7.077e-01
## dmt_type_overallcurrently on natalizumab             -1.477e-01  6.473e-01
## dmt_type_overallcurrently on ocrelizumab             -6.149e-01  6.453e-01
## dmt_type_overallcurrently on rituximab                1.532e+01  1.076e+03
## dmt_type_overallcurrently on teriflunomide            1.318e+00  9.016e-01
## symptoom_cluster1                                    -1.102e-01  2.981e-01
## symptoom_cluster2                                     3.252e+01  1.520e+03
## symptoom_cluster3                                    -4.485e-01  3.316e-01
##                                                      z value Pr(>|z|)
## (Intercept)                                           -0.021    0.983
## dmt_type_overallcurrently not using any DMT            0.038    0.970
## dmt_type_overallcurrently on alemtuzumab               0.001    0.999
## dmt_type_overallcurrently on another drug not listed  -0.626    0.532
## dmt_type_overallcurrently on cladribine               -1.395    0.163
## dmt_type_overallcurrently on dimethyl fumarate        -0.706    0.480
## dmt_type_overallcurrently on fingolimod               -0.189    0.850
## dmt_type_overallcurrently on glatiramer               -0.024    0.981
## dmt_type_overallcurrently on interferon               -1.483    0.138
## dmt_type_overallcurrently on natalizumab              -0.228    0.819
## dmt_type_overallcurrently on ocrelizumab              -0.953    0.341
## dmt_type_overallcurrently on rituximab                 0.014    0.989
## dmt_type_overallcurrently on teriflunomide             1.462    0.144
## symptoom_cluster1                                     -0.370    0.712
## symptoom_cluster2                                      0.021    0.983
## symptoom_cluster3                                     -1.352    0.176
## 
## (Dispersion parameter for binomial family taken to be 1)
## 
##     Null deviance: 635.59  on 738  degrees of freedom
## Residual deviance: 292.88  on 723  degrees of freedom
## AIC: 324.88
## 
## Number of Fisher Scoring iterations: 20

Symptoom kortademigheid

modelshortnessofbreath <- glm(shortness_breath ~ dmt_type_overall + symptoom_cluster1 + symptoom_cluster2 + symptoom_cluster3,  family = "binomial", data = vrouwenRRMS)
## Warning: glm.fit: fitted probabilities numerically 0 or 1 occurred
summary(modelshortnessofbreath)
## 
## Call:
## glm(formula = shortness_breath ~ dmt_type_overall + symptoom_cluster1 + 
##     symptoom_cluster2 + symptoom_cluster3, family = "binomial", 
##     data = vrouwenRRMS)
## 
## Coefficients:
##                                                        Estimate Std. Error
## (Intercept)                                            -33.2050  2333.0830
## dmt_type_overallcurrently not using any DMT             -0.4768     0.7810
## dmt_type_overallcurrently on alemtuzumab                10.6389 17198.8893
## dmt_type_overallcurrently on another drug not listed    -0.9213     0.7627
## dmt_type_overallcurrently on cladribine                 -0.0928     1.0698
## dmt_type_overallcurrently on dimethyl fumarate          -1.2596     0.7919
## dmt_type_overallcurrently on fingolimod                 -1.4977     0.8045
## dmt_type_overallcurrently on glatiramer                 -0.4326     0.9088
## dmt_type_overallcurrently on interferon                 -1.3804     0.9785
## dmt_type_overallcurrently on natalizumab                -0.6553     0.9088
## dmt_type_overallcurrently on ocrelizumab                -1.8365     0.9108
## dmt_type_overallcurrently on rituximab                  15.5987  1651.5823
## dmt_type_overallcurrently on teriflunomide              -1.9698     1.0451
## symptoom_cluster1                                       33.2772  2333.0832
## symptoom_cluster2                                        0.8412     1.2358
## symptoom_cluster3                                       -0.3680     0.4219
##                                                      z value Pr(>|z|)  
## (Intercept)                                           -0.014   0.9886  
## dmt_type_overallcurrently not using any DMT           -0.610   0.5416  
## dmt_type_overallcurrently on alemtuzumab               0.001   0.9995  
## dmt_type_overallcurrently on another drug not listed  -1.208   0.2271  
## dmt_type_overallcurrently on cladribine               -0.087   0.9309  
## dmt_type_overallcurrently on dimethyl fumarate        -1.591   0.1117  
## dmt_type_overallcurrently on fingolimod               -1.862   0.0626 .
## dmt_type_overallcurrently on glatiramer               -0.476   0.6341  
## dmt_type_overallcurrently on interferon               -1.411   0.1583  
## dmt_type_overallcurrently on natalizumab              -0.721   0.4709  
## dmt_type_overallcurrently on ocrelizumab              -2.016   0.0438 *
## dmt_type_overallcurrently on rituximab                 0.009   0.9925  
## dmt_type_overallcurrently on teriflunomide            -1.885   0.0595 .
## symptoom_cluster1                                      0.014   0.9886  
## symptoom_cluster2                                      0.681   0.4961  
## symptoom_cluster3                                     -0.872   0.3830  
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## 
## (Dispersion parameter for binomial family taken to be 1)
## 
##     Null deviance: 463.10  on 738  degrees of freedom
## Residual deviance: 192.88  on 723  degrees of freedom
## AIC: 224.88
## 
## Number of Fisher Scoring iterations: 21


Discussie resultaat

Onze descriptieve analyses zorgden ervoor dat we de dataset konden vereenvoudigen naar enkel vrouwen met relapsing remitting multiple sclerose (RRMS). Hieruit kwam de vraag of dat vrouwen met RRMS bepaalde symptomen meer vertonen indien ze een specifieke medicamenteuze behandeling ondergaan. Deze symptomen varieerden van vermoeidheid en keelpijn tot ernstige symptomen zoals kortademigheid en pneumonie.

De clustering liet zien dat er een groepering van symptomen was met een resultaat van 4 clusters. Deze clusteranalyse was niet significant ten opzichte van de voorspelde waardes. Dit wil zeggen dat dat clusters die we gevormd hebben niet verschillen van een willekeurige verdeling. Redenen hiervoor kunnen zijn:

Binaire data zijn minder geschikt voor de Ward’s methode omdat deze beter met euclidische afstanden berekend wordt. De manier waarop Ward afstanden tussen gegevens berekent, komt dus niet goed overeen met binaire data, die moeilijk om te vormen zijn naar een continue en meetbare afstanden. Voor deze specifieke data zouden complete en average linkage methoden geschikter zijn geweest.

We hebben enkel gekeken of er covid-19 symptomen aanwezig waren. Alle patienten waren dus “suspected” of “confirmed” cases van covid. Hieruit volgt dat we geen conclusies kunnen trekken uit onze data waarbij we de kans op COVID kunnen voorspellen. Variabele (“not answered”) werden omgezet naar (“no”) wat mogelijks heeft geleidt tot onderschatting van symptomen. Daarnaast is er een observationele bias aangezien de studie ook zelf gerapporteerde symptomen bevatten waarbij subjectieve interpretaties kunnen ontstaan.

Bespreking groepsproject

knitr::include_graphics("C:/Users/12001045/Documents/Afbeelding_Groepswerk_DAS.jpg")

```