Symptom Based Clustering of Women in the LURN Observational Cohort Study

Abstract

Purpose: Women with lower urinary tract symptoms are often diagnosed based on a predefined symptom complex or a predominant symptom. There are many limitations to this paradigm as often patients present with multiple urinary symptoms which do not perfectly fit the preestablished diagnoses. We used cluster analysis to identify novel, symptom based subtypes of women with lower urinary tract symptoms.

Materials and methods: We analyzed baseline urinary symptom questionnaire data obtained from 545 care seeking female participants enrolled in the LURN (Symptoms of Lower Urinary Tract Dysfunction Research Network) Observational Cohort Study. Symptoms were measured with the LUTS (lower urinary tract symptoms) Tool and the AUA SI (American Urological Association Symptom Index), and analyzed using a probability based consensus clustering algorithm.

Results: Four clusters were identified. The 138 women in cluster F1 did not report incontinence but experienced post-void dribbling, frequency and voiding symptoms. The 80 women in cluster F2 reported urgency incontinence as well as urgency and frequency but minimal voiding symptoms or stress incontinence. Cluster F3 included 244 women who reported all types of incontinence, urgency, frequency and mild voiding symptoms. The 83 women in cluster F4 reported all lower urinary tract symptoms at uniformly high levels. All but 2 of 44 LUTS Tool and 8 AUA SI questions significantly differed between at least 2 clusters (p <0.05). All clusters contained at least 1 member from each conventional group, including continence, and stress, urgency, mixed and other incontinence.

Conclusions: Women seeking care for lower urinary tract symptoms cluster into 4 distinct symptom groups which differ from conventional clinical diagnostic groups. Further validation is needed to determine whether management improves using this new classification.

Keywords: cluster analysis; diagnosis-related groups; lower urinary tract symptoms; overactive; surveys and questionnaires; urinary bladder.

Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1.

Consensus matrix as a color map. Each element of the 545 by 545 matrix represents the probability that the respective pair of participants both belong to the same cluster. Probability is color-coded: bright yellow represents probability close to one, dark blue – probability close to zero. Four bright yellow squares along the diagonal represent four identified clusters of participants. The dendrogram on top of the consensus matrix demonstrates four distinct clusters as well.

Figure 2.

Symptom signatures of four clusters as radar plots. Figure 2a represents signatures based on the LUTS tool questions, where each “spoke” is an average of symptoms’ severity and bother for the females within the given cluster. Figure 2b represents averaged answers within the cluster to the AUA-SI questions. Questions related to similar symptoms are grouped together and color-coded. LUTS questions are about: 1-frequency, 2-daytime frequency, 3-nocturia, 4-incomplete emptying, 5-trickle/dribble, 6-urgency, 7-hesitancy, 8-intermittency, 9-strain, 10-weak stream, 11-splitting/spraying, 12-urgency w/fear, 13-pain, 14-burning, 15-leakage, 16a-leakage post voiding, 16b-leakage w/urgency, 16c-leakage w/laugh, 16d- leakage w/exercise, 16f-leakage w/sex, 16g-leakage for no reason. AUA questions are about: 1-nocturia, 2-incomplete emptying, 3-frequency, 4-intermittency, 5-urgency, 6-weak stream, 7-strain. Circles represent the highest severity level (typically answer #5 to each question).

Figure 2.

Symptom signatures of four clusters as radar plots. Figure 2a represents signatures based on the LUTS tool questions, where each “spoke” is an average of symptoms’ severity and bother for the females within the given cluster. Figure 2b represents averaged answers within the cluster to the AUA-SI questions. Questions related to similar symptoms are grouped together and color-coded. LUTS questions are about: 1-frequency, 2-daytime frequency, 3-nocturia, 4-incomplete emptying, 5-trickle/dribble, 6-urgency, 7-hesitancy, 8-intermittency, 9-strain, 10-weak stream, 11-splitting/spraying, 12-urgency w/fear, 13-pain, 14-burning, 15-leakage, 16a-leakage post voiding, 16b-leakage w/urgency, 16c-leakage w/laugh, 16d- leakage w/exercise, 16f-leakage w/sex, 16g-leakage for no reason. AUA questions are about: 1-nocturia, 2-incomplete emptying, 3-frequency, 4-intermittency, 5-urgency, 6-weak stream, 7-strain. Circles represent the highest severity level (typically answer #5 to each question).

Figure 3.

Mean symptom severity levels by cluster, pairwise symptom severity differences between clusters and statistical significance. On-diagonal rectangles represent mean severity level for each of the LUTS tool symptoms for each cluster. Colored bars in the upper triangle of the matrix represent symptoms that are significantly different in each possible pair of four clusters. For instance, the second rectangle in the first row demonstrates that 14 symptoms are significantly different in cluster F1 versus cluster F2: one related to frequency, two to post-micturition, two to urgency, five to voiding, two to pain, and two to incontinence. The elements in the lower triangle of the matrix present the difference in the symptom severity levels between clusters; e.g., the first (upper) element in the triangle represents the difference between symptom severity levels in cluster F2 and cluster F1, indicating that urgency symptoms are more severe in cluster F2, while voiding, storage, and pain symptoms are more severe in cluster F1. Similarly, matrix in Supplemental Figure 2 is based on the bother level for each of LUTS Tool questions, while matrix in Supplemental Figure 3 is based on the AUA-SI questions.

Figure 4.

Non-urologic patient reported outcomes (PRO). Matrix of pairwise comparisons of the clusters based on adjusted regression models. Similarly to Figure 3, upper triangle of the matrix presents PROs significantly different in adjusted pairwise comparison of the clusters. Lower triangle presents adjusted estimated differences in PROs for each pair of clusters. On-diagonal rectangles represent mean scores for each PRO for each cluster. Note that since the PROs had varying scales, all scores were converted to Z-scores with mean 0 and variance 1, therefore negative values of PROs indicate that the average value for the cluster was below the overall mean score for a given PRO. PROs are: 1-GUPI Pain Subscale, 2-GUPI Urine Subscale, 3-GUPI QOL Subscale, 4-GUPI Total Score, 5-PODI-6, 6-CRADI-8, 7-UDI-6, 8-PFDI-20,9-PROMIS Constipation, 10-PROMIS Diarrhea, 11-PROMIS Bowel Incontinence, 12-Perceived Stress Scale, 13-PROMIS Sleep Dysfunction, 14-PROMIS Depression, 15-PROMIS Anxiety.

Figure 5.

Sankey diagram comparison of group membership. Conventional groups (on the left): dry (continent), stress urinary incontinent, urgency urinary incontinent, mixed urinary incontinent, and other urinary incontinent are compared with four clusters identified in this paper (on the right). Each of conventional groups contributes members to each of the new clusters. “Dry” means continent, SUI-stress urinary incontinent, UUI- urge urinary incontinent, MUI- mixed urinary incontinent, OUI- other urinary incontinent.