Serial Multiple Mediation of Mastery and Sleep Quality in the Relationship between Caregiving Burden and Anxiety among Parental Caregivers of Children with Leukemia in China

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Introduction
Leukemia is a malignant cancer that seriously threatens the physical health of children [1].Each year in China, approximately 15,000 children are newly diagnosed with leukemia [2].In terms of care, it is emphasized in Chinese society that the whole family engages in caring for the sick children, and parents usually bear the responsibility as the primary caregivers [3].Parental caregivers may experience negative consequences on fnancial resources, household activities, health, and leisure.Apart from the objective burden, parental caregivers of children with leukemia may also experience severe subjective burden [4,5].
Anxiety symptoms are prevalent among parental caregivers.It has been reported that nearly 50% of caregivers of patients with cancer are at a high risk of anxiety [6].Parental caregivers could be anxious about the outcomes of sick children's medication, operation, radiotherapy, chemotherapy, and rehabilitation [7].Indeed, caring for children with leukemia may be associated with heavy subjective burden on parental caregivers, which may negatively afect their mental health.Despite the growing research in caregivers' anxiety [8,9], there is a lack of attention to the psychological well-being of parental caregivers of children with leukemia in China.Moreover, the relationship between caregiving subjective burden and anxiety among those caregivers needs further exploration [10].Caregiving burden is a multidimensional concept and is often treated as the primary stressor for the general caregivers in the stress process model [11,12].In general, the caregiving burden can signifcantly elevate caregiver anxiety.However, according to a systematic review, the efect of caregiving burden on caregiver anxiety varies across groups [8].In addition, caregiving burden as a primary stressor can generate multiple secondary stressors that can also impact caregiver anxiety.However, less attention has been paid to the role of secondary stressors in the relationship between caregiving burden and anxiety [13].
Sleep quality is considered a predictor of caregiver anxiety.One systematic review shows that up to 76% of the population of general caregivers reported poor sleep quality [14].Similar fndings exist among parents caring for their sick children, such as when one study discovered caregiver anxiety signifcantly correlated with sleep quality among parents of children with cerebral palsy [15].Tis is mainly because poor sleep quality can negatively afect caregiver activities, which can lead to poor medical outcomes of sick children.Consequently, the anxiety level of caregivers could increase [16].Another study in China also suggested that family caregivers' sleep problems and anxiety were prevalent, and moderate to severe anxiety was caused by sleeplessness [17].
In terms of the relationships between caregiving burden, sleep quality, and caregivers' psychological well-being, to our best knowledge, only one study conducted among general community caregivers confrmed the mediating role of sleep quality between caregiving burden and anxiety [9].Tis is due to the positive efect of better sleep quality in maintaining the caregiver's physical and mental health [18].Poorer sleep quality also acts as a secondary stressor, resulting in severe consequences for the caregiver.Numerous studies have focused on the mediating efects of caregiver sleep quality in the relationship between caregiving burden and psychological well-being [9,19], but little is known about the role of sleep quality in that relationship in the case of parental caregivers of children with leukemia.
Some researchers suggested that caregivers' greater sense of mastery predicts lower anxiety [13,20].Mastery is an internal resource of individuals, and it refers to the degree to which one experiences control over what goes on in one's life [21,22].Tat is, a lack of mastery may increase psychological distress among caregivers [23].
According to the stress process model, caregiving burden can reduce the caregiver's ability to master; thereby, lower mastery is a secondary stressor that has negative impacts on caregivers [18,24].Many studies have confrmed the efect of caregiving burden on mastery [25,26].Moreover, previous studies found that mastery plays a mediating role in the relationship between caregiving burden and psychological distress [27,28].According to these fndings, mastery is likely to mediate the efect of caregiving burden on psychological well-being, but anxiety has been relatively neglected.Terefore, it needs to further verify whether mastery can play a mediating role between care burden and anxiety.
Te link between caregiving burden, mastery, sleep quality, and anxiety is complex and poorly understood.For the most part, mastery [29] and sleep quality [19] are signifcantly correlated with caregiving burden.However, the efects of mastery and sleep quality on caregiver anxiety were not consistent [18].Although high mastery and good sleep quality are viewed as personal resources of caregivers, prior studies showed that sleep quality signifcantly afected caregivers' experiences of unhealthy days due to physical health and/or mental health issues, while mastery did not [18].In addition, there is a lack of research on how mastery afects caregivers' sleep quality.We found only one study suggested that mastery has a signifcant efect on sleep quality among caregivers [30].Few studies considered both mastery and sleep quality in the context of caregiving burden and anxiety [31].
Parents are usually the primary caregivers of children with leukemia, and the continuous process of caregiving can have a detrimental impact on their mental health.According to the stress process model, caregivers with heavy caregiving burden may perceive low mastery, thus reducing their sleep quality and further lead to anxiety.Tis study aimed to examine the mediating efect of mastery and sleep quality in the relationship between caregiving burden and anxiety among parents caring for children with leukemia in China.Terefore, we hypothesized that (1) caregiving burden is positively associated with anxiety; (2) mastery mediates the positive link between caregiving burden and anxiety; (3) sleep quality mediates the positive link between caregiving burden and anxiety; and (4) mastery and sleep quality play a chain mediating role between caregiving burden and anxiety sequentially.

Participants and Procedures.
A cross-sectional design and convenient sampling method were adopted in this study.We used WeChat, an instant messaging and social media mobile app, to conduct an online survey.All participants were service utilizers of Diai Home, which is a nonproft organization located in Beijing that provides psycho-social support to oncological patients and their families nationwide.Diai Home disseminated the survey information to its service utilizers through WeChat and recruited participants.Service utilizers were told they were voluntary to take part in, and whether to participate in this survey or not was not associated with the services they could receive from Diai Home.Eligible participants were parental caregivers of children (0-18 years old) with leukemia.At the frst window of this online survey, there was an information statement for participants to indicate and agree to participate.A total of 397 questionnaires were collected.Among them, 55 were omitted because their children were older than 18 or did not sufer leukemia.Eventually, 342 2 Health & Social Care in the Community questionnaires were valid and included in the analysis.All patients sufered from acute leukemia, either acute myeloid leukemia or acute lymphocytic leukemia.Tis study was approved by the committee on Human Research Publication and Ethics, Renmin University of China.

Measures
2.2.1.Caregiving Burden.Te Zarit Care Burden scale (ZCBS) was used to assess the participants' caregiving burden [32].ZCBS evaluates the stress endured by the caregivers who care for those who are ill or injured.Consistent with the Zarit Burden Interview (ZBI) [33], ZCBS is also the classic scale for measuring caregiver burden, which focuses primarily on the subjective burden.It has been used in numerous studies to assess the caregiving burden of caring for children with leukemia [34,35].Te Chinese version of ZCBS has a high reliability [36].Te scale comprises 22 questions (e.g., "Do you think patient asks for more help than he/she needs?" "Do you think you are afraid of patient's future?" and "Do you think you are sufering in social life?") with a Likert-type rating scale, ranging from 1 � never to 5 � nearly always.Te total score ranged from 22 to 110, with higher scores indicating a greater burden [33].Cronbach's alpha for ZCBS was 0.926.

Mastery.
Te Personal Mastery Scale (PMS) was used to assess the sense of mastery among the caregivers [37].Tis scale consists of seven items that assess caregivers' belief that they have control over their life circumstances.For example, "Tere is really no way I can solve some of problems I have.""I have little control over the things that happen to me." "I can do just about anything I really set my mind to do." Te responses are graded on a 4-point scale ranging from "strongly agree" to "strongly disagree."Te negatively worded items require reverse coding prior to scoring, resulting in a score range of 7 to 28, with higher scores indicating higher levels of mastery.Cronbach's alpha for this tool was 0.816.[40,41].In our research, Cronbach's alpha was 0.936.

Anxiety.
Te Generalized Anxiety Disorder (GAD-7) questionnaire was used to assess the anxiety among the caregivers during the previous two weeks [42].Caregivers were asked to rate how often they had been bothered by problems such as feeling nervous or anxious, unable to manage or stop worrying, over-worrying, having trouble relaxing, and getting quickly irritated or feeling afraid [43].Te total score range for the GAD-7 is 0 to 21, with each item scored on a scale of 0 � not at all to 3 � nearly every day, and higher scores indicate higher anxiety levels.In China, this tool has received widespread validation [44].Te internal consistency of GAD-7 in this sample was high (Cronbach's alpha � 0.944).

Statistical Analysis.
Te data were analyzed using the statistical software package SPSS 25.Te background characteristics of the samples, including the parental caregiver and their ill child, were presented using descriptive analysis.Pearson's correlation analysis was employed to determine the relationships among caregiving burden, mastery, sleep quality, and anxiety.A multivariable mediation analysis was carried out to develop a mediating model of these variables.Tis approach allows for the inclusion of an independent variable (caregiving burden), a dependent variable (anxiety), and two sequential mediator variables (mastery and sleep quality).Te SPSS PROCESS macro (model 6) was used to calculate the total, direct, and indirect efects [45].Te total efect refers to the association between the caregiving burden and anxiety when mastery and sleep quality are not taken into account.For the multiple mediation analysis, the indirect efects are the efects of the caregiving burden on anxiety via mastery or sleep quality.A 95% confdence interval (CI) was calculated with 5,000 bootstrapping resamples.Te mediating efects are statistically signifcant if zero does not fall within the confdence interval range [46].

Results
Table 1 shows the characteristics of the overall sample and each subgroup.Te sample consisted of 342 respondents in total, aged between 24 and 54 with an average age of 37.79 years.Te sample was primarily female (61.11%), with less secondary education (62.57%), married (90.06%), and engaged in agricultural activities (74.27%).Most participants were rural residents (57.89%).Te mean of caring hours per day was 16.89 (SD � 7.02).Regarding the characteristics of the children, 26.90% were the only children, and the proportion of boys (64.62%) was higher than girls (35.38%).Te mean scores for anxiety, caregiving burden, mastery, and sleep quality are presented in Table 2. Table 2 also shows the results of Pearson's correlation analysis.Caregiving burden was positively associated with anxiety [47] (r � 0.433, p < 0.001).In addition, caregiving burden was inversely related to mastery (r � −0.424, p < 0.001) and positively correlated with sleep quality (r � 0.344, p < 0.001), which means that the heavier the caregiving burden, the worse the caregiver's mastery and sleep quality.Both mastery (r � −0.435, p < 0.001) and sleep quality (r � 0.605, p < 0.001) were signifcantly correlated with anxiety.
Te associations between caregiving burden, mastery, sleep quality, and anxiety are shown in Table 3 and Figure 1.It can be demonstrated that, after controlling for mastery or sleep quality, caregiving burden had a signifcant direct impact on anxiety (c′ � 0.052, p < 0.001).When the variables of mastery and sleep quality were uncontrolled, caregiving burden also had a total efect on anxiety (c � 0.113, p < 0.001).Tis indicates that mastery and sleep quality acted as mediators between the efects of caregiving burden and anxiety.
It can be concluded that the indirect efect of caregiving burden on anxiety through mastery was statistically relevant (standardized estimate � 0.027, CI � 0.014, 0.042), since the confdence interval range did not include zero.As a result, the positive connection between caregiving burden and anxiety was fully mediated by mastery.In addition, the indirect efect of caregiving burden on anxiety via sleep quality was statistically signifcant (standardized estimate � 0.024, CI � 0.007, 0.044), indicating that sleep quality played a mediating role in the relationship between caregiving burden and caregiver anxiety.Finally, we investigated whether mastery and sleep quality can mediate the path between caregiving burden and anxiety in a sequential manner.Te indirect efects of caregiving burden on anxiety through mastery and sleep quality were also statistically signifcant (standardized estimate � 0.009, CI � 0.002, 0.017), confrming that caregiving burden positively afected anxiety via mastery and sleep quality in serial.

Discussion
In this study, we tested the relationships between caregiving burden, mastery, sleep quality, and anxiety among parental caregivers of children with leukemia in China.Particularly, we examined the mediating role of mastery and sleep quality in the relationship between caregiving burden and anxiety.
Our results indicated that caregiving burden, directly and indirectly, afects anxiety among parental caregivers.For the direct efects, this study shows that caregiving burden signifcantly elevated caregiver anxiety symptoms.Tis is consistent with the theoretical hypothesis of the stress process model [11,12], and it is also consistent with previous empirical evidence [8,10].Generally, the responsibility to care for a child with leukemia is a primary stressor for parents and has an adverse efect on their mental health.Caregivers' anxiety increases along with caregiving burden.Our fnding indicated that reducing subjective caregiver burden may help reduce caregivers' anxiety.Previous studies on caregiving behaviors of parental caregivers of children with leukemia in China have focused on coping strategies [48], psychological well-being [5], and quality of life [49].We expanded previous fndings by focusing on the specifc pathways that caregiving burden afects anxiety.
Regarding the potential mediators or indirect efects, this study confrmed that sleep quality mediates the association between caregiving burden and anxiety.On the one hand, sleep quality was independently associated with caregiver anxiety which is in line with former studies [14,17], and on the other hand, a more substantial caregiving burden diminishes caregivers' sleep quality and further elevates their anxiety [50].Sleep disruption is a prevalent symptom reported by caregivers triggered by caregiving burden [9], and it can lead to caregivers' executive dysfunction and role strain [14].Tus, poor sleep quality mediates the efect from caregiving burden on anxiety [51].
Mastery has been linked to caregiver outcomes in a variety of prior studies [20,52].Lower mastery is a major risk factor of poor physical health for parents of children with developmental disabilities [52].Greater mastery is linked to lower anxiety symptoms among dementia caregivers [20], Previous research also showed mastery mediates the relationship between caregiving burden and depression symptoms [12].Caregivers' mastery, as an intrinsic psychological resource, is prone to fuctuate when caregivers' duties are fulflled [12].When caregivers are exposed to stressful events, mastery not only exerts a bufering efect but also is directly afected by the stressful event.Tus, the ongoing care process will weaken the caregivers' sense of mastery.Tus, the sense of mastery mediates the relationship between caregiving burden and anxiety.In line with previous research [30], this study showed a signifcant correlation between mastery and sleep quality, suggesting that a lower level of mastery is correlated to worse sleep quality.Simpson et al. found that mastery and sleep quality on caregivers' health were inconsistent, i.e., the two did not work together [18].However, the present study showed that both mastery and sleep quality can afect caregivers' anxiety.Tis suggests that for parents of children with leukemia, high mastery and good sleep quality can serve as resources for coping with psychological distress.More than that, mastery may also have an indirectly efect on anxiety through sleep quality.Tis implies the importance of mastery in maintaining a better sleep quality and thus relieving anxiety among caregivers.
Te primary strength of this study is it demonstrated that mastery and sleep quality play multiple mediating roles between caregiving burden and anxiety.In prior studies, mastery and sleep quality were mediators between caregiving burden and mental health, separately [9], while few studies tested the linkage between them or explored the dynamic of their efects.Tis study provided a more comprehensive analysis of the process as well as the direct and indirect efects of caregiving burden on anxiety symptoms.Te contribution of the results of this study is to expand the researchers' theoretical understanding of mastery and sleep quality in the stress process model.On the one hand, secondary stressors, triggered by caregiving burden, play a mediating role in the relationship between the primary stressor and the caregiver's psychological well-being.On the other hand, there are interactions between secondary stressors.
Te fndings also have important implications for practitioners.Tis study implies the necessity to facilitate healthcare workers to identify and reduce parental caregiving burden.Particularly, in order to maintain caregivers' high levels of mastery, some related services could be considered, such as to provide knowledge of caregiving, as well as the information of the benefts, risks, and accessibility of treatment options [53].Moreover, caregivers may need assistance to be clear about their personal values to make decisions for children [54,55].Emotional support to caregivers could also be helpful to relieve emotional isolation [56].Additionally, it would be benefcial to build supportive communities for parental caregivers to acquire fnancial and social resources they need [57].

Study Limitations.
Tis study has a couple of limitations to recognize.First, respondents are heterogeneous in the progression of the children's disease and treatment.Since the caregiving burden and psychological features can vary a lot, the fndings could have been more specifc with a more homogeneous study sample.Second, since our study adopted a cross-sectional design, it is difcult to draw valid causal relationships between variables.Tird, the relatively small sample infuenced the power of the tests, although the tests were performed via bootstrap.Finally, in the context of   Health & Social Care in the Community China, except for parental caregivers, it could be common that other family members and kin participate in taking care of the sick children throughout phases of treatment, and some of them bear the primary caregiving responsibilities.Further research on their caregiving burden and well-being is warranted.

. Conclusion
Tis study provided empirical evidence that caregiving burden is a primary stressor and can trigger anxiety among parental caregivers of children with leukemia in China.Low mastery and poor sleep quality can be treated as secondary stressors leading to negative psychological outcomes for the caregivers.Practitioners can use the fndings to enhance the psycho-social support of this vulnerable group by connecting needed resources and facilitating supportive communities to reduce their caregiving burden, improve their sense of mastery, and assist children in their treatment and rehabilitation phases.