Health literacy and fatigue, anxiety, depression, and somatic symptoms in patients with differentiated thyroid carcinoma from West China: A cross‐sectional study

Abstract Background and Aims Differentiated thyroid carcinoma (DTC) patients are associated with excellent prognosis but impaired health‐related quality of life (HRQOL) by initial and subsequent therapy. Health literacy plays a pivotal role in public health and medical settings, but data on its relationship with DTC patients' HRQOL are insufficient and equivocal. This study was designed to explore the relationship between health literacy and HRQOL in patients with DTC from West China areas. Methods A cross‐sectional study with a descriptive correlational design was conducted. 126 patients with DTC were recruited between 2020 and 2021. Levels of health literacy and HRQOL (including fatigue level, anxiety/depression status, and somatoform symptoms) were assessed by questionnaires. Pearson product–moment correlation and Stepwise multiple regression were used to examined the adjusted association of health literacy with HRQOL. Results Health literacy and receiving DTC‐related education together explained 16.2% of the variance in fatigue level. Patients who had higher health literacy, received more DTC‐related education were currently employed and less fatigue. Health literacy, fatigue level and DTC‐related education together explained 31.0% of the variance in anxiety and depression of DTC patients. Patients who had higher health literacy, received more DTC‐related education and less fatigue level were less anxious and depressive. Age explained 8.3% of the variance in DTC patients' somatoform symptoms. Older patients complained more somatoform symptoms. Conclusion Health literacy was positively associated with HRQOL in DTC patients regarding to fatigue level and anxiety/depression status across the entire sample. Interventions to improve HRQOL should take the patients' health literacy into account.


| INTRODUCTION
In recent decades, the incidence of differentiated thyroid cancer (DTC) has dramatically increased worldwide, mostly due to the advantages of thyroid gland imaging techniques and other diagnostic methods. 1,2 With incidence increasing every year, now DTC is the fifth most common cancer diagnosed in women in the United States in 2017, 3 and this trend can also be observed in China. 4 Papillary thyroid carcinoma and follicular thyroid carcinoma are the most common DTC, and its standard treatment includes thyroid surgery (either total thyroidectomy or hemithyroidectomy), for some, followed by radioiodine (131I) thyroid remnant ablation therapy and require thyroid hormone replacement. Most DTC patients can be cured by proper treatment, with approximately 90%-95% 10-year survival rate. 5 Although the good prognosis and moderate invasiveness of the common therapies, the health-related quality of life (HRQOL) 6,7 is still negatively affected in patients with DTC compared with general population. [8][9][10] Of note, the overdiagnosis of low-risk DTC has raised concerns recently, and the associated overtreatment also brought substantial impacts on the HRQOL of these patients. 1,11 For example, all the therapeutic options described above possess potential adverse effects and consequences, including vocal cord paralysis, hypoparathyroidism after thyroidectomy, and hyperthyroidism after supraphysiologic doses of thyroid hormone to suppress thyrotropin levels. 12 A couple of comparative studies found multiple aspects of HRQOL can be impaired by these treatments, including vitality, rolephysical, mental health, role-emotional and social functioning. [8][9][10]13 Health literacy is "the degree to which individuals have the capacity to obtain, process and understand basic health information and services needed to make appropriate health decisions," 14 defined by the US Department of Health and Human Services (HHS) and the National Academy of Medicine (NAM). Health literacy is one of the most important determinants of health and medical outcomes. Poor or inadequate health literacy results in difficulties in understanding health information, limited knowledge of diseases, increased risk for emergency care and hospitalizations, poor medication adherence, higher mortality rates, increased costs, and health disparities. [14][15][16] Increasing studies have shown that health literacy could directly or indirectly influence the HRQOL of patients. For example, health literacy was shown to be significantly associated with self-care skill and self-efficacy in patients with diabetes, 17 and limited health literacy was correlated with a poorer social quality of life in head and neck cancer patients. 18 However, other reports revealed that adjusting health literacy did not change self-efficacy and selfmanagement associations in diverse low-income populations in urban areas, 19 and no significant relationship between health literacy and HRQOL among patients with rheumatic diseases. 20 Despite the inconsistent findings in the literature, health literacy is needed for all people, for instance, to find their way to the right place in a hospital, fill out medical and insurance claim forms, and communicate with physicians and nurses. Health literacy is also important to DTC patients, since limited health literacy may lead to difficulties in interpreting thyroid stimulating hormone (TSH), free thyroxine 4 (FT4), free thyroxine 3 (FT3), and thyroglobulin (Tg) reading. It will also lead to poor performance in adjusting medication, avoiding iodized food intake, and performing other self-care activities.
Currently, the relationship between health literacy and HRQOL is still poorly defined. Nickel et al 21 identified that patients diagnosed with DTC reported wide-ranging HRQOL issues, but the correlation with health literacy was still unclear. Therefore, here we perform this study to decipher the association between health literacy and HRQOL in patients with DTC.

| Participants and setting
Our study relied on patients diagnosed with DTC who were initially received total thyroidectomy or hemithyroidectomy, and admitted

| Ethical considerations
This study was approved by the Ethical Committee of Sichuan Provincial People's Hospital (IRB No. CTR2020321). Each participant received an oral explanation of the research, and we received inform consent from all individuals who agreed to participate in the study. All data will be held securely in accordance with Data Protection Regulations. Patient confidentiality will be maintained at all times.
Findings will be widely disseminated in peer-reviewed journals, at conferences, through user networks, and to policy makers and relevant clinical groups.

| Socio-demographic characteristics
The following socio-demographic characteristics of patients were recorded: age, gender, ethnicities, educational level, marital status, employment status, living arrangement, and income level. The section of 'highest attained educational level' falls into five categories including: no formal schooling, elementary school (Grade 1-6), junior high school (Grade 7-9), high school (Grade 10-12), and college and above.
The attendance of DTC-related teaching classes held by Sichuan Provincial People's Hospital in the past 12 months was also recorded.

| Health literacy
The health literacy was measured by the scale of "Health Literacy for Chinese Citizens-Basic Knowledge and Skills (HLCCBKS)", which was developed by Chinese Ministry of Health in 2008. 22,23 This 66-item questionnaire addresses three dimensions: 25 items of basic knowledge and belief, 34 items of health lifestyle and behavior, and 7 items of basic skills. Scores are summed to give a total range from 0 to 66; higher scores represent greater health literacy.
In the current study, Cronbach's alpha coefficient was 0.82 for the overall scale, and for the three dimensions (basic knowledge and belief, health lifestyle and behavior, and basic skills), it was 0.81, 0.78, and 0.86, respectively.

| HRQOL questionnaires
Three health-related questionnaires that were validated by previous studies were used to measure the HRQOL of DTC patients.

Multidimensional Fatigue Index-20 (MFI-20)
Since posttreatment fatigue is one of the most common and important complaints in DTC patients, 24

Hospital Anxiety and Depression Scale (HADS)
The HADS is a well-established self-report tool to understand the emotional distress and anxiety in the setting of medical practice, 26,27 and is frequently utilized in various cancers, [28][29][30] and other diseases. 31,32 The HADS contains 14 items with seven to assess anxiety and seven to assess depression. Scores for the anxiety and depression subscale range from 0 to 21, and the score is interpreted as: 0-7, no depression or anxiety disorder; 8-10, mild depression or anxiety disorder; 11-14, moderate disorder; and 15-21, severe disorder. In the present study, Cronbach's alphas were 0.78.

Screening for Somatoform Symptoms-7 (SOMS-7)
This questionnaire covers all somatic symptoms mentioned as occurring in somatization disorder, according to Diagnostic and

Statistical Manual of Mental Disorders fourth edition (DSM-Ⅳ) and International Statistical Classification of Diseases and Related
Health Problem-10 (ICD-10). 33 The scale (51 items for men and 53 items for women) assesses the severity of signs and symptoms according to the grading criteria, which is from 0 for the lowest intensity to 4 for the maximum intensity. The total score expresses the extent of physical complaints presented in the last seven days. The Cronbach's alphas were 0.86 in the current study. Potential participants were screened for inclusion and exclusion criteria. If eligible, the investigator explained the study purposes and procedures, and the participant's rights to participate or to refuse participation without jeopardizing medical care. Individuals who were interested in participating in the study signed an informed consent that explained study procedures and assured confidentiality. After obtaining informed consent, participants were asked to complete the self-report questionnaires.

| Data analysis
The participants' demographics and study features were described using percentages, means, and standard deviations (SDs). The

| Relationships among health literacy associated with demographics, disease variables, health literacy, and HRQOL factors
The health literacy was found significantly associated with the employment status of the participants. The participants who were currently working at the time of interview showed a higher level of health literacy compared with those unemployed (t = 3.17, p = 0.002).
While in regarding to age, gender, marital status, education level, living arrangement, and frequency of having DTC education, no significant association with health literacy was identified (Table 1).

| Factors associated with fatigue level
The DTC patients' score of MFI-20 was not correlated with the sociodemographic characteristics as described in

| Factors associated with anxiety and depression
No association was detected between the demographic characteristics (gender, marital status, education level, employment status, and living arrangement) with anxiety and depression (HADS scores) of DTC patients (Table 1)

| Factors associated with somatoform symptoms
The basic demographics characteristics were not associated with DTC patients' somatoform symptoms, which was shown in Table 1.
The age of patients (r = 0.300, p = 0.001) were positively correlated with the SOMS-7 scores (

ACKNOWLEDGMENTS
The authors thank the study participants. No funding source or financial relationship have any role in the study design, data collection, analysis and interpretation, writing of the manuscript or the decision to submit the manuscript for publication.

CONFLICTS OF INTEREST
Some figures in this paper were created with the help of BioRender software. The authors declare no conflicts of interest.

DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request. Restrictions apply to the availability of these data, which were used under license for this study.

TRANSPARENCY STATEMENT
The lead author XianXiu Wen affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.