Coping with multiple sclerosis: reconciling significant aspects of health-related quality of life

For Peer Review Only Coping with Multiple Sclerosis: Reconciling significant aspects of health-related quality of life Journal: AIDS Care - Psychology, Health & Medicine - Vulnerable Children and Youth Studies Manuscript ID PHM-2021-09-1202.R1 Journal Selection: Psychology, Health & Medicine Keywords: Multiple Sclerosis, Coping Strategies, Social Support, Health Related Quality Of Life, risk and protective Factors URL: https://mc.manuscriptcentral.com/ac-phm-vcy Email: [email protected] Health Sciences This is an Accepted Manuscript version of the following article, accepted for publication in Psychology, Health & Medicine: GilGonzález, I., Martín-Rodríguez, A., Conrad, R., & Pérez-San-Gregorio, M. Á. (2023). Coping with multiple sclerosis: reconciling significant aspects of health-related quality of life. Psychology, Health & Medicine, 28(5), 1167–1180. https:// doi.org/10.1080/13548506.2022.2077395. It is deposited under the terms of the Creative Commons Attribution-NonCommercialNoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way For Peer Review Only Coping with Multiple Sclerosis: Reconciling significant aspects of health-related quality of life Multiple sclerosis (MS) symptoms and unpredictability can damage patient well-being. This study is aimed to investigate the relation between sociodemographic and clinical characteristics and the use of coping strategies as well as social support on health-related quality of life (HRQOL). We evaluated 314 MS outpatients of Virgen Macarena University Hospital in Sevilla/Spain (mean age 45 years, 67.8% women) twice over an 18-months follow up period by Brief COPE Questionnaire (COPE-28), Multidimensional Scale of Perceived Social Support (MSPSS) and 12-Item Short Form Health Survey (SF-12). Female gender was significantly related to religion (r=0.175, p<0.001), self-distraction (r=0.160, p<0.001) and self-blame (r=0.131, p<0.05). Age correlated positively with religion (r=0.240, p<0.001), and self-blame (r=0.123, p<0.05). Progressive MS as well as functional impairment (EDSS) showed a positive relation with denial (r=0.125, p<0.05; r=0.150, p<0.001). Longer duration since diagnosis was related to lower perceived support from family (r=-0.123, p<0.05). EDSS (β = -0.452, p < 0.001) was the strongest negative predictor of physical HRQOL followed by age (β = -0.123, p < 0.001), whereas family support was a protective factor (β = 0.096, p < 0.001). Denial (β=- 0.132, p< 0.05), self-blame (β=-0.156, p<0.05), female gender (β=-0.115, p<0.05) and EDSS (β=-0.108, p<0.05) negatively impacted on mental HRQOL 18 months later, whereas positive reframing (β=0.142, p<0.05) was a protective factor. Our study could identify sociodemographic and clinical variables associated with dysfunctional coping strategies, such as self-blame and denial, which specifically predict worse mental HRQOL as opposed to positive reframing. Diminishing dysfunctional coping and supporting cognitive reframing may contribute to improve HRQOL in MS. key words: Multiple Sclerosis; Coping Strategies; Social Support; Health Related Quality of Life; risk and protective Factors Page 1 of 29 URL: https://mc.manuscriptcentral.com/ac-phm-vcy Email: [email protected] Health Sciences For Peer Review Only Introduction Coping strategies play an essential role in adaptation to multiple sclerosis (MS) and Carnero Contentti et al. (2021) point out a negative relationship between maladaptive coping and HRQOL. Carver (1997) divided coping strategies into three categories: problem-focused, emotion-focused, and dysfunctional coping. Generally, active coping, problem solving, planning, positive reframing, acceptance, emotional and instrumental social support were related to a higher HRQOL in MS. Whilst, avoidance, behavioural disengagement, self-distraction, denial, emotion-focused, self-criticism and venting were associated with lower HRQOL (Gil-Gonzalez et al., 2020). Particularly, Bassi et al. (2021) found a negative association between avoidance coping and physical HRQOL. In addition, Cerea et al. (2021) discovered a positive association between mental HRQOL and problem solving and a negative with emotional discharge and passive coping (Cerea et al., 2021; Krstić et al., 2021). The scientific literature revealed that MS patients use less active and more avoidance and emotional coping than the general population (Keramat Kar et al., 2019). In dealing with MS, intrapsychic and interpersonal mechanisms are closely intertwined. A study by Homayuni et al. (2021) found that MS patients described coping strategies and social support as HRQOL facilitators. In fact, social support has been related to improvements regarding fatigue (Mikula et al., 2020), pain (Alphonsus & D’Arcy, 2021), depression and anxiety (Hanna & Strober, 2020; Mikula et al., 2020; Ratajska et al., 2020), thereby also protecting employment (Iwanaga et al., 2018). Social support also influences patients’ attitudes on medication selection as they consider significant others’ opinions (Visser et al, 2020). In summary, there is evidence that Page 2 of 29 URL: https://mc.manuscriptcentral.com/ac-phm-vcy Email: [email protected] Health Sciences For Peer Review Only directly and/or indirectly higher social support is related to better HRQOL (Bassi et al., 2021; Dȩbska et al., 2020; Gil-González et al., 2020; Kever et al., 2021; Ratajska et al., 2020), while lower social support is related to worse HRQOL (Costa et al., 2017; Strober, 2018). The present study aimed at investigating (1) sociodemographic and clinical factors underlying coping strategies and social support in adults with multiple sclerosis (MS), and (2) the role of coping strategies and social support as well as sociodemographic and clinical factors as predictors for quality of life in MS over an 18 months’ follow-up period. Method Participants and procedures The sample was recruited between June 2017 and May 2018 (T1), and December 2018 and December 2019 (T2) at Virgen de la Macarena University Hospital in Sevilla/Spain. Inclusion criteria were: (1) confirmed MS diagnosis; (2) age over 18, and (3) mental, physical and cognitive capability to participate and sign informed consent. The study was approved by the responsible Ethics Committee (0846-N-18). Instruments Clinical and sociodemographic information were collected from the medical data base and a questionnaire. Coping strategies The Spanish version of Brief COPE Questionnaire (COPE-28) was applied to study the patients use of different actions in dealing with stressful situations (Morán et al., 2010). Page 3 of 29 URL: https://mc.manuscriptcentral.com/ac-phm-vcy Email: [email protected] Health Sciences For Peer Review Only COPE-28 has 28 items grouped into the following 14 dimensions: (1) acceptance; (2) emotional support; (3) humor; (4) positive reframing; (5) religion; (6) active coping; (7) instrumental support; (8) planning; (9) behavioral disengagement; (10) denial; (11) selfdistraction; (l2) self-blaming; (13) substance use; (14) venting. Items are scored on a four-point Likert scale (from 0 to 3). Higher scores indicate greater use (Carver, 1997). Cronbach’s alpha ranged from 0.60 to 0.88 for the 14 subscales. Social Support Participants perception of social support was measured by the Multidimensional Scale of Perceived Social Support (MSPSS). The MSPSS comprises 12-items scored on a 7point Likert scale ranging from 1 to 7. The total score varies from 12 to 84 (Arechabala and Miranda, 2002; Zinnet, 1988). Cronbach’s alpha in our sample ranged from 0.91 to 0.96 for the subscales. Health related Quality of life The 12-Item Short Form Health Survey (SF-12) consists of 12 items scored on a 3 or 5point Likert scale. The SF-12 consists of eight domains: physical functioning, rolephysical, bodily pain, general health, vitality, social functioning, role-emotional and mental health. Subscales scores range from 0 (worst) to 100 (best). These subscales are combined to form the Physical Component Summary Score (PCS) and the Mental Component Summary Score (MCS) (Vilgaut et al., 2008; Ware et al., 2002). In our sample, dimensions Cronbach’s alpha ranged from 0.70 to 0.96 at T1 and from 0.64 to 0.96 at T2. Cronbach’s alpha for the PCS and MCS was 0.92 and 0.88, respectively (Maruish, 2012). Page 4 of 29 URL: https://mc.manuscriptcentral.com/ac-phm-vcy Email: [email protected] Health Sciences For Peer Review Only Statistics Pearson and Spearman correlations are presented for coping strategies/social support and clinical/demographic variables. Stepwise regression analyses identify quality of life predictors and determine their relative contribution. Two multivariate models were built with MCS and PCS scores at T2 as dependent variables. Sociodemographic (gender, age, partnership, educational level and occupation), clinical variables (EDSS, MS subtype, months since diagnosis and months since the outbreak), coping strategies and social support at T1 were considered as predictors. All tests were computed using SPSS-v26. Significance level was set to p< 0.05. Effect size coefficient were calculated using G*Power Software. Coefficients were interpreted according to Cohen (1988) guidelines; for correlations: p ≥ 0.10 small, ≥ 0.30 medium, and ≥ 0.50 large effect and in multiple regression: f2 ≥ 0.02 small, ≥ 0.15 medium, and ≥ 0.35 large effect. Results The final sample comprised 314 MS patients (dropout rate 19.69%; see figure 1). -Figure 1As can be seen in Table 1, the sample was composed of 213 (67.8%) females and 101 (32.2%) males. Mean age was 45.31 years (±10.77), range from 19 to 78 years. The predominant MS type was remittent 272 (86.6) and mean EDSS score was 3.17 (±1.92). -Table 1Sociodemographic/clinical variables and coping strategies Female gender correlated with higher use of self-distraction (r=0.160, p<0.001), religion Page 5 of 29 URL: https://mc.manuscriptcentral.com/ac-phm-vcy Email: [email protected] Health Sciences For Peer Review Only (r=0.175, p<0.001), and self-blame (r=0.131, p<0.05). Age also correlated positively with religion (r=0.240, p<0.001), and self-blame (r=0.123, p<0.05). Higher educational level was related to a higher use of planning (r=0.167, p<0.001), seeking emotional support (r=0.119, p<0.05), and venting (r=0.151, p<0.001). Being unemployed was related to a lower use of venting (r=-0.121, p<0.05) and higher use of denial (r=0.133, p<0.05) as well as religion (r=0.112, p<0.05). Progressive MS subtype showed a negative relation with venting (r=-0.134, p<0.05) and a positive relation with denial (r=0.125, p<0.05). Months since diagnosis positively correlated with self-blame (r=0.147, p<0.001), as well as months since the outbreak (r=0.143, p<0.05), which also correlated negatively with active coping (r=-0.115, p<0.05). EDSS was related to a higher use of behavioral disengagement (r=0.112, p<0.05), denial (r=0.150, p<0.001), substance use (r=0.124, p<0.05), and humor (r=0.120, p<0.05). There were no significant correlations in regard to partnership status in the use of coping strategies. Effect sizes coefficients (p) of significant correlations ranged from 0.33 to 0.48, medium effects (Table 2). - Table 2Sociodemographic/clinical variables and perceived social support Age (r=-0.130, p<0.05) and progressive MS subtype (r=-0.114, p<0.05) were negatively related with social support from friends (see Table 3). Being without a partner showed a negative relation with social support from significant others (r=-0.128, p<0.05). Page 6 of 29 URL: https://mc.manuscriptcentral.com/ac-phm-vcy Email: [email protected] Health Sciences For Peer Review Only Higher educational level (r=-0.119, p<0.05) and longer duration since diagnosis (r=-0.123, p<0.05) was related to lower perceived support from family. With regard to gender, occupation, months since diagnosis outbreak and EDSS no significant associations were found with social support. For significant results correlation effect sizes (p) were medium (from 0.34 to 0.38). - Table 3Physical and mental HRQOL predictors EDSS (β=-0.452, p<0.001) was the strongest negative predictor of PCS followed by age (β=-0.123, p<0.001). Higher EDSS and older age were related to lower PCS 18 months later. On the contrary, the variable family support (β=0.096, p<0.001) led to an increase of PCS (Table 4). All variables together accounted for 27.4% of PCS variance, with a large effect size (f2=0.377). Denial (β=-0.132, p<0.05), self-blame (β=-0.156, p<0.05), female gender (β=- 0.115, p<0.05) and EDSS (β=-0.108, p<0.05) negatively impacted on MCS 18 months later, whereas positive reframing (β=0.142, p<0.05) was a protective factor. All variables in the model together explained 10.1% of MCS, with small effect size (f2=0.112). (See Table 4). -Table 4Discussion HRQOL in MS depends on a wide spectrum of factors, which yet have to be fully understood. The present study explored associations and predictive value of sociodemographic and clinical features alongside coping strategies and social support for HRQOL in MS over an 18 months follow-up period. Page 7 of 29 URL: https://mc.manuscriptcentral.com/ac-phm-vcy Email: [email protected] Health Sciences For Peer Review Only Sociodemographic/clinical variables and coping strategies Female gender positively correlated with religion as an emotion-focused copingstrategy. The tendency of females to use emotion-focused coping strategies in MS is supported by previous researches (Holland et al., 2019; Zengin et al., 2017). Particularly, Zengin et al. (2017) found females to use religion more frequently as a coping strategy than men. Clinically even more important we found significant relationships with the two dysfunctional strategies self-blame and self-distraction. Older age was also related to a higher use of religion and self-blame. Keramat Kar et al. (2019) discussed that older people with MS tend to use religion as a coping strategy. The gender and age-related tendency to self-blame is significant in view of the identification of possible risk factors for maladaptive coping early in the diagnostic process. Higher level of education was related to a higher use of planning, a problemfocused strategy, and seeking emotional support, an emotion-focused strategy. It can be argued that higher educated MS patients can use their knowledge to choose more effective and adaptive strategies, and make a greater use of social support (Keramat Kar et al. 2019). On the contrary, higher educational level was related to a higher use of venting, classified as a dysfunctional strategy (Carver 1997; Ledesma et al., 2018; Meyer 2001). Unemployment was positively related to a higher use of religion, an emotionfocused coping strategy (Carver 1997; Meyer 2001) and denial, as well as lower use of venting. Our result confirms previous findings indicating that unemployed MS patients tend to a more emotion-oriented coping style (Keramat Kar et al., 2019), avoidance and maladaptive strategies (Holland et al., 2019; Keramat Kar et al., 2019). The lower use of venting contradicts it. Page 8 of 29 URL: https://mc.manuscriptcentral.com/ac-phm-vcy Email: [email protected] Health Sciences For Peer Review Only References Alphonsus, K. B., & D’Arcy, C. (2021). Is there an association between social support and pain among individuals living with multiple sclerosis?. Journal of Evidence-Based Integrative Medicine, 26, 1–6. https://doi.org/10.1177/2515690X21991995 Amtmann, D., Bamer, A. M., Nery-Hurwit, M. B., Liljenquist, K. S., & Yorkston, K. (2019). Factors associated with disease self-efficacy in individuals aging with a disability. Psychology, Health and Medicine, 24(10), 1171-1181. https://doi.org/10.1080/13548506.2019.1612082 Arechabala Mantuliz, M. C., & Miranda Castillo, C. (2002). Validation of a scale of perceived social support in a group of elders under control in a hypertension program in the metropolitan region. [Validacion de una escala de apoyo social percibido en un grupo de adultos mayores adscritos a un programa de hipertension de la region metropolitana] Ciencia y Enfermeria, 8(1), 49-55. Retrieved from www.scopus.com Assirelli, G., & Tosi, M. (2013). Education and Family Ties in Italy, France and Sweden. Journal of Educational and Social Research, 3(7), 379. Bassi, M., Grobberio, M., Negri, L., Cilia, S., Minacapelli, E., Niccolai, C., Pattini, M., Pietrolongo, E., Quartuccio, M. E., Viterbo, R. G., Allegri, B., Amato, M. P., Benin, M., De Luca G., Falautano, M., Gasperini, C., Patti, F., Trojano, M., & Delle Fave, A. (2021). The contribution of illness beliefs, coping strategies, and social support to perceived physical health and fatigue in multiple sclerosis. Journal of Clinical Psychology in Medical Settings, 28(1), 149-160. https://doi.org/10.1007/s10880-019-09692-6 Carnero Contentti, E., López, P. A., Alonso, R., Eizaguirre, B., Pettinicchi, J. P., Tizio, S., Tkachuk, V. & Caride, A. (2021). Coping strategies used by patients with relapsing multiple sclerosis from argentina: Correlation with quality of life and clinical features. Neurological Research, 43(2), 126-132. https://doi.org/10.1080/01616412.2020.1831304 Carver, C. S. (1997). You want to measure coping but your protocol's too long: Consider the brief COPE. International Journal of Behavioral Medicine, 4(1), 92-100. https://doi.org/10.1207/s15327558ijbm0401_6 Cerea, S., Ghisi, M., Pitteri, M., Guandalini, M., Strober, L. B., Scozzari, S., Crescenzo, F. & Calabrese, M. (2021). Coping strategies and their impact on quality of life and physical disability of people with multiple sclerosis. Journal of Clinical Medicine, 10(23). doi:10.3390/jcm10235607 Chandra, P. S., & Desai, G. (2007). Denial as an experiential phenomenon in serious illness. Indian Journal of Palliative Care, 13, 8-14. Cohen, J. (1988). Statistical power analysis for the behavioral sciences (2nd ed.). Hillside, NJ: Lawrence Erlbaum Associates. Costa, D. C., Sá, M. J., & Calheiros, J. M. (2017). Social support network and quality of life in multiple sclerosis patients. [Rede de apoio social e qualidade de vida de pacientes com esclerose múltipla] Arquivos De Neuro-Psiquiatria, 75(5), 267-271. https://doi.org/10.1590/0004282X20170036 Dȩbska, G., Milaniak, I., & Skorupska-Król, A. (2020). The quality of life as a predictor of social support for multiple sclerosis patients and caregivers. Journal of Neuroscience Nursing, 52(3), 106-111. https://doi.org/10.1097/JNN.0000000000000503 Freud, S. (1925). Die Verneinung. Imago, 11 (3), 217-21. Page 15 of 29 URL: https://mc.manuscriptcentral.com/ac-phm-vcy Email: [email protected] Health Sciences For Peer Review Only Fisher, P. L., Salmon, P., Heffer-Rahn, P., Huntley, C., Reilly, J., & Cherry, M. G. (2020). Predictors of emotional distress in people with multiple sclerosis: A systematic review of prospective studies. Journal of Affective Disorders, 276, 752-764. https://doi.org/10.1016/j.jad.2020.07.073 Gil-González, I., Martín-Rodríguez, A., Conrad, R., & Pérez-San-Gregorio, M. Á. (2020). Quality of life in adults with multiple sclerosis: A systematic review. BMJ Open, 10(11) https://doi.org/10.1136/bmjopen-2020-041249 Hanna, M., & Strober, L. B. (2020). Anxiety and depression in Multiple Sclerosis (MS): Antecedents, consequences, and differential impact on well-being and quality of life. Multiple Sclerosis and Related Disorders, 44, 102261. https://doi.org/10.1016/j.msard.2020.102261 Holland, D. P., Schlüter, D. K., Young, C. A., Mills, R. J., Rog, D. J., Ford, H. L., & Orchard, K. (2019). Use of coping strategies in multiple sclerosis: Association with demographic and disease-related characteristics. Multiple Sclerosis and Related Disorders, 27, 214–222. https://doi.org/10.1016/j.msard.2018.10.016 Homayuni, A., Abedini, S., Hosseini, Z., Etemadifar, M., & Ghanbarnejad, A. (2021). Explaining the facilitators of quality of life in patients with multiple sclerosis: A qualitative study. BMC Neurology, 21(1) doi:10.1186/s12883-021-02213-9 Iwanaga, K., Wu, J., Chen, X., Lee, B., Reyes, A., Phillips, B. N., Pfaller, J. & Chan, F. (2018). Personenvironment contextual factors as mediators for the relationship between symptom cluster and employment outcome in multiple sclerosis. Journal of Vocational Rehabilitation, 48(2), 197206. doi:10.3233/JVR-180930 Jensen, M. P., Ehde, D. M., Gertz, K. J., Stoelb, B. L., Dillworth, T. M., Hirsh, A. T., Molton, I. R., & Kraft, G. H. (2011). Effects of self-hypnosis training and cognitive restructuring on daily pain intensity and catastrophizing in individuals with multiple sclerosis and chronic pain. International Journal of Clinical and Experimental Hypnosis, 59(1), 45-63. https://doi.org/ 10.1080/00207144.2011.522892. Kever, A., Buyukturkoglu, K., Riley, C. S., De Jager, P. L., & Leavitt, V. M. (2021). Social support is linked to mental health, quality of life, and motor function in multiple sclerosis. Journal of Neurology, 268(5), 1827-1836. https://doi.org/10.1007/s00415-020-10330-7 Keramat Kar, M., Whitehead, L., & Smith, C. M. (2019). Characteristics and correlates of coping with multiple sclerosis: A systematic review. Disability and Rehabilitation, 41(3), 250-264. https://doi.org/10.1080/09638288.2017.1387295 Khader, H. A., Emran, B., Sulaimi, M. A., Abdulhadi, D. A., Obaidli, K. A., Deai, A. A., & Albatineh, A. N. (2019). Estimating the prevalence of cognition and mental health among multiple sclerosis patients: A population-based cross-sectional study. Multiple Sclerosis and Related Disorders, 36. https://doi.org/10.1016/j.msard.2019.101391 Krstić, D., Krstić, Z. D., Stojanović, Z., Kolundžija, K., Stojković, M., & Dinčić, E. (2021). The influence of personality traits and coping strategies on the quality of life of patients with relapsing-remitting type of multiple sclerosis. [Uticaj osobina ličnosti i strategija suočavanja sa stresom na kvalitet života obolelih od multiple skleroze relapsno remitentnog toka] Vojnosanitetski Pregled, 78(8), 805-810. doi:10.2298/VSP190502132K Kołtuniuk, A., Kazimierska-Zając, M., Cisek, K., & Chojdak-Łukasiewicz, J. (2021). The Role of Stress Perception and Coping with Stress and the Quality of Life Among Multiple Sclerosis Patients. Psycholy Research Behavior Management, 14, 805-815. Lazarus, R. S., and Folkman, S. (1984). Stress, Appraisal, and Coping. New York: Springer. Page 16 of 29 URL: https://mc.manuscriptcentral.com/ac-phm-vcy Email: [email protected] Health Sciences For Peer Review Only Ledesma, A. L. H., Méndez, A. J. R., Vidal, L. S. G., Cruz, G. T., García-Solís, P., & Esquivel, F. D. J. D. (2018). Coping strategies and quality of life in mexican multiple sclerosis patients: Physical, psychological and social factors relationship. Multiple Sclerosis and Related Disorders, 25, 122-127. https://doi.org/10.1016/j.msard.2018.06.001 Lex, H., Weisenbach, S., Sloane, J., Syed, S., Rasky, E., & Freidl, W. (2018). Social-emotional aspects of quality of life in multiple sclerosis. Psychology, Health and Medicine, 23(4), 411-423. https://doi.org/10.1080/13548506.2017.1385818 Lorefice, L., Fenu, G., Frau, J., Coghe, G., Marrosu, M. G., & Cocco, E. (2018). The burden of multiple sclerosis and patients’ coping strategies. BMJ Supportive and Palliative Care, 8(1), 38–40. https://doi.org/10.1136/bmjspcare-2017-001324 Maruish, M. E. (2012). User’s Manual for the SF-12v2 Health Survey (3rd Ed.). Lincoln: QualityMetric Incorporated. Meyer, B. (2001). Coping with severe mental illness: Relations of the brief COPE with symptoms, functioning, and well-being. Journal of Psychopathology and Behavioral Assessment, 23(4), 265-277. https://doi.org/10.1023/A:1012731520781 Mikula, P., Timkova, V., Linkova, M., Vitkova, M., Szilasiova, J., & Nagyova, I. (2020). Fatigue and suicidal ideation in people with multiple sclerosis: The role of social support. Frontiers in Psychology, 11. https://doi.org/10.3389/fpsyg.2020.00504 Morán, C., Landero, R., & González, M. T. (2010). COPE-28: A psychometric analysis of the spanish version of the brief COPE. [COPE-28: Un análisis psicométrico de la versión en Español del brief COPE] Universitas Psychologica, 9(2), 543-552. https://doi.org/10.11144/javeriana.upsy92.capv Ratajska, A., Glanz, B. I., Chitnis, T., Weiner, H. L., & Healy, B. C. (2020). Social support in multiple sclerosis: Associations with quality of life, depression, and anxiety. Journal of Psychosomatic Research, 138. https://doi.org/10.1016/j.jpsychores.2020.110252 Rommer, P. S., Sühnel, A., König, N., & Zettl, U. K. (2017). Coping with multiple sclerosis—the role of social support. Acta Neurologica Scandinavica, 136(1), 11–16. https://doi.org/10.1111/ane.12673 Santangelo, G., Corte, M. D., Sparaco, M., Miele, G., Garramone, F., Cropano, M., Esposito, S., Lavorgna, L., Gallo, A., Tedeschi, G., & Bonavita, S. (2021). Coping strategies in relapsing– remitting multiple sclerosis non-depressed patients and their associations with disease activity. Acta Neurologica Belgica, 121(2), 465-471. https://doi.org/10.1007/s13760-01901212-5 Strober, L. B. (2018). Quality of life and psychological well-being in the early stages of multiple sclerosis (MS): Importance of adopting a biopsychosocial model. Disability and Health Journal, 1–7. https://doi.org/10.1016/j.dhjo.2018.05.003 Ukueberuwa, D. M., & Arnett, P. A. (2019). Coping style as a protective factor for emotional consequences of structural neuropathology in multiple sclerosis. Journal of Clinical and Experimental Neuropsychology, 41(4), 390-398. https://doi.org/10.1080/13803395.2019.1566443 Vilagut, G., Valderas, J. M., Ferrer, M., Garin, O., López-García, E., & Alonso, J. (2008). Interpretation of SF-36 and SF-12 questionnaires in spain: Physical and mental components. [Interpretación de los cuestionarios de salud SF-36 y SF-12 en España: Componentes físico y mental]. Medicina Clinica, 130(19), 726-735. https://doi.org/10.1157/13121076 Page 17 of 29 URL: https://mc.manuscriptcentral.com/ac-phm-vcy Email: [email protected] Health Sciences For Peer Review Only Visser, L. A., Louapre, C., Uyl-de Groot, C. A., & Redekop, W. K. (2020). Patient needs and preferences in relapsing-remitting multiple sclerosis: A systematic review. Multiple Sclerosis and Related Disorders, 39. https://doi.org/10.1016/j.msard.2020.101929 Ware, J. E., Kosinski, M., Turner-Bowker, D. M., & Gandek, B. (2002). How to score Version 2 of the SF-12 Health Survey (with a supplement documenting Version 1). Lincoln: QualityMetric Incorporated. Wilski, M., Gabryelski, J., Brola, W., & Tomasz, T. (2019). Health-related quality of life in multiple sclerosis: Links to acceptance, coping strategies and disease severity. Disability and Health Journal, 12(4), 608-614. https://doi.org/10.1016/j.dhjo.2019.06.003 Zahn, R., Lythe, K. E., Gethin, J. A., Green, S., Deakin, J. F., Young, A. H., & Moll, J. (2015). The role of self-blame and worthlessness in the psychopathology of major depressive disorder. Journal of Affective Disorders, 186, 337-341. https://doi.org/10.1016/j.jad.2015.08.001 Zengin, O., Erbay, E., Yıldırım, B., & Altındağ, Ö. (2017). Quality of life, coping, and social support in patients with multiple sclerosis: A pilot study. [Multipl skleroz hastalarında yaşam kalitesi, baş etme ve sosyal destek: Pilot çalışma]. Turk Noroloji Dergisi, 23(4), 211-218. https://doi.org/10.4274/tnd.37074 Zimet, G. D., Dahlem, N. W., Zimet, S. G., & Farley, G. K. (1988). The multidimensional scale of perceived social support. Journal of Personality Assessment, 52(1), 30-41. https://doi.org/10.1207/s15327752jpa5201_2 Page 18 of 29 URL: https://mc.manuscriptcentral.com/ac-phm-vcy Email: [email protected] Health Sciences For Peer Review Only Table 1. Clinical and sociodemographic characteristics T1 Sample N=391 T2 Sample N=314 Gender n (%) Male 123 (31.5) 101 (32.2) Female 268 (68.5) 213 (67.8) Age (M±SD) 45.66±11.13 45.31±10.77 Partnership n (%) No partner 108 (27.6) 85 (27.1) Partner 283 (72.4) 229 (72.9) Occupation n (%) Employed/In education 135 (34.5) 116 (36.9) Unemployed 256 (65.5) 198 (63.1) Educational level n (%) Primary education 65 (16.6) 44 (14) Secondary education 128 (32.7) 102 (32.5) University or higher 198 (50.6) 168 (53.5) EDSS (M±SD) 3.38±2.06 3.17±1.92 MS subtype n (%) Remittent 326 (83.4) 272 (86.6) Progressive 65 (16.6) 42 (13.4) Months since diagnosis (M±SD) 145.31±89.49 145.68±89.56 Months since outbreak (M±SD) 184.90±108.47 186.11±111.18 Page 19 of 29 URL: https://mc.manuscriptcentral.com/ac-phm-vcy Email: [email protected] Health Sciences For Peer Review Only Table 2. Correlations between sociodemographic and clinical variables and coping strategies Active Coping Planning Instrumental Support Emotional Support Selfdistraction Venting Behavioral disengagement Positive Reframing Denial Acceptance Religion Substance use Humor Selfblame Gender 0.081 0.020 0.045 0.083 0.160** 0.036 0.047 0.040 0.056 0.021 0.175** 0.044 -0.039 0.131* p 0.28 0.14 0.21 0.28 0.40 0.18 0.22 0.20 0.24 0.14 0.42 0.21 0.20 0.36 Age 0.050 0.025 -0.079 -0.047 0.059 -0.102 0.007 -0.006 0.045 0.073 0.240** 0.030 -0.020 0.123* p 0.22 0.16 0.28 0.22 0.24 0.32 0.26 0.07 0.21 0.27 0.48 0.17 0.14 0.35 Partnership 0.038 -0.061 0.032 -0.055 0.093 0.029 -0.072 0.077 -0.033 0.072 0.078 0.090 0.022 0.071 p 0.19 0.25 0.18 0.23 0.30 0.17 0.26 0.28 0.18 0.27 0.28 0.30 0.15 0.26 Educational level 0.021 0.167** 0.090 0.119* 0.009 0.151** -0.092 -0.028 -0.024 -0.109 -0.004 -0.088 -0.061 -0.022 p 0.14 0.41 0.30 0.35 0.09 0.39 0.99 0.17 0.15 0.33 0.06 0.29 0.25 0.15 Occupation -0.008 -0.031 -0.024 0.002 0.060 -0.121* 0.077 -0.007 0.133* 0.032 0.112* 0.016 -0.055 0.037 p 0.28 0.18 0.15 00.04 0.24 0.35 0.28 0.08 0.36 0.18 0.33 0.13 0.23 0.19 MS Subtype 0.034 0.036 -0.011 0.017 0.075 -0.134* 0.068 -0.101 0.125* 0.039 0.073 0.095 -0.028 -0.013 p 0.184 0.19 0.10 0.13 0.27 0.37 0.26 0.32 0.36 0.20 0.27 0.30 0.17 0.11 Months since diagnosis -0.095 -0.029 -0.063 -0.073 0.062 -0.071 -0.038 -0.012 -0.092 0.044 0.093 -0.015 -0.020 0.147** p 0.30 0.17 0.25 0.27 0.24 0.27 0.19 0.11 0.30 0.21 0.30 0.12 0.14 0.38 Months since outbreak -0.115* -0.069 -0.050 -0.005 0.034 -0.101 0.036 -0.038 -0.044 0.028 0.084 -0.033 -0.041 0.143* p 0.34 0.26 0.22 0.07 0.18 0.31 0.19 0.19 0.20 0.16 0.28 0.18 0.20 0.38 EDSS -0.043 0.001 -0.065 -0.017 0.091 -0.045 0.112* -0.003 0.150** 0.030 0.027 0.124* 0.120* 0.059 p 0.20 0.03 0.25 0.13 0.30 0.21 0.33 0.05 0.39 0.17 0.16 0.35 0.34 0.24 EDSS, Expanded Disability Status Scale *p< 0.05, **p<0.001, p, effect size: ≥ 0.10 small, ≥ 0.30 medium, ≥ 0.50 large Page 20 of 29 URL: https://mc.manuscriptcentral.com/ac-phm-vcy Email: [email protected] Health Sciences For Peer Review Only Table 3. Correlations between sociodemographic and clinical variables and perceived social support EDSS, Expanded Disability Status Scale *p< 0.05, **p<0.001, p, effect size: ≥0.10 small, ≥0.30 medium, ≥0.50 large Family Friends Significant Others Total Score Gender -0.029 -0.044 -0.064 -0.062 p 0.17 0.20 0.25 0.25 Age -0.042 -0.130* -0.078 -0.106 p 0.20 0.36 0.27 0.32 Partnership -0.098 0.033 -0.128* -0.105 p 0.31 0.18 0.36 0.32 Educational level -0.119* -0.072 -0.102 -0.074 p 0.34 00.26 0.31 0.27 Occupation 0.065 -0.070 0.102 -0.040 p 0.25 0.26 0.31 0.20 MS Subtype 0.052 -0.114* 0.090 -0.068 p 0.22 0.38 0.30 0.26 Months since diagnosis -0.123* -0.077 -0.039 -0.101 p 0.35 0.27 0.19 0.31 Months since outbreak -0.074 -0.055 0.008 -0.053 p 0.27 0.23 0.08 0.23 EDSS -0.081 -0.103 0.010 -0.077 p 0.28 0.32 0.01 0.27 Page 21 of 29 URL: https://mc.manuscriptcentral.com/ac-phm-vcy Email: [email protected] Health Sciences For Peer Review Only Table 4. Physical and mental HRQL Multiple linear regression models *p<0.05, **p<0.001, §MSPSS Family Support Score Dependent variable physical HRQOL (PCS) F R2 R2adj B SE.B β 1-β f2 Model 1 104.556 (1,312) 0.251** 0.249** 54.737** 1.057 1 0.335 EDSS -2.912** 0.285 -0.501 Model 2 56.012 (2,311) 0.265** 0.260** 59.839** 2.357 1 0.360 EDSS -2.668** 0.300 -0.459 Age -0.130* 0.054 -0.125 Model 3 39.010 (3,310) 0.274** 0.267** 55.446** 3.224 1 0.377 EDSS -2.626** 0.299 -0.452 Age -0.128* 0.053 -0.123 Family§ 0.696* 0.350 0.096 Dependent variable mental HRQOL (MCS) F R2 R2adj B SE.B β 1-β f2 Model 1 11.736 (1,312) 0.036* 0.033* 48.548** 0.752 0.92 0.037 Denial -3.477** 1.015 -0.190 Model 2 9.557 (2,311) 0.058* 0.052* 50.401** 1.017 Denial -3.111* 1.014 -0.170 0.98 0.061 Self-blame -1.737* 0.650 -0.148 Model 3 8.54 (3,310) 0.076* 0.067* 48.017** 1.391 0.99 0.082 Denial -2.770* 1.015 -0.152 Self-blame -2.082* 0.659 -0.178 Positive Reframing 1.699* 0.683 0.140 Model 4 8.538 (4,309) 0.089* 0.078* 52.506** 2.537 0.99 0.097 Denial -2.702* 1.010 -0.148 Self-blame -1.872* 0.663 -0.160 Positive Reframing 1.716* 0.680 0.141 Gender -2.849* 1.350 -0.116 Model 5 6.910 (5,308) 0.101* 0.086* 54.341** 2.691 1 0.112 Denial -2.416* 1.016 -0.132 Self-blame -1.825* 0.660 -0.156 Positive Reframing 1.722* 0.676 0.142 Gender -2.829* 1.344 -0.115 EDSS -0.645 0.326 -0.108 Page 22 of 29 URL: https://mc.manuscriptcentral.com/ac-phm-vcy Email: [email protected] Health Sciences For Peer Review Only Figure 1. Study flow-chart. Page 23 of 29 URL: https://mc.manuscriptcentral.com/ac-phm-vcy Email: [email protected] Health Sciences For Peer Review Only Table 1. Clinical and sociodemographic characteristics T1 Sample N=391 T2 Sample N=314 Gender n (%) Male 123 (31.5) 101 (32.2) Female 268 (68.5) 213 (67.8) Age (M±SD) 45.66±11.13 45.31±10.77 Partnership n (%) No partner 108 (27.6) 85 (27.1) Partner 283 (72.4) 229 (72.9) Occupation n (%) Employed/In education 135 (34.5) 116 (36.9) Unemployed 256 (65.5) 198 (63.1) Educational level n (%) Primary education 65 (16.6) 44 (14) Secondary education 128 (32.7) 102 (32.5) University or higher 198 (50.6) 168 (53.5) EDSS (M±SD) 3.38±2.06 3.17±1.92 MS subtype n (%) Remittent 326 (83.4) 272 (86.6) Progressive 65 (16.6) 42 (13.4) Months since diagnosis (M±SD) 145.31±89.49 145.68±89.56 Months since outbreak (M±SD) 184.90±108.47 186.11±111.18 Page 24 of 29 URL: https://mc.manuscriptcentral.com/ac-phm-vcy Email: [email protected] Health Sciences