The physical and psychological aspects of quality of life mediates the effect of radiation‐induced urgency syndrome on disability pension in gynecological cancer survivors

Abstract Background Radiation‐induced fecal urgency syndrome is highly prevalent in gynecological cancer survivors. It is associated with decreased quality of life (QoL) and with disability pension. The literature remains unclear about the mediating role of physical and psychological aspects of QoL in the association between urgency syndrome and disability pension. Identifying the pathways between urgency syndrome and disability pension may help to create effective and timely interventions for increasing QoL and reducing disability pension among gynecological cancer survivors. Methods We used patient‐reported outcome measures from working‐age gynecological cancer survivors (n = 247) and data on their disability pension from the official register. The mediating role of physical and psychological aspects of QoL was studied by utilizing mediation analysis based on the counterfactual framework, appropriate for binary outcome, binary mediator with an exposure–mediator interaction. The total effect (TE) was divided into direct and indirect effects using single mediation analysis. Adjusted relative risks and percentage mediated (95% confidence intervals) were calculated. All statistical tests were two‐sided. Results Urgency syndrome increased the risk of disability pension both directly and indirectly (via QoL). Satisfaction with sleep mediated half of the TE (RR = 2.2 (1.1–4.1)) of urgency syndrome on disability pension. Physical health also mediated a similar proportion of the TE (RR = 2.1 (1.2–3.9)). The proportions mediated were higher for physical aspects of QoL (35%–71%) than for psychological aspects (2%–47%). Conclusions The investigated aspects of the self‐assessed QoL of gynecological cancer survivors may play a role in these women's continuing work‐life. It appears that physical health, satisfaction with sleep, psychological well‐being, and other investigated aspects of QoL mediate the urgency syndrome–disability pension association.

Anal pain Har Du haft smarta i ändtarmsöppningen In an earlier publication from our research team, self-reported radiation-induced symptoms were analyzed using modified exploratory factor analysis approach and factor loadings for each symptom, factor-specific factor-loading cutoffs and factor scores were estimated (Steineck et al. https://doi.org/10.1371/journal.pone.0171461 ) Appendix S2: Single-item questions on different aspects of self-reported quality of life (QoL) and answer alternatives from the postal questionnaire

English translation
Original Swedish text

Global quality of life
How has your quality of life been in the last 6 months? 1 = No quality of life at all 7 = Best possible quality of life Hur har Din livskvalitet varit, det senaste halvåret? 1 = Ingen livskvalitet alls 7 = Bästa möjliga livskvalitet

Physical strength (condition)
How has your physical strength (condition) been in the last 6 months?-26% Estimates of natural direct effect, indirect effect, total effect, and proportion of effect mediated were obtained by using an aspect of self-assessed quality of life as a mediator(M) for the association between urgency syndrome(X) and disability pension(Y) in presence of XM-interaction † Adjusted relative risk with bootstrap bias corrected 95% confidence interval.‡ Proportion mediated = NDE*(NIE-1)/(NDE*NIE-1), with bootstrap bias corrected 95% confidence interval.§Wald 95% confidence interval.Bold numbers indicate a statistically significant effect at 5% level of significance.NDE = the contrast between the counterfactual outcome while being exposed and the counterfactual outcome while the same individual was not exposed, mediator assuming value it would have taken while being not exposed.NIE = the contrast, having set the exposure =Yes, exposed between the counterfactual outcome (mediator assumed whatever value it would have taken at a value of the exposure =Yes, exposed and the counterfactual outcome if the mediator assumed whatever value, it would have taken at a reference value of the exposure =not exposed).3.9 1.0 (0.9-1.3) 1.1 †Adjusted relative risk † (95% confidence interval (CI)).E-values for NDE and NIE describes the strength of the confounder-disability pension association and the approximate strength of the confounder-Qol association that, together, would be required to explain away the observed direct and indirect effect, respectively.‡To completely explain away the observed indirect effect (RR=1.6) of global Qol, an unmeasured confounder associated with both global Qol and disability pension with approximate relative risk of 2.5 each, above and beyond the measured confounding, could suffice, but weaker confounding could not.To shift the confidence interval to the null, an unmeasured confounding associated with both global Qol and disability pension with approximate relative risk of 2.5 each, above and beyond the measured confounding, could suffice, but weaker confounding could not.

Satisfied with memory
Table S4: Adjusted natural direct effect (NDE), indirect effect (NIE), and total effect (TE) of radiation-induced urgency syndrome on disability pension in absence of exposure-mediator interaction (n=247 gynecological cancer survivors).Data on disability pension was obtained from the official register; the table shows the findings of mediation analysis while adjusting for age (in years) , marital status, occupation-based socio-economic group, and number of comorbidities

Figure S1 :
Figure S1: Flowchart of recruitment and selection of gynecological cancer survivors 1 = No strength 7 = Best imaginable strength Hur har Din kroppsliga ork (kondition) varit, det senaste halvåret? 1 = Ingen ork 7 = Bästa tänkbara ork Depressed or feeling sad Have you felt down or depressed in the last 6 months? 1 = Never 7 = All the time Har Du känt Dig nedstämd eller deprimerad, det senaste halvåret?How satisfied have you been with your concentration in the last 6 months? 1 = Not at all satisfied 7 = Completely satisfied Hur nöjd har Du varit med Din situation, det senaste halvåret?Koncentration 1 = Inte alls nöjd 7 = Helt nöjd Appendix S1: Self-reported gastrointestinal symptoms included in urgency syndrome and their estimated factor loading (symptom intensity)

Table S1 .
Association between suffering from urgency syndrome (in 2006) and being awarded a disability pension (in 2008) in all survivors fulfilling the rigorous inclusion criterion (age <65 years and no earlier disability pension during[2004][2005][2006] How satisfied have you been with your memory in the last 6 months? 1 = Not at all satisfied 7 = Completely satisfied Hur nöjd har Du varit med Din situation, det senaste halvåret?Minne 1 = Inte alls nöjd 7 = Helt nöjd Clearly describe the interventions or exposures, mediators, outcomes, confounders, and moderators that were used in the analyses.Specify how and when they were measured, the measurement properties, and whether blinded assessment was used 8─10 Measurement levels 13 If relevant, describe the levels at which the exposure, mediator, and outcome were measuredFrom: Lee H, Cashin AG, Lamb SE, Hopewell S, Vansteelandt S, VanderWeele TJ, et al.A Guideline for Reporting Mediation Analyses of Randomized Trials and Observational Studies.The AGReMA Statement.JAMA.2021;326(11):1045-1056. doi:10.1001/jama.2021.14075

Table S2 :
Adjusted natural direct effect (NDE), indirect effect (NIE), and total effect (TE) of radiation-induced urgency syndrome on disability pension in presence of exposure-mediator interaction (n=187 gynecological cancer survivors).Data on disability pension was obtained from the official register; the table shows the findings of mediation analysis while adjusting for age (in years) , marital status, occupation-based socio-economic group, and number of comorbidities

Table S3 :
Sensitivity analysis of an unmeasured confounding using mediational E-values