A mixed method study to explore the feasibility and patient satisfaction of two different 1 exercise programs in systemic sclerosis associated microstomia.

Systemic sclerosis (SSc) is a severe autoimmune disease often leading to fibrotic cutaneous 48 involvement of the face. Reduced oral aperture is associated with impaired food intake, oral 49 hygiene and secondary dental problems. Stretching and oral augmentation exercises can 50 increase oral aperture but are often hampered by low adherence rates. The aim of this mixed 51 method study was to explore feasibility, patient satisfaction and effectiveness of two exercise 52 programs in SSc-associated microstomia. We included 6 women and 3 men, median age 60 years (range 40-75) and median disease 69 duration 8 years (range 3-22). At 6 months, all patients in group A (n=4) and 4 in group B (n=5) 70 improved with a median of 9mm (range 2-10) and 7mm (range 4-11), respectively. The 71 proportion of executed to the planned number of exercises ranged between 63.7% and 98,9% 72 in group A and between 48.5% and 97,4% in group B. Maintenance of the increase in oral 73 aperture was noted in patients that continued to exercise daily. All 9 patients attended the 74 interview that revealed three themes: drivers, challenges and perceived improvement. Both interventions improve maximal oral aperture. The adherence to therapy was high but none of the patients considered it feasible to continue practicing 3 times/day. Future 79 studies are needed in order to define feasible long-term exercise programs.


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1 Division of Rheumatology, University Hospitals Leuven, Leuven, Belgium 8 2 Laboratory of Tissue Homeostasis and Disease, Department of Development and 9 Regeneration, KU Leuven, Leuven, Belgium  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43 44 Formatted: Right: 0.25" Background 93 Systemic sclerosis (SSc) is a severe autoimmune disease and fibrotic cutaneous involvement 94 of hands and face is a typical disease feature (1). Oral involvement with reduced oral 95 aperture is frequent and associated with impaired food intake, reduced oral hygiene and 96 secondary dental problems (2). Microstomia is defined as an interincisal distance smaller 97 than 40mm (3). In SSc, microstomia is primarily caused by submucosal collagen deposits in 98 perioral tissue (4). Various interventions have been examined. Exercises (5-8) as well as 99 injection therapy (9) have been suggested to restore or maintain mouth opening and 100 freedom of lip movement to improve patients' quality of life. Several studies have shown 101 that stretching (placing the thumbs in opposite corners of the mouth and pulling outward) 102 and oral augmentation exercises (training with tongue depressors) can increase oral 103 aperture in patients with SSc (5-8). In a study by Yuen (10) the authors could not show a 104 significant improvement and highlighted the low exercise adherence rate. The passive jaw 105 motion therapeutic device Therabite is effective in increasing the range of motion in 106 patients with temporomandibular joint and muscle disorders, but data in SSc-associated 107 microstomia are lacking (2) (11). Furthermore, there are no studies investigating the 108 feasibility of these exercises. 109

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In this pilot study, we aim to explore feasibility, patient satisfaction and effectiveness of two 111 different exercise programs, Therabite and orofacial exercises, in SSc

Study timeline and assessments 171
A detailed study timeline can be found in Figure 2. Baseline visit was followed by a 3-month 172 non-interventional observation period. The interventional phase of the study lasted for 3 173 months (from 3 to 6 months), followed by a post-interventional observation period of 3 174 months (from 6 to 9 months). Patients were assessed at baseline, 3, 6 and 9 months 175 The interventional period ended at time point 6 months. When completing the interventional 220 phase, patients were at liberty to continue exercising at their own pace, continuing diary 221 recording but without follow-up telephone calls. The end of the interventional period (6 222 months) included a one-to-one interview, performed by ES, using a semi-structured interview 223 guide (Table 2). Interviews were recorded, transcribed verbatim, anonymized and 224 systematically analyzed using QUAGOL (15). ES read and reread all transcripts, and important 225 units of meaning were systematically extracted, and grouped into natural subthemes and then 226 overarching themes. A subset was independently analyzed by EDL and this was followed by a 227 team discussion of combined findings together with our rheumatologists, a nurse and an 228 occupational therapist. Based on these discussions the final themes and subthemes were 229 refined.  To what extent have your expectations been met? What has happened differently than you expected? What benefit did the practice have for you? What improvements do you experience since the start of the oral training? What is getting worse/harder since the start of the oral training? What feeling do you get when you now hear the word 'Therabite'/mouth exercises? What are the strengths/possibilities of the 'Therabite'/mouth exercises according to you? What are the weaknesses/downsides/pitfalls of the 'Therabite'/mouth exercises according to you? Which exercises did you not like and why? Which exercises did you prefer? Which aspects of the 'Therabite'/mouth exercises did you find less pleasant? Feasibility How did exercising influence your daily routines? How do you see the feasibility of the training in the long term? How did you manage to continue to do the exercises daily? What influenced whether or not to carry out the exercises? What provided support/help? What was annoying/disruptive? If you could decide yourself how to continue the exercises, how would you do this? Is there anything else you want to tell or share about your experiences with mouth training? Do you have any questions or additions? Is there something that was overlooked?

Patient recruitment 240
During the 1-year recruitment period, 34 patients were considered eligible for the study. 9 241 patients consented to participate. The reasons to decline participation were as follows: 242 absence of subjective complaints (n = 8), participation not deemed feasible due to the travel 243 time (n=6), other physical complaints that were of higher priority to the patient (n=6), full-244 time occupation (n=3), jaw complaints (n=1) and lack of motivation to practice (n=1).

Efficacy and compliance 259
At time point 6 months, oral aperture improved in all patients in group A (n=4) and 4 patients 260 in group B (n=5) with a median of 9mm (range 2-10) and 7mm (range 4-11), respectively (Fig.  261 3). In one patient of group B, maximal oral aperture decreased 2mm over time. Compliance 262 ranged from 63.7% to 98,9% in group A and 48.5% to 97,4% in group B. During the follow-up 263 period there was always a decrease in oral aperture among the participants who stopped 264 practicing; there was also a decrease among the participants who had practiced at the start 265 of the follow-up period but discontinued later on. There was lasting improvement if they had 266 continued exercising 3 times/week, 1 time/day and maximal improvement at 2 times/day.

Semi-structured interviews 289
All 9 participants of the exercise program participated in the interview that lasted 30-60 min. 290 Three main themes emerged from the data: drivers, challenges and perceived improvement 291 (Table 4). Mouth opening (mm)

Need of routines. 366
Participants highlighted how important it was to develop a routine, otherwise it was hard to 367 persist and to remember to perform the exercises. To support daily routine, most of them 368 combined their exercises with another activity that they were doing on a daily base. Two participants found that the device was too large, so they did not like to take the device 412 along when leaving the house. increase feasibility of the exercises. It is important to take into account that different 505 participants maintained a high adherence rate solely because of their participation in a trial. 506 Supportive factors are also an attentive partner and/or involved health professionals. To 507 continue exercising, the device or the papers with the exercises were always placed within 508 reach, as a memory aid. In the future it would also be possible to work with a mobile 509 application that gives a notification. If there are few supporting factors in patients, it may be 510 important to provide more support via telephone monitoring. 511

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Various challenges also emerged from this study. The time investment and the mental 513 struggle to keep up exercising threatened the feasibility of continuing to practice 3 514 times/day in the long term. All participants considered 1 time/day to be feasible. In clinical 515 practice health professionals could recommend adults with microstomia to exercise 516 intensively (3 times/day) for 3 months to obtain an improvement and to maintain this 517 improvement by exercising once a day. It is also important to try to do the exercises 518 together with a routine daily activity. It was hardest to exercise at mid-day and all 519 participants preferred the morning or the evening. The follow-up telephone call after 1 520 week is crucial to be able to offer support and to prevent physical complaints such as pain in 521 the corners of the mouth or cramps in the neck. It is crucial to downsize the instructions 522 'keep the mouth as large as possible': is has to be as large as possible without getting pain 523 during or after the exercise. Patient underestimated that they had to keep the same position 524 for 30 seconds. further than the device itself. Everyone in the manual group had an exercise they did with 533 less pleasure, as therapist it will be important to coach the patient and to adapt the 534 exercises according to the needs of the patient. 535

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Most of the participants felt improvement in daily activities. The participants hope to retain 537 progress without exercising but are willing to continue if they feel that their obtained results 538 are diminishing. They all believe that practicing should be part of their lives, but they hope it 539 can be less intensive. Further research is needed into feasible exercise programs with a 540 lower frequency. 541 A recent study (9) suggests that a treatment with injections (hyaluronic acid and platelet-rich 542 plasma) also improve both maximal oral aperture as quality of life. It is noteworthy that 543 these injections require general anesthesia and are invasive procedures. Exercises are 544 accessible for everyone and can be done without substantial costs. 545 The strengths of this study are the availability of qualitative interview results for all patients, 546 providing insight into the psychosocial aspects associated with feasibility of the proposed 547 exercise programs. Limitations are the low number of participants precluding statements on 548