Participants and setting
To achieve the power (1-β) of 0.80 under the probability of type I error (α) of 0.05, hypothetical mean scores of Psychosocial Health Summary Score were 82.0 and 87.0 in the case and control groups, respectively, with a standard deviation of 10. The sample size was determined by using the formula of n = (σ((z1−α/2 + z1−β)/(μA−μB)))2. A minimum of 139 subjects was required for the case and control groups, respectively. A cohort of 134 children with ICPP and their primary caregivers was recruited from a Triple A children’s hospital from April to September 2019 in Chongqing by using the convenience sampling method, and 210 gender- and age-matched subjects were selected concurrently from two primary schools in Chongqing by the stratified sampling method.
The case group met the following inclusion criteria: 1) new diagnosis of ICPP, 2) previously diagnosed ICPP undergoing treatment, and 3) age of 5 to 12 years. Exclusion criteria were: 1) chronic illnesses such as asthma, kidney or heart diseases, epilepsy, or other comorbidities that influence HRQoL; 2) a history of psychological trauma such as the death of a family member; or 3) refusal of either the patient or their primary caregivers to participate. The control group met the following inclusion criteria: 1) age of 5 to 12 years, and 2) voluntary participation of the patient and their caregivers. Children with recent or past diagnoses of ICPP or who had other diseases that influence HRQoL were excluded from the control group. This study was approved by the Ethics Committee of Children’s Hospital of Chongqing Medical University. All caregivers provided written informed consent.
Procedure
The investigators were trained before data collection to ensure the quality of clinical research practices. In the case group, parents completed a demographic questionnaire and the PedsQLTM FIM, whereas patients completed the PedsQLTM4.0 GCS at the time of diagnosis or during outpatient follow-up. In the control group, children completed the PedsQLTM4.0 GCS and brought the demographic questionnaire and the PedsQLTM4.0 FIM to their parents for completion, which were returned to the head teacher on the following day, and were then collected by the investigators.
Measures
Demographic variables included age, gender, weight, height; number of children in the family; and caregiver relationship (e.g., parents or grandparents). The caregivers’ basic information included living environment (e.g., urban, rural), educational level (primary school, middle school, high school, or university and higher), employment status (employed, unemployed/housewives) and monthly income (<5000, 5,000-10,000, >10,000 Chinese Yuan [CNY]). Clinical characteristics of children with ICPP included whether they were newly diagnosed or already undergoing follow-up; age at diagnosis; disease duration; type of treatment (e.g., GnRHa or GnRHa combined with growth hormone); route of administration (e.g., intramuscular or subcutaneous injection); and duration of treatment.
The PedsQLTM GCS questionnaire was developed by Varin et al. [18] to assess the impact of disease and treatment on pediatric patients’ HRQoL during the preceding month. It consists of 23 items divided into four dimensions including physical (8 items), emotional (5 items), social (5 items) and school (5 items) functioning. A 5-point Likert scale was used to estimate problem frequencies: 0=never, 1=almost never, 2= sometimes, 3=often, 4=always. Items are then reverse scored and transformed into a scale of 0-100 (0=100, 1=75, 2=50, 3=25, 4=0), with higher scores representing better HRQoL status. The Total Summary Score was calculated as the sum of all 23 items divided by the number of items answered. The Total Summary Score can be further divided into the subscales of Physical Health Summary Score and Psychosocial Health Summary Score. The Psychosocial Health Summary Score was computed as the sum of 15 items of emotional, social and school functioning divided by the number of items answered. This study used self-reports of the Chinese version of the PedsQLTM GCS, which was cross-culturally adapted by Hao et al [19]. The instrument showed good internal consistency and reliability, with Cronbach’ s alpha coefficients of 0.862 in the case group and 0.745 in the control group.
The PedsQLTM FIM was developed by Varin et al [20] as a parent-reported instrument to measure the impact of pediatric chronic disease on parents’ HRQoL and family functioning. The questionnaire consists of 36 items divided into 8 dimensions including physical functioning (6 items), emotional functioning (5 items), social functioning (4 items), cognitive functioning (5 items), communication (3 items), worry (5 items), daily activities (3 items), and family relationships (5 items). The former 6 dimensions measure parents’ self-reported HRQoL, whereas the latter 2 dimensions measure parent-reported family functioning. Each item has five Likert response options to assess the frequency of problems: 0 (never), 1 (almost never), 2 (sometimes), 3 (often), and 4 (almost). Items are then linearly transformed to a 0-100 scale (0 = 100, 1 = 75, 2 = 50, 3 = 25, 4 = 0), so that higher scores indicate lower family impact. The total score is calculated as the sum of all 36 items divided by the number of items answered. The parents’ HRQoL Summary Score is calculated as the sum of the 20 items of physical, emotional, social, cognitive functioning subscales divided by the number of items answered, and the family functioning summary score is calculated as the sum of the 8 items of daily activities and family relationships subscales divided by the number of items answered. We used the Chinese version of PedsQLTM FIM translated by Chen et al [21]. It has shown good internal consistency and reliability, with Cronbach’ s alpha coefficients of 0.969 in the case group and 0.943 in the control group.
Statistical analyses
All data were analyzed using IBM SPSS version 25.0. Continuous and categorical variables were described as mean ± standard deviation (SD) and frequency (percentage n [%]), respectively. First, t-test and Chi-square (χ2) test analyses were used to compare the demographic characteristics of the two groups. Second, the t-test was used to examine differences of the PedsQLTM GCS and PedsQLTM FIM scores between the two groups. Finally, Pearson correlation coefficients (r values) were calculated to explore the association between patients’ HRQoL and family impact of case group. P-value<0.05 (two-sided) was considered statistically significant.