Effectiveness of lower limb rehabilitation protocol using mobile health on quality of life, functional strength and functional capacity among knee osteoarthritis patients who were overweight and obese: A randomized controlled trial

Objective: This study aimed to investigate the effectiveness of the lower limb rehabilitation protocol (LLRP) using mobile health (mHealth) on quality of life (QoL), functional strength, and functional capacity among knee OA patients who were overweight and obese. Materials and Methods: In the current trial, 114 patients were recruited and randomized into either the rehabilitation group with mobile health (RGw-mHealth) receiving reminders by using mHealth to carry on the strengthening exercises of LLRP and instructions of daily care (IDC), the rehabilitation group without mobile health (RGwo-mHealth) following the strengthening exercises of LLRP and instructions of daily care (IDC) and control group (CG) only following the IDC for duration of 12-weeks. The reminders for using mHealth were provided two times a day for three days a week. Primary outcome measures were QoL assessed by the Western Ontario and McMaster Universities Osteoarthritis Index summary score, and functional strength by Five-Repetition Sit-To-Stand Test. Secondary outcome measure was functional capacity assessed by the Gait Speed Test. The assessments of QoL, functional strength, and functional capacity were taken at baseline and posttest after 12-weeks of intervention. Results: After 12 weeks of intervention, patients in all three groups had statistically signi[fi]cant improvement in QoL within groups (p < 0.05). Furthermore, patients in the RGw-mHealth and RGwo-mHealth had statistically significant improvement in functional strength and walking gait speed within groups (p < 0.05). The pairwise between-group comparisons (Bonferroni post hoc test) of the mean changes in QoL, functional strength, and functional capacity at posttest assessments revealed that patients in the RGw-mHealth had statistically significant greater mean change in QoL, functional strength and functional capacity relative to both the RGwo-mHealth and CG (p < 0.001). Conclusion: Improvement in QoL, functional strength, and functional capacity was larger among patients in the RGw-mHealth compared with the RGwo-mHealth or CG. Keywords: Osteoarthritis, knee, overweight, rehabilitation. mobile health.

review found that mHealth app users were more satisfied to manage their health than those of conventional care. The mHealth app users have resulted in a positive impact on health outcomes and health-related behaviors (13).
Exercise therapy is a safe and low-cost method for treating Knee OA that has been shown to delay disease progression and improve knee function (14). The Ottawa Panel found evidence to support the use of therapeutic exercises, especially strengthening exercise and general physical activity, for the improvement of functional characteristics in OA patients (15). A current systematic review on non-pharmacological interventions for treating symptoms of knee OA in overweight or obese patients resulted that the most effective intervention that showed improvement of knee function was strengthening exercise (16). Non-pharmacological interventions, primarily strengthening exercise and more recently strengthening exercises of the lower limbs in non-weight-bearing positions, are recommended as the first line of treatment among overweight or obese knee OA patients (17). The novelty of the current study could have been mediated by two factors, firstly it was provided as text messages and secondly the researchers designed a new lower limb rehabilitation protocol (LLRP) to treat overweight and obese knee OA patients. The training sessions of the LLRP are the strengthening exercises of the major muscle groups of the lower limbs in non-weight-bearing sitting and lying positions to reduce the mechanical load on the knee. However, there is insufficient evidence on the effectiveness of the LLRP by using mHealth on QoL, functional strength, and functional capacity among overweight or obese knee OA patients. Therefore, the objective of the current study was to investigate the effectiveness of the LLRP using mHealth on QoL, functional strength, and functional capacity among knee OA patients who were overweight and obese.

Design and setting
The assessments of outcome measures of the current randomized controlled trial (RCT) were conducted in the Teaching Bay. The study was approved by the regional Ethical Committee with approval No: RAIC PESSI /Estt/2019/487 on date 28-08-2019 and the trial was registered in the Chinese Clinical Trial Registry with registration number：ChiCTR1900028600 on date 28-12-2019. The first patient in the trial was enrolled on the date 02-01-2020. Pre-defined questionnaire of inclusion and exclusion criteria was used for screening of the patients.
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Study patients
Patients diagnosed with knee OA who were overweight or obese from the urban community were screened. According to World Health Organization, the individuals who have BMI ≥ 25kg/m 2 are known as overweight and individuals who have BMI ≥ 30kg/m 2 are known as obese (18). The sample included males and females diagnosed with 2-mild or 3-moderate OA according to Kellgren and Lawrence radiographic scale (19). The anteroposterior and lateral view of plain radiography of the affected knee/s were performed in the standing position.
The inclusion criteria were as follows: both males and females, overweight and obese knee OA patients; age 45-60 years; residing in an urban community. The exclusion criteria were as follows: system lupus erythematosus, rheumatoid arthritis, spondyloarthropathies, sjogren's syndrome, gout, scleroderma, infectious arthritis; history of metabolic, hormonal, orthopaedic, cardiovascular disease; spinal deformities; flat feet; previous surgery of knee/s of any cause or injection of knee/s for the last 6-months. The experimental procedures, risks, and benefits associated with the study were explained to all patients prior to providing written informed consent.

Sample size
Sample size estimation was performed using the G* Power 3.1.3 software. By assuming the medium effect size f = 0.70, setting α = 0.05, power (1-B) = 0.80, the total sample size estimated was 30 patients for each group. After considering 20% drop-out rates, the sample size of 114 patients for the three groups was decided.

Patient's recruitment and selection
Patients were recruited from the urban area using convenience sampling by active recruitment strategies through the political and welfare organizations. A study coordinator explained the criteria of knee OA patients as well as benefits of study participation to the political and welfare organizations. These organizations explained the benefits to the expected knee OA patients in the recruitment area via word of mouth and presented a list of expected knee OA patients to a study coordinator. The study coordinator prepared a list of potential patients based on the inclusion and exclusion criteria of the study and approved a final list of patients to contact. Then, the study coordinator called patients to attend a meeting in the Teaching Bay to further assess eligibility. Patients who were eligible and . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted January 10, 2022. ; https://doi.org/10.1101/2022.01.05.21268595 doi: medRxiv preprint interested in participating completed a written informed consent for their participation in the study. Prior to the intervention, patients' baseline measurements were completed

Blinding and Allocation
The coordinators collecting data were independent individuals from the trials and were unaware of the group allocation. There were different coordinators at the baseline and post-test evaluation. Individuals performing the statistical analysis were kept blinded by labelling the groups with non-identifying terms (such as X and Y).

Study Randomization
After completing the screening for eligibility, the selected patients were randomized into one of three groups: rehabilitation group with mobile health (RGw-mHealth), rehabilitation group without mobile health (RGwo-mHealth) or control group (CG) by a computer-generated number. Each group consisted of thirty-eight patients. All patients were also given a diary and asked to record the attendance of completion their interventions based on leaflets.

Rehabilitation group without mobile health (RGwo-mHealth)
Patients in the RGwo-mHealth were taught on how to perform the strengthening exercises of LLRP by following the IDC. The contents of IDC were explained elsewhere (17). Patients were advised to continue performing the training sessions of LLRP 3-times a week for 12-weeks at home. These trainings included strengthening exercises for the lower limbs in non-weight-bearing sitting, or lying positions (Table 1) without putting a mechanical load on the knee.
Each training session started with ten minutes of warm-up, forty-five to sixty minutes of lower limb strengthening exercises, and ten minutes of cool down at the end of the training protocol ( Table 1). The study demonstrated that dynamic stretching is recommended for warm-up to avoid a decrease in strength and performance (20). When the static stretching was used as part of a warm-up immediately prior to exercise, then it causes harm to muscle strength (21). The study explained that after two to four repetitions of static stretching, there is no increase in muscle elongation (22). A cool-down period is essential after a training session and should last approximately 5 to ten minutes (23, 24).
Additionally, regular messages were also sent to the RGwo-mHealth for intention control.

Rehabilitation group with mobile health (RGw-mHealth)
. CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted January 10, 2022. ; https://doi.org/10.1101/2022.01.05.21268595 doi: medRxiv preprint Patients in the RGw-mHealth were prescribed with the LLRP as described in the RGwo-mHealth. Additionally, they receive regular reminders to carry out of LLRP using mHealth in the form of periodic manual WhatsApp messages. Two text messages per day for three days a week for a period of 12-weeks were sent to patients in the RGw-mHealth.
Patients in this group received a total 72 text messages. The researcher sent text messages between 7:00 to 9:00 a.m. and 5:00 to 7:00 p.m. during the days of Wednesday, Friday, and Sunday. A study reported that sending text messages in the morning was to make sure that the patients have enough time to plan and do exercise during the day (25). The screen view for sending the text messages is shown in additional file 1.

Control group (CG)
Patients in the CG only followed the IDC for the duration of 12-weeks. The IDC contents include advice on general guidelines of mobility and healthy eating ( Table 2). The contents of IDC were translated into Urdu language by two language experts to ensure better patients' understanding based on a recent pilot study (17). Regular messages were also sent to the CG for intention control.

Measurements
Patient's demographics, QoL, functional strength, and functional capacity were assessed at baseline before randomization. Similarly, the assessments of demographics, QoL, functional strength, and functional capacity were repeated at posttest after 12 weeks of intervention. The demographic questionnaire covered age, gender, socioeconomic status, and employment. Outcome measures were categorized into primary and secondary outcome measures.

Primary Outcome Measures
Primary outcome measures were QoL and functional strength. To evaluate QoL, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) summary score that was already adapted and validated was used (26). Three dimensional (pain, stiffness, and physical function) QoL questionnaire was designed for the evaluation of the hip and knee OA. The WOMAC score ranges from 0 to 4 on a Likert-type scale, with higher scores indicating an increase in pain, joint stiffness, and reduced functionality (27).
The FRSST was used for the assessment of lower body functional strength. The FRSST has a high test-retest reliability for adults and subjects with knee OA (28, 29). A straight armless chair with 43 cm of back support height was stabilized on the wall. Patients . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted January 10, 2022. ; https://doi.org/10.1101/2022.01.05.21268595 doi: medRxiv preprint were asked to come forward on the chair seat in a position of standing, until the feet are flat on the floor. Patients were instructed to stand up and sit down once without using the upper limbs as a test purpose. For those who needed assistance, assistance was provided to complete the test. Patients were then asked to stand up and sit down as quickly as possible five times. Timing with a stopwatch was started on the command go and ceased when the patient completed the 5th set of sit to stand. The time taken was recorded as the patients' score.

Secondary outcome measures
Secondary outcome measure was the functional capacity. The Gait Speed Test (GST) was used for the assessment of the functional capacity. In the GST, the time was recorded when the patient completed a distance of 20 feet and then divided the distance to time for the calculation of gait speed. Gait speed measures obtained during a single test session are reliable. The coefficients (0.90) of comfortable gait speed were highly reliable (30). The GST is used as an outcome measure in rehabilitation (31) and in trials of interventions to delay the onset of disability or frailty (32).

Statistical procedures
The Statistical Package for Social Sciences, version 22, Chicago, IL, was used to analyze the data. Continuous variables were presented as mean (standard deviation [SD]) based on data distribution. The Shapiro-Wilk test was used to assess the normality of all variables. Categorical variables were presented as frequencies (n) and percentages (%). For categorical demographic variables, the One-Way Analysis of Variance (ANOVA) was used to compare for differences between variables. Since all data was normally distributed; the Paired Samples t-test was used to analyze differences between the baseline and post-test assessments within the groups.
The overall treatment effects on change in clinical outcome measures were estimated using the One Way ANOVA (unadjusted results) and Analyses of Covariance (ANCOVA, adjusted results) for mean changes (95% confidence interval [CI]) from baseline to posttest assessments in the continuous outcome data. The ANCOVA model included the changes as the dependent variable, with group as a main effect and the baseline scores as an additional covariate. The purpose of using the pretest (baseline) scores as a covariate in ANCOVA with a pretest-posttest design is to reduce the error variance and eliminate systematic bias [33]. The pairwise comparisons between groups were estimated . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

(which was not certified by peer review)
The copyright holder for this preprint this version posted January 10, 2022. ; https://doi.org/10.1101/2022.01.05.21268595 doi: medRxiv preprint using Bonferroni post hoc test. The value of p ≤ 0.05 was considered statistically significant. Figure 1 shows a patient flow chart in the current study. A total of 156 overweight and obese knee OA patients were initially enrolled and assessed for eligibility. Among them, 42 patients were excluded for reasons as shown in Figure 1. The remaining 114 were randomized equally into three groups. The post-intervention outcomes were not obtained for the 18 withdrawn patients. Figure 1 demonstrates the study flow chart including reasons given by patients who did not complete the study. A final total of 96 patients (32 in the RGw-mHealth, 32 in the RGwo-mHealth, and 32 in the CG) were included in the analysis of QoL, functional strength and functional capacity.

RESULTS
Non-completers did not differ significantly from completers in terms of age, gender, socioeconomic status, employment, QoL, functional strength, and functional capacity.
Similarly, retention did not differ among the groups (RGw-mHealth, 84%; RGwo-mHealth, 84%; CG, 84%). Two serious adverse events (one appendix surgery in the RGw-mHealth and one gallbladder surgery in the RGwo-mHealth) were unrelated to the study. One nonserious adverse event of muscle spasm in the CG was noted during the study and it was related to the study.
Summary of the overall and baseline demographic characteristics and assessment scores of the QoL, functional strength, and functional capacity are described in Table 3.
After participation in the 12-weeks of intervention, a statistically significant improvement compared to baseline was observed for QoL, functional strength, and functional capacity scores in the RGw-mHealth and RGwo-mHealth. In the CG, improvement in QoL score was also statistically significant (Table 4).

(which was not certified by peer review)
The copyright holder for this preprint this version posted January 10, 2022.  There was also a statistically significant difference in the mean change in functional capacity between RGwo-mHealth and CG (difference, -7.82 [-12.56, -3.08]; p < 0.001) as shown in Table 6.

DISCUSSION
The core recommended treatments for OA in OA clinical guidelines are lower limb muscle strengthening (34). Exercise is often indicated as one of the main components in the rehabilitation process (35). Effectiveness of rehabilitation combined with mHealth may provide more objective data than the standard rehabilitation approaches we are using today to treat overweight and obese knee OA patients. Therefore, the current study investigated the effectiveness of the LLRP using mHealth on QoL, functional strength, and functional capacity among knee OA patients who were overweight and obese. We reached the . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

(which was not certified by peer review)
The copyright holder for this preprint this version posted January 10, 2022. ; https://doi.org/10.1101/2022.01.05.21268595 doi: medRxiv preprint conclusion that in RGw-mHealth patients, the scores of QoL, functional strength, and functional capacity were significantly higher than RGwo-mHealth or CG. The results indicated that patients in the RGw-mHealth who received additional reminders of the intervention combined with WhatsApp messages showed greater improvements in QoL, functional strength, and functional capacity than did the patients in the RGwo-mHealth or CG. In the current study, knee OA was more common in females, while there was no difference in terms of age. The mean age of the overall sample was 53.00 years (SD = 4.60 years). The majority of the study patients were employed (60.5%), and had lower socioeconomic status (69.3%).
In a randomized clinical trial of 316 overweight or obese elderly men and women with knee OA, it was noted that the combination of diet and exercise was more successful in improving health-related QoL, if compared with exercise or diet as single interventions In a meta-analysis, it was indicated that the number of directly supervised exercise sessions can influence the extent of the treatment effect (43). In the current study, the strengthening exercise sessions in the RGw-mHealth were performed 3 times a week for 12 weeks (36 sessions) by sending periodic manual WhatsApp messages as a reminder to perform their intervention. Therefore, the treatment effects of patients in the RGw-mHealth were better than the patients in the RGwo-mHealth and CG.
Based on these findings, the strengthening exercises of LLRP using mHealth are expected to be more effective in terms of improving functional strength, functional capacity, and QoL than any other rehabilitation intervention among overweight and obese knee OA patients. The strengthening exercises of LLRP by using mHealth may have the potential to improve QoL, functional strength, and functional capacity among overweight and obese knee OA patients. These exercises may have the great contribution to the body of knowledge internationally because these are performed in non-weight bearing sitting or lying positions with minimal load at the knee joint. In addition, this rehabilitation protocol is easy to use in the home care setting and may be helpful in treating many bedridden conditions such as multiple sclerosis, hemiplegia, paraplegia and neurological diseases with lower limb weakness.
The present study had some limitations. It was conducted in a single centre to recruit patients. No long-term follow-up records were taken. Thus, further blinded studies across multiple centres and long-term follow-up are required to confirm the results of the strengthening exercises of the LLRP combined with mHealth in overweight and obese knee OA patients. Additionally, physical activity, psychosocial, and comorbidity factors may . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

(which was not certified by peer review)
The copyright holder for this preprint this version posted January 10, 2022. ; https://doi.org/10.1101/2022.01.05.21268595 doi: medRxiv preprint influence the outcomes. Therefore, further research considering these additional factors is required to confirm the findings of the study.
In conclusion, patients in the RGw-mHealth had better improvement in functional strength, functional capacity, and QoL than those in the RGwo-mHealth and CG. The results of the current study suggest that improvements in functional strength, functional capacity, and QoL among knee OA patients who are overweight or obese, are augmented better by the implementation of the LLRP using mHealth to rehabilitation or general treatment without mHealth.

Declaration of conflicting interests
The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

Funding
The authors received no financial support for the research and/or authorship of this article.

Data Availability
The data used to support the findings of the study are available from the corresponding author upon request. . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

(which was not certified by peer review)
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(which was not certified by peer review)
The copyright holder for this preprint this version posted January 10, 2022. ; Table 1 is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

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The copyright holder for this preprint this version posted January 10, 2022. ; https://doi.org/10.1101/2022.01.05.21268595 doi: medRxiv preprint When there is option of sitting than standing, then prefer to sitting. Prefer your sitting on high stool or chair rather than low level.

Standing from Sitting
When you are standing from sitting position, and then initially sit at the edge of bed, chair or stool with the feet on the ground at the level of hips. Use the hands to push up from the bed, chair or stool. Walking Do not walk, jog or run as an exercise plan. Walking stick can be used on the opposite hand of the affected knee OA. If both knees are affected, then walker can be used. Use of knee brace and jogging shoes with well cushioned soles during walking is highly recommended. Stair Climbing Avoid stair climbing. But if there is need of stair climbing then support the side rails with your hands by placing the affected foot first on a stair step then the unaffected foot on the same step. Working Prefer working on a high stool or chair.

Body Weight
Try to reduce your weight by avoiding taking of sugary foods, drinks and high fat foods. Eat mostly plant-based foods. Add omega-3 fatty acids in your daily diet. IDC: Instructions of daily care . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

(which was not certified by peer review)
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(which was not certified by peer review)
The copyright holder for this preprint this version posted January 10, 2022.  is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

(which was not certified by peer review)
The copyright holder for this preprint this version posted January 10, 2022.    is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted January 10, 2022. ; https://doi.org/10.1101/2022.01.05.21268595 doi: medRxiv preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted January 10, 2022. ; https://doi.org/10.1101/2022.01.05.21268595 doi: medRxiv preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted January 10, 2022. ; https://doi.org/10.1101/2022.01.05.21268595 doi: medRxiv preprint