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Table of Contents
Year : 2022  |  Volume : 5  |  Issue : 4  |  Page : 348-356

Anxiety, Depression, Disease Disability, and Health-Related Quality of Life in Rheumatoid Arthritis Patients during the Coronavirus Disease 2019 Pandemic: A Cross-Sectional Study

1 Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
2 Department of Medicine, Rheumatology Unit, King Fahad Medical City, Riyadh, Saudi Arabia
3 Department of Clinical Pharmacy, Pharmacy Administration Service, King Fahad Medical City, Riyadh, Saudi Arabia
4 Department of Medicine, Rheumatology Unit, King Saud University Medical City, Riyadh, Saudi Arabia

Date of Submission01-Mar-2022
Date of Decision01-Jun-2022
Date of Acceptance11-Sep-2022
Date of Web Publication12-Oct-2022

Correspondence Address:
Shiekha S Alaujan
Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh 14511
Saudi Arabia
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jnsm.jnsm_24_22

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Purpose: The coronavirus disease 2019 (COVID-19) pandemic has posed a threat to global health, including mental health. This study aimed to examine the impact of the pandemic on psychological health and to identify the factors associated with anxiety in patients with rheumatoid arthritis (RA) in Saudi Arabia. Materials and Methods: A cross-sectional observational study was conducted between September and November 2020, at the rheumatology clinics of two tertiary care hospitals. Eligible participants were adults with a confirmed diagnosis of RA. Data collected included socio-demographics, contact history, commitment to COVID-19 precautionary measures, medication-taking behavior, the hospital anxiety and depression scale (HADS), the European Quality of Life (QoL) measure (EQ-5D-3L), and the health assessment questionnaire disability index (HAQ-DI). Results: Of the 252 invited eligible patients, 204 agreed to participate. The majority were aged 41–50 years (28.2%), female (86.5%), and nonsmokers (96%), had at least one comorbidity (38.8%), had missed medications (8.8%), and had psychiatric illnesses or were on psychiatric medication for the past 3 months (15.4%). Borderline-abnormal anxiety levels were reported in 32.8% of patients. The mean standard deviation score for HADS depression was 3 (3), that for the EQ-5D-3L index was 0.587 (0.378), and that for the HAQ-DI was 0.947 (0.887). After adjusting for age, sex, presence of psychiatric illnesses or psychiatric medication use and noncompliance with medication, higher levels of anxiety were significantly associated with a higher level of depression, RA disability index, and pain intensity (p-value< 0.05). In contrast, higher health-related QoL was significantly associated with lower levels of anxiety (p-value< 0.001). Conclusion: During the mid-phase of the pandemic in Saudi Arabia, almost one-third of RA patients reported the presence of anxiety symptoms. Higher anxiety levels were found to be associated with depression, health-related QoL, and disease disability in RA patients.

Keywords: Anxiety, coronavirus disease 2019, depression, disease activity, quality of life, rheumatoid arthritis

How to cite this article:
Alaujan SS, Almalag HM, Alshehri SM, Alkendi JM, Almansour MA, Alanizy LN, Omair M. Anxiety, Depression, Disease Disability, and Health-Related Quality of Life in Rheumatoid Arthritis Patients during the Coronavirus Disease 2019 Pandemic: A Cross-Sectional Study. J Nat Sci Med 2022;5:348-56

How to cite this URL:
Alaujan SS, Almalag HM, Alshehri SM, Alkendi JM, Almansour MA, Alanizy LN, Omair M. Anxiety, Depression, Disease Disability, and Health-Related Quality of Life in Rheumatoid Arthritis Patients during the Coronavirus Disease 2019 Pandemic: A Cross-Sectional Study. J Nat Sci Med [serial online] 2022 [cited 2023 Feb 9];5:348-56. Available from: https://www.jnsmonline.org/text.asp?2022/5/4/348/358411

  Introduction Top

The coronavirus disease 2019 (COVID-19) outbreak started in Wuhan City, China, in November 2019 and resulted in a global pandemic. On March 2, 2020, the Saudi Ministry of Health announced the first local case of COVID-19 infection.[1] As of September 13, 2020, around 28, 637,952 cumulative cases, and 917,417 cumulative deaths have been reported globally.[2]

Severe complications and worse prognosis have been reported in the elderly (>60 years), smokers, and in patients with medical comorbidities, including autoimmune diseases requiring immunosuppressive medication use, cancer, obesity, diabetes mellitus, cardiovascular diseases, and lung diseases.[3] With the rapid spread of COVID-19 and the uncertainties regarding its fatalities, numerous studies have reported a negative impact of the disease outbreak on the mental health of the general population, including anxiety, depression, stress, and insomnia.[4],[5],[6],[7] A meta-analysis of the general populations of Asia and Europe found that the prevalence of anxiety, depression, and stress was as high as 31.9% (95% confidence interval [CI], 27.5–36.7), 33.7% (95% CI, 27.5–40.6), and 29.6% (95% CI, 24.3–35.4), respectively.[7]

Patients with rheumatoid arthritis (RA) are considered to be at high risk of severe COVID-19-related complications due to immune dysregulation, immunosuppressive therapy, physical inactivity, and older age.[8] Moreover, it is known that psychological diseases such as depression and anxiety are prevalent among RA patients.[9],[10] These factors render RA patients more vulnerable to psychological complications during the pandemic, which can lead to poor quality of life (QoL). Moreover, a significant inverse relationship has been found between QoL and disease disability in such patients.[11]

It is well-recognized that patients on immunosuppressants are more vulnerable to poor prognosis of COVID-19.[12] As such, the medication-taking behavior of patients with rheumatic diseases such as RA may tend to change during the pandemic. A recent study conducted in Australia which investigated the concerns of rheumatic disease patients during COVID-19 found that the highest ranked concern was regarding their medications increasing the severity of COVID-19 symptoms (76.1%), followed by concerns regarding their medications increasing their risk of contracting COVID-19 (55.7%).[13] Another study by Seyahi et al. reported that 18.7% of RA patients reported a change in their medication-taking behavior during the pandemic.[14]

Based on numerous studies reporting that patients with comorbidities such as RA are at greater risk for COVID-19-associated complications, we postulated that the pandemic affects both the psychological status and medication-taking behavior of RA patients in Saudi Arabia. Therefore, the primary aim of this study was to examine the prevalence of anxiety and to identify the contributing factors of anxiety in RA patients during the COVID-19 pandemic. Our secondary objective was to assess the impact of COVID-19 on depression, disease disability, health-related QoL, and medication-taking behavior in such patients.

  Materials and Methods Top

Study design and setting

A cross-sectional observational study was conducted at the rheumatology clinics of two hospitals, King Saud University Medical City (KSUMC) and King Fahad Medical City (KFMC), in Riyadh, Saudi Arabia. Eligible patients were adults (≥18 years old) with a confirmed diagnosis of RA according to the 2010 American College of Rheumatology criteria and able to read and write.[15] Any patient with unconfirmed RA diagnosis or aged <18 or unable to read and write were excluded from the study. All patients who visited the ambulatory rheumatology clinics were invited to participate. The study was observational in nature and was guided by the Strengthening of Observational Studies in Epidemiology checklist.[16] The study was in line with the Helsinki Declaration.[17] The study protocol was approved by the Institutional Review Board of KSUMC on September 16, 2020 (Ref: E-20-5264) and by KFMC on Sep 10, 2020 (Ref: 20-594).

Study procedure

A predesigned paper-based survey in Arabic was distributed to the eligible participants. The paper-based method was chosen to ensure the completeness of the data and to avoid any technical problems that might occur with online-based surveys. While the survey was completed by participants, members of the research team were available to clarify any ambiguous statements. The study period was between September 15 and November 30, 2020. This was when curfew measures were minimized in health-care facilities, and health-care services partially shifted from virtual to face-to-face clinics. Before the start of the study, some Saudi cities were placed under curfew with travel restrictions since March 23, 2020, which affected Saudi residents in different aspects, including education and health. Many patients were unable to attend their health appointments, and appointments were often canceled or virtually conducted by health-care facilities. All eligible participants were informed about the study's purpose and provided informed consent before participating to the study.

Variables, data tools, and measurements (the surveys)

The used surveys evaluated several aspects, including demographics, behavioral and psychological impact, health-related QoL, and disease disability of RA. Translated and validated tools were utilized, and the surveys were subjected to face validity before the data collection process.

The first part of the survey included the following demographic data: age, gender, occupation, marital status, education level, other comorbidities, presence of psychiatric diseases, use of psychiatric medication for at least 3 months, smoking status, source of COVID-19 educational data (such as family/friends, social media, brochures, TV, and radio, and among others), hours of television or social media engagement, previous diagnosis of COVID-19, COVID-19 community exposure, and overall satisfaction with the available medical support and information about the pandemic.

The second part evaluated the behavioral aspect of medication intake, including adherence to RA medication, possible reasons for discontinuation or change in doses of RA medication, and any intake of hydroxychloroquine for COVID-19 prevention purposes.

The psychological impact, namely depression, and anxiety, was assessed using the Arabic-translated and validated Hospital Anxiety and Depression Scale (HADS).[18],[19] The HADS assesses symptoms of anxiety (7 items) and depression (7 items), with the total score ranging from normal (0–7), to borderline abnormal (8–10), and abnormal (11–21).

The fourth part of the survey involved the European Quality of Life, five dimensions and three levels version-5D-3L (EQ-5D-3L) questionnaire to assess health-related QoL.[20] The Arabic version of the questionnaire has been validated previously in many countries including Saudi Arabia.[21] The questionnaire involves five domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.[20] Each domain was scored based on three levels of severity (no problems, some problems, and severe problems). As no value set was available for Saudi Arabia, the United Kingdom value set was used to derive the EQ-5D index score. The index score ranged from 0 (a health state equivalent to death) to 1 (perfect health). Any score <0 represents a health state worse than death.[22] The EQ-5D-3L visual analog scale (VAS) score (0–100) was also assessed.

The disease disability of RA was assessed using the Arabic-translated and validated Health Assessment Questionnaire Disability Index (HAQ-DI) in the final part of the survey.[23],[24] The first section of the HAQ-DI questionnaire is composed of eight categories, including questions about dressing, arising, eating, walking, hygiene, reach, grip, and activities, each with a disability score ranging from 0 to 3. The second section is composed of questions about the requirement for aids and assistive devices in any of the eight categories. The score is computed by taking the highest score in each category, adjusting for the need for assistive devices, and then dividing by 8 (the total number of categories). The total HAQ-DI score ranges from 0 to 3, where 0 indicates no disability and 3 indicates complete disability. The third part of the HAQ-DI includes two visual analog scales, one of which assesses pain using a score of 0–100 (where 0 represents “no pain”, and 100 represents “severe pain”), and the other assesses the overall disease impact on health using a score of 0–100 (where 0 represents “very well” and 100 represents “very poor”).

Statistical analysis

For required sample size, based on an effect size of 33% of the psychological impact and fear of COVID-19 in patient with rheumatological illnesses reported in a study by Hassen et al., with a 95% confidence level and a 5% margin of error, the calculated sample size a total of 340 participants are required.[25] Data were coded and entered into the Statistical Package for the Social Sciences (SPSS) software IBM corporation, released 2019, IBM statistics for Windows, version 26, (Armonk, NY, USA).[26] Mean and standard deviation (SD) were used to present normally distributed data, while median and interquartile ranges (25th and 75th percentile values) were used for nonnormally distributed data. The presentation of data was stratified into three classes based on HADS anxiety levels: normal (0–7), borderline to abnormal (8–10), and abnormal (11–21). The HADS anxiety domain was chosen for data stratification.

Univariate analysis was performed using the Chi-square test, Fisher's exact test, nonparametric Kruskal–Walls test, Student's t-test, or the analysis of variance, whenever appropriate. As multiple categories were compared, post hoc Bonferroni test was calculated to further explore significantly different variables. Linear regression was used to predict the relationship between anxiety levels (HADS-anxiety) and demographics, disease disability (HAQ-DI), and health-related QoL (EQ-5D-3L). Multiple linear regression was performed to determine the adjusted predictive values of disease disability and health-related QoL for anxiety (as a contentious variable), with patient age, sex, and presence of psychiatric illnesses considered confounding variables. Although the normality of the anxiety scale was violated, we persisted with the multiple linear regression analysis as our sample size was >50. A p-value< 0.05 was considered statistical significance. A complete case analysis was conducted.

  Results Top

Of the 252 patients recruited between September 15 and November 30, 2020, 204 patients (response rate, 81%) agreed to participate in this study. The majority of patients were aged 41–50 years (28.2%), female (86.5%), married (77.3%), unemployed (72.9%), had low education levels (58.2%), were nonsmokers (96.0%), had at least one comorbidity (38.8%), and had psychiatric illnesses or were on psychiatric medication for at least the past 3 months (15.4%). Normal levels of anxiety were observed in 137 patients (67.2%), while borderline and abnormal levels were observed in 26 (12.7%) and 41 patients (20.1%), respectively. In addition, normal, borderline, and abnormal levels of depression were seen in 94.6% (n = 193), 2.9% (n = 6), and 1.5% (n = 3), respectively. On univariate analysis stratified by HADS anxiety levels, patients with greater anxiety were more likely to be on psychiatric medication (p-value= 0.005). No other baseline demographic factors were significant [Table 1].
Table 1: Baseline demographic data of participants stratified by hospital anxiety and depression scale anxiety levels with univariate analysis of differences

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With regards to the sources of COVID-19 information and medication-taking behavior [Table 2], the most reported sources included television (77.8%), social media (61.1%), and family and friends (49.8%). Patients reported using the aforementioned source for 1–2 h (34.0%). A history of COVID-19 infection was reported in 10.9% of patients, while 31.8% had a relative or friend with positive COVID-19 history. In relation to commitment to COVID-19 precautionary measures, 97% were fully committed, while 2.1% were less committed. Workplace commitment during the pandemic, such as social distancing and mask-wearing, was observed in 34 (17.6%) patients. On attending rheumatology clinic appointments, 42.2% of patients attended regularly, while 34.1% did not have appointments. When asked about medication adherence during the pandemic, 89.3% stated that they were as adherent as before, while 8.8% reported missed medications due to several reasons, including pregnancy (n = 5, 2.6%), side effects (n = 4, 2.1%), and RA disease improvement (n = 1, 0.5%). In terms of hydroxychloroquine use for COVID-19 prevention, 2.5% of patients reported recent initiation of use, while 13.1% were already prescribed the drug for RA. All results of the univariate analysis are summarized in [Table 2]. Brochures and other sources of information for COVID-19 were the only factors significantly related to anxiety (p-value< 0.05).
Table 2: Source of coronavirus disease 2019-related information and medication-taking behavior stratified by hospital anxiety and depression scale anxiety levels with univariate analysis of differences

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With regard to psychological factors, scores on all outcome measures showed an approximately normal distribution [Table 3]. The HADS depression scale showed a mean (SD) of 6 (2), 4 (2), and 2 (2) for abnormal, borderline, and normal anxiety levels, respectively (p-value< 0.001). The average EQ-5D-3L index scores were significantly different (p-value< 0.001), with 0.290 (0.392), 0.508 (0.320), and 0.702 (0.325) for abnormal, borderline, and normal anxiety levels, respectively. The EQ-5D-3L VAS score was also significantly different (p-value< 0.001). The average HAQ-DI (SD) scores were 1.616 (0.963), 1.168 (0.992), and 0.705 (0.720) for abnormal, borderline, and normal anxiety levels, respectively (p-value< 0.001). Both HAQ-VAS scores for pain and disease effect on life were significantly different, with p-value= 0.002 and 0.013, respectively. Among the EQ-5D-3L domains, the highest reported problems (some and severe) were in the pain/discomfort domain (71.0%), followed by the mobility (59.2%), usual activities (59.1%), anxiety/depression (48.9%), and self-care (42.8%) domains. A graphical representation of the EQ-5D-3L domains is shown in [Figure 1].
Table 3: Psychological status, health-related quality of life, and disease disability stratified by hospital anxiety and depression scale anxiety levels

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Figure 1: EQ-5D-3L domain results of the study sample, EQ-5D-3L: European Quality of Life, five dimensions and three levels version

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Anxiety was analyzed as a continuous variable using linear regression, the results showed that patients were mostly female and had a greater risk of having psychiatric illnesses or psychiatric medication use for at least 3 months, with betas of 2.029 (95% CI, −0.008–4.067; P = 0.051) and 2.642 (95% CI, 0.750–4.534; P = 0.006), respectively. Patients with missed medication were more prone to anxiety, with a beta of 3.581 (95% CI, 1.052–6.110; P = 0.006). Moreover, EQ-5D-3 L index score and VAS resulted in a beta of −6.894 (95% CI, −8.489–5.299; P < 0.001) and −0.113 (95% CI, −0.140–0.087; p-value< 0.001), respectively. The HAQ-DI disability domain and higher anxiety levels were significantly associated, with a beta of 2.807 (95% CI, 2.129–3.486; p-value< 0.001). Both pain score and disease effect on life of the VAS were also positively correlated with anxiety, with betas of 0.059 (95% CI, 0.035–0.083; p-value< 0.001) and 0.018 (95% CI, 0.035–0.083; p-value< 0.001), respectively. The values remained significant after adjusting for confounding variables, including age, sex, presence of psychiatric illnesses or psychiatric medication use for at least 3 months, and the presence of missed medication. Data of unadjusted and adjusted beta for anxiety, with the respective 95% CIs and p-values, are shown in [Table 4].
Table 4: Multiple linear regression to predict hospital anxiety and depression scale anxiety as a contentious variable

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  Discussion Top

The current study evaluated the impact of the COVID-19 pandemic on RA patients using a multidimensional approach. The pandemic had an unprecedented impact on government policies, healthcare systems, healthcare workers, caregivers, and at-risk patients. Organizational disruption included the interruption of regular patient services, prioritization of care for critical patients, provision of COVID-19 testing, introduction and expansion of telemedicine, and the use of unproven therapies.[27] Rheumatologists and patients alike are challenged with the inability to conduct face-to-face disease assessment, shortage of treatment, switching from intravenous to subcutaneous routes, and inadequate management of disease flares during the pandemic.[27]

The impact of COVID-19 on psychological well-being, particularly anxiety, was prevalent in our study. Hassen et al. assessed the fear of 637 patients with rheumatic diseases in a cross-sectional study during the pandemic (March–April 2020) in Saudi Arabia.[25] The majority of the participants were RA patients (42.7%) who reported a fear of contracting COVID-19 (33.4%) or experiencing disease flares due to the COVID-19 infection (51.8%).[25] The psychological impact on RA patients reported in different communities ranged from minimal impact in a Dutch study,[28] to a significant impact in Filipino, Italian, and Turkish studies during the pandemic.[29],[30],[31] Before the pandemic, Itaya et al. assessed the anxiety and depression of 108 RA patients in Japan using the HADS scale in May 2019, then reassessed the same measures during COVID-19 in August 2020.[32] The results showed an increase in abnormal and borderline anxiety levels during the pandemic from 9% to 12% and 8%–15%, respectively. However, only borderline depression increased from 16% to 21%, while abnormal levels remained unchanged (10%). In our study, higher proportions of abnormal anxiety levels were observed, while lower cases of borderline anxiety levels and depression were seen when compared to RA patients in Japan during the pandemic.

Changes in medication-taking behavior and adherence in rheumatic disease patients during COVID-19 have been addressed previously.[25],[33],[34],[35] In the Saudi study by Hassen et al., 47.9% of patients reported difficulty in acquiring their medications.[25] A mixed methods US-based study from March 25, 2020, on RA patients (n = 530) found that 14% reported self-imposed changes to their medication list or dosages.[33] Moreover, the perceived risk with immunosuppressive medication was present in these patients, who viewed discontinuation of medication as lowering the risk of contracting COVID-19 and reducing disease severity.[33] This was supported by two studies from Greece and Mexico, which found that 2.2% to 3.7% of patients reported discontinuation of medication due to fear.[34],[35] In our study, 5.6% reported decreased or missed dosages; however, the reasons for nonadherence were not explored. Missed medication was a predictor of increased anxiety in our study.

One of the cardinal outcome measures to assess the impact of RA is the HAQ-DI. In our sample, a greater degree of disability was observed when compared to the study by Itaya et al. (mean HAQ-DI = 0.55, SD = 0.67).[32] In addition, a significant association between HAQ-DI scores and HADS anxiety levels was found in our study, which is in line with the findings of Itaya et al.(HAQ-DI β =0.21; 95% CI, 0.04–0.38; p-value= 0.014).[32] With regards to health-related QoL, very limited studies have investigated the effects of COVID-19 on such aspects in RA patients. The health-related QoL of our patients was observed to be worse than those of RA patients in a small Romanian study (n = 14, average EQ-5D-5L index score = 0.77, SD = 0.17),[36] those of the general population in a Chinese study (n = 1,139, EQ-5D-3L index score = 0.949, SD = 102),[37] and those of nonhealth-care practitioners in a German study (n = 10 639, EQ-5D-3L VAS score = 79).[38] Regarding the EQ-5D-3L domains, pain and mobility were the mainly affected domains in our patients. These findings were in parallel to those of Sirbu et al.,[36] whereby the EQ-5D-5L domain scores of 14 patients revealed that 42.86%, 18.43%, 14.29%, 14.28%, and 7.14% reported moderate, severe, and extreme problems in the pain, mobility, self-care, usual activities, and anxiety/depression domains, respectively.

Increased age, female sex, presence of psychiatric illnesses or psychiatric medication use in the last 3 months, and presence of missed medication were the contributing factors to anxiety in our sample population. Missed medication was the only modifiable factor which could be justified. Pregnancy was one of the reasons for missed medication and was considered a valid reason to discontinue medication under healthcare professional supervision. The development of side effects was also reported as a reason for missed medication. Furthermore, the lack of continuous patient monitoring during the pandemic could also be a reason for nonadherence, which may be related to the perceived improvement of disease in patients. Patient counseling and monitoring may therefore improve the medication adherence and psychological well-being of patients. Meanwhile, the female sex was observed as a strong predictor of anxiety in our study. Although Zhong et al. reported that females were significantly more compliant than males during the pandemic,[39] females had a two- to three-fold increased risk of anxiety compared to males in a Turkish and Chinese study.[40],[41] In addition, psychiatric illnesses were also strong predictors of anxiety in our study, which is in line with the literature.[40],[42]

The strengths of the current study include its multicenter involvement, the adequate representation of different age groups, and the use of HAQ-DI and EQ-5D-3L index scores. However, the limitations of the study include its cross-sectional design, and the variations in the mode of consultation (e.g., face-to-face visits and telemedicine) according to patient preference. Patients who chose face-to-face visits may be associated with more severe medical outcomes, given the need to attend clinics physically. Furthermore, the study is conducted in Saudi Arabia which may limit the generalizability of the findings.

One of the implications of the current findings, as reported previously,[43] is the need for guidance on healthy lifestyle measures within COVID-19 restrictions to support the psychological well-being of RA patients. In addition, psychological telemedicine platforms, psychological interventions, and support groups are highly warranted.

  Conclusion Top

During the COVID-19 pandemic, the psychological status, health-related QoL, and disease disability of RA patients were significantly affected and correlated with anxiety disorders. Strategies to decrease the psychological impact of COVID-19 and to prevent disease worsening in this vulnerable population are highly warranted.

Informed consent statement

All participants provided informed consent to participate in the survey.

Data availability statement

The data presented in this study are available upon request from the corresponding author. Such data are not publicly available due to the confidentiality of patients.

Author contributions

SSA and HMA contributed equally to this work, and are considered as first co-authors. SSA: conceptualization, methodology, data curation, formal analysis, writing– original draft, and writing–review and editing. HMM: Data curation, formal analysis, funding acquisition, methodology, writing– original draft, and writing– review and editing. SMA, JMA, MAA, LNA, and MAO: Data collection, and writing– review and editing. All authors have approved the final manuscript and agree with its submission.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

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  [Figure 1]

  [Table 1], [Table 2], [Table 3], [Table 4]


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