This study was conducted in Shaanxi Province in northwest China between May 2018 and October 2018. This is one of the regions with the most cases of KBD in China . Two counties (Yongshou and Linyou) were randomly selected from total 62 endemic counties of Shaanxi Province. In the two counties, 6 villages of each county were selected randomly, and every available adult in these villages were invited to participate in this study.
Diagnostic criteria of KBD
In 2010, the National Health and Family Planning Commission of the People’s Republic of China issued new Diagnostic Criteria for Kashin-Beck Disease (Diagnostic code: WS/T207-2010) . The criteria of KBD include: a history of living in a KBD prevalent area, clinical manifestations (typically, short fingers, enlargement of finger joints, flexion of the distal finger and deformed fingers in hands) and radiography of the right hand (typically, irregular sclerosis and reappearance of a calcification zone in the metaphysis of the metacarpus and phalange). The diagnostic grade criteria for grading were as follows: Grade I, enlarged finger joints, limited motion and pain in the joints of the limbs; Grade II, shortened fingers and clinical symptoms of the first stage; and Grade III, dwarfism and clinical symptoms of the second stage.
Sample size calculation
The present study included a sample of patients with KBD and the general population. The KBD detected rate of 3.39% was expected based on a study conducted in Shaanxi Province in 2007 . A sample size of 140 participants was estimated according to the following formula: Z2a/2 p(1-p)/d2 (where a =0.05, Z a/2 = 1.96, p =0.0 339, d =0.03). This calculation is used to determine sample size in cross-sectional survey design , considering a sampling error of 3% and a confidence interval of 95%. To decrease the missing data, we recruited 167 KBD patients. Therefore, 169 general subjects with joint pain in same area were used as a comparison group in the present study.
Patients with KBD were recruited from Shaanxi Province in China. At the time of screening, patients underwent a medical history evaluation, complete physical examination, and examination of the right hand radiographs. The clinical diagnosis of KBD was determined by at least two senior orthopedic surgeons from the local hospital according to the Diagnostic Criteria for KBD (WS/T207-2010).
Inclusion and exclusion criteria
Patients were included if they were diagnosed with KBD, were able to understand Mandarin, and had no cognitive impairment. Patients with concurrent rheumatoid arthritis, any other type of inflammatory arthritis, fibromyalgia, another chronic pain disorder or communication difficulties (e.g., hearing or speech impairments) were excluded. Ultimately, a total of 167 patients with KBD were recruited in this study.
During the course of sampling, the subjects who did not meet the diagnostic criteria for KBD were compared as a control group to better understand the pain characteristics of patients with KBD. Three hundred twenty-five local residents with similar age and sex were recruited. Patients with communication difficulties (e.g., hearing or speech impairments) were excluded. Out of these 325 subjects,169 answered yes to the question: “Are you generally bothered with joint pain?” Thus, 169 general participants were used as a comparison group in the present study.
Patients with KBD and the general subjects completed a demographic questionnaire that obtained information on age, sex, ethnicity, marital status, occupation, and educational level.
Pain characteristic assessment
For both the KBD patients and the general subjects, pain was measured, including prevalence, duration, intensity, location, frequency, quality and method of treatment. The included subjects were asked to indicate whether they had pain. If they answered in the affirmative, we continued to ask about the sites, qualities (e.g., pins & needles, swelling, burning, could-freezing, throbbing and itching), the frequency of pain in the last month, and pain duration from initial onset until now. In addition, participants were asked which pain treatments they used (i.e., analgesics, physical therapy or surgery).
Participants marked the site of pain using a body pain drawing, which is the most common method for assessing the site and distribution of joint pain . The subjects were asked to shade areas where they had a specific side of pain (left/right/both) over the prior 6 months. The sites included the following joints: 1) knee, 2) ankle, 3) hip, 4) shoulder, 5) elbow, 6) wrist, 7) interphalangeal joints, and 8) toe. The number of joint pain sites was summed. In this study, the interphalangeal joint and toe joints were not easily counted; therefore, all painful interphalangeal joints were counted as one site of pain. In the analysis, we assessed a total of 16 joints. The number of joints affected in each patient ranged from 0 to 16.
Pain frequency (i.e., how often one experiences pain within a certain time frame) is an important component of the chronic pain experience . The one-month period was recommended as a reliable recall period  and has been applied in various studies [27, 28]. The frequency of joint pain in the last month was classified as “never,’’ “some of the days,’’ ‘‘about half of the days,’’ “most of the days,” or “every day’’. Persistent pain was defined as frequent (most days) or constant (every day) pain .
Subjects were asked to provide separate intensity ratings for different pain sites. Pain intensity was measured on an 11-point numeric rating scale (NRS). The NRS is a one-dimensional pain assessment tool with scores ranging from 0 (no pain) to 10 (the worst pain imaginable), with higher scores indicating greater pain intensity. The NRS has been validated for use in the arthritis population .
The graded chronic pain scale (GCPS)
The GCPS is a multidimensional measure that assesses two dimensions of overall chronic pain severity during the past 6 months: pain intensity and pain-related disability. The GCPS consists of seven items. The pain intensity is calculated as the average of 3 questions concerning the present, worst, and average pain, as measured on a 0 to 10 scale, ranging from ‘‘no pain’’ to “pain as bad as could be”. ‘‘Disability days’’ refers to the number of days for which pain prevented usual activities. The pain-related disability is calculated as the average of three questions on pain interference with daily activities, social and working activities; the three items are rated on an 11-point scale (0 = no interference/change, 10 = unable to carry on activities/extreme change). Scores on these two subscales range from 0-100, where higher scores reflect greater pain intensity and disability. Pain severity was graded into 5 hierarchical categories: grades 0 to IV: Grade 0: no pain; Grade I, low disability-low intensity; Grade II, low disability-high intensity; Grade III, high disability-moderately limiting; and Grade IV, high disability-severely limiting. Because all the participants had pain in the current study, pain severity was graded into 4 hierarchical categories: grades I to IV. The GCPS is a valid and reliable instrument and suitable for use in all chronic pain conditions, including chronic musculoskeletal (MSK) pain . The Chinese version of the GCPS possesses good psychometric properties, and the Cronbach α values for disability and characteristic intensity scales were 0.87 and 0.68, respectively .
The EuroQol (EQ-5D-3L) questionnaire
The impact of pain is a key aspect to consider along with assessing the severity of pain . The EuroQol (EQ-5D-3L) is a standardized preference-based measure of health that provides a simple, generic measure for clinical and economic assessment . The participants were asked to complete the EQ-5D questionnaire (Chinese version). The EQ-5D records the level of self-reported problems in five dimensions (i.e., mobility, self-care, usual activities, pain/discomfort and anxiety/depression). Each of the dimensions is divided into three levels of perceived problems: no problem (level 1), some problems (level 2) and extreme problems (level 3). China EQ-5D-3L value sets were used in this study . The scores on the EQ-5D index range from −0.149 to 1, where 1 indicates no problem, zero indicates death and negative values indicate a health status worse than death. The EQ-5D-3L Chinese Version demonstrated fair to moderate levels of test–retest reliability and adequate construct validity in KBD individuals in China .
Because nearly one-third of the subjects were illiterate, data were collected in face-to-face interviews by survey teams consisting of four Ph.D. students at the Department of Public Health at Xi’an Jiaotong University. All of the survey members had been trained in survey questionnaire procedures. Six staff members of the local Center for Disease Control and Prevention (CDC) helped us connect the included subjects, and our surveys were carried out at local community hospital. Completing the survey took approximately 20 to 25 minutes.
At the end of the survey, each participant received a thank you gift, such as a kitchen utensil. At the end of each day of interviews, all questionnaires were double-checked to check the quality of the questionnaires.
Continuous variables are presented as the mean ± standard deviation, and categorical variables are presented as frequencies and proportions. The differences were evaluated using Chi-square tests, independent samples t-tests (for continuous variables), and Mann–Whitney U tests (for ordinal data); paired samples t-tests were used to determine differences between the left and right sides (within subjects) in joint pain intensity and 1-way ANOVA tests, or Kruskal-Wallis tests were used for multiple group comparisons.
All data were analyzed using IBM SPSS Statistics for Windows, Version 22.0 (Armonk, NY: IBM Corp.). The level for significance in all analyses was defined as P < 0.05.
All enrolled subjects were informed of the goal and design of this study and were assured of confidentiality before they provided written informed consent to participate in the study. The study was approved by the human ethics committee of the Health Science Center, Xi’an Jiaotong University.