Development and Assessment of The Quality of Life Instruments for Chronic Diseases-Gout(QLICD-GO) (V2.0)

Background: To develop and assess the Quality of Life Instruments for Chronic Diseases-Gout (QLICD-GO [V2.0]). Methods: The instrument was developed using a programmatic decision-making method to combine the general module of the Quality of Life Instruments for Chronic Diseases and a new specic module. The instrument was assessed by measuring the quality of life of 116 patients with gout. Results: The QLICD-GO(V2.0) included 28 items from the general module of chronic diseases and 12 items in three facets from the specic module. In addition to the eld of physiological function, the internal consistency reliability of other elds and dimensions of the instrument was >0.7 and the split-half reliability was >0.5. Three common factors were extracted from the specic module, with a cumulative variance contribution rate of 57.54%. The standardized response means of the specic module and the whole instrument were 0.94 and 1.20, respectively. Conclusions: The QLICD-GO(V2.0) has good reliability, validity, and responsiveness. The instrument comprehensively and objectively reects the quality of life of patients with gout, and it can be used to assess treatment regimens developed by medical staff.


Background
In recent years, despite the variations in reports across countries, there has been a clear upward trend in the incidence of gout [1]. Gout is a chronic disease caused by an elevation in the serum urate level [2]. In Western Europe, 1-2% of adults have been affected by gout, while the proportions have reached 4% in developed countries such as the United States and the United Kingdom [3]. Male patients outnumber female patients at a ratio of approximately 3:1. The prevalence of gout in China is about 1.1%, which is increasing year by year. The age of gout is also becoming younger [4]. The prevalence of gout is increasing with socioeconomic development and changes in diet structure [5]. This system includes a general module (QLICD-GM, V1.0), which can be used with all types of chronic disease patients, and speci c modules for different diseases, with each module being used for only the relevant disease [6]. Based  League Against Rheumatism Gout Classi cation Criteria [7]. The eligible patients had basic literacy skills. Pre-and posttreatment quality of life (QOL) assessments were performed after informed consent was obtained.

Instrument development
The QLICD-GO(V2.0) was developed by combining the widely recognized general module of the Quality of Life Instruments for Chronic Diseases (QLICD-GM) with a speci c module for gout. This general module, consisting of 28 items in three domains (physical function, psychological function, and social function), has previously been formulated on the basis of topic discussion, interviews with and investigations in patients with different chronic diseases and medical staff, and multiple discussions, analyses, screening, and revisions by research team members.
With reference to relevant literature and QOL instruments (universal and speci c instruments) for patients with gout from China and abroad and in combination with clinical expertise on gout, we proposed a pool of 34 health-related QOL items speci cally for patients with gout, covering gout-induced impacts on the physical, psychological, and social functioning of patients, and drug-related side effects. Each potential item for the gout-speci c module was analyzed at meetings of the topic panel and core panel. Thirteen items for the speci c module were selected and were organized into a patient questionnaire and a medical staff questionnaire. Based on ve methods to screen items and the opinions of clinical experts, a 12-item gout-speci c module was formed.
The QLICD-GO(V2.0) is divided into four aspects, including physical symptoms and signs (six items), functional limitation to daily life (one item), common drug-related side effects (two items), and unique psychological effects (three items). A ve-point Likert scoring method is used, with possible scores between 1 and 5 or between −5 and −1. The higher the score of a positive item, the better the QOL; the greater the absolute value of the score of a negative item, the worse the QOL. For positive items, there is no need to convert, the original score is the item score, for reverse items, it is necessary to "forward transform", that is, subtract the original score from 6 to get the item score. October 2015 and December 2016, the investigator brie y explained the purpose of the survey and distributed  the instrument to the patients, who lled in the instrument independently according to their actual conditions in the Rheumatic immune   clinic and rheumatic immune Department of A liated Hospital of Guangdong Medical University. Because most patients with gout were outpatients, the subjects ll out the instrument on the day of initial consultation and on the day of subsequent consultation. Inclusion criteria: gout was diagnosed according to the 2015 American rheumatology society / European anti rheumatism alliance gout classi cation standard [8]. Primary school and above education level, clear awareness can ll in the questionnaire. No mental illness or consciousness disorder. No exclusion criteria. Exclusion criteria: The patient had joint pain and dysfunction caused by other rheumatic diseases.

Data collection Between
Combined with hypertension, diabetes and other chronic history and cancer history. It is associated with heart, liver, lung, kidney and other visceral diseases. Illiterate, delirious, mentally ill, critically ill, unwilling to cooperate. we use SF-36 as the calibration standard, because the calibration validity is lack of gold standard, and SF-36 is a widely recognized tool for measuring QOL [9].

Statistical analysis
SPSS 21.0 statistical software was used for data entry and analysis. The statistical methods included the following two categories: methods for instrument item screening (coe cient of variation, correlation analysis, and factor analysis) and methods for instrument assessment (paired t-test and correlation analysis).

Patient and Public Involvement
In this experiment, QLICD-GO(V2.0) was developed by combining the common module of chronic diseases with the speci c module of gout. The common module of chronic diseases is now mature. We need to develop a speci c module of gout. It is divided into issue group and core group, mainly composed of life quality researchers, rheumatology immunologists, epidemiologists, public health scholars, sociologists and other personnel at all levels. The selection of the main items of the topic group, the later development and evaluation of the main scale of the core group, nally formed the speci c module of the gout scale.
The scale is patient self-rated. The researcher made a brief introduction to the questionnaire to the respondents. Under the condition of the patients' willingness, the questionnaire was distributed to the patients, and then it was taken back after the patients completed the questionnaire, and carefully checked whether there was any missing item. If there was any missing item, the researcher reminded the respondents to supplement it. If it still could not be lled in, it was treated as the default value and recorded the reason. Since the majority of gout patients are outpatients, in principle, the subjects ll in a questionnaire on the day of inquiry and the day of follow-up.

General information
A total of 116 outpatients (aged 46.81 ± 16.38 years) with gout were investigated in this study. The details are presented in Table 1.   Table 2 for details).

Construct validity
Since assessment of the construct validity of the general module of the instrument has been completed at an early stage, only the construct validity of the speci c module was assessed in this section, mainly using exploratory factor analysis and itemdimension correlation analysis.
Exploratory factor analysis: Bartlett's test of sphericity of the speci c module of the instrument yielded a χ 2 value of 471.93 (P < 0.001), indicating that the variables were not independent and were suitable for factor analysis. In addition, the Kaiser-Meyer-Olkin (KMO) measure of sampling adequacy was 0.76 in this study, indicating that factor analysis was suitable (factor analysis is not suitable when KMO is <0.5).
The principal component analysis method was used to extract common factors. According to the above discussion and eigenvalue >1, three common factors were extracted for the instrument after varimax rotation. The cumulative variance contribution rate was 57.54%. Factor I included GO7 and GO10-GO12 and mainly re ected the psychological changes in patients with gout; Factor II included GO1-GO4 and mainly re ected the clinical symptoms and signs in patients with gout; Factor III included GO5, GO6, GO8, and GO9, and it mainly re ected the persistent conditions and long-term drug-related side effects in patients with gout. The contribution rates of the three factors were 34.79%, 11.89%, and 10.86%, respectively. Among them, Factor I had the highest contribution rate. Broad consistency between the items re ected by these factors and the results obtained after screening and discussion of speci c module items in the instrument indicates relatively good construct validity of the speci c module items. The speci c module factors and the factor loading coe cients of items are presented in Table 3 and Figure1. Item-dimension correlation: Coe cients of correlation between each item of the QLICD-GO (V2.0) and the scores of the general module's physical, psychological, and social domains and the gout-speci c module were calculated. Correlation analysis showed relatively large coe cients of correlation between most items and their domains but small coe cients of correlation between these items and other domains, and the r values were mostly above 0.4. For example, the items of speci c module unsurprisingly had closer correlations with the speci c module areas than with the other three areas. It can be concluded that there were good correlations between QLICD-GO(V2.0) items and their dimensions and therefore satisfactory construct validity (see Table 4 for details).   Table 5). The QLICD-GO(V2.0) therefore has relatively good criterion validity.

Responsiveness analysis
To evaluate the responsiveness of the QLICD-GO (V2.0), differences between pre-and posttreatment scores were calculated for each domain, the general module, and the whole instrument using the paired t-test, and the SRM was also calculated. The SRM is de ned as the absolute ratio of the mean difference between pre-and posttreatment values to the standard deviation of the difference between pre-and posttreatment values. The analysis showed signi cant differences between pre-and posttreatment scores for the domains, the general module, the speci c module, and the whole instrument (P < 0.05). The SRMs were above 0.90 for the whole instrument and all domains except psychological function and social function, indicating that the QLICD-GO(V2.0) has favorable responsiveness and is sensitive in re ecting changes in the QOL of patients with gout. The details are presented in Table 6 and Figure 2.

Discussion
The QLICD-GO (V2.0) has been developed for patients with gout based upon the foundation of the QLICD system, namely, the general module of the QLICD (QLICD-GM). The QLICD-GO(V2.0) re ects the clinical signs and symptoms, drug-related side effects, and psychological changes speci c to patients with gout. The QLICD-GO (V2.0) consists of two parts, the mature general module and the speci c module developed in this study, which includes 12 items (six items in clinical signs and symptoms, two items in drug-related side effects, and four items in unique psychological changes).
Item screening is one of the key steps in the development of any QOL instrument, which should adhere to the principles of high sensitivity, good representativeness, strong independence, su cient certainty, and great signi cance [10]. Reliability refers to the repeatability or consistency of item scores [11]. Validity re ects the degree of conformity between the measured results of the instrument and the expected results [12]. Content validity refers to whether the selected items are capable of representing the characteristics of the measured content or subject [13]. Construct validity performs a factor analysis of all items based on the results of the survey, and classi es the items according to the loading of each item on each factor [14]. Responsiveness re ects the sensitivity to re ect changes in characteristic values of a subject [15]. Based on the assessment results, the QLICD-GO (V2.0) has good reliability, validity, and responsiveness. Zhang [16] has recommended 0.70 as the minimal Cronbach's α coe cient of internal consistency that would indicate relatively good internal consistency reliability. The The QLICD-GO (V2.0) has been carefully developed according to an established scienti c program, and it has shown good reliability, validity, and responsiveness in this initial assessment. It can objectively and comprehensively re ect the QOL of patients with gout and can be used by clinical staff to assess treatment regimens. The QLICD-GO (V2.0) was developed in the context of Chinese culture and provides a good basis and platform for measurement and assessment of the QOL of patients with gout in China.

Strengths And Limitations Of This Study
After many times of modi cation and investigation, the QLICD-GO(V2.0) has been investigated and modi ed on the basis of QLICD-GO (1.0), which has better reliability, validity, and responsiveness. QLICD-GO(V2.0) has the characteristics of Chinese cultural background, which provides a good foundation and platform for the measurement and evaluation of gout patients' quality of life in China. However, there are some shortcomings. The sample size of QLICD-GO(V2.0) is not large, which may affect the experimental results. QLICD-GO(V2.0) needs to be further validated, and the sample size needs to be expanded to provide more accurate results. Our sample objects are mainly from the outpatient department of the hospital. For patients who do not visit the outpatient department of the hospital, the applicability may not be strong. The longitudinal reactivity has not been tested in this study. In the long run, it is very important to see if QLICD-GO(V2.0) changes.
These are also aspects that we need to actively modify in the future.
In general, QLICD-GO(V2.0) can be used as a useful tool to measure and evaluate the quality of life of Chinese speaking gout patients. We thank all the participants for their contribution to this work.

Conclusion
Author contributions QL L and X L contributed equally to this work. QL L and CH W designed the study. XH X and XJ W did the literature search, study quality assessment and data extraction. JW R and XS Z performed the statistical analysis and drafted the tables and gures. X L wrote the rst draft of this analysis, and QL L helped to nish the nal version. All authors approved the conclusions of our study.
Ethics approval and consent to participate: After reviewing the ethics committee of the Guangdong Medical University A liated Hospital, the project is reasonably designed, advanced and practical. The study is in line with the declaration of Helsinki (WMA) and follows the standards of the ethics committee in conducting clinical studies. or this research, we have reached a consensus with the hospital and the hospital ethics committee. After the discussion of the ethics committee, the ethics committee agreed to adopt this research. Before we investigate the patient, we verbally explain the reason and purpose of the investigation to the patient. Patients verbally agreed that we would investigate them. We asked the patient's consent before we started the questionnaire. This step of verbally soliciting the patient's consent is in line with the requirements of the hospital ethics committee. The hospital ethics committee agreed with us. We have obtained the oral consent of the participants, and the ethics committee has approved this.

Consent for publication
Not applicable.
Availability of data and material The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.