Assessment of Health-related Quality of Life of Children with Idiopathic Nephrotic Syndrome and their caregivers in China

Assessment of Health-related Quality of Life of Children with Idiopathic Nephrotic Syndrome and their caregivers in China | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Assessment of Health-related Quality of Life of Children with Idiopathic Nephrotic Syndrome and their caregivers in China Xia Wang, Danny Junyi Tan, Lejing Guan, Yifei Shao, Jingjing Wang, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4922299/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 29 Oct, 2024 Read the published version in Health and Quality of Life Outcomes → Version 1 posted 11 You are reading this latest preprint version Abstract Aims : The primary aim of this study was to characterize the health-related quality of life (HRQoL) and identify the associated factors among children aged 2 to 18 years in China diagnosed with idiopathic nephrotic syndrome (INS). Additionally, the study aimed to evaluate the HRQoL and caregiving burden of their caregivers, as well as to investigate the correlation between the HRQoL of the children and that of their caregivers. Methods : This study recruited 181 children with a diagnosis of INS from Children’s Hospital, Zhejiang University School of Medicine in China. The proxy-reported PedsQL Generic Core Module (PedsQL GCM) was used to measure the HRQoL of children, and the five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) was applied to measure caregivers’ HRQoL. Differences in scale scores and total scores of PedsQL GCM were assessed using t tests and one-way ANOVA. Multivariate linear regression analysis was used to identify the associated factors of children’s HRQoL. Pearson correlation analysis was performed to assess the correlation between children’s HRQoL and caregiver’s HRQoL. Results : HRQoL of Children with INS declines with increasing age, and children aged 5-18 years had lower scores in physical functioning, emotional functioning, school functioning, psychosocial health summary score, and total PedsQL GCM score compared to healthy children. Various factors, including the mother filling out the questionnaire, the father being unemployed, and use of other medications except for steroids were associated with worse HRQoL of children (p values < 0.05). Additionally, there is a correlation between children's HRQoL and their caregivers' HRQoL. Conclusion: This study evaluated the HRQoL of children aged 2-18 years diagnosed with INS in China, along with the HRQoL of their caregivers. HRQoL of children was potentially influenced by multiple factors. A significant correlation was observed between the HRQoL of the children and that of their caregivers, who frequently experienced varying levels of caregiving burden. Therefore, it is recommended that healthcare professionals prioritize the optimization of HRQoL for both children with INS and their caregivers. quality of life idiopathic nephrotic syndrome burden of disease children caregiver Figures Figure 1 Figure 2 Background Numerous glomerular disorders in pediatric populations present as nephrotic syndrome, with a majority being idiopathic in origin. Idiopathic Nephrotic Syndrome (INS), a common manifestation of chronic kidney disease, represents a major cause of morbidity and mortality globally among children and young adults ( 1 , 2 ). INS is clinically defined by the triad of proteinuria, hypoalbuminemia, and edema ( 3 , 4 ). The incidence of INS ranges from 1.15 to 16.9 per 100,000 children, with variations observed across different races and geographical regions ( 5 ). Clinical manifestations in children can range from mild to severe, with unpredictable patterns of relapse and remission ( 4 , 6 ). The standard initial therapeutic intervention typically involves the administration of glucocorticoids. INS is frequently categorized based on the clinical response to steroid treatment into steroid-sensitive (SS) and steroid-resistant (SR) forms. In cases where the disease is SR or in instances of relapse, the use of oral immunosuppressive drugs (OID) may be required for certain pediatric patients ( 5 , 7 , 8 ). The extended treatment duration and propensity for relapse of INS have significant implications for the health-related quality of life of affected children and their families ( 8 ). The prolonged duration of treatment and the tendency for relapse in INS have considerable implications for the health-related quality of life of affected children and their families. Health-related quality of life (HRQoL) encompasses multiple dimensions, including physical, psychological, and social aspects related to health. This concept serves as a critical indicator, complementing traditional health outcomes such as morbidity and mortality ( 9 , 10 ). HRQoL is influenced by both individual and environmental characteristics ( 11 ). Impaired HRQoL in children with INS has been well-documented in previous studies ( 11 – 15 ). Factors associated with HRQoL include the duration of INS, gender, race, socioeconomic status, frequency of relapse, steroid resistance, and the use of calcineurin inhibitors (CNI) ( 6 , 7 , 9 , 11 , 14 , 16 – 19 ). However, the majority of these studies have been conducted in developed countries, with limited data available from developing countries. A review of the literature reveals studies on the HRQoL of children with INS from Sudan, Egypt, India, Iran, and one study from China ( 9 , 11 , 17 , 20 – 22 ). Furthermore, prior research has been constrained by relatively small sample sizes, especially among younger children, which has led to an incomplete understanding of the current status and determinants affecting the quality of life of Chinese children with INS. Additionally, there is a paucity of data concerning the quality of life of caregivers of patients with INS. Therefore, we conducted this study to evaluate the HRQoL of pediatric patients diagnosed with INS and their caregivers. The primary objective was to characterize the HRQoL and identify the associated factors among children aged 2 to 18 years in China with INS. Additionally, we aimed to assess the HRQoL of caregivers and investigate the correlation between children’s HRQoL and the HRQoL of their caregivers. Methods Study design and participants This was a cross-sectional, questionnaire-based survey that was led by the Department of Child Health Care and Department of Nephrology in Children's Hospital, Zhejiang University School of Medicine. Participants were recruited from both outpatient and inpatient populations at the hospital where the study was conducted, as well as from an online community facilitated through a WeChat group designed for clinician-patient communication. WeChat, a multifunctional Chinese application, supports instant messaging, social media interaction, and payment services. The WeChat group served as a significant adjunct to healthcare by disseminating disease-related knowledge and family care skills to caregivers, thereby providing them with both professional and peer support. The inclusion criteria for the study encompassed children who ( 1 ) had been diagnosed with idiopathic nephrotic syndrome and ( 2 ) were under 18 years of age. The exclusion criteria comprised children who ( 1 ) had significant physical or psychiatric disorders and ( 2 ) whose caregivers were unable to comprehend and complete the questionnaire. Primary caregivers, who were well-acquainted with the children's health status, were invited to participate in the survey. This online survey was administered from January to August 2024. Ultimately, caregivers of 181 patients with idiopathic nephrotic syndrome completed the questionnaire. Ethical approval statements This study was conducted according to the Declaration of Helsinki ( 23 ), and was approved by the Medical Ethics Committee of the Children's Hospital, Zhejiang University School of Medicine (2024-IRB-190). All caregivers gave their consents to participate in the study. Data collection An expert panel was convened to develop the questionnaire, comprising three senior clinicians (XW, JW, and JM) and one clinical epidemiologist (GB). The questionnaire was drafted following two rounds of discussion, informed by a review of the literature and expert opinions. Subsequently, a pre-test pilot was conducted with 20 caregivers of children with INS. Additionally, brief face-to-face interviews were conducted with 8 caregivers post-pilot to gather their feedback and suggestions.A revised version of the electronic questionnaire was ultimately employed for this study, comprising four sections: general characteristics, disease- and treatment-related characteristics, health-related quality of life of children, and health-related quality of life of caregivers. The electronic questionnaire was developed and visualized by two research assistants (LG and YS) utilizing Wenjuanxing ( https://www.wjx.cn/ ), a widely-used online platform for creating survey questionnaires. We produced and disseminated posters featuring the QR code throughout the clinics and wards of the Department of Nephrology at the hospital where the study was conducted. Additionally, the QR code was distributed through the WeChat group. Clinicians participating in this study provided detailed explanations of its objectives to caregivers, ensuring comprehensive understanding prior to obtaining their informed consent for participation. General characteristics encompass socio-demographic factors, such as children's age and gender, parental education, household income, marital status, and employment status, as well as medical insurance. Clinical characteristics include the onset time of idiopathic nephrotic syndrome (INS), disease duration, patient type (i.e., inpatient or outpatient), complications (e.g., hematuria, hypertension), and prescribed medications. Children's health-related quality of life (HRQOL) was assessed using the proxy-reported PedsQL™ 4.0 Generic Core Module (PedsQL™ 4.0 GCM). Prior to data collection, authorization to use this instrument was obtained through a request on the Mapi Research Trust website ( https://eprovide.mapi-trust.org/instruments/pediatric-quality-of-life-inventory ), which allowed us to download the PedsQL™ without a license fee for unfunded research. The proxy-reported PedsQL™ 4.0 GCM is administered to evaluate HRQOL in children and adolescents aged 2–18 years. For children aged 2 to 4 years, the instrument comprises 21 items distributed across four scales: physiological functioning (eight items), emotional functioning (five items), social functioning (five items), and school functioning (three items). In contrast, the instrument designed for children aged 5 to 18 years includes 23 items, also organized into four scales: physiological functioning (eight items), emotional functioning (five items), social functioning (five items), and school functioning (five items). Each item is presented with five response options on a scale ranging from 0 to 4, where 0 indicates "never a problem," 1 indicates "seldom a problem", 2 indicates "sometimes a problem", 3 indicates "often a problem", and 4 indicates "always a problem". To standardize these items on a 0–100 scale, a linear transformation is applied as follows: 0 is transformed to 0, 1 to 25, 2 to 50, 3 to 75, and 4 to 100. Scale scores and total scores are computed by summing the item scores and dividing by the number of items responded to. A higher score reflects a better HRQoL. The instrument was previously validated in China, demonstrating satisfactory reliability and validity (Chen et al., 2011; Ji et al., 2011). In the current study, we computed Cronbach’s alpha coefficients, with the results detailed in Supplementary Table S1 . The health-related quality of life of caregivers was assessed utilizing the five-level EuroQol five-dimensional questionnaire (EQ-5D-5L). The EQ-5D descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, each rated on a five-level scale ranging from no problems to extreme problems. Furthermore, the EQ visual analogue scale (EQ-VAS), which spans from 0 (indicating the worst imaginable health) to 100 (indicating the best imaginable health), was employed to evaluate the overall health perception of the respondent completing the questionnaire. In addition, we selected five question items from Zarit Caregiver Burden Interview (ZBI) ( 24 ) to measure specific caregiver’s burden due to taking care children with INS. The five questions are ( 1 ) “Do you feel that being with your child means you don't have enough time for yourself”, ( 2 ) “Do you feel stressed to take care of your child while also striving to balance other family or work responsibilities”, ( 3 ) “Do you feel that taking care of children has affected your own health”, ( 4 ) “Do you feel that apart from other personal expenses, you do not have enough money to take care of your child”, and ( 5 ) “Overall, how much burden do you think it is to take care of your child”. Statistical analysis Initially, descriptive analysis was conducted to compute means and standard deviations (SDs) for continuous variables exhibiting a normal distribution, and medians with interquartile ranges for continuous variables with a non-normal distribution. For categorical variables, frequencies and percentages were determined. Subsequently, the mean scores of the scales and the overall score of the PedsQL 4.0 Generic Core Scales (GCS) were compared with the corresponding scores of age-matched healthy children as reported in the extant literature ( 25 , 26 ). Next, we employed two-independent-samples t-tests and one-way ANOVA to evaluate the differences in mean scores of the scales and the overall score of the PedsQL 4.0 GCM across various subgroups. Despite achieving statistical significance, we additionally calculated effect sizes, i.e., Cohen's d and partial eta squared (η p 2 ), to evaluate the clinical relevance of our findings. Cohen's d is calculated as the absolute value of the difference in mean scores between two groups divided by the largest standard deviation. The interpretation of Cohen's d is as follows: 0.2 ≤ d < 0.5 indicates a small effect size, 0.5 ≤ d < 0.8 indicates a moderate effect size, and d ≥ 0.8 indicates a large effect size ( 27 ). η p 2 was calculated to estimate the effect size of a difference across three or more subgroups. Effect sizes are indicated as 0.01 ≤ η p 2 < 0.06 indicates a small difference, 0.06 ≤ η p 2 < 0.14 indicates a moderate difference, and η p 2 ≥ 0.14 indicates a large difference. Finally, variables that demonstrated statistical significance were subsequently incorporated into the multivariate linear regression models to assess the independent associated factors of HRQoL of INS children. Regarding caregiver’s HRQoL, we calculated proportions of reported caregiver burden across the five dimensions and the utility score of the EQ-5D-5L based on the value set of Chinese adult population ( 28 ). The means and standard deviations (SD) of the utility score and EQ-VAS scores were utilized to evaluate overall health-related quality of life. The relationships between the scale scores and total scores of the PedsQL 4.0 Generic Core Scales (GCS) with the utility score and EQ-VAS score were analyzed using Pearson correlation analysis. In addition, we calculated the proportions reported caregiver’s burden across five questions from ZBI. All the statistical analyses were conducted by using SPSS version 27.0 (SPSS Inc., Chicago, USA). The statistical significance was indicated when p value < 0.05. Results 3.1. General characteristics of the study population Table 1 presents the general characteristics of the study population. The median age of children was 4.0 years, and 68.5% were boys. Mothers filled out 76.2% of the questionnaires. 37.6% of mothers and 42.5% of fathers had a high educational level, i.e., a bachelor’s degree or above. 37.6% of families lived in urban areas. Additionally, 82.9% of the parents had someone at home to care for the sick child. 81.8% of children had health insurance. Table 1 General and clinical characteristic of children with idiopathic nephrotic syndrome (n = 181) Characteristic Values* Age of the child, year 4.0 [4.0, 5.0] Age groups 2–4 years old 35 (19.3) 5–7 years old 59 (32.6) 8–12 years old 50 (27.6) 13–18 years old 37 (20.4) Gender Boys 124 (68.5) Girls 57 (31.5) Current weight of the child, kilogram (kg) 25.00 [18.05, 43.00] Current Height, centimeter (cm) 122.00 [108.00, 149.50] BMI (kg/m²) 16.41 [14.79, 20.20] Caregiver who filled out the questionnaire Mother 138 (76.2) Father and others 43 (23.7) Maternal educational level Middle school or lower 65 (35.9) High school 48 (26.5) Bachelor degree or higher 68 (37.6) Paternal educational level Middle school or lower 56 (31.0) High school 48 (26.5) Bachelor degree or higher 77 (42.5) Employment of mother Yes 130 (71.8) No 51 (28.2) Employment of father Yes 172 (95.0) No 9 (5.0) Annual household income (RMB) Less than 100,000 95 (52.5) 100,000 to 200,000 35 (19.3) More than 200,000 51 (28.2) Parental marital status Married 175 (96.7) Divorced 6 (3.3) Residence Urban 68 (37.6) Town or rural 113 (62.4) Having a health insurance No 33 (18.2) Yes 148 (81.8) Having someone at home to take care of the sick child Yes 150 (82.9) No 31 (17.1) Having a sibling or siblings Yes 110 (60.8) No 71 (39.2) * Values presented in this table presents medians, interquatile ranges, numbers, and percentages. 3.2. Clinical characteristics of the study population Table 2 presents a summary of the clinical characteristics of the study population. The median age at disease onset was 3.7 years, which was also the median age at diagnosis of INS. At the time of this study, 29.8% of the children were making their initial hospital visit. Over the last six months, the median number of visits to a tertiary hospital was 2. The prevalence of hematuria, renal insufficiency, and hypertension among the participants was 5.0%, 9.9%, and 6.1%, respectively. Table 2 summarizes clinical characteristics of the study population. The median age of disease onset was 3.7 years, and the median age of having the diagnosis of INS was 3.7 years. 29.8% of children visited the hospital when this study was conducted for the first time. In the last six months, the median of times of visiting a tertiary hospital was 2. The percentage of presenting blood in urine, renal insufficiency and high blood pressure was 5.0%, 9.9%, and 6.1%, respectively. In the study, 27.6% of children were treated exclusively with steroids. Additionally, 48.6% utilized oral immunosuppressive drugs (OID), 28.2% received rituximab (RTX), and 28.2% were administered other medications. Notably, 71.3% of caregivers expressed that their primary concern regarding idiopathic nephrotic syndrome (INS) was its incurability. Table 2 Clinical characteristics of children with idiopathic nephrotic syndrome (n = 181) Characteristic Values * Age of onset of INS (year) 3.7 (2.3, 8.0) Age of diagnosis of INS (year) 3.7 (2.3 ,7.7) First-time visit of the hospital, yes 54 (29.8) Number of visiting tertiary hospitals in the last 6 months 2 (1, 3) Presence of hematuria, yes 9 (5.0) Renal insufficiency, yes 18 (9.9) Presence of hypertension, yes 11 (6.1) Only using the steroid, yes 50 (27.6) Medications used for treatment except for steroid Oral immunosuppressive drug 88 (48.6) Rituximab 51 (28.2) Other medications 51 (28.2) Immunosuppressive medications used for treatment Levamisole 1 (0.6) Mycophenolate mofetil 41 (22.7) Cyclophosphamide 5 (2.8) Tacrolimus 58 (32.0) Cyclosporine A 7 (3.9) Other 5 (2.8) Primary concern regarding illness perceived by parents Nephrotic syndrome cannot be cured 129 (71.3) The physical discomforts caused by INS 11 (6.1) Psychological problems caused by INS 8 (4.4) Concerns about adverse effects of medications 12 (6.6) Concerns about sequelae 9 (5.0) The negative impact of illness on children's education 3 (1.7) Psychological problems of caregivers 1 (0.6) The financial burden due to the disease 7 (3.9) Other concerns 1 (0.6) * Values presented in this table are medians, interquatile ranges, numbers, and percentages. 3.3. Scales scores and total scores of PedsQL GCM in INS children at different age groups Table 3 presents the means and standard deviations of scale scores and total scores of PedsQL GCM in INS children at different age groups in our study. Children aged 13–18 years had significantly lower scores in all scales as well as lower total score compared with scores at other age groups (p values < 0.05). The effect sizes ranged from 0.044 to 0.338. In addition, we compared the mean scores of PedsQL GCM in our study population with the published scores from healthy children at the same age ( 25 , 26 ). The results are presented in the Supplementary Table S2 . For children aged 2 to 4 years, both the total score and the average of scale scores were significantly higher than the averages of the healthy controls ( p values < 0.05) except for the mean score of school functioning (p = 0.121). For children aged 5 to 18 years, the averages of scale scores and the total score were significantly lower than the averages of the healthy controls ( p values < 0.05) except for the mean score of social functioning scale (p = 0.171) . Table 3 。 Means and standard deviations of scales and total scores of PedsQL GCM among children with idiopathic nephrotic syndrome at different age groups (n = 181) 2–4 years (n = 35) 5–7 years (n = 59) 8–12 years (n = 50) 13–18 years (n = 37) p value Effect size (η p 2 ) Physical functioning 89.20 ± 14.57 75.37 ± 17.60 53.64 ± 15.84 70.61 ± 21.64 < 0.001 0.338 Emotional functioning 82.29 ± 20.98 72.80 ± 18.06 74.50 ± 21.62 68.11 ± 27.01 0.048 0.044 Social functioning 90.86 ± 12.57 83.56 ± 19.41 84.70 ± 15.76 62.25 ± 18.08 < 0.001 0.255 School functioning 84.13 ± 24.42 69.75 ± 16.98 73.30 ± 18.51 65.27 ± 26.77 0.010 0.067 Psychosocial Health Summary Score 86.72 ± 18.03 75.17 ± 14.93 77.47 ± 15.19 65.35 ± 21.05 < 0.001 0.124 Total score 87.93 ± 16.46 75.24 ± 14.08 69.18 ± 14.41 67.18 ± 20.48 < 0.001 0.141 Values presented in this table are means and standard deviations. *Effect size: we calculated partial eta squared (η p 2 ) for ANOVAs to estimate the effect size. Effect sizes are indicated as small (η p 2 = 0.01), medium (η p 2 = 0.06), and large (η p 2 = 0.14) effects. 3.4 Differences in average scores of PedsQL GCM scales and total score Table 4 presents differences in the mean values of PedsQL 4.0 GCM scales and total scores in the study population. We showed the variables with at least one statistically significant difference (i.e., when p value < 0.05) regarding the average scores of PedsQL 4.0 GCM scales and total scores, and the rest results are presented in Supplementary table S3 . Notably, when mothers filled out the questionnaire, children had lower average scores in the scale of emotional functioning (p = 0.004), school functioning (p = 0.045), psychosocial health summary score (p = 0.010), and total score (p = 0.023) compared to those scores when fathers or others filled out the questionnaire. The average scores were significantly higher in social functioning (p < 0.001), school functioning (p = 0.017), psychosocial health summary score (p = 0.013) as well as total scores (p = 0.016) in children whose mothers had a high education compared to their counterparts. Children who visited the hospital for the first time had higher average scores in social functioning (p = 0.005), psychosocial health summary score (p = 0.016), and total scores (p = 0.023). Children on steroid-exclusive regimens had relatively higher mean score in all scales and total scores (p values < 0.05). More specifically, in terms of medical treatments, we also compared the scores of PedsQL GCM in children who exclusively used steroids with those using two or more medications. Results are shown in the Supplementary Table S3 . Children had highest mean scores in all scales and total score compared to patients using oral immunosuppressive drugs (OID) and/or rituximab (RTX). Children using both OID and RTX had the lowest mean scores in all scales as well as the total score. Furthermore, we applied the Post hoc comparison and found that it indicates there was only significant differences in averages of total score of PedsQL GCM when only using steroids vs. only using OID as well as only using steroid vs. using both OID and RTX (see Supplementary table S5 ). Table 4 Comparing the average scale and total scores of PedsQL GCM across groups in children with idiopathic nephrotic syndrome (n = 181) Characteristics Physical functioning Emotional functioning Social functioning School functioning Psychosocial Health Summary Score Total score Gender Boy 73.26 ± 20.36 74.88 ± 20.95 82.06 ± 18.83 72.63 ± 21.15 76.09 ± 16.64 74.56 ± 15.97 Girl 66.31 ± 22.86 72.54 ± 24.15 78.47 ± 20.93 69.58 ± 22.09 73.18 ± 20.32 70.53 ± 19.35 p value 0.042 0.508 0.251 0.388 0.325 0.155 Effect size 0.32 0.10 0.18 0.14 0.16 0.23 Caregiver who filled out the questionnaire Mother 69.82 ± 21.29 71.52 ± 22.46 79.90 ± 20.21 69.89 ± 20.99 73.28 ± 17.66 71.65 ± 16.88 Father and others 75.06 ± 21.36 82.56 ± 18.07 84.24 ± 16.94 77.96 ± 22.19 81.89 ± 17.48 78.99 ± 17.38 p value 0.161 0.004 0.204 0.045 0.010 0.023 Effect size 0.25 0.54 0.23 0.37 0.49 0.43 Maternal educational level Middle school or lower 68.08 ± 22.58 71.85 ± 23.64 74.20 ± 21.37 65.52 ± 26.89 70.34 ± 21.10 69.12 ± 20.16 High school 69.08 ± 23.21 75.00 ± 22.41 79.88 ± 20.80 74.00 ± 17.31 75.24 ± 16.76 72.40 ± 16.24 College or above 75.33 ± 18.19 75.74 ± 20.04 88.10 ± 13.71 75.98 ± 16.39 79.85 ± 13.85 77.96 ± 13.38 p value 0.111 0.568 < .001 0.017 0.013 0.016 Effect size 0.03 0.01 0.10 0.05 0.05 0.05 Paternal educational level Middle school or lower 65.80 ± 23.42 71.07 ± 24.38 73.28 ± 21.72 67.31 ± 23.76 70.24 ± 20.73 68.12 ± 19.86 High school 74.40 ± 23.59 78.33 ± 22.30 83.80 ± 16.66 73.93 ± 23.05 78.07 ± 16.91 76.23 ± 17.52 College or above 72.82 ± 17.58 73.77 ± 19.67 84.71 ± 18.09 73.36 ± 18.16 76.88 ± 15.69 75.10 ± 14.00 p value 0.078 0.240 0.002 0.215 0.056 0.033 Effect size 0.05 0.03 0.11 0.02 0.04 0.04 Employment status of father Yes 71.69 ± 21.48 75.44 ± 20.89 82.04 ± 18.73 72.71 ± 20.76 76.31 ± 17.23 74.21 ± 16.77 No 59.12 ± 15.47 49.44 ± 28.33 59.80 ± 23.49 52.59 ± 25.62 54.55 ± 18.29 56.14 ± 16.64 p value 0.085 < 0.001 < 0.001 0.006 < 0.001 0.002 Effect size 0.67 1.05 1.05 0.86 1.22 1.08 First visit to the hospital for the diagnosis of INS Yes 75.24 ± 21.13 77.78 ± 21.69 87.17 ± 15.96 76.81 ± 20.28 80.52 ± 16.55 78.13 ± 16.69 No 69.29 ± 21.30 72.60 ± 21.98 78.28 ± 20.34 69.66 ± 21.63 73.08 ± 18.07 71.37 ± 17.10 p value 0.086 0.147 0.005 0.054 0.016 0.023 Effect size 0.28 0.24 0.49 0.34 0.43 0.40 Presence of renal insufficiency Yes 61.43 ± 19.73 71.39 ± 23.57 70.41 ± 22.75 68.44 ± 20.87 68.90 ± 20.34 65.38 ± 17.27 No 72.13 ± 21.32 74.45 ± 21.84 82.09 ± 18.86 71.96 ± 21.55 75.79 ± 17.60 74.07 ± 17.04 p value 0.043 0.576 0.016 0.533 0.144 0.054 Effect size 0.52 0.14 0.56 0.17 0.36 0.51 Presence of hypertension Yes 60.34 ± 20.16 67.73 ± 24.94 67.84 ± 19.50 64.50 ± 19.92 65.80 ± 17.96 63.42 ± 17.48 No 71.76 ± 21.31 74.56 ± 21.78 81.78 ± 19.28 72.08 ± 21.52 75.73 ± 17.81 73.86 ± 17.05 p value 0.086 0.319 0.021 0.280 0.089 0.063 Effect size 0.55 0.29 0.72 0.37 0.56 0.60 Only using steroid treatment Yes 77.04 ± 19.97 80.70 ± 21.92 87.43 ± 15.22 80.61 ± 21.38 82.81 ± 17.08 80.41 ± 16.76 No 68.79 ± 21.51 71.64 ± 21.54 78.45 ± 20.45 68.41 ± 20.62 72.39 ± 17.48 70.66 ± 16.69 p value 0.020 0.013 0.005 0.001 < 0.001 0.001 Effect size 0.40 0.42 0.50 0.58 0.60 0.58 Values presented in this table are means and standard deviations. *Effect size were calculated as Cohen’s d and partial eta squared (η p 2 ) to estimate clinical relevance. Effect sizes are indicated as small (d = 0.2, η p 2 = 0.01), medium (d = 0.5, η p 2 = 0.06), and large (d = 0.8, η p 2 = 0.14) difference. 3.5 Associated factors of the total PedsQL GCM score Table 5 shows results of multivariate linear regression analyses to assess associated factors of the HRQoL in children with INS measured by PedsQL GCM. Factors significantly associated with children’s HRQoL include mothers filling out the questionnaire (β = 6.20; 95% CI: 0.12, 12.27; p = 0.046), non-emoloyment status of fathers (β=-12.12; 95% CI: -23.42, -0.82; p = 0.036) and not exclusively using steroid treatment (β= -6.60; 95% CI: -12.62, -0.58; p = 0.032). The adjusted R 2 is 0.132. Table 5 Associated factors of total PedsQL GCM score in the multivariate linear regression analyses PedsQL GCM Total score β (95% confident interval ) P value Caregiver who filled the questionnaire Mother (n = 138) Reference Father and others (n = 43) 6.20 (0.12, 12.27) 0.046 Maternal educational level University or higher (n = 68) Reference High school (n = 48) -5.75 (-13.82, 2.32) 0.161 Middle school or lower (n = 65) -6.13 (-16.21, 3.95) 0.232 Paternal educational level University or higher (n = 77) Reference High school (n = 48) 3.41 (-4.86, 11.68) 0.417 Middle school or lower (n = 56) -1.29 (-11.11, 8.53) 0.796 Employment of father Yes (n = 172) Reference No (n = 9) -12.12 (-23.42, -0.82) 0.036 First onset of symptoms Yes (n = 54) Reference No (n = 127) -3.27 (-9.32, 2.77) 0.286 Steroid Yes (n = 50) Reference No (n = 131) -6.60 (-12.62, -0.58) 0.032 Adjusted R 2 0.132 3.6 Caregiver’s Health-related Quality of Life and Caregiver’s burden Caregiver’s HRQoL profile composed of the five health dimensions is shown in Fig. 1 . The percentage of reporting “no problem” in mobility, looking after themselves, doing usual activities, pains and discomforts and feeling worried, sad or unhappy was 52.41%, 76.47%, 93.58%, 95.19% and 94.12%, respectively. Notably, 38.50% of caregivers reported slight problems in the dimension ‘feeling worried, sad or unhappy’, 8.02% moderate problems, 0.53% severe problems and 0.53% extreme problems. As shown in the Supplementary Table S6 , the mean of EQ-5D-5L utility score is 0.94 with a standard deviation as 0.08, and the median of EQ-5D-5L VAS score is 89 (interquartile range: 79, 100). Futhermore, Table 6 shows the scale scores and total score of PedsQL GCM are statistically significantly correlated to EQ-5D-5L utility score and VAS score (p values <0.05). In addition, Fig. 2 demonstrates the specific caregiver’s burden due to taking care of children with INS. Table 6 The correlation between PedsQL GCM scale/total scores and EQ-5D-5L utility and VAS score Utility score VAS Pearson r P value Pearson r P value Physical functioning 0.299 < 0.001 0.285 < 0.001 Social functioning 0.223 0.003 0.246 < 0.001 Emotional functioning 0.338 < 0.001 0.270 < 0.001 School functioning 0.338 < 0.001 0.241 0.002 Psychosocial Health Summary Score 0.352 < 0.001 0.302 < 0.001 Total score 0.374 < 0.001 0.337 < 0.001 Discussion In the present study, we have conducted an assessment of the health-related quality of life (HRQoL) among children aged 2 to 18 years with Idiopathic Nephrotic Syndrome (INS) in China, as well as the HRQoL of their caregivers and the burden experienced by caregivers in managing children with INS. Our findings indicate that children's HRQoL declines with increasing age. Various factors, including parental educational level, father's employment status, and medication treatment plans, may be associated with children's HRQoL. Additionally, there is a correlation between children's HRQoL and their caregivers' HRQoL. Nearly 70% of caregivers reported experiencing a significant burden due to the responsibilities of caring for children with INS. We found that the health-related quality of life (HRQOL) of children aged 2 to 4 years was superior to that reported for healthy children in the existing literature ( 25 ). This discrepancy may be attributed to the relatively small sample sizes in both our study (n = 35) and the referenced study (n = 36) ( 25 ). Additionally, the referenced study was conducted in 2005, which may not accurately reflect the current HRQOL profile of Chinese children aged 2–4 years ( 25 ). Our study found HRQOL of children aged 2 to 4 years in our study was better than that reported for healthy children in the existing literature ( 25 ). This discrepancy may be attributed to the relatively small sample size of children in both our study (n = 35) and the referenced study (n = 36) ( 25 ). Additionally, the referenced study was conducted in 2005, which may not accurately reflect the current HRQOL profile of Chinese children aged 2–4 years ( 25 ). Furthermore, the clinical stage and duration of INS may also impact children’s HRQOL. Roussel et al. demonstrated that HRQOL scores for children with steroid-dependent nephrotic syndrome and steroid-resistant nephrotic syndrome were elevated and nearly comparable to those of children without chronic illness ( 8 ). This finding is attributed to the fact that the study populations were in a stable remission period, which is associated with higher HRQOL scores. Similarly, children aged 2 to 4 years experienced a relatively short duration of the disease and a lower frequency of relapse, potentially resulting in a quality of life comparable to that of the general population. Our study found HRQOL of children aged 5 to 18 years in our study to be worse than that reported for healthy children in the existing literature ( 25 ), which is consistent with previous studies ( 4 , 9 , 11 , 17 , 29 ). Selewski et al. observed that INS children exhibited lower scores on measures of social and school functioning. Similarly, a study conducted in India involving 102 patients revealed that their scores in physical, social, and school functioning were significantly lower compared to those of healthy children, with school functioning being the most adversely affected ( 4 , 17 ). Additionally, a recent study from the Netherlands indicated that children aged 8 to 18 years experienced a notable decline in scores related to physical and emotional functioning, as well as in the overall HRQoL ( 29 ). These discrepancies may be attributable to variations in cultural contexts, healthcare systems across different nations, and the stage and relapse frequency of the disease in patients ( 7 , 11 , 20 ). In our study, the scores for emotional functioning, school functioning, psychosocial health summary, and the overall total were higher when fathers completed the questionnaire compared to when mothers did. This discrepancy may be attributed to fathers' lower emotional sensitivity, which could result in a relatively more optimistic outlook and reduced anxiety. It is noteworthy that the score for physical functioning did not reach statistical significance. This phenomenon could be attributed to the objective nature of the physical functioning questions in the PedsQL GCM. Our findings aligned with previous research, which also indicated that caregivers who completed the questionnaire reported similar outcomes ( 30 ). Our findings indicate that children’s HRQoL is significantly better, both at the scale level and overall, when their parents possess higher educational attainment and are employed. This observation aligns with the earlier study by ( 31 ), which demonstrated a positive correlation between paternal education and proxy-reported HRQoL. It is plausible that families with relatively higher socioeconomic status are better equipped to offer the necessary support for managing the care of ill children, thereby contributing to an enhanced HRQoL. Remarkably, we identified that when fathers were unemployed, children's HRQoL was significantly impaired across all scales and at the overall level, with the effect size indicating moderate to large differences. Even after adjusting for other covariates, this variable remained statistically significant in the regression model. Considering the social and cultural context of China, paternal unemployment can have a substantial impact on the family, particularly in medical decision-making. In this study, children with newly diagnosed INS exhibited higher scores in social functioning, psychosocial health summary, and overall PedsQL GCM scores. This observation is attributed to their early stage of the disease, during which they experienced relatively minimal adverse effects from treatment and pain. Conversely, patients experiencing disease recurrence and prolonged duration demonstrated a significantly diminished quality of life compared to those with initial onset, with the effect size approaching a moderate level. Our findings are consistent with previous studies that have documented the adverse effects of relapse on HRQoL ( 4 , 9 , 11 , 17 , 29 ). Furthermore, our study indicates that social and psychosocial functioning are particularly impacted by relapse. This phenomenon may be attributed to the necessity for frequent hospital visits, reduced social interaction, the cumulative psychological impact of complications such as edema, obesity, and hirsutism, and the resultant isolation from peers ( 11 , 17 , 20 ). Regarding pharmacological interventions, our study found that patients on a steroid-exclusive regimen were reported a higher quality of life compared to those who used oral immunosuppressive drugs (OID) and/or rituximab (RTX). This association remained statistically significant even after adjusting for covariates. This observation is plausible, as children treated with only steroids most likely were in the initial stages of the disease and experienced less disease-related pain and fewer complications. Children undergoing treatment with OID or RTX required frequent hospitalizations and experienced the discomfort associated with RTX infusions, which adversely impacted their emotional well-being and reduced their time for social interactions and school activities. Strengths and limitations This study exhibits several strengths. Firstly, it investigates the HRQoL of children with INS in China, encompassing a relatively large sample size of patients aged 2 to 18 years. Notably, the study employs specialized PedsQL GCM scales for children aged 2 to 4 years, thereby enhancing the evaluation of quality of life in this younger age cohort. Secondly, we conducted a thorough assessment of a wide range of potential influencing factors to enhance the understanding of health status and medical care among children with INS. Additionally, we employed effect size metrics, specifically Cohen’s d and η p ², to evaluate the clinical relevance of differences in HRQoL scores across subgroups. This approach addresses the limitations of relying solely on statistical significance. However, the study presents several limitations that warrant attention. Firstly, it is a single-center study lacking large-sample standard data of Chinese children as a healthy control group. Secondly, the cross-sectional design precludes follow-up quality of life (QOL) measurements over time, thereby limiting the ability to establish causality. Additionally, even though the previous study showed strong agreement that the proxy-reported questionnaire is reliable ( 17 ), incorporating both proxy- and self-reported outcomes may provide more comprehensive insights. Conclusion This study evaluated the HRQoL of children aged 2–18 years diagnosed with INS in China, along with the HRQoL and caregiving burden of their caregivers. The findings indicate a decline in children's HRQoL with increasing age, potentially influenced by factors such as parental education, paternal employment status, and medication regimens. A significant correlation was observed between the HRQoL of the children and that of their caregivers, who frequently experience varying levels of caregiving burden. Therefore, it is recommended that healthcare professionals prioritize the optimization of HRQoL for both children with INS and their caregivers. Abbreviations HRQoL - Health-related Quality of Life INS - Idiopathic Nephrotic Syndrome PedsQL GCM - Pediatric Quality of Life Inventory Generic Core Module EQ-5D-5L - EuroQol five-dimensional questionnaire, five-level version OID - Oral Immunosuppressive Drugs RTX - Rituximab SS - Steroid-Sensitive SR - Steroid-Resistant CNI - Calcineurin Inhibitors BMI - Body Mass Index ZBI - Zarit Burden Interview VAS - Visual Analogue Scale SPSS - Statistical Package for the Social Sciences SD - Standard Deviation ANOVA - Analysis of Variance CI - Confidence Interval RMB - Renminbi (Chinese currency) Declarations Ethics approval and consent to participate: The study protocol was conducted according to the Declaration of Helsinki, and was approved by the Medical Ethics Committee of the Children's Hospital, Zhejiang University School of Medicine (2023-IRB-190). All caregivers gave their consents and voluntarily participated in the study. Consent for publication: not applicable. Availability of data and materials: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Competing interests: The authors declare that they have no competing interests. Funding: There is no funding related to the present study. Authors' contributions: Xia Wang, Jianhua Mao and Guannan Bai were involved in the study conceptualization and design. Xia Wang, Jingjing Wang, Chunyue Feng, Haidong Fu, Huijun Shen, and Xiujuan Zhu collected data. Lejing Guan and Yifei Shao carried out statistical analyses and prepared all the tables /figures. and G.B. wrote the main manuscript texts. Abdul Rafay prepared the supplementary tables. Xia Wang, Danny Junyi Tan and Guannan Bai wrote the first draft of this manuscript. Jianhua Mao and Guannan Bai supervised the whole project. All authors reviewed the manuscript and provided critical revisions of the article for important intellectual content. All the authors contributed to the interpretation of the data and approved the article's final version. Acknowledgements: We gratefully thank all the INS patients and their families who were willing to participate in this study. We thank the Pediatric Evidence-based Medical and Clinical Research Laboratory, an internal institute of the National Clinical Research Center for Child Health, for the great support in terms of methodology and data analysis. References Noone DG, Iijima K, Parekh R. Idiopathic nephrotic syndrome in children. The Lancet. 2018;392(10141):61-74. Zhu H, Qi J, Schoepf J, Savage RH, Tang C, Lu M, et al. Prevalence and associated risk factors of pulmonary embolism in children and young adults with nephrotic syndrome: a Chinese large cohort study. Journal of Thoracic Imaging. 2021;36(5):326-32. Gipson DS, Massengill SF, Yao L, Nagaraj S, Smoyer WE, Mahan JD, et al. Management of childhood onset nephrotic syndrome. Pediatrics. 2009;124(2):747-57. Selewski DT, Troost JP, Massengill SF, Gbadegesin RA, Greenbaum LA, Shatat IF, et al. The impact of disease duration on quality of life in children with nephrotic syndrome: a Midwest Pediatric Nephrology Consortium study. Pediatric Nephrology. 2015;30:1467-76. Eddy AA, Symons JM. Nephrotic syndrome in childhood. The lancet. 2003;362(9384):629-39. Gipson DS, Selewski DT, Massengill SF, Wickman L, Messer KL, Herreshoff E, et al. Gaining the PROMIS perspective from children with nephrotic syndrome: a Midwest pediatric nephrology consortium study. Health Qual Life Outcomes. 2013;11:30. Khullar S, Banh T, Vasilevska-Ristovska J, Chanchlani R, Brooke J, Licht CPB, et al. Impact of steroids and steroid-sparing agents on quality of life in children with nephrotic syndrome. Pediatr Nephrol. 2021;36(1):93-102. Roussel A, Delbet JD, Micheland L, Deschênes G, Decramer S, Ulinski T. Quality of life in children with severe forms of idiopathic nephrotic syndrome in stable remission-A cross-sectional study. Acta Paediatr. 2019;108(12):2267-73. Abbasi A, Valizadeh M, Fahimi D, Moghtaderi M, Bazargani B, Mojtahedi SY, et al. Heath-Related Quality of Life in Iranian Children with Nephrotic Syndrome. Iranian Journal of Pediatrics. 2022;32(2). Centers for Disease Control and Prevention. Health-Related Quality of Life (HRQOL). Centers for Disease Control and Prevention. 2021. Eid R, Fathy AA, Hamdy N. Health-related quality of life in Egyptian children with nephrotic syndrome. Quality of Life Research. 2020;29:2185-96. Assadi F. Psychological impact of chronic kidney disease among children and adolescents: Not rare and not benign. Journal of nephropathology. 2013;2(1):1. Gerson AC, Wentz A, Abraham AG, Mendley SR, Hooper SR, Butler RW, et al. Health-related quality of life of children with mild to moderate chronic kidney disease. Pediatrics. 2010;125(2):e349-e57. McKenna AM, Keating LE, Vigneux A, Stevens S, Williams A, Geary DF. Quality of life in children with chronic kidney disease—patient and caregiver assessments. Nephrology Dialysis Transplantation. 2006;21(7):1899-905. Mujais SK, Story K, Brouillette J, Takano T, Soroka S, Franek C, et al. Health-related quality of life in CKD patients: correlates and evolution over time. Clinical Journal of the American Society of Nephrology. 2009;4(8):1293-301. Manti P, Giannakopoulos G, Giouroukou E, Georgaki-Angelaki H, Stefanidis CJ, Mitsioni A, et al. Psychosocial and cognitive function in children with nephrotic syndrome: association with disease and treatment variables. BioPsychoSocial medicine. 2013;7:1-7. Mazahir R, Anand K, Pruthi P. Quality of life in children with nephrotic syndrome: a cross-sectional study using Hindi version of PedsQL 4.0 Generic Core Scales. Clinical and Experimental Nephrology. 2022;26(6):552-60. Rahman M, Afroz S, Ali R, Hanif M. Health Related Quality of Life in Children with Nephrotic Syndrome in Bangladesh. Mymensingh medical journal: MMJ. 2016;25(4):703-9. Rüth E-M, Landolt MA, Neuhaus TJ, Kemper MJ. Health-related quality of life and psychosocial adjustment in steroid-sensitive nephrotic syndrome. The Journal of pediatrics. 2004;145(6):778-83. Allam N, Bashar A, Eid R. Assessment of health-related quality of life in Sudanese children with nephrotic syndrome: a questionnaire-based study. Pan African Medical Journal. 2022;43(1). Imani PD, Aujo J, Kiguli S, Srivaths P, Brewer ED. Chronic kidney disease impacts health-related quality of life of children in Uganda, East Africa. Pediatric Nephrology. 2021;36:323-31. Li N, Hao J, Fu T, Du Y. Evaluating the Quality of Life of 231 Children With Primary Nephrotic Syndrome and Assessing Parental Awareness of the Disease. Front Pediatr. 2021;9:745444. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. Jama. 2013;310(20):2191-4. Bédard M, Molloy DW, Squire L, Dubois S, Lever JA, O'Donnell M. The Zarit Burden Interview: a new short version and screening version. Gerontologist. 2001;41(5):652-7. Chan LF, Chow SM, Lo SK. Preliminary validation of the Chinese version of the Pediatric Quality of Life Inventory. International Journal of Rehabilitation Research. 2005;28(3):219-27. Hao Y, Tian Q, Lu Y, Chai Y, Rao S. Psychometric properties of the Chinese version of the Pediatric Quality of Life Inventory™ 4.0 generic core scales. Quality of Life Research. 2010;19:1229-33. Cohen J. Statistical power analysis for the behavioral sciences: routledge; 2013. Luo N, Liu G, Li M, Guan H, Jin X, Rand-Hendriksen K. Estimating an EQ-5D-5L Value Set for China. Value Health. 2017;20(4):662-9. Veltkamp F, Teela L, Luijten MA, van Oers HA, Mak-Nienhuis EM, Haverman L, et al. Health-related quality of life of children with first onset steroid-sensitive nephrotic syndrome. European Journal of Pediatrics. 2023;182(10):4605-14. Mishra K, Ramachandran S, Firdaus S, Rath B. The impact of pediatric nephrotic syndrome on parents′ health-related quality of life and family functioning: An assessment made by the PedsQL 4.0 family impact module. Saudi journal of kidney diseases and transplantation. 2015;26(2):285-92. Didsbury MS, Kim S, Medway MM, Tong A, McTaggart SJ, Walker AM, et al. Socio‐economic status and quality of life in children with chronic disease: A systematic review. Journal of paediatrics and child health. 2016;52(12):1062-9. Additional Declarations No competing interests reported. Supplementary Files AdditionalFileSupplementaryTableS1.docx AdditionalFileSupplementaryTableS2.docx AdditionalFileSupplementaryTableS3.docx AdditionalFileSupplementaryTableS4.docx AdditionalFileSupplementaryTableS5.docx AdditionalFileSupplementaryTableS6.docx Cite Share Download PDF Status: Published Journal Publication published 29 Oct, 2024 Read the published version in Health and Quality of Life Outcomes → Version 1 posted Editorial decision: Revision requested 22 Sep, 2024 Reviews received at journal 22 Sep, 2024 Reviews received at journal 18 Sep, 2024 Reviews received at journal 12 Sep, 2024 Reviewers agreed at journal 09 Sep, 2024 Reviewers agreed at journal 08 Sep, 2024 Reviewers agreed at journal 02 Sep, 2024 Reviewers invited by journal 26 Aug, 2024 Editor assigned by journal 16 Aug, 2024 Submission checks completed at journal 16 Aug, 2024 First submitted to journal 16 Aug, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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EQ-5D-5L\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-4922299/v1/ce19d1dea854dbdf4bbfb85f.png"},{"id":66540985,"identity":"83a736fc-fd43-4b3e-9412-0f32071b52ae","added_by":"auto","created_at":"2024-10-14 07:41:00","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":927524,"visible":true,"origin":"","legend":"\u003cp\u003eSpecific Caregiver’s burden due to taking care of children with INS. (A) Frequency of four specific caregiver’s burden. Question 1: “Do you feel that being with your child means you don't have enough time for yourself”, Question 2:“Do you feel stressed to take care of your child while also striving to balance other family or work responsibilities”, Question 3:“Do you feel that taking care of children has affected your own health”, Question 4: “Do you feel that apart from other personal expenses, you do not have enough money to take care of your child”; (B). Frequency of overall rating of caregiver’s burden\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-4922299/v1/91d360e293e3c478b9fc2745.png"},{"id":68206328,"identity":"98ade241-5c1e-4dc8-9f06-d6307bd823f6","added_by":"auto","created_at":"2024-11-04 16:30:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2525675,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4922299/v1/f45005d1-81b6-419b-a4e4-e1cb8b3f2b38.pdf"},{"id":66539543,"identity":"f3c08987-20e0-497d-916b-58c7f8ed9882","added_by":"auto","created_at":"2024-10-14 07:33:00","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":18031,"visible":true,"origin":"","legend":"","description":"","filename":"AdditionalFileSupplementaryTableS1.docx","url":"https://assets-eu.researchsquare.com/files/rs-4922299/v1/7e88143a5764d9c081db7a86.docx"},{"id":66539542,"identity":"b12ece30-0006-4416-8233-7fcec5395692","added_by":"auto","created_at":"2024-10-14 07:33:00","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":19655,"visible":true,"origin":"","legend":"","description":"","filename":"AdditionalFileSupplementaryTableS2.docx","url":"https://assets-eu.researchsquare.com/files/rs-4922299/v1/117c5340390541ece10b03d5.docx"},{"id":66539545,"identity":"8bf48590-2806-4e85-a972-b96033cdc525","added_by":"auto","created_at":"2024-10-14 07:33:00","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":24700,"visible":true,"origin":"","legend":"","description":"","filename":"AdditionalFileSupplementaryTableS3.docx","url":"https://assets-eu.researchsquare.com/files/rs-4922299/v1/c1e870bdec340fe8767b174d.docx"},{"id":66539547,"identity":"9ae014b3-d52f-4a75-af3f-59153e90d0e9","added_by":"auto","created_at":"2024-10-14 07:33:00","extension":"docx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":18166,"visible":true,"origin":"","legend":"","description":"","filename":"AdditionalFileSupplementaryTableS4.docx","url":"https://assets-eu.researchsquare.com/files/rs-4922299/v1/84f7225979e4c1efa9a14179.docx"},{"id":66540986,"identity":"720c42b2-2853-4bbd-b73e-0ddbac09a7d2","added_by":"auto","created_at":"2024-10-14 07:41:00","extension":"docx","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":18911,"visible":true,"origin":"","legend":"","description":"","filename":"AdditionalFileSupplementaryTableS5.docx","url":"https://assets-eu.researchsquare.com/files/rs-4922299/v1/393cd6d04bf2620533040e07.docx"},{"id":66541460,"identity":"231576e0-32d9-4e5d-8982-10fa5473382f","added_by":"auto","created_at":"2024-10-14 07:49:00","extension":"docx","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":16874,"visible":true,"origin":"","legend":"","description":"","filename":"AdditionalFileSupplementaryTableS6.docx","url":"https://assets-eu.researchsquare.com/files/rs-4922299/v1/f8a0449ad42048a5ac9f3017.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Assessment of Health-related Quality of Life of Children with Idiopathic Nephrotic Syndrome and their caregivers in China","fulltext":[{"header":"Background","content":"\u003cp\u003eNumerous glomerular disorders in pediatric populations present as nephrotic syndrome, with a majority being idiopathic in origin. Idiopathic Nephrotic Syndrome (INS), a common manifestation of chronic kidney disease, represents a major cause of morbidity and mortality globally among children and young adults (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). INS is clinically defined by the triad of proteinuria, hypoalbuminemia, and edema (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). The incidence of INS ranges from 1.15 to 16.9 per 100,000 children, with variations observed across different races and geographical regions (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Clinical manifestations in children can range from mild to severe, with unpredictable patterns of relapse and remission (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). The standard initial therapeutic intervention typically involves the administration of glucocorticoids. INS is frequently categorized based on the clinical response to steroid treatment into steroid-sensitive (SS) and steroid-resistant (SR) forms. In cases where the disease is SR or in instances of relapse, the use of oral immunosuppressive drugs (OID) may be required for certain pediatric patients (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). The extended treatment duration and propensity for relapse of INS have significant implications for the health-related quality of life of affected children and their families (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). The prolonged duration of treatment and the tendency for relapse in INS have considerable implications for the health-related quality of life of affected children and their families.\u003c/p\u003e \u003cp\u003eHealth-related quality of life (HRQoL) encompasses multiple dimensions, including physical, psychological, and social aspects related to health. This concept serves as a critical indicator, complementing traditional health outcomes such as morbidity and mortality (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). HRQoL is influenced by both individual and environmental characteristics (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Impaired HRQoL in children with INS has been well-documented in previous studies (\u003cspan additionalcitationids=\"CR12 CR13 CR14\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Factors associated with HRQoL include the duration of INS, gender, race, socioeconomic status, frequency of relapse, steroid resistance, and the use of calcineurin inhibitors (CNI) (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan additionalcitationids=\"CR17 CR18\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). However, the majority of these studies have been conducted in developed countries, with limited data available from developing countries. A review of the literature reveals studies on the HRQoL of children with INS from Sudan, Egypt, India, Iran, and one study from China (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan additionalcitationids=\"CR21\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). Furthermore, prior research has been constrained by relatively small sample sizes, especially among younger children, which has led to an incomplete understanding of the current status and determinants affecting the quality of life of Chinese children with INS. Additionally, there is a paucity of data concerning the quality of life of caregivers of patients with INS.\u003c/p\u003e \u003cp\u003eTherefore, we conducted this study to evaluate the HRQoL of pediatric patients diagnosed with INS and their caregivers. The primary objective was to characterize the HRQoL and identify the associated factors among children aged 2 to 18 years in China with INS. Additionally, we aimed to assess the HRQoL of caregivers and investigate the correlation between children\u0026rsquo;s HRQoL and the HRQoL of their caregivers.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and participants\u003c/h2\u003e \u003cp\u003e This was a cross-sectional, questionnaire-based survey that was led by the Department of Child Health Care and Department of Nephrology in Children's Hospital, Zhejiang University School of Medicine. Participants were recruited from both outpatient and inpatient populations at the hospital where the study was conducted, as well as from an online community facilitated through a WeChat group designed for clinician-patient communication. WeChat, a multifunctional Chinese application, supports instant messaging, social media interaction, and payment services. The WeChat group served as a significant adjunct to healthcare by disseminating disease-related knowledge and family care skills to caregivers, thereby providing them with both professional and peer support.\u003c/p\u003e \u003cp\u003eThe inclusion criteria for the study encompassed children who (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) had been diagnosed with idiopathic nephrotic syndrome and (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) were under 18 years of age. The exclusion criteria comprised children who (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) had significant physical or psychiatric disorders and (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) whose caregivers were unable to comprehend and complete the questionnaire. Primary caregivers, who were well-acquainted with the children's health status, were invited to participate in the survey. This online survey was administered from January to August 2024. Ultimately, caregivers of 181 patients with idiopathic nephrotic syndrome completed the questionnaire.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eEthical approval\u003c/strong\u003e \u003cp\u003e \u003cb\u003estatements\u003c/b\u003e \u003c/p\u003e \u003c/p\u003e \u003cp\u003eThis study was conducted according to the Declaration of Helsinki (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e), and was approved by the Medical Ethics Committee of the Children's Hospital, Zhejiang University School of Medicine (2024-IRB-190). All caregivers gave their consents to participate in the study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eData collection\u003c/h2\u003e \u003cp\u003eAn expert panel was convened to develop the questionnaire, comprising three senior clinicians (XW, JW, and JM) and one clinical epidemiologist (GB). The questionnaire was drafted following two rounds of discussion, informed by a review of the literature and expert opinions. Subsequently, a pre-test pilot was conducted with 20 caregivers of children with INS. Additionally, brief face-to-face interviews were conducted with 8 caregivers post-pilot to gather their feedback and suggestions.A revised version of the electronic questionnaire was ultimately employed for this study, comprising four sections: general characteristics, disease- and treatment-related characteristics, health-related quality of life of children, and health-related quality of life of caregivers. The electronic questionnaire was developed and visualized by two research assistants (LG and YS) utilizing Wenjuanxing (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.wjx.cn/\u003c/span\u003e\u003cspan address=\"https://www.wjx.cn/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e), a widely-used online platform for creating survey questionnaires. We produced and disseminated posters featuring the QR code throughout the clinics and wards of the Department of Nephrology at the hospital where the study was conducted. Additionally, the QR code was distributed through the WeChat group. Clinicians participating in this study provided detailed explanations of its objectives to caregivers, ensuring comprehensive understanding prior to obtaining their informed consent for participation.\u003c/p\u003e \u003cp\u003eGeneral characteristics encompass socio-demographic factors, such as children's age and gender, parental education, household income, marital status, and employment status, as well as medical insurance. Clinical characteristics include the onset time of idiopathic nephrotic syndrome (INS), disease duration, patient type (i.e., inpatient or outpatient), complications (e.g., hematuria, hypertension), and prescribed medications.\u003c/p\u003e \u003cp\u003eChildren's health-related quality of life (HRQOL) was assessed using the proxy-reported PedsQL\u0026trade; 4.0 Generic Core Module (PedsQL\u0026trade; 4.0 GCM). Prior to data collection, authorization to use this instrument was obtained through a request on the Mapi Research Trust website (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://eprovide.mapi-trust.org/instruments/pediatric-quality-of-life-inventory\u003c/span\u003e\u003cspan address=\"https://eprovide.mapi-trust.org/instruments/pediatric-quality-of-life-inventory\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e), which allowed us to download the PedsQL\u0026trade; without a license fee for unfunded research. The proxy-reported PedsQL\u0026trade; 4.0 GCM is administered to evaluate HRQOL in children and adolescents aged 2\u0026ndash;18 years. For children aged 2 to 4 years, the instrument comprises 21 items distributed across four scales: physiological functioning (eight items), emotional functioning (five items), social functioning (five items), and school functioning (three items). In contrast, the instrument designed for children aged 5 to 18 years includes 23 items, also organized into four scales: physiological functioning (eight items), emotional functioning (five items), social functioning (five items), and school functioning (five items). Each item is presented with five response options on a scale ranging from 0 to 4, where 0 indicates \"never a problem,\" 1 indicates \"seldom a problem\", 2 indicates \"sometimes a problem\", 3 indicates \"often a problem\", and 4 indicates \"always a problem\". To standardize these items on a 0\u0026ndash;100 scale, a linear transformation is applied as follows: 0 is transformed to 0, 1 to 25, 2 to 50, 3 to 75, and 4 to 100. Scale scores and total scores are computed by summing the item scores and dividing by the number of items responded to. A higher score reflects a better HRQoL. The instrument was previously validated in China, demonstrating satisfactory reliability and validity (Chen et al., 2011; Ji et al., 2011). In the current study, we computed Cronbach\u0026rsquo;s alpha coefficients, with the results detailed in Supplementary Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003eThe health-related quality of life of caregivers was assessed utilizing the five-level EuroQol five-dimensional questionnaire (EQ-5D-5L). The EQ-5D descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, each rated on a five-level scale ranging from no problems to extreme problems. Furthermore, the EQ visual analogue scale (EQ-VAS), which spans from 0 (indicating the worst imaginable health) to 100 (indicating the best imaginable health), was employed to evaluate the overall health perception of the respondent completing the questionnaire. In addition, we selected five question items from Zarit Caregiver Burden Interview (ZBI) (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e) to measure specific caregiver\u0026rsquo;s burden due to taking care children with INS. The five questions are (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) \u0026ldquo;Do you feel that being with your child means you don't have enough time for yourself\u0026rdquo;, (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) \u0026ldquo;Do you feel stressed to take care of your child while also striving to balance other family or work responsibilities\u0026rdquo;, (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) \u0026ldquo;Do you feel that taking care of children has affected your own health\u0026rdquo;, (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) \u0026ldquo;Do you feel that apart from other personal expenses, you do not have enough money to take care of your child\u0026rdquo;, and (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) \u0026ldquo;Overall, how much burden do you think it is to take care of your child\u0026rdquo;.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eInitially, descriptive analysis was conducted to compute means and standard deviations (SDs) for continuous variables exhibiting a normal distribution, and medians with interquartile ranges for continuous variables with a non-normal distribution. For categorical variables, frequencies and percentages were determined. Subsequently, the mean scores of the scales and the overall score of the PedsQL 4.0 Generic Core Scales (GCS) were compared with the corresponding scores of age-matched healthy children as reported in the extant literature (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). Next, we employed two-independent-samples t-tests and one-way ANOVA to evaluate the differences in mean scores of the scales and the overall score of the PedsQL 4.0 GCM across various subgroups. Despite achieving statistical significance, we additionally calculated effect sizes, i.e., Cohen's d and partial eta squared (η\u003csub\u003ep\u003c/sub\u003e\u003csup\u003e2\u003c/sup\u003e), to evaluate the clinical relevance of our findings. Cohen's d is calculated as the absolute value of the difference in mean scores between two groups divided by the largest standard deviation. The interpretation of Cohen's d is as follows: 0.2\u0026thinsp;\u0026le;\u0026thinsp;d\u0026thinsp;\u0026lt;\u0026thinsp;0.5 indicates a small effect size, 0.5\u0026thinsp;\u0026le;\u0026thinsp;d\u0026thinsp;\u0026lt;\u0026thinsp;0.8 indicates a moderate effect size, and d\u0026thinsp;\u0026ge;\u0026thinsp;0.8 indicates a large effect size (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). η\u003csub\u003ep\u003c/sub\u003e\u003csup\u003e2\u003c/sup\u003e was calculated to estimate the effect size of a difference across three or more subgroups. Effect sizes are indicated as 0.01\u0026thinsp;\u0026le;\u0026thinsp;η\u003csub\u003ep\u003c/sub\u003e\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.06 indicates a small difference, 0.06\u0026thinsp;\u0026le;\u0026thinsp;η\u003csub\u003ep\u003c/sub\u003e\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.14 indicates a moderate difference, and η\u003csub\u003ep\u003c/sub\u003e\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;\u0026ge;\u0026thinsp;0.14 indicates a large difference. Finally, variables that demonstrated statistical significance were subsequently incorporated into the multivariate linear regression models to assess the independent associated factors of HRQoL of INS children.\u003c/p\u003e \u003cp\u003eRegarding caregiver\u0026rsquo;s HRQoL, we calculated proportions of reported caregiver burden across the five dimensions and the utility score of the EQ-5D-5L based on the value set of Chinese adult population (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). The means and standard deviations (SD) of the utility score and EQ-VAS scores were utilized to evaluate overall health-related quality of life. The relationships between the scale scores and total scores of the PedsQL 4.0 Generic Core Scales (GCS) with the utility score and EQ-VAS score were analyzed using Pearson correlation analysis. In addition, we calculated the proportions reported caregiver\u0026rsquo;s burden across five questions from ZBI.\u003c/p\u003e \u003cp\u003eAll the statistical analyses were conducted by using SPSS version 27.0 (SPSS Inc., Chicago, USA). The statistical significance was indicated when p value\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e3.1. General characteristics of the study population\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e presents the general characteristics of the study population. The median age of children was 4.0 years, and 68.5% were boys. Mothers filled out 76.2% of the questionnaires. 37.6% of mothers and 42.5% of fathers had a high educational level, i.e., a bachelor\u0026rsquo;s degree or above. 37.6% of families lived in urban areas. Additionally, 82.9% of the parents had someone at home to care for the sick child. 81.8% of children had health insurance.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eGeneral and clinical characteristic of children with idiopathic nephrotic syndrome (n\u0026thinsp;=\u0026thinsp;181)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eValues*\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge of the child, year\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4.0 [4.0, 5.0]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge groups\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u0026ndash;4 years old\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e35 (19.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u0026ndash;7 years old\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e59 (32.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u0026ndash;12 years old\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e50 (27.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e13\u0026ndash;18 years old\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e37 (20.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBoys\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e124 (68.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGirls\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e57 (31.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCurrent weight of the child, kilogram (kg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e25.00 [18.05, 43.00]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCurrent Height, centimeter (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e122.00 [108.00, 149.50]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m\u0026sup2;)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16.41 [14.79, 20.20]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCaregiver who filled out the questionnaire\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMother\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e138 (76.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFather and others\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e43 (23.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal educational level\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiddle school or lower\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e65 (35.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHigh school\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e48 (26.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBachelor degree or higher\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e68 (37.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePaternal educational level\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiddle school or lower\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e56 (31.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHigh school\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e48 (26.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBachelor degree or higher\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e77 (42.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEmployment of mother\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e130 (71.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e51 (28.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEmployment of father\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e172 (95.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9 (5.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnnual household income (RMB)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLess than 100,000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e95 (52.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e100,000 to 200,000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e35 (19.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMore than 200,000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e51 (28.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParental marital status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMarried\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e175 (96.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDivorced\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6 (3.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eResidence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrban\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e68 (37.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTown or rural\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e113 (62.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHaving a health insurance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e33 (18.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e148 (81.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHaving someone at home to take care of the sick child\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e150 (82.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e31 (17.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHaving a sibling or siblings\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e110 (60.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e71 (39.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003e*\u003c/b\u003e Values presented in this table presents medians, interquatile ranges, numbers, and percentages.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e3.2. Clinical characteristics of the study population\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e presents a summary of the clinical characteristics of the study population. The median age at disease onset was 3.7 years, which was also the median age at diagnosis of INS. At the time of this study, 29.8% of the children were making their initial hospital visit. Over the last six months, the median number of visits to a tertiary hospital was 2. The prevalence of hematuria, renal insufficiency, and hypertension among the participants was 5.0%, 9.9%, and 6.1%, respectively. Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e summarizes clinical characteristics of the study population. The median age of disease onset was 3.7 years, and the median age of having the diagnosis of INS was 3.7 years. 29.8% of children visited the hospital when this study was conducted for the first time. In the last six months, the median of times of visiting a tertiary hospital was 2. The percentage of presenting blood in urine, renal insufficiency and high blood pressure was 5.0%, 9.9%, and 6.1%, respectively. In the study, 27.6% of children were treated exclusively with steroids. Additionally, 48.6% utilized oral immunosuppressive drugs (OID), 28.2% received rituximab (RTX), and 28.2% were administered other medications. Notably, 71.3% of caregivers expressed that their primary concern regarding idiopathic nephrotic syndrome (INS) was its incurability.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical characteristics of children with idiopathic nephrotic syndrome (n\u0026thinsp;=\u0026thinsp;181)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eValues *\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge of onset of INS (year)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.7 (2.3, 8.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge of diagnosis of INS (year)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.7 (2.3 ,7.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFirst-time visit of the hospital, yes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54 (29.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of visiting tertiary hospitals in the last 6 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (1, 3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresence of hematuria, yes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (5.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRenal insufficiency, yes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (9.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresence of hypertension, yes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (6.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOnly using the steroid, yes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50 (27.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedications used for treatment except for steroid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOral immunosuppressive drug\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e88 (48.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRituximab\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51 (28.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther medications\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51 (28.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImmunosuppressive medications used for treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLevamisole\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMycophenolate mofetil\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41 (22.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCyclophosphamide\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (2.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTacrolimus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e58 (32.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCyclosporine A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (3.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (2.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimary concern regarding illness perceived by parents\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNephrotic syndrome cannot be cured\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e129 (71.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThe physical discomforts caused by INS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (6.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePsychological problems caused by INS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (4.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConcerns about adverse effects of medications\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (6.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConcerns about sequelae\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (5.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThe negative impact of illness on children's education\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (1.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePsychological problems of caregivers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThe financial burden due to the disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (3.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther concerns\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003e*\u003c/b\u003e Values presented in this table are medians, interquatile ranges, numbers, and percentages.\u003c/p\u003e \u003cp\u003e \u003cb\u003e3.3. Scales scores and total scores of PedsQL GCM in INS children at different age groups\u003c/b\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e presents the means and standard deviations of scale scores and total scores of PedsQL GCM in INS children at different age groups in our study. Children aged 13\u0026ndash;18 years had significantly lower scores in all scales as well as lower total score compared with scores at other age groups (p values\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The effect sizes ranged from 0.044 to 0.338.\u003c/p\u003e \u003cp\u003eIn addition, we compared the mean scores of PedsQL GCM in our study population with the published scores from healthy children at the same age (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). The results are presented in the Supplementary Table \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003e. For children aged 2 to 4 years, both the total score and the average of scale scores were significantly higher than the averages of the healthy controls (\u003cem\u003ep\u003c/em\u003e values\u0026thinsp;\u0026lt;\u0026thinsp;0.05) except for the mean score of school functioning (p\u0026thinsp;=\u0026thinsp;0.121). For children aged 5 to 18 years, the averages of scale scores and the total score were significantly lower than the averages of the healthy controls (\u003cem\u003ep\u003c/em\u003e values\u0026thinsp;\u0026lt;\u0026thinsp;0.05) except for the mean score of social functioning scale (p\u0026thinsp;=\u0026thinsp;0.171) .\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e。 \u003cb\u003eMeans and standard deviations of scales and total scores of PedsQL GCM among children with idiopathic nephrotic syndrome at different age groups (n\u0026thinsp;=\u0026thinsp;181)\u003c/b\u003e\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u0026ndash;4 years (n\u0026thinsp;=\u0026thinsp;35)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5\u0026ndash;7 years (n\u0026thinsp;=\u0026thinsp;59)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8\u0026ndash;12 years (n\u0026thinsp;=\u0026thinsp;50)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13\u0026ndash;18 years (n\u0026thinsp;=\u0026thinsp;37)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eEffect size\u003c/p\u003e \u003cp\u003e(η\u003csub\u003ep\u003c/sub\u003e\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhysical functioning\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e89.20\u0026thinsp;\u0026plusmn;\u0026thinsp;14.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e75.37\u0026thinsp;\u0026plusmn;\u0026thinsp;17.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e53.64\u0026thinsp;\u0026plusmn;\u0026thinsp;15.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e70.61\u0026thinsp;\u0026plusmn;\u0026thinsp;21.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.338\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEmotional functioning\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e82.29\u0026thinsp;\u0026plusmn;\u0026thinsp;20.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e72.80\u0026thinsp;\u0026plusmn;\u0026thinsp;18.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e74.50\u0026thinsp;\u0026plusmn;\u0026thinsp;21.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e68.11\u0026thinsp;\u0026plusmn;\u0026thinsp;27.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.048\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.044\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSocial functioning\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e90.86\u0026thinsp;\u0026plusmn;\u0026thinsp;12.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e83.56\u0026thinsp;\u0026plusmn;\u0026thinsp;19.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e84.70\u0026thinsp;\u0026plusmn;\u0026thinsp;15.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e62.25\u0026thinsp;\u0026plusmn;\u0026thinsp;18.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.255\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSchool functioning\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e84.13\u0026thinsp;\u0026plusmn;\u0026thinsp;24.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e69.75\u0026thinsp;\u0026plusmn;\u0026thinsp;16.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e73.30\u0026thinsp;\u0026plusmn;\u0026thinsp;18.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e65.27\u0026thinsp;\u0026plusmn;\u0026thinsp;26.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.010\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.067\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePsychosocial Health Summary Score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e86.72\u0026thinsp;\u0026plusmn;\u0026thinsp;18.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e75.17\u0026thinsp;\u0026plusmn;\u0026thinsp;14.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e77.47\u0026thinsp;\u0026plusmn;\u0026thinsp;15.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e65.35\u0026thinsp;\u0026plusmn;\u0026thinsp;21.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.124\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e87.93\u0026thinsp;\u0026plusmn;\u0026thinsp;16.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e75.24\u0026thinsp;\u0026plusmn;\u0026thinsp;14.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e69.18\u0026thinsp;\u0026plusmn;\u0026thinsp;14.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e67.18\u0026thinsp;\u0026plusmn;\u0026thinsp;20.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.141\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eValues presented in this table are means and standard deviations.\u003c/p\u003e \u003cp\u003e*Effect size: we calculated partial eta squared (η\u003csub\u003ep\u003c/sub\u003e\u003csup\u003e2\u003c/sup\u003e) for ANOVAs to estimate the effect size. Effect sizes are indicated as small (η\u003csub\u003ep\u003c/sub\u003e\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.01), medium (η\u003csub\u003ep\u003c/sub\u003e\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.06), and large (η\u003csub\u003ep\u003c/sub\u003e\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.14) effects.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.4 Differences in average scores of PedsQL GCM scales and total score\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e presents differences in the mean values of PedsQL 4.0 GCM scales and total scores in the study population. We showed the variables with at least one statistically significant difference (i.e., when p value\u0026thinsp;\u0026lt;\u0026thinsp;0.05) regarding the average scores of PedsQL 4.0 GCM scales and total scores, and the rest results are presented in Supplementary table \u003cspan refid=\"MOESM3\" class=\"InternalRef\"\u003eS3\u003c/span\u003e. Notably, when mothers filled out the questionnaire, children had lower average scores in the scale of emotional functioning (p\u0026thinsp;=\u0026thinsp;0.004), school functioning (p\u0026thinsp;=\u0026thinsp;0.045), psychosocial health summary score (p\u0026thinsp;=\u0026thinsp;0.010), and total score (p\u0026thinsp;=\u0026thinsp;0.023) compared to those scores when fathers or others filled out the questionnaire. The average scores were significantly higher in social functioning (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), school functioning (p\u0026thinsp;=\u0026thinsp;0.017), psychosocial health summary score (p\u0026thinsp;=\u0026thinsp;0.013) as well as total scores (p\u0026thinsp;=\u0026thinsp;0.016) in children whose mothers had a high education compared to their counterparts. Children who visited the hospital for the first time had higher average scores in social functioning (p\u0026thinsp;=\u0026thinsp;0.005), psychosocial health summary score (p\u0026thinsp;=\u0026thinsp;0.016), and total scores (p\u0026thinsp;=\u0026thinsp;0.023). Children on steroid-exclusive regimens had relatively higher mean score in all scales and total scores (p values\u0026thinsp;\u0026lt;\u0026thinsp;0.05). More specifically, in terms of medical treatments, we also compared the scores of PedsQL GCM in children who exclusively used steroids with those using two or more medications. Results are shown in the Supplementary Table \u003cspan refid=\"MOESM3\" class=\"InternalRef\"\u003eS3\u003c/span\u003e. Children had highest mean scores in all scales and total score compared to patients using oral immunosuppressive drugs (OID) and/or rituximab (RTX). Children using both OID and RTX had the lowest mean scores in all scales as well as the total score. Furthermore, we applied the Post hoc comparison and found that it indicates there was only significant differences in averages of total score of PedsQL GCM when only using steroids vs. only using OID as well as only using steroid vs. using both OID and RTX (see Supplementary table \u003cspan refid=\"MOESM5\" class=\"InternalRef\"\u003eS5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparing the average scale and total scores of PedsQL GCM across groups in children with idiopathic nephrotic syndrome (n\u0026thinsp;=\u0026thinsp;181)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePhysical functioning\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eEmotional functioning\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSocial functioning\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSchool functioning\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePsychosocial Health Summary Score\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eTotal score\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBoy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e73.26\u0026thinsp;\u0026plusmn;\u0026thinsp;20.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e74.88\u0026thinsp;\u0026plusmn;\u0026thinsp;20.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e82.06\u0026thinsp;\u0026plusmn;\u0026thinsp;18.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e72.63\u0026thinsp;\u0026plusmn;\u0026thinsp;21.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e76.09\u0026thinsp;\u0026plusmn;\u0026thinsp;16.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e74.56\u0026thinsp;\u0026plusmn;\u0026thinsp;15.97\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGirl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e66.31\u0026thinsp;\u0026plusmn;\u0026thinsp;22.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e72.54\u0026thinsp;\u0026plusmn;\u0026thinsp;24.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e78.47\u0026thinsp;\u0026plusmn;\u0026thinsp;20.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e69.58\u0026thinsp;\u0026plusmn;\u0026thinsp;22.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e73.18\u0026thinsp;\u0026plusmn;\u0026thinsp;20.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e70.53\u0026thinsp;\u0026plusmn;\u0026thinsp;19.35\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.042\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.508\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.251\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.388\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.325\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.155\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEffect size\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.23\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003eCaregiver who filled out the questionnaire\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMother\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e69.82\u0026thinsp;\u0026plusmn;\u0026thinsp;21.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e71.52\u0026thinsp;\u0026plusmn;\u0026thinsp;22.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e79.90\u0026thinsp;\u0026plusmn;\u0026thinsp;20.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e69.89\u0026thinsp;\u0026plusmn;\u0026thinsp;20.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e73.28\u0026thinsp;\u0026plusmn;\u0026thinsp;17.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e71.65\u0026thinsp;\u0026plusmn;\u0026thinsp;16.88\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFather and others\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e75.06\u0026thinsp;\u0026plusmn;\u0026thinsp;21.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e82.56\u0026thinsp;\u0026plusmn;\u0026thinsp;18.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e84.24\u0026thinsp;\u0026plusmn;\u0026thinsp;16.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e77.96\u0026thinsp;\u0026plusmn;\u0026thinsp;22.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e81.89\u0026thinsp;\u0026plusmn;\u0026thinsp;17.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e78.99\u0026thinsp;\u0026plusmn;\u0026thinsp;17.38\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.161\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.204\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.045\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.010\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.023\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEffect size\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.43\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003eMaternal educational level\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiddle school or lower\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e68.08\u0026thinsp;\u0026plusmn;\u0026thinsp;22.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e71.85\u0026thinsp;\u0026plusmn;\u0026thinsp;23.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e74.20\u0026thinsp;\u0026plusmn;\u0026thinsp;21.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e65.52\u0026thinsp;\u0026plusmn;\u0026thinsp;26.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e70.34\u0026thinsp;\u0026plusmn;\u0026thinsp;21.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e69.12\u0026thinsp;\u0026plusmn;\u0026thinsp;20.16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHigh school\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e69.08\u0026thinsp;\u0026plusmn;\u0026thinsp;23.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e75.00\u0026thinsp;\u0026plusmn;\u0026thinsp;22.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e79.88\u0026thinsp;\u0026plusmn;\u0026thinsp;20.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e74.00\u0026thinsp;\u0026plusmn;\u0026thinsp;17.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e75.24\u0026thinsp;\u0026plusmn;\u0026thinsp;16.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e72.40\u0026thinsp;\u0026plusmn;\u0026thinsp;16.24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCollege or above\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e75.33\u0026thinsp;\u0026plusmn;\u0026thinsp;18.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e75.74\u0026thinsp;\u0026plusmn;\u0026thinsp;20.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e88.10\u0026thinsp;\u0026plusmn;\u0026thinsp;13.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e75.98\u0026thinsp;\u0026plusmn;\u0026thinsp;16.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e79.85\u0026thinsp;\u0026plusmn;\u0026thinsp;13.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e77.96\u0026thinsp;\u0026plusmn;\u0026thinsp;13.38\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.111\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.568\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.016\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEffect size\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003ePaternal educational level\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiddle school or lower\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e65.80\u0026thinsp;\u0026plusmn;\u0026thinsp;23.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e71.07\u0026thinsp;\u0026plusmn;\u0026thinsp;24.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e73.28\u0026thinsp;\u0026plusmn;\u0026thinsp;21.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e67.31\u0026thinsp;\u0026plusmn;\u0026thinsp;23.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e70.24\u0026thinsp;\u0026plusmn;\u0026thinsp;20.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e68.12\u0026thinsp;\u0026plusmn;\u0026thinsp;19.86\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHigh school\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e74.40\u0026thinsp;\u0026plusmn;\u0026thinsp;23.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e78.33\u0026thinsp;\u0026plusmn;\u0026thinsp;22.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e83.80\u0026thinsp;\u0026plusmn;\u0026thinsp;16.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e73.93\u0026thinsp;\u0026plusmn;\u0026thinsp;23.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e78.07\u0026thinsp;\u0026plusmn;\u0026thinsp;16.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e76.23\u0026thinsp;\u0026plusmn;\u0026thinsp;17.52\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCollege or above\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e72.82\u0026thinsp;\u0026plusmn;\u0026thinsp;17.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e73.77\u0026thinsp;\u0026plusmn;\u0026thinsp;19.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e84.71\u0026thinsp;\u0026plusmn;\u0026thinsp;18.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e73.36\u0026thinsp;\u0026plusmn;\u0026thinsp;18.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e76.88\u0026thinsp;\u0026plusmn;\u0026thinsp;15.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e75.10\u0026thinsp;\u0026plusmn;\u0026thinsp;14.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.078\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.240\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.215\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.056\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.033\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEffect size\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003eEmployment status of father\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e71.69\u0026thinsp;\u0026plusmn;\u0026thinsp;21.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e75.44\u0026thinsp;\u0026plusmn;\u0026thinsp;20.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e82.04\u0026thinsp;\u0026plusmn;\u0026thinsp;18.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e72.71\u0026thinsp;\u0026plusmn;\u0026thinsp;20.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e76.31\u0026thinsp;\u0026plusmn;\u0026thinsp;17.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e74.21\u0026thinsp;\u0026plusmn;\u0026thinsp;16.77\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59.12\u0026thinsp;\u0026plusmn;\u0026thinsp;15.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49.44\u0026thinsp;\u0026plusmn;\u0026thinsp;28.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e59.80\u0026thinsp;\u0026plusmn;\u0026thinsp;23.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e52.59\u0026thinsp;\u0026plusmn;\u0026thinsp;25.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e54.55\u0026thinsp;\u0026plusmn;\u0026thinsp;18.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e56.14\u0026thinsp;\u0026plusmn;\u0026thinsp;16.64\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.085\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEffect size\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.08\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003eFirst visit to the hospital for the diagnosis of INS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e75.24\u0026thinsp;\u0026plusmn;\u0026thinsp;21.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e77.78\u0026thinsp;\u0026plusmn;\u0026thinsp;21.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e87.17\u0026thinsp;\u0026plusmn;\u0026thinsp;15.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e76.81\u0026thinsp;\u0026plusmn;\u0026thinsp;20.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e80.52\u0026thinsp;\u0026plusmn;\u0026thinsp;16.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e78.13\u0026thinsp;\u0026plusmn;\u0026thinsp;16.69\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e69.29\u0026thinsp;\u0026plusmn;\u0026thinsp;21.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e72.60\u0026thinsp;\u0026plusmn;\u0026thinsp;21.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e78.28\u0026thinsp;\u0026plusmn;\u0026thinsp;20.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e69.66\u0026thinsp;\u0026plusmn;\u0026thinsp;21.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e73.08\u0026thinsp;\u0026plusmn;\u0026thinsp;18.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e71.37\u0026thinsp;\u0026plusmn;\u0026thinsp;17.10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.086\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.147\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.054\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.023\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEffect size\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.40\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003ePresence of renal insufficiency\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61.43\u0026thinsp;\u0026plusmn;\u0026thinsp;19.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e71.39\u0026thinsp;\u0026plusmn;\u0026thinsp;23.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e70.41\u0026thinsp;\u0026plusmn;\u0026thinsp;22.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e68.44\u0026thinsp;\u0026plusmn;\u0026thinsp;20.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e68.90\u0026thinsp;\u0026plusmn;\u0026thinsp;20.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e65.38\u0026thinsp;\u0026plusmn;\u0026thinsp;17.27\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e72.13\u0026thinsp;\u0026plusmn;\u0026thinsp;21.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e74.45\u0026thinsp;\u0026plusmn;\u0026thinsp;21.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e82.09\u0026thinsp;\u0026plusmn;\u0026thinsp;18.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e71.96\u0026thinsp;\u0026plusmn;\u0026thinsp;21.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e75.79\u0026thinsp;\u0026plusmn;\u0026thinsp;17.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e74.07\u0026thinsp;\u0026plusmn;\u0026thinsp;17.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.043\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.576\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.533\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.144\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.054\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEffect size\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.51\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003ePresence of hypertension\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60.34\u0026thinsp;\u0026plusmn;\u0026thinsp;20.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67.73\u0026thinsp;\u0026plusmn;\u0026thinsp;24.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e67.84\u0026thinsp;\u0026plusmn;\u0026thinsp;19.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e64.50\u0026thinsp;\u0026plusmn;\u0026thinsp;19.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e65.80\u0026thinsp;\u0026plusmn;\u0026thinsp;17.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e63.42\u0026thinsp;\u0026plusmn;\u0026thinsp;17.48\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e71.76\u0026thinsp;\u0026plusmn;\u0026thinsp;21.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e74.56\u0026thinsp;\u0026plusmn;\u0026thinsp;21.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e81.78\u0026thinsp;\u0026plusmn;\u0026thinsp;19.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e72.08\u0026thinsp;\u0026plusmn;\u0026thinsp;21.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e75.73\u0026thinsp;\u0026plusmn;\u0026thinsp;17.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e73.86\u0026thinsp;\u0026plusmn;\u0026thinsp;17.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.086\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.319\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.280\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.089\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.063\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEffect size\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.60\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003eOnly using steroid treatment\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e77.04\u0026thinsp;\u0026plusmn;\u0026thinsp;19.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e80.70\u0026thinsp;\u0026plusmn;\u0026thinsp;21.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e87.43\u0026thinsp;\u0026plusmn;\u0026thinsp;15.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e80.61\u0026thinsp;\u0026plusmn;\u0026thinsp;21.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e82.81\u0026thinsp;\u0026plusmn;\u0026thinsp;17.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e80.41\u0026thinsp;\u0026plusmn;\u0026thinsp;16.76\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e68.79\u0026thinsp;\u0026plusmn;\u0026thinsp;21.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e71.64\u0026thinsp;\u0026plusmn;\u0026thinsp;21.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e78.45\u0026thinsp;\u0026plusmn;\u0026thinsp;20.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e68.41\u0026thinsp;\u0026plusmn;\u0026thinsp;20.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e72.39\u0026thinsp;\u0026plusmn;\u0026thinsp;17.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e70.66\u0026thinsp;\u0026plusmn;\u0026thinsp;16.69\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEffect size\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.58\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eValues presented in this table are means and standard deviations.\u003c/p\u003e \u003cp\u003e*Effect size were calculated as Cohen\u0026rsquo;s d and partial eta squared (η\u003csub\u003ep\u003c/sub\u003e\u003csup\u003e2\u003c/sup\u003e) to estimate clinical relevance. Effect sizes are indicated as small (d\u0026thinsp;=\u0026thinsp;0.2, η\u003csub\u003ep\u003c/sub\u003e\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.01), medium (d\u0026thinsp;=\u0026thinsp;0.5, η\u003csub\u003ep\u003c/sub\u003e\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.06), and large (d\u0026thinsp;=\u0026thinsp;0.8, η\u003csub\u003ep\u003c/sub\u003e\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.14) difference.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.5 Associated factors of the total PedsQL GCM score\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e shows results of multivariate linear regression analyses to assess associated factors of the HRQoL in children with INS measured by PedsQL GCM. Factors significantly associated with children\u0026rsquo;s HRQoL include mothers filling out the questionnaire (β\u0026thinsp;=\u0026thinsp;6.20; 95% CI: 0.12, 12.27; p\u0026thinsp;=\u0026thinsp;0.046), non-emoloyment status of fathers (β=-12.12; 95% CI: -23.42, -0.82; p\u0026thinsp;=\u0026thinsp;0.036) and not exclusively using steroid treatment (β= -6.60; 95% CI: -12.62, -0.58; p\u0026thinsp;=\u0026thinsp;0.032). The adjusted R\u003csup\u003e2\u003c/sup\u003e is 0.132.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAssociated factors of total PedsQL GCM score in the multivariate linear regression analyses\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003ePedsQL GCM Total score\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eβ (95% confident interval\u003c/b\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eP\u003c/b\u003e \u003cb\u003evalue\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCaregiver who filled the questionnaire\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMother (n\u0026thinsp;=\u0026thinsp;138)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFather and others (n\u0026thinsp;=\u0026thinsp;43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.20 (0.12, 12.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.046\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMaternal educational level\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUniversity or higher (n\u0026thinsp;=\u0026thinsp;68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHigh school (n\u0026thinsp;=\u0026thinsp;48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-5.75 (-13.82, 2.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.161\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiddle school or lower (n\u0026thinsp;=\u0026thinsp;65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-6.13 (-16.21, 3.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.232\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePaternal educational level\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUniversity or higher (n\u0026thinsp;=\u0026thinsp;77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHigh school (n\u0026thinsp;=\u0026thinsp;48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.41 (-4.86, 11.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.417\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiddle school or lower (n\u0026thinsp;=\u0026thinsp;56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-1.29 (-11.11, 8.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.796\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEmployment of father\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes (n\u0026thinsp;=\u0026thinsp;172)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo (n\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-12.12 (-23.42, -0.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.036\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFirst onset of symptoms\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes (n\u0026thinsp;=\u0026thinsp;54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo (n\u0026thinsp;=\u0026thinsp;127)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-3.27 (-9.32, 2.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.286\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSteroid\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes (n\u0026thinsp;=\u0026thinsp;50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo (n\u0026thinsp;=\u0026thinsp;131)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-6.60 (-12.62, -0.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.032\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAdjusted R\u003c/b\u003e\u003csup\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e0.132\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.6 Caregiver\u0026rsquo;s Health-related Quality of Life and Caregiver\u0026rsquo;s burden\u003c/h2\u003e \u003cp\u003eCaregiver\u0026rsquo;s HRQoL profile composed of the five health dimensions is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The percentage of reporting \u0026ldquo;no problem\u0026rdquo; in mobility, looking after themselves, doing usual activities, pains and discomforts and feeling worried, sad or unhappy was 52.41%, 76.47%, 93.58%, 95.19% and 94.12%, respectively. Notably, 38.50% of caregivers reported slight problems in the dimension \u0026lsquo;feeling worried, sad or unhappy\u0026rsquo;, 8.02% moderate problems, 0.53% severe problems and 0.53% extreme problems. As shown in the Supplementary Table \u003cspan refid=\"MOESM6\" class=\"InternalRef\"\u003eS6\u003c/span\u003e, the mean of EQ-5D-5L utility score is 0.94 with a standard deviation as 0.08, and the median of EQ-5D-5L VAS score is 89 (interquartile range: 79, 100). Futhermore, Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e shows the scale scores and total score of PedsQL GCM are statistically significantly correlated to EQ-5D-5L utility score and VAS score (p values \u0026lt;0.05). In addition, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e demonstrates the specific caregiver\u0026rsquo;s burden due to taking care of children with INS.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe correlation between PedsQL GCM scale/total scores and EQ-5D-5L utility and VAS score\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eUtility score\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eVAS\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePearson \u003cem\u003er\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePearson \u003cem\u003er\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhysical functioning\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.299\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.285\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSocial functioning\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.223\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.246\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEmotional functioning\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.338\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.270\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSchool functioning\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.338\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.241\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePsychosocial Health Summary Score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.352\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.302\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.374\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.337\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn the present study, we have conducted an assessment of the health-related quality of life (HRQoL) among children aged 2 to 18 years with Idiopathic Nephrotic Syndrome (INS) in China, as well as the HRQoL of their caregivers and the burden experienced by caregivers in managing children with INS. Our findings indicate that children's HRQoL declines with increasing age. Various factors, including parental educational level, father's employment status, and medication treatment plans, may be associated with children's HRQoL. Additionally, there is a correlation between children's HRQoL and their caregivers' HRQoL. Nearly 70% of caregivers reported experiencing a significant burden due to the responsibilities of caring for children with INS.\u003c/p\u003e \u003cp\u003eWe found that the health-related quality of life (HRQOL) of children aged 2 to 4 years was superior to that reported for healthy children in the existing literature (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). This discrepancy may be attributed to the relatively small sample sizes in both our study (n\u0026thinsp;=\u0026thinsp;35) and the referenced study (n\u0026thinsp;=\u0026thinsp;36) (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). Additionally, the referenced study was conducted in 2005, which may not accurately reflect the current HRQOL profile of Chinese children aged 2\u0026ndash;4 years (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOur study found HRQOL of children aged 2 to 4 years in our study was better than that reported for healthy children in the existing literature (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). This discrepancy may be attributed to the relatively small sample size of children in both our study (n\u0026thinsp;=\u0026thinsp;35) and the referenced study (n\u0026thinsp;=\u0026thinsp;36) (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). Additionally, the referenced study was conducted in 2005, which may not accurately reflect the current HRQOL profile of Chinese children aged 2\u0026ndash;4 years (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). Furthermore, the clinical stage and duration of INS may also impact children\u0026rsquo;s HRQOL. Roussel et al. demonstrated that HRQOL scores for children with steroid-dependent nephrotic syndrome and steroid-resistant nephrotic syndrome were elevated and nearly comparable to those of children without chronic illness (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). This finding is attributed to the fact that the study populations were in a stable remission period, which is associated with higher HRQOL scores. Similarly, children aged 2 to 4 years experienced a relatively short duration of the disease and a lower frequency of relapse, potentially resulting in a quality of life comparable to that of the general population.\u003c/p\u003e \u003cp\u003eOur study found HRQOL of children aged 5 to 18 years in our study to be worse than that reported for healthy children in the existing literature (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e), which is consistent with previous studies (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e). Selewski et al. observed that INS children exhibited lower scores on measures of social and school functioning. Similarly, a study conducted in India involving 102 patients revealed that their scores in physical, social, and school functioning were significantly lower compared to those of healthy children, with school functioning being the most adversely affected (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Additionally, a recent study from the Netherlands indicated that children aged 8 to 18 years experienced a notable decline in scores related to physical and emotional functioning, as well as in the overall HRQoL (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e). These discrepancies may be attributable to variations in cultural contexts, healthcare systems across different nations, and the stage and relapse frequency of the disease in patients (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn our study, the scores for emotional functioning, school functioning, psychosocial health summary, and the overall total were higher when fathers completed the questionnaire compared to when mothers did. This discrepancy may be attributed to fathers' lower emotional sensitivity, which could result in a relatively more optimistic outlook and reduced anxiety. It is noteworthy that the score for physical functioning did not reach statistical significance. This phenomenon could be attributed to the objective nature of the physical functioning questions in the PedsQL GCM. Our findings aligned with previous research, which also indicated that caregivers who completed the questionnaire reported similar outcomes (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). Our findings indicate that children\u0026rsquo;s HRQoL is significantly better, both at the scale level and overall, when their parents possess higher educational attainment and are employed. This observation aligns with the earlier study by (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e), which demonstrated a positive correlation between paternal education and proxy-reported HRQoL. It is plausible that families with relatively higher socioeconomic status are better equipped to offer the necessary support for managing the care of ill children, thereby contributing to an enhanced HRQoL. Remarkably, we identified that when fathers were unemployed, children's HRQoL was significantly impaired across all scales and at the overall level, with the effect size indicating moderate to large differences. Even after adjusting for other covariates, this variable remained statistically significant in the regression model. Considering the social and cultural context of China, paternal unemployment can have a substantial impact on the family, particularly in medical decision-making.\u003c/p\u003e \u003cp\u003eIn this study, children with newly diagnosed INS exhibited higher scores in social functioning, psychosocial health summary, and overall PedsQL GCM scores. This observation is attributed to their early stage of the disease, during which they experienced relatively minimal adverse effects from treatment and pain. Conversely, patients experiencing disease recurrence and prolonged duration demonstrated a significantly diminished quality of life compared to those with initial onset, with the effect size approaching a moderate level. Our findings are consistent with previous studies that have documented the adverse effects of relapse on HRQoL (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e). Furthermore, our study indicates that social and psychosocial functioning are particularly impacted by relapse. This phenomenon may be attributed to the necessity for frequent hospital visits, reduced social interaction, the cumulative psychological impact of complications such as edema, obesity, and hirsutism, and the resultant isolation from peers (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eRegarding pharmacological interventions, our study found that patients on a steroid-exclusive regimen were reported a higher quality of life compared to those who used oral immunosuppressive drugs (OID) and/or rituximab (RTX). This association remained statistically significant even after adjusting for covariates. This observation is plausible, as children treated with only steroids most likely were in the initial stages of the disease and experienced less disease-related pain and fewer complications. Children undergoing treatment with OID or RTX required frequent hospitalizations and experienced the discomfort associated with RTX infusions, which adversely impacted their emotional well-being and reduced their time for social interactions and school activities.\u003c/p\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eStrengths and limitations\u003c/h2\u003e \u003cp\u003eThis study exhibits several strengths. Firstly, it investigates the HRQoL of children with INS in China, encompassing a relatively large sample size of patients aged 2 to 18 years. Notably, the study employs specialized PedsQL GCM scales for children aged 2 to 4 years, thereby enhancing the evaluation of quality of life in this younger age cohort. Secondly, we conducted a thorough assessment of a wide range of potential influencing factors to enhance the understanding of health status and medical care among children with INS. Additionally, we employed effect size metrics, specifically Cohen\u0026rsquo;s d and η\u003csub\u003ep\u003c/sub\u003e\u0026sup2;, to evaluate the clinical relevance of differences in HRQoL scores across subgroups. This approach addresses the limitations of relying solely on statistical significance.\u003c/p\u003e \u003cp\u003eHowever, the study presents several limitations that warrant attention. Firstly, it is a single-center study lacking large-sample standard data of Chinese children as a healthy control group. Secondly, the cross-sectional design precludes follow-up quality of life (QOL) measurements over time, thereby limiting the ability to establish causality. Additionally, even though the previous study showed strong agreement that the proxy-reported questionnaire is reliable (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e), incorporating both proxy- and self-reported outcomes may provide more comprehensive insights.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study evaluated the HRQoL of children aged 2\u0026ndash;18 years diagnosed with INS in China, along with the HRQoL and caregiving burden of their caregivers. The findings indicate a decline in children's HRQoL with increasing age, potentially influenced by factors such as parental education, paternal employment status, and medication regimens. A significant correlation was observed between the HRQoL of the children and that of their caregivers, who frequently experience varying levels of caregiving burden. Therefore, it is recommended that healthcare professionals prioritize the optimization of HRQoL for both children with INS and their caregivers.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eHRQoL - Health-related Quality of Life\u003c/p\u003e\n\u003cp\u003eINS - Idiopathic Nephrotic Syndrome\u003c/p\u003e\n\u003cp\u003ePedsQL GCM - Pediatric Quality of Life Inventory Generic Core Module\u003c/p\u003e\n\u003cp\u003eEQ-5D-5L - EuroQol five-dimensional questionnaire, five-level version\u003c/p\u003e\n\u003cp\u003eOID - Oral Immunosuppressive Drugs\u003c/p\u003e\n\u003cp\u003eRTX - Rituximab\u003c/p\u003e\n\u003cp\u003eSS - Steroid-Sensitive\u003c/p\u003e\n\u003cp\u003eSR - Steroid-Resistant\u003c/p\u003e\n\u003cp\u003eCNI - Calcineurin Inhibitors\u003c/p\u003e\n\u003cp\u003eBMI - Body Mass Index\u003c/p\u003e\n\u003cp\u003eZBI - Zarit Burden Interview\u003c/p\u003e\n\u003cp\u003eVAS - Visual Analogue Scale\u003c/p\u003e\n\u003cp\u003eSPSS - Statistical Package for the Social Sciences\u003c/p\u003e\n\u003cp\u003eSD - Standard Deviation\u003c/p\u003e\n\u003cp\u003eANOVA - Analysis of Variance\u003c/p\u003e\n\u003cp\u003eCI - Confidence Interval\u003c/p\u003e\n\u003cp\u003eRMB - Renminbi (Chinese currency)\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u0026nbsp;\u003c/strong\u003eThe study protocol was conducted according to the Declaration of Helsinki, and was approved by the Medical Ethics Committee of the Children's Hospital, Zhejiang University School of Medicine (2023-IRB-190). All caregivers gave their consents and voluntarily participated in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u0026nbsp;\u003c/strong\u003enot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u003c/strong\u003e The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u0026nbsp;\u003c/strong\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eThere is no funding related to the present study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions:\u0026nbsp;\u003c/strong\u003eXia Wang, Jianhua Mao and Guannan Bai were involved in the study conceptualization and design.\u0026nbsp;Xia Wang, Jingjing Wang, Chunyue Feng, Haidong Fu, Huijun Shen, \u0026nbsp;and Xiujuan Zhu\u0026nbsp;collected data.\u0026nbsp;Lejing Guan and Yifei Shao\u0026nbsp;carried out statistical analyses and prepared all the tables /figures. and G.B. wrote the main manuscript texts.\u0026nbsp;Abdul Rafay\u0026nbsp;prepared the supplementary tables. Xia Wang,\u0026nbsp;Danny Junyi Tan and\u0026nbsp;Guannan Bai wrote the first draft of this manuscript.\u0026nbsp;Jianhua Mao and\u0026nbsp;Guannan Bai supervised the whole project. All authors reviewed the manuscript and provided critical revisions of the article for important intellectual content. All the authors contributed to the interpretation of the data and approved the article's final version.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe gratefully thank all the INS patients and their families who were willing to participate in this study. We thank the Pediatric Evidence-based Medical and Clinical Research Laboratory, an internal institute of the National Clinical Research Center for Child Health, for the great support in terms of methodology and data analysis.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eNoone DG, Iijima K, Parekh R. Idiopathic nephrotic syndrome in children. The Lancet. 2018;392(10141):61-74.\u003c/li\u003e\n\u003cli\u003eZhu H, Qi J, Schoepf J, Savage RH, Tang C, Lu M, et al. Prevalence and associated risk factors of pulmonary embolism in children and young adults with nephrotic syndrome: a Chinese large cohort study. Journal of Thoracic Imaging. 2021;36(5):326-32.\u003c/li\u003e\n\u003cli\u003eGipson DS, Massengill SF, Yao L, Nagaraj S, Smoyer WE, Mahan JD, et al. Management of childhood onset nephrotic syndrome. Pediatrics. 2009;124(2):747-57.\u003c/li\u003e\n\u003cli\u003eSelewski DT, Troost JP, Massengill SF, Gbadegesin RA, Greenbaum LA, Shatat IF, et al. The impact of disease duration on quality of life in children with nephrotic syndrome: a Midwest Pediatric Nephrology Consortium study. Pediatric Nephrology. 2015;30:1467-76.\u003c/li\u003e\n\u003cli\u003eEddy AA, Symons JM. Nephrotic syndrome in childhood. The lancet. 2003;362(9384):629-39.\u003c/li\u003e\n\u003cli\u003eGipson DS, Selewski DT, Massengill SF, Wickman L, Messer KL, Herreshoff E, et al. Gaining the PROMIS perspective from children with nephrotic syndrome: a Midwest pediatric nephrology consortium study. Health Qual Life Outcomes. 2013;11:30.\u003c/li\u003e\n\u003cli\u003eKhullar S, Banh T, Vasilevska-Ristovska J, Chanchlani R, Brooke J, Licht CPB, et al. Impact of steroids and steroid-sparing agents on quality of life in children with nephrotic syndrome. Pediatr Nephrol. 2021;36(1):93-102.\u003c/li\u003e\n\u003cli\u003eRoussel A, Delbet JD, Micheland L, Desch\u0026ecirc;nes G, Decramer S, Ulinski T. Quality of life in children with severe forms of idiopathic nephrotic syndrome in stable remission-A cross-sectional study. Acta Paediatr. 2019;108(12):2267-73.\u003c/li\u003e\n\u003cli\u003eAbbasi A, Valizadeh M, Fahimi D, Moghtaderi M, Bazargani B, Mojtahedi SY, et al. Heath-Related Quality of Life in Iranian Children with Nephrotic Syndrome. Iranian Journal of Pediatrics. 2022;32(2).\u003c/li\u003e\n\u003cli\u003eCenters for Disease Control and Prevention. Health-Related Quality of Life (HRQOL). Centers for Disease Control and Prevention. 2021.\u003c/li\u003e\n\u003cli\u003eEid R, Fathy AA, Hamdy N. Health-related quality of life in Egyptian children with nephrotic syndrome. Quality of Life Research. 2020;29:2185-96.\u003c/li\u003e\n\u003cli\u003eAssadi F. Psychological impact of chronic kidney disease among children and adolescents: Not rare and not benign. Journal of nephropathology. 2013;2(1):1.\u003c/li\u003e\n\u003cli\u003eGerson AC, Wentz A, Abraham AG, Mendley SR, Hooper SR, Butler RW, et al. Health-related quality of life of children with mild to moderate chronic kidney disease. Pediatrics. 2010;125(2):e349-e57.\u003c/li\u003e\n\u003cli\u003eMcKenna AM, Keating LE, Vigneux A, Stevens S, Williams A, Geary DF. Quality of life in children with chronic kidney disease\u0026mdash;patient and caregiver assessments. Nephrology Dialysis Transplantation. 2006;21(7):1899-905.\u003c/li\u003e\n\u003cli\u003eMujais SK, Story K, Brouillette J, Takano T, Soroka S, Franek C, et al. Health-related quality of life in CKD patients: correlates and evolution over time. Clinical Journal of the American Society of Nephrology. 2009;4(8):1293-301.\u003c/li\u003e\n\u003cli\u003eManti P, Giannakopoulos G, Giouroukou E, Georgaki-Angelaki H, Stefanidis CJ, Mitsioni A, et al. Psychosocial and cognitive function in children with nephrotic syndrome: association with disease and treatment variables. BioPsychoSocial medicine. 2013;7:1-7.\u003c/li\u003e\n\u003cli\u003eMazahir R, Anand K, Pruthi P. Quality of life in children with nephrotic syndrome: a cross-sectional study using Hindi version of PedsQL 4.0 Generic Core Scales. Clinical and Experimental Nephrology. 2022;26(6):552-60.\u003c/li\u003e\n\u003cli\u003eRahman M, Afroz S, Ali R, Hanif M. Health Related Quality of Life in Children with Nephrotic Syndrome in Bangladesh. Mymensingh medical journal: MMJ. 2016;25(4):703-9.\u003c/li\u003e\n\u003cli\u003eR\u0026uuml;th E-M, Landolt MA, Neuhaus TJ, Kemper MJ. Health-related quality of life and psychosocial adjustment in steroid-sensitive nephrotic syndrome. The Journal of pediatrics. 2004;145(6):778-83.\u003c/li\u003e\n\u003cli\u003eAllam N, Bashar A, Eid R. Assessment of health-related quality of life in Sudanese children with nephrotic syndrome: a questionnaire-based study. Pan African Medical Journal. 2022;43(1).\u003c/li\u003e\n\u003cli\u003eImani PD, Aujo J, Kiguli S, Srivaths P, Brewer ED. Chronic kidney disease impacts health-related quality of life of children in Uganda, East Africa. Pediatric Nephrology. 2021;36:323-31.\u003c/li\u003e\n\u003cli\u003eLi N, Hao J, Fu T, Du Y. Evaluating the Quality of Life of 231 Children With Primary Nephrotic Syndrome and Assessing Parental Awareness of the Disease. Front Pediatr. 2021;9:745444.\u003c/li\u003e\n\u003cli\u003eWorld Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. Jama. 2013;310(20):2191-4.\u003c/li\u003e\n\u003cli\u003eB\u0026eacute;dard M, Molloy DW, Squire L, Dubois S, Lever JA, O\u0026apos;Donnell M. The Zarit Burden Interview: a new short version and screening version. Gerontologist. 2001;41(5):652-7.\u003c/li\u003e\n\u003cli\u003eChan LF, Chow SM, Lo SK. Preliminary validation of the Chinese version of the Pediatric Quality of Life Inventory. International Journal of Rehabilitation Research. 2005;28(3):219-27.\u003c/li\u003e\n\u003cli\u003eHao Y, Tian Q, Lu Y, Chai Y, Rao S. Psychometric properties of the Chinese version of the Pediatric Quality of Life Inventory\u0026trade; 4.0 generic core scales. Quality of Life Research. 2010;19:1229-33.\u003c/li\u003e\n\u003cli\u003eCohen J. Statistical power analysis for the behavioral sciences: routledge; 2013.\u003c/li\u003e\n\u003cli\u003eLuo N, Liu G, Li M, Guan H, Jin X, Rand-Hendriksen K. Estimating an EQ-5D-5L Value Set for China. Value Health. 2017;20(4):662-9.\u003c/li\u003e\n\u003cli\u003eVeltkamp F, Teela L, Luijten MA, van Oers HA, Mak-Nienhuis EM, Haverman L, et al. Health-related quality of life of children with first onset steroid-sensitive nephrotic syndrome. European Journal of Pediatrics. 2023;182(10):4605-14.\u003c/li\u003e\n\u003cli\u003eMishra K, Ramachandran S, Firdaus S, Rath B. The impact of pediatric nephrotic syndrome on parents\u0026prime; health-related quality of life and family functioning: An assessment made by the PedsQL 4.0 family impact module. Saudi journal of kidney diseases and transplantation. 2015;26(2):285-92.\u003c/li\u003e\n\u003cli\u003eDidsbury MS, Kim S, Medway MM, Tong A, McTaggart SJ, Walker AM, et al. Socio‐economic status and quality of life in children with chronic disease: A systematic review. Journal of paediatrics and child health. 2016;52(12):1062-9.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"health-and-quality-of-life-outcomes","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"hqlo","sideBox":"Learn more about [Health and Quality of Life Outcomes](http://hqlo.biomedcentral.com)","snPcode":"12955","submissionUrl":"https://submission.nature.com/new-submission/12955/3","title":"Health and Quality of Life Outcomes","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"quality of life, idiopathic nephrotic syndrome, burden of disease, children, caregiver","lastPublishedDoi":"10.21203/rs.3.rs-4922299/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4922299/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eAims\u003c/strong\u003e: The primary aim of this study was to characterize the health-related quality of life (HRQoL) and identify the associated factors among children aged 2 to 18 years in China diagnosed with idiopathic nephrotic syndrome (INS). Additionally, the study aimed to evaluate the HRQoL and caregiving burden of their caregivers, as well as to investigate the correlation between the HRQoL of the children and that of their caregivers.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: This study recruited 181 children with a diagnosis of INS from Children’s Hospital, Zhejiang University School of Medicine in China. The proxy-reported PedsQL Generic Core Module (PedsQL GCM) was used to measure the HRQoL of children, and the five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) was applied to measure caregivers’ HRQoL. Differences in scale scores and total scores of PedsQL GCM were assessed using t tests and one-way ANOVA. Multivariate linear regression analysis was used to identify the associated factors of children’s HRQoL. Pearson correlation analysis was performed to assess the correlation between children’s HRQoL and caregiver’s HRQoL.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: HRQoL of Children with INS declines with increasing age, and children aged 5-18 years had lower scores in physical functioning, emotional functioning, school functioning, psychosocial health summary score, and total PedsQL GCM score compared to healthy children. Various factors, including the mother filling out the questionnaire, the father being unemployed, and use of other medications except for steroids were associated with worse HRQoL of children (p values \u0026lt; 0.05). Additionally, there is a correlation between children's HRQoL and their caregivers' HRQoL.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e This study evaluated the HRQoL of children aged 2-18 years diagnosed with INS in China, along with the HRQoL of their caregivers. HRQoL of children was potentially influenced by multiple factors. A significant correlation was observed between the HRQoL of the children and that of their caregivers, who frequently experienced varying levels of caregiving burden. Therefore, it is recommended that healthcare professionals prioritize the optimization of HRQoL for both children with INS and their caregivers.\u003c/p\u003e","manuscriptTitle":"Assessment of Health-related Quality of Life of Children with Idiopathic Nephrotic Syndrome and their caregivers in China","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-14 07:32:55","doi":"10.21203/rs.3.rs-4922299/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-09-22T19:26:48+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-22T19:19:43+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-18T15:41:41+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-12T08:17:59+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"311962625189029753546951364718041540398","date":"2024-09-09T11:29:24+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"20554388569271569615262272841207390625","date":"2024-09-08T15:28:18+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"53605041136594586166819170301281231235","date":"2024-09-02T09:51:34+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-08-26T07:26:19+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-08-16T11:42:14+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-08-16T11:40:15+00:00","index":"","fulltext":""},{"type":"submitted","content":"Health and Quality of Life Outcomes","date":"2024-08-16T04:01:50+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"health-and-quality-of-life-outcomes","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"hqlo","sideBox":"Learn more about [Health and Quality of Life Outcomes](http://hqlo.biomedcentral.com)","snPcode":"12955","submissionUrl":"https://submission.nature.com/new-submission/12955/3","title":"Health and Quality of Life Outcomes","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"fb68e1d2-3a7f-4b7f-91f3-a1531a7612a3","owner":[],"postedDate":"October 14th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-11-04T16:20:59+00:00","versionOfRecord":{"articleIdentity":"rs-4922299","link":"https://doi.org/10.1186/s12955-024-02310-6","journal":{"identity":"health-and-quality-of-life-outcomes","isVorOnly":false,"title":"Health and Quality of Life Outcomes"},"publishedOn":"2024-10-29 16:12:51","publishedOnDateReadable":"October 29th, 2024"},"versionCreatedAt":"2024-10-14 07:32:55","video":"","vorDoi":"10.1186/s12955-024-02310-6","vorDoiUrl":"https://doi.org/10.1186/s12955-024-02310-6","workflowStages":[]},"version":"v1","identity":"rs-4922299","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4922299","identity":"rs-4922299","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}