The relationship among social support, experienced stigma, psychological distress, and quality of life among tuberculosis patients in China

The complex relationships among social support, experienced stigma, psychological distress, and quality of life (QOL) among tuberculosis (TB) patients are insufficiently understood. The purpose of this study was to explore the interrelationships among social support, experienced stigma, psychological distress, and QOL and to examine whether experienced stigma and psychological distress play a mediating role. A cross-sectional survey was conducted between November 2020 and March 2021 in Dalian, Liaoning Province, Northeast China. Data were obtained from 473 TB patients using a structured questionnaire. Structural equation modelling was used to examine the hypothetical model. The research model provided a good fit to the measured data. All research hypotheses were supported: (1) social support, experienced stigma and psychological distress were associated with QOL; (2) experienced stigma fully mediated the effect of social support on psychological distress; (3) psychological distress fully mediated the effect of experienced stigma on QOL; and (4) experienced stigma and psychological distress were sequential mediators between social support and QOL. This study elucidated the pathways linking social support, experienced stigma, and psychological distress to QOL and provides an empirical basis for improving the QOL of TB patients.


Methods
Study design and setting. A cross-sectional, questionnaire-based survey was carried out between November 2020 and March 2021 at three TB medical institutions in Dalian, Liaoning Province, Northeast China. The three medical institutions were selected based on the number of patients attending, type of patient and location. The first is the only tertiary specialized hospital for TB prevention and control in Dalian and is divided into northern and southern parts located in Ganjingzi District and Pulandian District, respectively. It currently has nearly 500 beds, serving the whole city's TB patients, especially critically ill TB patients, as the main medical institution for TB patients in Dalian. The other two institutions are TB dispensaries located in Lushunkou District and Zhuanghe City (a county-level city), which serve only local TB patients with a milder instance of the disease.

Participants. TB patients who attended the selected TB medical institutions between November 2020 and
March 2021 were recruited as participants. The inclusion criteria were patients with a definite TB diagnosis according to national TB program guidelines, aged 18 years or older and with a new or relapsed case of TB undergoing treatment. The exclusion criteria were patients with psychosis, communication problems, or difficulty understanding the questionnaire and completion of treatment. A total of 481 patients were recruited and completed a structured questionnaire. Of the 481 questionnaires obtained, eight were excluded due to logical errors or large amounts of missing data. Ultimately, this study included 473 TB patients, with a participation rate of 98.34%.
Ethics procedure. Ethical approval was provided by the Ethics Committee of Dalian Medical University, Liaoning Province, China. Before participating in the study, each participant was informed of the purpose of the study and how the results would be presented and received guarantees that their personal information would not be disclosed. Each participant voluntarily signed an informed consent form to participate in our study. All methods in our study were conducted in accordance with relevant guidelines and regulations (Declaration of Helsinki).

Measurement.
A structured questionnaire consisting of questions concerning demographic characteristics, treatment status, social support, experienced stigma, psychological distress, and QOL was developed by reading a large amount of relevant literature and consulting experts in related fields. Demographic characteristics included sex, age, marital status and education level. Treatment status included the category of TB treatment, phase of treatment and self-assessed disease severity.
Social support. Social support was measured using the Oslo 3-item social support scale, a 3-item questionnaire that is commonly used to assess social support-related issues in clinical and community settings 44 . This questionnaire contains questions that ask patients about the number of people they feel close to and on whom they could count on for serious problems, how much people cared about them and the ease with which they could receive practical help from neighbours. Its overall score ranges from 3 to 14, with a high score indicating a high level of social support. In the current study, the scale's Cronbach's α reliability coefficient was 0.718.
Experienced stigma. Experienced stigma was assessed using a 9-item stigma questionnaire developed in accordance with Chinese social and cultural contexts 45 . The questionnaire assesses the stigma experienced by patients on the three dimensions of prejudice, discrimination, and rejection. Responses to each item were rated on a 4-point Likert scale, ranging from strongly disagree (= 1) to strongly agree (= 4). The scores of each item were summed to obtain the total score (range 9-36). Higher scores indicate higher levels of stigma experienced by TB patients. The scale showed good reliability and validity, and its Cronbach's α in this study was 0.946.
Psychological distress. The Kessler Psychological Distress Scale (K-10) questionnaire was used to assess psychological distress in TB patients 46 . Numerous studies have demonstrated the reliability and validity of this scale 30 . The scale is composed of 10 items divided among four subscales: nervousness, agitation, fatigue and negative affect 47 . Negative affect includes hopelessness, low mood, sadness and a sense of worthlessness. An example of such an item is "How often did you feel hopeless in the last 30 days?". The frequency of each item was recorded on a 5-point Likert scale, ranging from none of the time (= 1) to all the time (= 5). The overall score ranged from a low of 10 to a high of 50, indicating an increase in psychological distress. In this study, the scale had high internal consistency (Cronbach's α = 0.929).
QOL. The QOL is an index of the satisfaction levels of the body, spirit, family and social life and the overall evaluation of life 48 . In the current study, a 6-item quality of life scale (QOL-6) developed by Phillips in 2002 was used to measure QOL in TB patients 49 . This scale consists of six items covering physical health, psychological health, economic circumstances, work, family relationships and relationships with nonfamily members. Patients were asked to rate the extent to which the six traits reflected their actual life situation over the past month. Each item was recorded on a 5-point Likert scale, ranging from very poor (= 1) to excellent (= 5). The overall score ranged from 6 to 30, with a high score reflecting good QOL. This scale has been used to assess the QOL of differ- Statistical analysis. The complete and correct questionnaires were inputted into the database established using EpiData 3.1 software (EpiData Association, Odense, Denmark) by double entry to ensure the accuracy of the data. The data were exported to SPSS 21.0 (IBM Corporation, Armonk, State of New York) for preliminary statistical analysis. Descriptive statistical analysis included the frequency and percentage of classified data and the mean and standard deviation (SD) of continuous data. T tests and analysis of variance were used to compare QOL scores among different groups. Pearson correlation analysis was used to evaluate bivariate correlations. All comparisons were two-tailed, and P < 0.05 was considered statistically significant. When multiple potential mediating variables and complex relationships were considered in the research model, we used AMOS 23.0 software (IBM Corporation, Armonk, New York, USA) to conduct structural equation modelling (SEM) to test the hypotheses. Confirmatory factor analysis (CFA) was carried out to test the reliability and validity of the constructs and combined with SEM to improve the research model 42 . The maximum likelihood method was used to estimate the parameters. Additionally, the 95% confidence interval (CI) was calculated using bootstrapping with 5000 resamples for all effects 52 . The bootstrapping performed was a non-parametric test that does not rely on assumptions of normal distribution, and the effect was considered statistically significant if the 95% CI did not include zero. The goodness-of-fit index (GFI), comparative fit index (CFI), Tucker-Lewis index (TLI), standardized root mean square residual (SRMR), and root mean squared error of approximation (RMSEA) were calculated to examine the fit of the model. GFI, CFI and TLI values were greater than 0.900, and SRMR and RMSEA values were less than 0.080, indicating adequate goodness of fit 53 .

Results
Participants' demographic characteristics and treatment status. Among the 473 participants, the mean age was 48.36 (SD = 17.58) years, and most participants (60.04%) were aged 45 years or older. There were more than twice as many male participants (69.13%) as female participants (30.87%). There were slightly more participants with a high school education or above (34.88%) than those with a middle school education (33.19%) or a primary education or below (31.92%). Nearly two-thirds of the participants (65.33%) were married, and only 72 (15.22%) had relapsed. More than half of the patients (59.20%) were in a continuous phase of treatment, and nearly one-third (29.60%) felt that their current condition was severe. Among the respondents, the average QOL score was 20.41 (SD = 3.65). Age, marital status, education level, treatment category, treatment phase and self-assessed severity were significantly associated with QOL (P < 0.05) ( Table 1).  18.86 (SD = 7.14), and 19.62 (SD = 7.49), respectively. Social support was negatively correlated with experienced stigma (r = − 0.263, P < 0.01) and psychological distress (r = − 0.151, P < 0.01) and positively correlated with QOL (r = 0.579, P < 0.01). In addition, experienced stigma was positively correlated with psychological distress (r = 0.453, P < 0.01) and negatively correlated with QOL (r = − 0.429, P < 0.01). Psychological distress was negatively correlated with QOL (r = − 0.480, P < 0.01) ( Table 2).
Reliability and validity of the constructs. Through factor analysis, the unstandardized estimates of each item were significant (P < 0.001), and the standardized factor loadings of each item were > 0.5, which met the physical requirements of factor analysis, indicating that each item has a substantial effect on the measurement of latent variables. The CR value represents the internal consistency of the construct. The higher the CR is, the greater the internal consistency of the tested factors. In this study, all CR values were > 0.7, indicating that the constructs exhibited acceptable internal consistency. Moreover, AVE is the average of the explanatory power of the calculated latent variable to the observed variable. The higher the AVE is, the higher the convergent validity. The value of AVE is recommended to be greater than 0.5. In this study, the AVE ranged from 0.500 to 0.819, which implied that the interpretation degree of latent variables with respect to the observed variables was good and the convergent validity of the constructs was high. The values of √ AVE s in the diagonal were greater than or slightly lower than the Pearson correlation coefficient of other related constructs. This fact indicates that the discriminant validity among factors is significant and that each factor can be well separated. Overall, these constructs exhibited good reliability and validity 54,55 (Tables 3, 4). Table 5 shows the fit indices of the overall research model. To evaluate the fit of the overall model, the following commonly used fitness indices were used: Chi-square test of the model fit = 395.162; degrees of freedom = 125; Chi-square/DF = 3.161; GFI = 0.914; CFI = 0.939; TLI = 0.916; SRMR = 0.072; RMSEA = 0.068. In this context, GFI, CFI and TLI values greater than 0.900 indicate good model fit. SRMR and RMSEA values less than 0.080 suggest adequate model fit. All the fitness indices in the current study met the practical standards or thresholds and reached the ideal level, which indicated that the overall research model fit well 56 (Table 5).   Figure 2 shows the research model with unstandardized path coefficients. Age, marital status, education level, treatment category, treatment phase and self-assessed severity acted as covariates. Education level was positively associated with QOL (β = 0.131, P < 0.001), while selfassessed severity was negatively associated with QOL among TB patients (β = − 0.095, P < 0.05). As shown in Table 6, the total effect of social support on psychological distress was − 0. , accounting for 88.36% of the total effect. In addition, social support significantly predicted QOL via the sequential mediation variables of experienced stigma and psychological distress (95% CI (0.017, 0.058) and (0.016, 0.057)), whose estimated multiple indirect effect was only 0.033, accounting for 6.30% of the total effect. In sum summary, all the hypotheses were supported (Fig. 2, Table 6).

Discussion
Patients with TB often have symptoms such as cough, chest pain, low fever, fatigue, and loss of appetite. In addition, the treatment of TB is a complex and lengthy process, requiring many medications and a long period of treatment. These factors significantly affect the QOL of patients 17 . However, to date, the complex relationships among social support, experienced stigma, psychological distress, and QOL in patients with TB have not been fully explored. To our knowledge, this study was the first to use SEM to explore the interrelationships among social support, experienced stigma, psychological distress, and QOL and to examine whether experienced stigma and psychological distress play mediating roles.
In the current study, factor analysis indicated that each construct displayed good reliability and validity, which further verified the stable structure of the scale in TB patients and provides a basis for future studies to measure the social support, experienced stigma, psychological distress, and QOL of TB patients. More importantly, the fitness indices exhibited good model fit, indicating that our proposed research model is reasonable and provides key information for improving the QOL of TB patients. Moreover, this study found that education level was associated with QOL in terms of demographic characteristics. Previous studies have also demonstrated that education level is an important predictor of QOL, such that a higher education level has a positive effect on the QOL of TB patients 2,9 . Patients with higher levels of education contribute to greater knowledge about TB from the outside world. Knowledge of TB can improve health-related behaviors such as taking anti-TB drugs on time and seeking care in a timely manner 57 . This will contribute to the effective control of the disease and reduce the  58 . Patients with low self-efficacy also have stronger stigma experience 59 , which increases the risk of psychological distress and affects the QOL of patients. This study also found that patients with perceived severe illness had worse QOL than those with mild illness. Previous studies have also demonstrated that worse physical symptoms are associated with lower physical health-related QOL and higher mental health-related QOL among TB patients 60 . Understandably, patients with more severe disease have more complex clinical conditions and longer treatment times, as well as increased patient concerns, which may be particularly damaging to QOL. In addition, it is understandable that the more severe the illness are, the more obvious the symptoms. Obvious symptoms, especially a prolonged cough, may lead to a greater degree of accidental disclosure of the illness. This will have a negative impact on access to social support, increase stigma and psychological distress and threaten QOL.
The results also showed that social support demonstrated a significant, direct effect on the QOL of patients with TB. Social support helps improve patients' QOL 20 , which has also been found in studies on patients with traumatic brain injury 61 . A possible explanation is that patients who receive adequate social support might have improved health outcomes. Moreover, consistent with previous studies, stigma was a predictor of QOL 62 . Stigma can damage patients' self-esteem and self-efficacy, lead to patients' isolation from society and self-concealment, and ultimately endanger patients' QOL 63 . In addition, psychological distress exerted a direct effect on QOL in our study. Studies have reported that untreated depression is independently associated with poorer QOL 39 . Another study also demonstrated that mental distress had a significant effect on QOL 6 . Patients with psychological distress were less likely to adhere to treatment regimens, thus eliminating the chance of successful treatment, impairing their function, and reducing QOL 39,64 .
Previous research has demonstrated that patients who receive an adequate amount of social support are likely to have the best mental health outcomes 20 . Our results suggest that social support can also have an indirect negative effect on psychological distress through experienced stigma. Sufficient social support can increase patients' self-esteem and make patients more likely to be diagnosed in a timely manner and to comply with treatment, thus reducing the occurrence of psychological distress 65,66 . In addition, our results confirmed that psychological distress moderated the relationship between experienced stigma and QOL. It is not difficult to understand that the experience of stigma will lead to patients' feelings of inferiority, lack of confidence and low emotional well-being, which threaten patients' emotions and cause psychological distress, thus affecting their QOL 33 . Our results also indicated that experienced stigma and psychological distress are sequential mediators from social support to QOL, a relationship that has not been demonstrated in previous studies. However, the findings seem www.nature.com/scientificreports/ logical because patients with better social support have more emotional and financial resources, which makes them face less discrimination and stress, and are likely to use drugs with fewer side effects; thus, they may have improved QOL 65,67 .
In the current study, SEM was used to test the mediating variables. In epidemiological studies, the assessment of mediation has been widely used to open up the "black box", allowing us to discern complex relationships between variables 68 . In practice, understanding the interrelationships among social support, experienced stigma, psychological distress and QOL provides an opportunity to intervene effectively in QOL among patients with TB, and it allows for interventions to be tailored to these specific pathways. Specifically, interventions aimed at improving the QOL of TB patients should focus on increasing social support for patients. At the same time, the role of experienced stigma and psychological distress should also be understood and addressed. Given that experienced stigma and psychological distress mediated the effect of social support on QOL in TB patients, interventions should be combined with measures to eliminate stigma and reduce psychological distress. This was essential for improving the QOL of TB patients. Previous studies have demonstrated that family functions and doctor-patient communication are the most important sources of social support for patients 69 . The attitude of family members has an important influence on TB patients. There are widespread psychological burdens among TB patients, such as lack of confidence in a cure and fear of treatment failure 70 . Constant encouragement from and care by family members can increase patients' confidence and their feelings of being taken care of. Therefore, family members can be educated and trained to provide better support for patients. Doctors also play an important role in the treatment of TB, and a good doctor-patient relationship is the fundamental factor to ensure the normal operation of the treatment process. It is necessary to require medical staff to establish the concept of patient-centred service and to show respect and humanistic care in the process of medical service delivery 71 . It is also important to provide more financial support for patients. Although the country has established some free TB treatment policies, some items, such as the cost of expensive adjuvant drugs, are not included in the free package. Previous studies have also found that TB clubs, composed of health workers and TB patients, have been successful in reducing stigma among TB patients 72 . In addition, community awareness and patient education may contribute significantly to a reduction in stigma 73 .
This study has several limitations that need to be addressed in future studies. First, although SEM was applied, the causal relationship between the variables could not be inferred due to the cross-sectional nature of the data. Therefore, longitudinal studies are needed to validate the current findings. Second, the study sample only included TB patients from Dalian, Liaoning Province, Northeast China, which limited the ability to generalize the results to individuals from other regions with different social and cultural backgrounds. Future research should www.nature.com/scientificreports/ expand the study area to determine the suitability of our study model. Additionally, the study was limited to TB patients who already had access to health care, while those who did not seek any care were not recruited. The latter are probably the most marginalized and affected by TB, and their participation could enrich our findings. The study also did not include healthy people as controls. Therefore, the results may not capture the impact of TB on patients alone. Finally, only quantitative analysis was conducted in this study, and data were collected through patient self-reports. Patients may hide certain facts, which may cause our results to be underestimated. Extensive interviews and qualitative analysis are needed for a more comprehensive assessment.

Conclusion
This study empirically explored the interrelationships among social support, experienced stigma, psychological distress, and QOL and tested whether experienced stigma and psychological distress played a mediating role.
Using the SEM method, we found that (1) social support, experienced stigma and psychological distress affect the QOL of patients with TB; (2) experienced stigma mediates the relationship between social support and psychological distress; (3) psychological distress mediates the relationship between experienced stigma and QOL; and (4) experienced stigma and psychological distress are sequential mediators from social support to QOL. Understanding and managing the QOL of TB patients may lead to better outcomes, and the results of this study provide useful information to help TB patients achieve better QOL.

Data availability
The datasets generated and/or analysed during the current study are available from the corresponding author on reasonable request.