Denosumab is a human monoclonal antibody that targets nuclear factor-kappa B ligand and is highly effective in blocking bone resorption. Bibliometrics can intuitively show the research development process, research status, research hotspots and development trend of a certain topic for researchers. This study assessed the course of research and development for denosumab in terms of publications over the past 2 decades. Web of Science databases were searched to identify publications related to research on denosumab from January 1, 2005 to December 31, 2022. The VOS Viewer software (version 1.6.17) and Bibliometrix package in R (version 4.1.3) were used in this study. There were 5119 denosumab-related publications during this period. The total number of citations of denosumab-related publications reached 94917. The most articles were published in the field of Endocrinology Metabolism. As an international language, English remains the most popular language for writing papers. Five of the top ten institutions originated in the USA. Through the VOS Viewer analysis, we found that the relationships between Amgen Inc. with its collaborations were grouped into 4 clusters, the USA was the mainland for research and development on denosumab, closely collaborating with many other countries, such as Canada, Japan, England, and China. Wagman RB from USA was the most prolific author with 119 publications. The journal with the most publications was Osteoporosis International (481 publications). The most cited article was “Denosumab for Prevention of Fractures in Postmenopausal Women with Osteoporosis” with 2053 citations. The clinical trial comprised 6 of the 10 most frequently cited publications, and the rest consisted of reviews. The most frequent keywords for publications since January 1, 2014 were “prevention” and “management,” indicating that a number of prevention and management measures have been developed to regulate the use of denosumab in treating osteoporosis. Our research provided a comprehensive review of denosumab-related publications, suggesting that the development of denosumab is a long process and numerous clinical trials have been conducted before applications in clinical settings. Osteoclasts are the primary bone-resorbing cells derived from the monocyte/macrophage lineage. In bone tissues, osteoclast genesis is mediated by a receptor activator of the nuclear factor-kappa B ligand (RANKL), a protein crucial for the differentiation of osteoclasts involved in bone resorption. The realization that RANKL is the final cytokine involved in the resorption process quickly led to lines of therapy. Denosumab is a human monoclonal antibody that targets RANKL and is proven to be highly effective in blocking bone resorption. It successfully reduces fractures and is now one of the therapeutic options for osteoporosis treatment.Osteoporosis is a most common bone disease of low bone mass and increased bone fragility, usually leading to a consequent increase in fracture risk. Bibliometrics conducts clustering and other operations on literature information through software. After several rounds of iteration , it can intuitively show the research development process, research status, research hotspots and development trend of a topic for researchers, and provide decision-making information for researchers. Before our study was conducted, although there had been many studies on denosumab, no bibliometric articles were published.Bibliometrics is an interdisciplinary science that uses mathematical and statistical methods to quantitatively analyze all knowledge carriers. It is a comprehensive knowledge system that integrates mathematics, statistics and literature, and pays attention to quantification. Literature information such as authors, vocabulary size, and number of documents is effective information for finding research frontiers and foci.In this study, we assessed all research publications on denosumab from the Web of Science database from January 1, 2005 to December 31, 2022. We utilized Bibliometrics to analyze the research and development course of denosumab for publication trends, journals, institutions, and citations. We look forward to providing insightful information about the research and development for denosumab.We performed a computerized Bibliometric analysis from January 1, 2005 to December 31, 2022 for papers about “denosumab” retrieved from the Web of Science database. In detail, to identify all publications, we used “denosumab” as the TOPIC and refined the timespan to “January 1, 2005 to December 31” . Data were collected in December 2022. The search and data extraction were independently conducted by 2 of our investigators. The titles and abstracts of potentially eligible publications were reviewed and the unrelated were excluded. Mismatched choices were resolved involving a third independent researcher and the final decision was made by consensus among researchers.https://www.vosviewer.com/) and Bibliometrix package in R  were used for data and text-mining, analysis, and visualization. GraphPad Prism (version 8.0) and Adobe Illustrator (version 15.0.0) were used for generating figures.All extracted publications from the Web of Science starting from January 1, 2005 to December 31, 2022 were finally retrieved and analyzed. The impact factor of each publication was obtained from the 2022 journal citation report (JCR) database, and the citations of each included publication were retrieved from the Web of Science tools. (JCR region) in the JCR was based on the journal impact factor in the year, and the journals were classified into 4 regions: Q1, Q2, Q3, and Q4, in that order: Q1 > Q2 > Q3 > Q4 (Q: Quartile in category). The journal ranking and impact factor might measure the journal influence and research worth. For Bibliometric analysis, we applied the inherent functions of the Web of Science to detect the trends and characteristics, such as countries/regions of origin, institutions, citation counts, h index, journals, and so on. We also identified the top 10 cited institutions, articles, and authors. VOS Viewer software .We identified a total of 16,769 researchers who participated in publishing the denosumab publications. The top 10 most productive paper-published authors were Wagman RB (119), Libanati C (108), Wang A (107), Brown JP (105), Lewiecki EM (99), Bone HG (89), Reginster JY (78), Kendler DL (77), Mcclung MR (72), and Miller PD (70) Fig. A–B. InteOsteoporosis International ranked first with 481 published articles, followed by Journal of Bone and Mineral Research with 320 and Bone with 144. According to the JCR (2022), Journal of Bone and Mineral Research, Journal of Clinical Oncology, Annals of the Rheumatic Diseases, Journal of Clinical Endocrinology and Metabolism, Annals of Oncology, Arthritis Rheumatology, and Value in Health were classified as Q1, while Osteoporosis International, Bone and Archives of Osteoporosis were classified as Q2.The types and categories of denosumab-related publications are shown in Figure  in New England Journal of Medicine. This is followed by a review, “Osteoporosis: Now and the future” by Rachner Tilman D. et al in Lancet. The third most frequently cited article was a clinical trial, “Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: A randomized, double-blind study” by Fizazi Karim. et al in Lancet, it is worth mentioning that this article had been retracted for unknown reasons on December 1, 2011 .The top 10 most cited articles  for denosumab are listed in Table To detect the trends and directions of denosumab-related publications, we performed VOS Viewer analysis on the distributions of co-occurring keywords, which met the minimum number of occurrences of a keyword no < 50 times. The results of the analysis presented that the keywords were divided into 3 categories: “indications (purple),” “medications (green),” and “treatments (yellow)” Fig. A–B. In t–14 In this study, we conducted a Bibliometric analysis of denosumab-related publications from January 1, 2005 to December 31, 2022. We found that denosumab-related publications rapidly increased by nearly a hundredfold since January 1, 2005. The USA dominated in denosumab research and development, closely followed by Canada and Japan. In our data, most publications originated from companies and institutions in the USA, such as Amgen Inc., Harvard University, and University of California system. These organizations worked with a variety of academic institutions and hospitals to promote clinical trials and use of denosumab. There was also a considerable gap between other major countries and the USA in the number of publications. Specifically, we found the scale of the USA articles largely determined the trend of global publications. Note that the USA occupied the highest number of articles published in all countries in 2014. After that, however, the number of articles published in the USA fell to the lowest level in 2016 and then gradually increased to another peak in 2019. In comparison, the number of articles published in Japan gradually increased since 2009 and only slightly decreased until 2020.Increasing evidences have confirmed the efficacy of denosumab on the treatment of bone loss, including postmenopausal osteoporosis, primary bone tumor, and bone metastases.,13 It has been reported that denosumab could lead to a positive increase in bone mineral density and a low rate of fractures and is safe and effective in patients with severe renal impairment. However, in view of correlating to rare adverse events, like osteonecrosis of the jaw and atypical femoral fractures, many drug candidates will need to be investigated. Thus, dominant countries like the USA, Canada, and China should strengthen their support in completing high-quality clinical trials.According to the JCR (2022), most journals that published denosumab-related publications were classified as Q1, indicating a high research and impact value. Most journals that published denosumab-related publications were in the field of osteoporosis, especially clinical research. With the increasing number of clinical trials, researchers have expanded from osteoporosis to primary bone tumor, such as osteosarcoma and giant cell tumor of bone.In the top 10 most cited denosumab-related articles, 6 were clinical researches and 4 were reviews. Nowadays, the concept of translational medicine is continually being strengthened because it bridges the vital gap between basic research and clinical applications. Our data also confirmed that the characteristics of denosumab-related publications are according to the perception of translational medicine.,17Thus, it is not surprising that “prevention” and “management” appeared more commonly during the latest 8 years.Likewise, our findings indicated the changes in hot topics over the past years. For instance, the keywords related to “zoledronicacid,” “double-blind,” “osteoporosis,” and “bisphosphonates” were popular from 2005 to 2013, whereas the recent keywords associated with clinical applications, such as “prevention” and “management,” appeared from 2014 to 2022. This result indicates that with the increasing evidences of the clinical effectiveness of denosumab, numerous prevention and management measures have been developed to regulate the use of denosumab in the treatment of osteoporosis.Unavoidably, there are limitations in our current research. For example, we only searched publications in the Web of Science database, which may result in the exclusion of other types of publications and, in turn, incomplete data collection. Citations and h-index reports for some publications may have been delayed as well, leading to systematic bias in this research.Our research provided a comprehensive review of denosumab-related publications, suggesting that the development of denosumab is a long process and numerous clinical trials have been conducted before applications in clinical settings.We would like to thank all the members participated in this study.Conceptualization: Qingjun Wei.Data curation: Xiaohong Jiang, Yun Liu.Formal analysis: Tianyu Xie, Mingwei He.Investigation: Shijie Liao.Methodology: Shijie Liao, Shenglin Lu.Software: Wenyu Feng, Zhaojie Qin.Supervision: Qingjun Wei.Validation: Zhaojie Qin.Visualization: Wenyu Feng, Zhaojie Qin.Writing – original draft: Xiaohong Jiang.Writing – review & editing: Yun Liu, Shenglin Lu, Mingwei He.


The prevalence of primary aldosteronism (PA) varies from 5% to 20% in patients with hypertension but is largely underdiagnosed. Expanding screening for PA to all patients with hypertension to improve diagnostic efficiency is needed. A novel and portable prediction tool that can expand screening for PA is highly desirable.Clinical characteristics and laboratory data of 1,314 patients with hypertension were collected for modeling and randomly divided into a training cohort  and an internal validation cohort . Additionally, an external dataset (n = 285) was used for model validation. Machine learning algorithms were applied to develop a discriminant model. Sensitivity, specificity, and accuracy were used to evaluate the performance of the model.Seven independent risk factors for predicting PA were identified, including age, sex, hypokalemia, serum sodium, serum sodium-to-potassium ratio, anion gap, and alkaline urine. The prediction model showed sufficient predictive accuracy, with area under the curve (AUC) values of 0.839 (95% CI: 0.81–0.87), 0.814 (95% CI: 0.77–0.86), and 0.839 (95% CI: 0.79–0.89) in the training set, internal validation, and external validation set, respectively. The calibration curves exhibited good agreement between the predictive risk of the model and the actual risk. An online prediction model was developed to make the model more portable to use.The online prediction model we constructed using conventional clinical characteristics and laboratory tests is portable and reliable. This allowed it to be widely used not only in the hospital but also in community health service centers and may help to improve the diagnostic efficiency of PA. Primary aldosteronism (PA) is the most common cause of secondary hypertension, characterized by high blood pressure, decreased plasma renin, and excessive aldosterone secretion from one or both the glomerulosa zona of the adrenal cortex –4. The pMeasurement of plasma aldosterone concentrations and renin activity to assess the plasma aldosterone-to-renin ratio (ARR) is the most recommended screening method for PA –20. It rMedical applications of artificial intelligence and machine learning, particularly in disease prediction and prognostic prediction, have made remarkable progress –28. PrevConsecutive patients definitely diagnosed with essential hypertension (EH) and PA from The First Affiliated Hospital, Sun Yat-sen University, were included in the study between January 2018 and December 2020. Furthermore, we also collected an external validation set from Sun Yat-sen Memorial Hospital, Sun Yat-sen University, between January 2020 and December 2020.Patients with PA were diagnosed according to Endocrine Society and European Society of Hypertension recommendations , 20. A t2, or both, for greater than 3 months) ; patients with any kind of cancer or history of cancer, diabetes mellitus, thyroid disease, chronic kidney disease  < 60 ml/min per 1.73 m months) , urinaryThis study selected eligible patients from The First Affiliated Hospital, Sun Yat-sen University, and Sun Yat-sen Memorial Hospital, Sun Yat-sen University. Clinical characteristics including age, gender, systolic blood pressure (SBP), and diastolic blood pressure (DBP) were collected from the hospital information system (HIS). The laboratory tests including serum potassium (K), serum sodium (NA), serum chlorine (CL), serum creatinine (CREA), serum uric acid (UA), serum anion gap (AG), serum calcium (CA), serum total cholesterol (CHOL), serum triglyceride (TG), serum high-density lipoprotein cholesterol (HDL-C), serum low-density lipoprotein cholesterol (LDL-C), and urine pondus hydrogenii (urine pH) were the first test results during the hospitalization and collected from laboratory information system (LIS). All serum specimens were detected by using the automatic biochemical analyzer AU5800  with the manufacturer’s reagent kits, while urine specimens were measured by using the automatic urine analyzer COBOI-xs  with the manufacturer’s reagent kits. Internal quality control was performed daily, and external quality assessment was performed as required.https://www.r-project.org/) and the Deepwise and Beckman Coulter DxAI platform (https://dxonline.deepwise.com). Categorical variables were presented as frequencies with percentages, and continuous variables were presented as mean ± standard deviation (SD) or median with interquartile range (IQR). PA group and essential hypertension group from The First Affiliated Hospital, Sun Yat-sen University, were randomly assigned to the training cohort and internal validation cohort, respectively, in a ratio of 7:3. Clinical characteristics and laboratory test results between the PA group and essential hypertension group and between the training cohort and internal validation cohort were compared by using Student’s t-test, Mann–Whitney test, or chi-square test, as appropriate. Feature selection was carried out using R software. Univariate logistic regression analysis was conducted in the training cohort to screen the variables associated with PA. The magnitude of the association was expressed by odds ratio  with a 95% confidence interval (95% CI). p < 0.05 was considered statistically significant. The variables with statistical significance  in the previous univariable logistic analysis were selected for a step-backward multivariate logistic regression analysis to identify the independent risk factors (p < 0.1) for the prediction of PA. The Hosmer–Lemeshow test was conducted to measure the fitness of the logistic regression model, and p > 0.05 means that the model was a good fit. Multicollinearity analysis for all predictor variables was conducted using the R software with the car package, and a variance inflation factor (VIF) of less than 4 means that there is no multicollinearity between predictor variables.All statistical analyses were conducted in R software for Windows . The model was applied to 1,000 bootstrap resamples in the training cohort for internal validation and external validation to validate the predictive ability. Receiver operating characteristic (ROC) curves were presented to measure the discrimination ability of the prediction model, and areas under the curve (AUCs) were calculated. AUC ranges from 0.5 to 1.0, and a higher value indicates better predictive ability. Calibration curves were conducted to assess how close the model predicted risk is to the actual risk. Decision curve analysis (DCA) was carried out to assess the utility of models for decision making. All reported p-values were two-tailed, and p < 0.05 was statistically significant.The prediction model was developed using R software with the rms package and displayed online through Deepwise and Beckman Coulter DxAI platform (p < 0.001). Likewise, serum K, serum NA, serum CA, serum UA, AG, serum CHOL, TG, LDL, and serum NA-to-K ratio also showed significant differences between the two groups. However, neither SBP nor DBP showed statistically significant differences.The study flowchart was presented in p > 0.05). Clinical and biochemical characteristics of patients in the training cohort, internal validation cohort, and external validation cohort are shown in Then, we randomly divided 1,314 patients into the training cohort and the internal validation cohort in a 70%  to 30%  comparison. The characteristics of the training and internal validation cohorts are summarized in detail in To confirm the possible risk factors of PA, we conducted univariate and multivariate logistic regression analyses in the training cohort. As shown in A further multivariate logistic analysis shown in We included the above seven risk factors as the possible predictors of PA to build up a prediction model and presented a nomogram graph as shown in p-value of the Hosmer–Lemeshow test for this model was 0.122, indicating that the model was well-fitted. As shown in The ROC curves in DCA was performed to compare the clinical usability and benefits of the prediction model. As shown in https://dxonline.deepwise.com/prediction/index.html?baseUrl=%2Fapi%2F&id=5244&topicName=undefined&from=share).The visualization of the prediction model was displayed online through Deepwise and Beckman Coulter DxAI platform as p = 0.002; Among all 490 PA patients, only 79 patients had undergone AVS. A total of 29 patients were defined as unilateral PA, and the other 50 patients were diagnosed as bilateral PA. The scores of the unilateral PA tend to be higher than those of the bilateral PA  and much better than using aldosterone > 15 ng/dl . When compared with PFK score established by another study, our model exhibited higher AUC  than the PFK score  has not received attention as a predictor of PA until it was included in a formula to screen the PA in a previous study in Japan . The res+ and H+ . Moreove+ and H+ –38. Wome+ and H+ –41. Nevep = 0.091) and much better than using a threshold of aldosterone > 15 ng/dl (p < 0.001). It appeared that the performance of our model would be the same with more selective thresholds, which met different clinical needs. Moreover, we compared the results with the PFK score established in a previous study (p < 0.001).As a prediction tool, our model showed a good performance on the diagnosis of PA in a threshold value of 54%, with AUC values of 0.839, 0.814, and 0.839 and high accuracy of 0.779, 0.749, and 0.793 for training, internal, and external validation sets, respectively. This meant that, in actual clinical practice, our prediction model could accurately diagnose PA patients in hypertensive patients. It would be helpful for clinicians to make a quick recognition of high-risk patients with PA. Additionally, it is undeniable that pinpointing the patients who had unilateral PA would provide further useful information for clinical decisions and patient management as well as resource allocation. Hence, we tried to evaluate the performance of our model for the diagnosis of unilateral PA. The validation results showed that our model also performed well for the diagnosis of unilateral PA, with an AUC of 0.786 and high sensitivity of 96.6% , 43 to aus study , which iThere were some limitations to our study. Firstly, some indicators like hormones renin or aldosterone estimation were not included in our prediction model, which might affect the accuracy of the model. However, screening PA through ARR is not available in healthcare centers, community hospitals, and even some municipal hospitals in China due to the lack of professional equipment; additionally, the aim of our study was to create a portable model for clinical practice; the indicators that were routine and easily obtained from health examination were considered. Results showed that our prediction model exerted a good discrimination ability of PA recognition. Secondly, although our model exhibited good discrimination ability within cohorts in the study, whether it can be extended to other populations remains unknown. Therefore, further study should be needed to verify our prediction model. Additionally, the prevalence of hypokalemia in our study was about 50%, which was higher than in previous studies. The reason might be most of the patients in our hospital received anti-hypertension treatment for a long time in community healthcare clinics and transferred to our hospital for further treatment because of resistant hypertension and severe hypokalemia. However, this was the most important reason that we conducted this online prediction model, which helped primary care physicians to identify PA and EH early. We included the normal variables in the model, which were all available even in the community healthcare clinics. Our online prediction model showed good discriminative ability and was well-fitted. Finally, as reported in previous studies, the metabolic factors may play an important role in diabetic patients with PA, which was not the same as non-diabetics , 45, andIn conclusion, this study created an online prediction model using a new dataset in the Chinese population to screen PA in patients with hypertension for the first time. This would be helpful for expanding screening for PA in all patients with hypertension and helpful for clinicians for fast screening of hypertensive patients who required further complicated tests for PA diagnosis.This is the first study to develop an online prediction model for primary aldosteronism in all patients with hypertension by using common clinical characteristics and laboratory tests. The sharing online of the prediction model allowed it to be widely and portably used by clinicians in hospital and community health services and may help to improve the diagnostic efficiency of primary aldosteronism.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by the Ethics Committee of The First Affiliated Hospital, Sun Yat-sen University and Sun Yat-sen Memorial Hospital, Sun Yat-sen University. Written informed consent was not required for this study, in accordance with the local legislation and institutional requirements.WL conceived and designed the study, analyzed the data, and wrote the original draft. WG and PF analyzed the data and revised the manuscript. LZ and ZY prepared the figures and tables. WH conceived and designed the study, funding acquisition, and supervision. PC and NY conducted the formal analysis and revised the manuscript. All authors read and approved the final manuscript.This work was supported by the China Postdoctoral Science Foundation (2021M703708).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Objectives: This study investigates the association between a cancer protective lifestyle (defined based on the revised World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) cancer prevention recommendations) and mortality in Switzerland.Methods: Based on the cross-sectional, population-based National Nutrition Survey, menuCH (n = 2057), adherence to the WCRF/AICR recommendations was assessed via a score. Quasipoisson regression models were fitted to examine the association of adherence to the WCRF/AICR recommendations with mortality at the Swiss district-level. Spatial autocorrelation was tested with global Moran’s I. Integrated nested Laplace approximation models were fitted when significant spatial autocorrelation was detected.Results: Participants with higher cancer prevention scores had a significant decrease in all-cause , all-cancer , upper aero-digestive tract cancer , and prostate cancer  mortality, compared to those with lower scores.Conclusion: The inverse association between adherence to the WCRF/AICR recommendations and mortality points out the potential of the lifestyle recommendations to decrease mortality and especially the burden of cancer in Switzerland. In 2019, cancer was the leading cause of death among men and second leading cause of death among women in Switzerland  . Hence, In 2018, the World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) published a revised version of their 2007 WCRF/AICR cancer prevention recommendations, providing updated guidelines on an overall healthy and cancer-protective lifestyle at the individual level . The tenIn 2016, Lohse et al. observed an inverse association between adherence to the WCRF/AICR cancer prevention recommendations and cancer mortality for men living in Switzerland using data of the years 1977–1979 and 1983–1992 .n = 2057), the Swiss mortality data (2015–2019), and the Swiss census data (2015–2019) provided by the Federal Statistical Office (FSO). The data sets were linked at the district-level. The structure of this article followed the STROBE-nut guidelines , was conducted in ten centres across Switzerland. The survey was a cross-sectional population-based study with a target sample of 4,627,878 Swiss residents of 18–75 years of age. The study included one questionnaire , “normal weight” (18.5 kg/m2 ≤ BMI <25.0 kg/m2), “overweight” (25.0 kg/m2 ≤ BMI <30.0 kg/m2) or “obese” (BMI ≥30 kg/m2)  of the software GloboDiet® , Lyon, France , 20; ada14.02.27 pictures , 21. Aftpictures . In the pictures  using thTo be consistent with the menuCH study, we used Swiss mortality and census data of the age range 18–75 years.All-cause, all-cancer, and cancer-specific mortality based on the documented definitive cause of death were examined. Based on the existing evidence on health behaviour factors and their link to cancer prevention , the folThe mortality data provided by the FSO were linked to the dietary data by the place of residence of the participants using postal code information. Based on the indirect method, which uses the Swiss population as reference population, standardized mortality ratios (SMR) were calculated at the district-level. The SMR were standardized for sex, age, and year of death.In 2018, the WCRF and AICR published ten recommendations on cancer prevention , of whicThe physical activity recommendation was assessed using the short-form IPAQ. Dietary components were investigated as consumed average amount in grams per day (mean of the two 24HDR interviews). For the fast-food component, an adapted NOVA classification system was applied to categorize foods as ultra-processed or non-ultra-processed . The NOVA classification was adapted to the cancer prevention recommendation score to ensure no double penalization for red and processed meat consumption and intake of sugar-sweetened drinks. Closer adherence to the WCRF/AICR cancer prevention recommendations lead to a higher score, indicating a healthier lifestyle. In the analyses, the score was used as a continuous variable, ranging from zero to seven points, and as a categorical variable with the following predefined three categories: low adherence (0-<3 points), moderate adherence (3-<5 points), and high adherence (5–7 points).The menuCH participants’ characteristics and the SMR at the district-level were analysed descriptively.To investigate the association between the cancer prevention score and all-cause and cancer mortality, Quasipoisson regression models, which are a generalized version of Poisson models, were fitted at the individual level. The outcome variable modeled by a Quasipoisson regression model is a count variable, that shows under- or overdispersion, i.e., the mean and the variance of the outcome data are not equal and therefore, the variance will be estimated by an additional parameter, the dispersion parameter. As the menuCH survey is not a longitudinal study and therefore lacks a mortality follow-up, an additional data set, the Swiss mortality data from 2015 until 2019, was used to determine the outcome variable. The Swiss mortality data were linked to the menuCH data geographically at the district level. The outcome variable was the observed number of deaths documented between 2015 and 2019 in the menuCH participant’s sex, age, and district group. The total number of residents in the corresponding sex, age, and district group was added as an offset term. The cancer prevention score was used as explanatory variable . The models were further adjusted for sex, age, smoking status, education level, language region, nationality, civil status, and mean daily energy intake .A sensitivity analysis excluding the physical activity recommendation due to a high percentage of missing observations was conducted. Furthermore, a second sensitivity analysis was performed, which included the seven previous recommendations and additionally the recommendation on dietary supplement use as a binary score .I statistic was used to investigate the existence and degree of spatial autocorrelation  simulations were calculated to check the evidence for a significant, non-random spatial pattern of the residuals aggregated at the district-level. Local Moran’s I were calculated and tested for significance based on a permutation test (n = 1000). The lower limit of the p-value is given by the number of simulations  model was fitted when evidence for spatial autocorrelation was observed. A omponent . For botomponent . For eacThe menuCH participants’ data were weighted for sex, age, major living region in Switzerland, marital status, household size, and nationality. Variables on dietary factors were additionally weighted for weekday and season of the 24HDR interview day .n = 524), the education level (n = 3), and smoking category (n = 4). Hence, to include all 2057 participants in the analyses, we conducted multivariate imputation by chained equations . With each imputed data set the analyses were run separately. Afterwards, the results were pooled.Some participants had missing values for the physical activity level  and in the software R . The stIn comparison to the overall study population, several differences in the menuCH participants’ characteristics were observed across the adherence categories . ParticiFrom 2015 until 2019, 106,140 all-cause deaths, including 46,220 all-cancer, 4022 colorectal cancer, 2923 UADT cancer, 1525 stomach cancer, 2248 liver cancer, 3841 pancreatic cancer, 3818 breast cancer (among women), and 1913 prostate cancer deaths (among men) were reported. In Regarding the Quasipoisson regression models, the complete case analyses and the analyses based on imputed data revealed similar results, hence only the latter results are presented and used for subsequent analyses. When using the score as continuous variable, no statistically significant rate ratio was observed for any of the mortality outcomes .In the regression models using the score as categorical variable, there was evidence among participants to have a 5% decrease in all-cause , a 7% decrease in all-cancer , a 13% decrease in UADT cancer , and a 19% decrease in prostate cancer  mortality when comparing the high adherence with low adherence group. For prostate mortality, even participants with moderate adherence had a reduced mortality by 14% compared to the low adherence group . Evidence for an increase in colorectal cancer mortality by 8% was observed in the moderate compared to the low adherence group . Apart from the latter result, there was an overall tendency for a decrease in mortality in the moderate adherence group and an even stronger decrease in mortality in the high adherence group compared to the low adherence group.The results of the sensitivity analyses can be found in I statistic based on the regression models including the score as continuous and as categorical variable, respectively. Both models revealed similar results.I: −0.014; observed global Moran’s I: 0.143  and 0.152 (continuous score), respectively). In I statistic for liver cancer mortality are visualised in a LISA cluster map, providing more detailed information on the statistically significant spatial pattern indicated by the global Moran’s I statistic. Independent of including the score as categorical or continuous variable in the regression model, four districts revealed significant evidence for spatial outliers or spatial clusters, indicating to be the core of a spatial pattern.Only the residuals of the regression model for liver cancer mortality revealed evidence for spatial autocorrelation at the district-level   .n = 3)  . In addiThe results of our study regarding colorectal cancer mortality were in contrast to the findings of Romaguera et al. , who repOn the other hand, our study found evidence for a lower mortality from UADT and prostate cancer in the high compared to the low adherence group. These results are in line with the findings of Lohse et al. , who repMoreover, Lohse et al. observed in the high 5–9 points) compared to the low adherence group (0–3 points) a decrease in stomach cancer mortality by 66%  ( points cAs the study by Lohse et al. , our stuThe lack of significance or unexpected associations of the score with mortality in our study could be due to the lack of mortality data for menuCH participants, reverse causation inherent in the cross-sectional study design of the menuCH study, low numbers of observed deaths, and age differences across the adherence groups, leading to less observed deaths in groups with mainly younger participants.I statistic and the LISA cluster map, there was significant evidence in four districts to be spatial clusters or spatial outliers. The fixed effects estimates of the INLA model (The Swiss mortality data from the years 2015–2019 showed different geographical patterns across causes of death. The underlying causes for these various spatial patterns could be manifold, e.g., differences in diet culture , communiLA model  and the LA model  were aliIn comparison to the results of the main analysis, the sensitivity analysis excluding the physical activity recommendation resulted in an attenuation of the significance of the investigated associations . The attFurthermore, the second sensitivity analysis, including the recommendation on supplement use, lead to an attenuation of the inverse associations, such that they were no longer statistically significant . HoweverOur study had several strengths. The menuCH weighting strategy allowed our final sample of 2057 participants for being representative of a target population of 4,627,878 Swiss residents. The 24HDR and the lifestyle questionnaire provided detailed information in order to operationalize seven of the ten 2018 WCRF/AICR cancer prevention recommendations for our main analyses and to follow the index by Shams-White et al. , 25 closvia two non-consecutive 24HDR using the software GloboDiet® has been shown to yield reliable estimates (However, our study had some limitations. First, the menuCH survey is a cross-sectional study, which, by nature, is prone to reverse causation. Given the self-reported dietary data, assessed with two 24HDR, the possibility of recall bias leading to over- and underestimating of dietary intakes cannot be excluded. However, the assessment of consumed foods stimates , 20. SecTo conclude, using the menuCH data our study was able to overcome the main limitations of the Swiss study by Lohse et al. , and pro


A lack of physical activity (PA) is a threat to public health. However, for the elderly, most PA abilities are limited. By focusing on the types and intensity of PA that the elderly can bear, this study aimed to reveal whether preferences regarding types of PA  and their intensity were associated with health status. The main forms of PA include shopping, cooking, cleaning, walking, cycling, various fitness activities and other activities with a certain intensity.n = 119), the abnormal group  and the healthy group (n = 94). Multiple regressions were used to test the relationship between the various types, durations and intensities of PA the elderly individuals participated in and their health status.Surveillance data on chronic diseases and their risk factors were collected from one district of Shanghai in 2017-2018. A Kish table was used for sampling 500 older adults, including the diagnosed group , and more people met the WHO recommendation . Diagnosis was associated with performing housework- and transport-related PA and moderate-intensity PA and with meeting the WHO's recommendation. Higher education levels were a positive factor for elderly individuals to participate in PA.All three groups included a large proportion of older adults who participated in housework- and transport-related PA. The diagnosed group had the largest proportion  and median minutes . The diagnosed group had more metabolic equivalents (METs) of moderate-intensity PA than the two other groups (H = 33.01, Transportation and housework activities are good targets for increasing PA in older adults. Diagnosis is associated with older adults' more PA. Physical activity (PA) has significant health benefits and contributes to the prevention and treatment of non-communicable diseases (NCDs), such as diabetes, cardiovascular disease, hypertension, and some cancers –4. PatieThis is because increased age involves declining PA and increased chronic disease risk . A studyThe worldwide epidemic of chronic diseases is strongly linked to population aging . A cohorObviously, not every type of PA is suitable for elderly individuals or elderly individuals with chronic diseases. This raises an interesting question that considers elderly people's PA ability: what PAs are preferred by elderly individuals? Currently, guidelines predominantly focus on healthy age-stratified target groups of children and adolescents, adults, and older adults, but the target group of individuals with NCDs has received scant consideration . StudiesShanghai, a metropolitan city, was the first city in China to enter the aging society and is a large city with the highest degree of aging in China . In 2018This study aimed to reveal whether resident's preferences regarding types of PA  and their duration and intensity were associated with resident's health status. It is believed that this study will provide information to improve the guidelines for elderly people.The data came from the Shanghai Centres for Disease Control and Prevention's Regular Monitoring of Chronic Diseases in Yangpu District from October 2017 to March 2018. This survey included 1,004 residents from 240 households in all 12 community streets in Yangpu District, Shanghai. Twenty households were randomly selected from each street. A Kish table was used for sampling, and a household survey was conducted. The questionnaire was administered by professional investigators, who input the investigation results into the information collection system at the same time as inquiry. In addition to answering the questionnaire, the selected people received a unique bar code and went to a designated medical institution to participate in the physical examination, which included height, weight, blood pressure, and blood and urine tests. The examination results were recorded in the body measurement table and entered into the database by the investigators. This analysis was approved by the research ethics committee of Tongji University (ref: LL-2016-ZRKX-017).The survey was divided into three sections: i) basic personal information, including age, sex, education level, marital status, and occupation; ii) personal PA habits, including the self-reported frequency of PA in a typical week and the self-reported cumulative minutes of PA per day; and iii) personal health status: the body mass index (BMI), fasting glucose, glycosylated hemoglobin, total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG), urinary protein-to-creatinine ratio, aSBP and aDBP were tested in a health institution; the self-reported history of chronic diseases diagnosed by doctors. In part ii, the data were collected using the Global Physical Activity Questionnaire (GPAQ) . In the In total, 1,004 people were invited to participate, and 28 people whose physiological indicators were missing were eliminated (the effective response rate was 97.21%). If an individual had a disease that may cause movement restriction, such as heart disease, lung disease, or cerebral infarction, their records were eliminated. Those who were under 60 years old and those over 60 who were still working were also eliminated. Finally, a total of 500 older adults were included, of whom 119 had self-reported chronic diseases diagnosed by doctors (diagnosed group), 287 had some abnormal indicators on our survey but did not have a doctor's diagnosis since the indicators did not support disease status , and 94 were healthy .GPAQ Analysis Guide  are commonly used to express the intensity of PA. One MET is defined as the energy cost of sitting quietly and is equivalent to a caloric consumption of 1 kcal/kg/h. When calculating a person's overall energy expenditure using GPAQ data, 4 METs are assigned to time spent in moderate activities and 8 METs are assigned to time spent in vigorous activities. The minimum time that adults need in order to benefit from PA is at least 150–300 min of moderate-intensity PA, at least 75–150 min of vigorous-intensity PA, or an equivalent combination of moderate- and vigorous-intensity activity throughout the week . We seleWe examined the binary outcome variables of i) performing various types of PA or not  and ii) meeting WHO recommendations on PA for health or not  and examined the continuous outcome variable of total minutes spent on various types of PA per day.The demographic variables in the data were age, sex, education, marital status, and occupation. According to the WHO statistics , age wasp-value below 0.05 was considered statistically significant.Basic demographic characteristics and binary outcome variables are presented as percentages for each group. Continuous outcome variables of the duration of various PAs are presented as medians. Statistical significance was determined by Pearson's chi-square test or Kruskal-Wallis H test. GraphPad Prism 8  was used to draw a scatter bar chart of minutes spent on PA per day. Logistic regression models were constructed to analyse the relationship between the types of various PAs and independent variables (models 1 to 3 and models 7 to 9). Linear regression models were used to analyse the relationship between the continuous outcome variables and independent variables (models 4 to 6 and models 10 to 12). All statistical tests were conducted using Stata 14 . A P < 0.01). The proportion of married older adults was over 90.00%. The three groups had a higher proportion of normal BMI and overweight, and the two proportions were close in the diagnosed and healthy groups. The differences in the proportions of age group, sex, marital status and BMI level in the three groups were not statistically significant.As shown in 2 = 21.01, P < 0.01), while the proportion of older adults who performed transport-related PA was 87.39, 54.01, and 57.45%, respectively, in the three groups . The proportion of recreation-related PA was lower than 17%, and the difference among the three groups was not statistically significant . P < 0.01). A median of 0 does not mean that everyone did not participate in housework-related PA but that more than half of people spent 0 min on housework-related PA. The median times of transport-related PA were 30.00, 8.57, and 13.58 min, respectively, in the three groups . The older adults in the three groups spent little time on recreational PA, and the difference among the three groups was not statistically significant .2 = 41.74, P < 0.01). The proportion of vigorous-intensity PA was lower than 7%, and the difference among the three groups was not statistically significant . The diagnosed group also had the largest proportion (79.83%) of older adults who met the WHO's recommendation for PA per week . P < 0.01). The median MET of vigorous-intensity PA in the three groups was 0.00, and the difference among the three groups was not statistically significant . The total METs of PA in the diagnosed group was 1,800, higher than the other two groups .P < 0.01 for the abnormal group; OR = 0.47, P < 0.05 for the healthy group in model 1) and transport-related PA  more than those in the diagnosed group. Performing PA was associated with higher education levels in models 1 to 3. However, the abnormal and healthy groups were not associated with recreation-related PA . The older adults in the diagnosed group spent more minutes on housework-related PA  and transport-related PA  than the older adults in the abnormal group but not more than the older adults in the healthy group. The association was not statistically significant in model 6. The minutes older adults spent on the three types of PA were associated with higher education levels in models 4 to 6.P < 0.01 for the abnormal group; OR = 0.19, P < 0.05 for the healthy group in model 1) and meet WHO recommendations . Moderate-intensity PA and meeting WHO recommendations were associated with higher education levels in models 7 and 9. More METs of moderate-intensity PA were associated with healthy status  in model 10, as in model 12. Females in the diagnosed group  with higher education levels  reported more METs of moderate-intensity PA, as did model 12.The results of the multiple regression  showed tShanghai Resident Fitness Development Report 2018, Shanghai residents enjoy walking and cycling. Aging is associated with a progressive loss of bone-muscle mass and strength  and premature death –37. PublThis study shows that nearly 80% of the older adults in the diagnosed group meet the WHO's recommendation , 23, andWe also observed that education has a positive effect on whether older adults participate in PA. In this study, the mean age of the group observed was 68.64 ± 7.43 years, and higher education was related to more time spent in PA. Earlier studies showed that high physical activity is related to a higher educational level , 46. IndFirst, given the self-reported nature of the questionnaire, it is possible that reporting bias led to some data distortion. To better meet social expectations, patients with chronic diseases may report values that are longer than the actual PA time. Second, because this study was cross-sectional, the results of this study only showed that at the time point considered, the diagnosis group spent more time on PA than the other two groups. The correlation between diagnosis and PA needs to be further explored. Finally, the proportion and time of older adults participating in recreational activities were the lowest. Encouraging the participation of older adults with chronic diseases is worth further exploration. We will continue to explore this direction in future research.In conclusion, our results of representative data from Shanghai showed that elderly people generally participated more in transportation and activities at housework. A diagnosis of chronic disease was associated with time spent on PA and PA MET-minutes. This finding suggests that the possibility for older adults, especially those with abnormal health indicators, to participate in PA should be considered in the prevention and control of chronic diseases. When carrying out community-based chronic disease prevention in Shanghai that promotes PA for elderly people, priority can be given to recommending moderate-intensity housework or transportation , which are preferred by elderly people. More research is needed to understand the mechanisms of diagnostic information on the participation in PA among residents with chronic diseases.The original contributions presented in the study are included in the article/supplementary materials, further inquiries can be directed to the corresponding authors.The studies involving human participants were reviewed and approved by the Research Ethics Committee of the Tongji University. The patients/participants provided their written informed consent to participate in this study.XH, WZ, JS, and ZW designed the study. XH, DY, HJ, and WY conduct literature analysis. JH, XG, XH, and JS conducted the data analysis, YL, LZ, JH, and JS made all tables. YY, NC, and XH produced all figures. DY, JS, and ZW guarantee access to research resources. All authors participated in the writing, revision, final review of the manuscript, read, and approved the final manuscript.This study was supported by the Shanghai Education Science Research Project (Grant Number: C2021039). Data extraction was financially funded by the Natural Science Foundation of China (Grant Numbers: 71774116 and 71603182). The analysis and interpretation of the data guided by the statisticians were funded by the grants from the Shanghai Public Health Outstanding Young Personnel Training Program (Grant Number: GWV-10.2-XD07). The writing and revision, including the language improvement, were sponsored by Shanghai Pujiang Program (Grant Number: 2019PJC072), and Shanghai Leading Talents (Grant Number: YDH-20170627). The research presented in this article is that of the authors and does not reflect the official policy of the NHC.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The physicians were further well-informed about the indications  and monitoring requirements . The pharmacists were more knowledgeable about the drug targets  and their mechanisms of action . Male respondents as compared with females , and physicians as compared with pharmacists , were more confident in using bDMARDs than conventional treatment in RA patients. Our findings show that the respondents were familiar with the attributes of bDMARDs and the standard management guidelines for RA care. Our results may be relevant in creating new methods, guidelines, and treatments to enhance RA treatment adherence, satisfaction, and health outcomes.Treatment of rheumatoid arthritis (RA) is complicated, with numerous aspects influencing decision-making, including disease severity, comorbidities, and patient preferences. The present study aimed to evaluate healthcare professionals’ (HCPs) knowledge of biological disease-modifying anti-rheumatic drugs (bDMARDs) and their compliance with the standard management guidelines for assuring optimal RA therapy. The cross-sectional, survey-based study was performed in various healthcare and academic settings in Karachi, Pakistan to probe HCPs’ knowledge of bDMARDs and their compliance with the European League against Rheumatism (EULAR) recommendations for the management of RA patients. Overall,  Persistent musculoskeletal pain is a global health issue that has a detrimental impact on people’s well-being. Osteoarthritis (OA), rheumatoid arthritis (RA), and spine-related neck and back problems are the most frequent musculoskeletal ailments. Musculoskeletal problems are the leading cause of disability in working-age individuals . RA is aDMARDs are immunosuppressive and immunomodulatory medicines that may either be conventional or biologic in nature. Methotrexate, hydroxychloroquine, leflunomide, and sulfasalazine are examples of commonly used conventional DMARDs (csDMARDs) . BiologiThe bDMARDs are specialized and target a particular pathway of the immune system . Their oThe management of RA is complicated, with numerous aspects influencing decision-making for clinicians, including comorbidities, disease severity and activity, and patient preferences . RA manaThe cross-sectional, survey-based study was performed between June and August 2021 (12 weeks). The responses were collected from different public and private sector healthcare and academic settings in Karachi, Pakistan. The respondents were approached through email or personal contacts and invited to complete the survey form. The approach of convenience sampling was used, and the respondents were selected based on their ease of availability and proximity.Those who were registered with the appropriate professional body for accreditation;Those who provided a written consent form for their voluntary participation in the study.The respondents were either physicians or pharmacists and considered eligible only if the following conditions were met:N = 20,000 , x is the confidence interval of 95%, E is the margin of error set at 5%, and the expected response rate is set at 50% [n = 377.The Raosoft sample size calculator was used to compute the sample size needed for this study, based on the Formula (1) below:t at 50% ; based on = 30 respondents  to evaluate the content validity and, thereby, to ascertain the consistency and acceptability of the questionnaire items. Slight modification was desired after the pilot testing. The internal consistency of the questionnaire was determined by calculating the Cronbach’s alpha value, which was determined to be within acceptable limits (α  =  0.7). The data obtained from the respondents included in the pilot study were excluded from the final analysis. It was then distributed through email or personal contacts among the potential respondents for data collection.To design the questionnaire utilized in this study, a comprehensive literature analysis of previous studies was undertaken in the PubMed/MEDLINE database to generate potential questions. After an extensive literature review of the previous studies published on the topic and the recommended guidelines for the management of RA patients, the study tool consisting of 30 items was developed in English language ,20,21. TAlong with the six questions associated with the respondents’ baseline information, the survey form consisted of three sections: The first section comprised of 10 close-ended questions with “true”, “false”, and “do not know” options to examine respondents’ understanding of bDMARDs. The second section included twelve questions corresponding to the EULAR recommendations for the management of RA. The items were scored on a five-point Likert scale, ranging from strongly agree = 5 to strongly disagree = 1, with the aim of assessing respondents’ attitudes and perceptions towards the initiation of therapy with DMARDs, treatment targets, their practices of shared decision-making, prospects of substituting bDMARDs, and the inclination of using bDMARDs in clinical practice. The third section included questions about the respondents’ concerns towards the safety and efficacy of bDMARDs, their information sources to decide on the use of biosimilar products, their perceived significant factors, and barriers of using bDMARDs in their clinical practice.The survey-based data were gathered from HCPs working in various healthcare and academic settings in Karachi. Respondents were provided with the questionnaire after being informed about the study’s purpose, benefits, and risks. The questionnaires were filled out anonymously by the respondents. The questionnaires, together with the consent form, were collected later, as per the convenience of the respondents. Respondents were neither compensated nor offered any gifts in exchange for their participation in the survey. All questionnaires were carefully reviewed, and those with a completion rate of more than 90% were included in the analysis. The responses of the HCPs were kept anonymous and voluntary.p-values of less than 0.05 as significant. SPSS for Windows version 24.0.0  was used for data analysis.Descriptive statistics were used to evaluate the baseline characteristics of the respondents. Continuous data were expressed as means and standard deviations (SDs), while categorical variables were expressed as percentages. To determine the type of data distribution, the Kolmogorov–Smirnov test was used. To analyze statistical differences among groups, inferential statistics  were employed, considering a n = 23 physicians and n = 9 pharmacists did not show a willingness to participate. Seventeen survey forms were omitted from the study, as the consent forms had not been duly filled out. Lastly, n = 413 completed surveys were incorporated into the investigation, with a response rate of 82.6%. The respondents’ mean age was 31.8 ± 12.8 years. Among them, 33.4% (n = 138) were males and 66.5% (n = 275) were females. The physicians made up 73.1% (n = 302), with a majority of them working in internal medicine, whereas 26.8% (n = 111) were pharmacists. The detailed demographic information of the respondents is demonstrated in Among the respondents approached for the study, n = 150) and 32.4% (n = 134) of the respondents considered themselves to be extremely and moderately familiar with the recent developments in bDMARDs, respectively. Their level of familiarity was significantly associated with their gender (p = 0.03), professional specialty (p = 0.005), and working organization (p = 0.002), while a numerical tendency was observed in association with experience (p = 0.057). The physicians were more well-informed regarding the indications  and monitoring requirements . The pharmacists were more informed regarding the targets of the drugs  and their mechanisms of action  as compared with physicians. Experienced respondents were more informed about the examples of disease-modifying anti-rheumatic drugs (p = 0.001), drug targets (p = 0.004), monitoring requirements (p = 0.003), and the general precautions associated with them (p = 0.001). The majority of physicians  and pharmacists  were aware that, before using bDMARDs, the functional capacity and damage to the joints, disease progression, pregnancy status, other comorbidities, extra-articular manifestations, and immunization history should be evaluated in their patients. Similarly, around two-thirds of the respondents, i.e., 70.8% (n = 214) of physicians and 75.6% (n = 84) of pharmacists, were aware that all patients should be screened for active or latent TB and HBV infections before initiating therapy with bDMARDs.n = 273) of the respondents agreed that DMARD therapy should be initiated immediately upon the RA diagnosis being confirmed. (p = 0.018). The majority of them  stated that, if therapy with an initial bDMARD is unsuccessful, substituting another bDMARD could be needed. The pharmacists were more willing to substitute with another bDMARD as compared with physicians . Around 80% of the respondents agreed that, in the event of not accomplishing the treatment objective with the first csDMARD, other csDMARDs should be considered or a bDMARD should be added. More than 75% of the respondents agreed that, if the use of methotrexate is contraindicated in a patient, leflunomide or sulfasalazine should be included in the initial treatment strategy.On inquiring about the respondents’ compliance with the RA standard management guidelines, 66.0% (nfirmed.  The respp = 0.009) and that patients should be educated about their therapy with bDMARDs (p = 0.028). Slightly more than half of the respondents  stated that the patient should engage in collaborative decision-making when opting to employ bDMARDs in their therapy. Male respondents as compared with females , and physicians as compared with pharmacists , were more confident in using bDMARDs than using conventional treatment in RA patients. More than 70% of the respondents showed their likelihood of using bDMARDs in their practice setting once approved by the U.S. Food and Drug Administration (FDA).The respondents having clinical experience of more than ten years were more likely to state that bDAMRDs should only be prescribed by experienced rheumatologists (n = 273) considered bDMARDs effective in controlling symptoms and preventing complications of RA, whereas 44.3% (n = 183) of respondents deemed bDMARDs important to stimulate innovation in biological medicine. Approximately 30% of the respondents consider bDMARDs important to encourage competition in the biological market and as an effective alternative in the event of a drug shortage.n = 237), potential drug–drug interactions , and unexpected adverse effects among patients . Product safety , professional/medical society guidelines , and the products’ efficacy  were the respondents’ perceived important sources to decide on the use of biosimilar products (products .Streptococcus pneumoniae (pneumococcus), and influenza, people with RA should continue to get certain immunizations to limit the occurrence of infections [The current study provided a glimpse into HCPs’ knowledge of bDMARDs and their compliance with the standard management guidelines for the management of RA using DMARDs. The research conducted so far depicting HCPs’ prescribing patterns and compliance with standard guidelines for RA care has been scarce, and ours is the first questionnaire-based study on the issue among Pakistani HCPs, specifically among physicians and pharmacists. To be proactive in the RA treatment strategy, HCPs must be aware of, understand, and agree with the standard recommendations of the guidelines . The curfections .In RA patients taking methotrexate or biologics, the standard recommendations for the use of biologic and non-biologic treatment explicitly recommend immunization against pneumococcus, hepatitis B, and influenza . VaccinaIn the present study, more than 65% of the respondents agreed that DMARD therapy should be started as soon as the RA diagnosis is confirmed. One more study inquiring into respondents’ opinions on the best period to start DMARD therapy reported that some HCPs indicated ‘within the first 6 months of diagnosis’, while 35% indicated ‘after a trial of NSAIDs or steroids’, and 5% indicated ‘at least 6 months after diagnosis’ . In overIt would have been difficult to assess the respondents’ adherence to the RA standard care recommendations, as every patient may have a distinct course of illness, which may influence the physicians’ management decisions. A treatment decision might have long-term implications, as well as significant uncertainty and compromises. One of the important competencies required for patients to participate in treatment decisions is the capacity to interpret risk information . The purSeveral limitations may have an impact on the current study’s findings. To begin with, HCPs’ recommendations were employed as the sole measure of adherence in the current study. Furthermore, the nature of the study was cross-sectional. Ideally, HCPs’ compliance should be assessed using a more comprehensive indicator that considers the kind of therapy, attainment of treatment objectives, follow-up, and monitoring.The present findings revealed that HCPs were well-versed with the attributes and uses of bDMARDs and the standard management guidelines for RA care. The outcomes may have provided a platform for identifying disparities between current management practices and standard guidelines, which may be valuable in designing future initiatives to standardize and deliver optimal RA patient care.


This study aims to determine the associations of dietary patterns with metabolic syndrome (MetS) and its components in Chinese children and adolescents aged 7–17 in 2016–2017. Using the data from the China National Nutrition and Health Surveillance of Children and Lactating Mothers in 2016–2017, the sociodemographic information, diet, anthropometric measurements and clinical examinations of subjects were obtained, and a total of 13,071 school-aged children and adolescents were included in this study. The Cook criteria were used to define MetS and its components. Dietary intake was derived from 24-h dietary records for three consecutive days, combined with the weighing method. Factor analysis was used to identify major dietary patterns. The associations of dietary patterns with MetS and its components were examined by logistic regression analysis. Consequently, five distinct dietary patterns were identified by factor analysis, and the relationships between dietary patterns with MetS and its components were observed. After adjusting for covariates, the animal product and vegetable patterns may have a positive association with MetS; the condiment pattern was positively associated with low HDL-C; the fruit and junk food patterns had positive relationships with MetS, abdominal obesity and high TG; the cereals and tubers pattern was positively associated with MetS, abdominal obesity, high TG and low HDL-C; the beans pattern was positively associated with high TG. Metabolic syndrome (MetS), also known as “Syndrome X” and “Insulin Resistance Syndrome”, is a complex group of metabolic disorders of energy use and storage, characterized by the combination of abdominal obesity, elevated blood pressure (BP), high triglycerides (TG), elevated fast blood glucose (FBG) and low high-density lipoprotein cholesterol (HDL-C) . This syImportant factors associated with MetS include genetic, socio-economic and environmental factors, unhealthy dietary habits and urbanization development . HoweverThus, this study is designed to investigate whether dietary patterns and MetS are correlated in a national sample of 7–17-year-old Chinese children and adolescents.Data were obtained from the China National Nutrition and Health Surveillance of Children and Lactating Mothers in 2016–2017. A complex, stratified, multi-stage cluster random sampling design was performed to provide a representative sample of 31 provinces, autonomous regions and municipalities in China. A total of 275 survey sites were randomly selected. Two townships/subdistricts were randomly chosen from every survey site, and two communities/villages were randomly selected from each township/subdistrict. At least 280 children and adolescents aged 6–17 were selected in school from each survey site, with equal numbers of males and females. The details of the study design have been explained in an earlier publication [This study was approved by the ethical committee of the National Institute for Nutrition and Health of the Chinese Center for Disease Control and Prevention. The ethical approval number was 201614. All participants provided informed consent before the study, either by themselves or via their guardian.(1)Abdominal obesity: WC ≥ age- and sex-specific 90th percentile, determined by the cutoff points for Chinese children and adolescents ;(2)Elevated blood pressure: SBP or DBP ≥ 90th percentile for age, sex and height ;(3)High triglycerides: serum TG ≥ 1.24 mmol/L;(4)Low HDL-C: HDL-C ≤ 1.03 mmol/L;(5)Elevated fast blood glucose: FBG ≥ 6.1 mmol/L.Cook’s criteria , modifieThe measurements were conducted by trained investigators. Anthropometric measurements included height, waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure (DBP). The height was measured to the nearest 0.1 cm with a stadiometer (TZG) with the participants standing in an upright position. The WC measurement was taken twice with a soft tape at the midpoint between the bottom of the rib cage and above the top of the iliac bone. We ensured that the error between the two measurements was less than 2 cm and recorded the average value. After resting for at least 5 min, SBP and DBP were measured three times in one-minute intervals by an electronic sphygmomanometer  with accuracy to 1 mmHg, and the mean of SBP and DBP were calculated and considered as an individual’s blood pressure.Clinical examinations included the concentration of triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and fast blood glucose (FBG). In this study, 6 mL fasting venous blood samples of participants were obtained in the morning and used for clinical testing. TG and HDL-C were tested using enzyme colorimetry . FBG was measured using the glucokinase method .Data on sociodemographic variables such as sex, age, living area, income, food expenses, physical activity, smoking and alcohol drinking were collected by a standardized questionnaire provided by the China Center for Disease Control and Prevention (the China CDC) project group.The living area was dichotomized into urban and rural areas. In this study, we divided all the subjects into three age groups  to reflect the prepubertal, pubertal and post-pubertal stages, respectively, according to the Chinese classification . The smoAll dietary information was collected using the 24-h dietary record method for three consecutive days (two weekdays and one weekend day) by professionally trained investigators. Condiment consumption was also recorded using the weighing method. The average amount of each type of food group and energy intake was calculated by each individual (grams per day per reference man) for data analysis. Dietary energy intake was calculated based on the Chinese Food Composition Tables ,22.For dietary pattern analysis, food variables were generated first because quantitative data such as the 3 days of food consumption were used. A total of 14 food groups based on similarity and food group classification were finally included for factor analysis with varimax rotation to explore the latent dietary pattern (DP) in our samples, including cereals (mainly rice and wheat products), tubers (mainly potatoes and sweet potatoes), mixed beans , legumes (mainly soybeans), vegetables, fruits, nuts , meat and poultry , fish and shrimp, milk, eggs, junk food , oil  and salt. The number of factors was determined based on eigenvalues , the scree plot and the interpretability of the derived factors . Each DPp for trends were presented. Two-sided p values < 0.05 were considered to be statistically significant.All analyses were conducted with SAS software  and the plot in this study was created using R software (Version 4.1.2). The categorical data were reported as numbers (percentages) and the Rao–Scott Chi-square test was performed to compare the distribution of different characteristics between subgroups. In order to maintain national representativeness, the PROC SURVEYFREQ program was applied. The weight of the sample was calculated by data from the China National Bureau Statistics in 2010. Factor analysis was conducted by the PROC FACTOR program. Multivariate logistic regression analysis was applied to explore the associations between DPs with MetS and its components. The model was adjusted for sex, residence area, age, Engel’s coefficient, physical activity, smoking and alcohol drinking, and all the covariables were transformed into dummy variables before conducting the adjustive process. The odds ratios (ORs), 95% confidence intervals (CIs) and p < 0.05). Moreover, 46.58% of all subjects were living in urban areas and 53.42% were living in rural areas. Participants classified as “living in urban areas” showed a higher prevalence of MetS than those living in rural areas . MetS was more prevalent in participants at post-pubertal stage . The rate of participants who engaged in physical activity was at least 78.12%. However, it was noted that the number of participants who were smoking was up to 45.03% and the drinking rate was 16.94%.Characteristics of 13,071 children and adolescents aged 7–17 are displayed in As shown in The results of the distribution of five DPs are presented in p for trend < 0.0001). DP2 was significantly associated with decreased odds of abdominal obesity (p for trend < 0.05) and elevated FBG , and increased odds of low-HDL-C . DP3 was positively associated with metabolic syndrome  and abdominal obesity (p for trend < 0.0001), high TG , but was negatively associated with low HDL-C . Positive associations were observed between DP4 and metabolic syndrome , abdominal obesity , high TG  and low HDL-C (p for trend < 0.05). DP5 was negatively associated with abdominal obesity  and positively associated with high TG .The results of associations between DPs with MetS and its components are shown in In the present study, five dietary patterns among Chinese children and adolescents aged 7–17 were identified using factor analysis, including the animal product and vegetable pattern, condiment pattern, fruit and junk food pattern, cereals and tubers pattern and beans pattern. The relationships between DPs and MetS and its components were observed.Among the five DPs, DP4—the cereals and tubers pattern—was mainly observed in all the subjects, followed by the beans pattern and fruit and junk food pattern, which indicated that there was a predominantly plant-based diet among subjects. DP1  appeared in the participants living in urban areas, where there is an abundant supply of food and better economic conditions. Additionally, DP5 (beans pattern) appeared in the participants whose Engel’s coefficient was greater than 40% and participants who drank alcohol. In other words, DP5 appeared in the participants who had a worse economic condition and an unhealthy lifestyle. Meanwhile, it was also noted that the rate of participants who were smoking was up to 45.03% and the drinking rate was 16.94%, and immediate intervention is necessary.p for this trend was statistically significant. Given the low intake of fish and shrimp and nuts, we speculated that the vegetables and legumes in DP1 may provide protection against low HDL-C. A few studies had reported that the consumption of dietary fiber contained in vegetables could improve lipid profiles and have beneficial effects on HDL-C [DP1, named the animal product and vegetable pattern in our study, which was rich in meat and poultry, fish and shrimp, vegetables, eggs and legumes, was found to have a positive association with metabolic syndrome. This dietary pattern was similar to the modern dietary pattern of nutrition and diet investigation projects in Jiangsu Province of China  and the on HDL-C ,32,33. Ion HDL-C .DP2, named the condiment pattern, was characterized by high factor loadings from oil and salt. To our surprise, DP2 was found to be negatively associated with abdominal obesity and elevated BP. In general, salty food could stimulate the brain to crave them and also be responsible for the increased incidence of obesity . Furtherp for this trend was not statistically significant. We speculated that the bioactive components of fruits and nuts, including fiber and some antioxidants, displayed a beneficial effect on lipid profiles [DP3, named the fruit and junk food pattern, was characterized by high consumption of fruits, junk food , nuts and eggs. It was significantly associated with an increased likelihood of having MetS, abdominal obesity and high TG. Apparently, the consumption of junk food, which has high energy density and low nutritional value, was an important component of DP3, which could lead to excessive energy accumulation, obesity and other metabolic diseases . Regularprofiles ,48. Howeprofiles , and morDP4, which referred to the cereals and tubers pattern, was rich in cereals, tubers and vegetables and low in junk food. The consumption of vegetables has been described in the DP1 discussion as a beneficial factor for MetS and its components. Cereals and tubers provide rich dietary fiber, less fat and less protein than animal foods . The fibThe soy food in DP5 (the beans pattern),which was rich in legumes, mixed beans and tubers, but was low in eggs, is one of the most common dietary components and has been demonstrated to have numerous health benefits. For instance, it is a major food source of isoflavones, phytosterols, lecithin, polyunsaturated fatty acids and dietary fiber ,55. We oThe main limitation of this study was the cross-sectional nature of the data, which prevented us from reaching causal conclusions. In addition, the data on food consumption that were collected by the 24-h dietary record and weighing method were not representative of whole-year consumption. Further, the allocation of oil and salt was based on the proportion of the reference for men, which could lead to slight errors in the analysis of individual intake because of individual differences. Fourthly, residual confounding effects cannot be avoided in any observational study. Well-designed, large-scale prospective studies are warranted in the future. In addition to its limitations, our study had strengths as well. Above all, using the scientific sampling method and rigorous quality control measures, the sample size of this study was large and the results can be generalized to the entire population. Furthermore, we controlled for the potential confounders in our analysis as much as possible, including physical activity, family economic condition, smoking and alcohol drinking, which play important roles in disease development.Five dietary patterns were obtained through factor analysis among Chinese children and adolescents aged 7–17 in 2016–2017: the animal product and vegetable pattern, condiment pattern, fruit and junk food pattern, cereals and tubers pattern and beans pattern. The cereals and tubers pattern mainly appeared in all subjects, followed by the beans pattern and the fruit and junk food pattern, which demonstrated that there was a predominantly plant-based diet among subjects. The animal product and vegetable pattern may have a positive association with MetS, but was negatively associated with low-HDL-C. The condiment pattern was negatively associated with abdominal obesity and elevated BP, and positively associated with low HDL-C. The fruit and junk food pattern had positive relationships with MetS, abdominal obesity and high TG, but was negatively related to low HDL-C. The cereals and tubers pattern was positively associated with MetS, abdominal obesity, high TG and low HDL-C. The beans pattern was negatively associated with abdominal obesity and positively associated with high TG.In brief, we identified five mutually exclusive dietary patterns and explored the associations between them and MetS and its components, which may indicate the potential for MetS prevention through effective dietary intervention. Our results could also have benefits in preventing possible type 2 diabetes and cardiovascular disease among Chinese children and adolescents. More large-scale, prospective studies are needed to explore the relationship between dietary patterns and metabolic syndrome.


Fibrinogen to albumin ratio (FAR) is a newly investigated indicator for inflammation. The study aimed to explore the potential ability of FAR in assessing the severity of inflammation in spondyloarthritis.The clinical data of 196 spondyloarthritis (SpA) patients, 66 osteoarthritis (OA) patients, and 81 healthy controls (HC) were collected in this retrospective study. The SpA group included 69 psoriatic arthritis patients, 47 reactive arthritis patients and 80 ankylosing spondylitis patients. Chi-square test and Mann–Whitney U test, Spearman’s correlation test, regression analysis, and ROC analyses were used for the analysis of FAR.FAR level in group SpA was higher than in OA or HC. In the SpA group, the reactive arthritis group was characterized by the highest FAR level. After matching the erythrocyte sedimentation rate, a significant difference occurred between groups SpA and OA, but not in SpA subgroups. The FAR level was significantly related to erythrocyte sedimentation rate and C-reactive protein. After regression and receiver operating characteristics analysis, FAR was considered the most potential pointer to evaluate inflammation in SpA with the area under curve of 0.95. The recommended cut-off value of FAR was 9.44 for serious inflammation and 8.34 for mild conditions.FAR is closely related to inflammatory biomarkers and can be a potential indicator in the assessment of inflammation in spondyloarthritis.The online version contains supplementary material available at 10.1186/s12891-022-05797-6. Spondyloarthritis (SpA) is composed of a group of inflammatory diseases affecting the joints and spine, such as psoriatic arthritis (PsA), arthritis related to inflammatory bowel disease (IBDA), reactive arthritis (ReA), a subgroup of juvenile idiopathic arthritis (JIA), and ankylosing spondylitis (AS) . The preNonetheless, the discriminability of FAR in assessing the severity of inflammation between various arthritis or different SpA subgroups remains obscure. In this study, a comparison between group SpA and OA aims at the first question, while an exploration between group AS, PsA and ReA aims at the second. Analyses after CRP or ESR matching aim to investigate the discernibility ability of FAR when the level of inflammation is similar. Then the study investigates the correlation between FAR and CRP/ESR, a subjective part of the criteria in evaluating disease activity, to search for the potential value of FAR in the assessment of spondyloarthritis. In addition, the ability of possible indicators is meticulously examined to select the optimal one and figure out the recommended cut-off value.This study was designed as a single-center, retrospective study with 343 cases involved. All patients’ data were from Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, with a complete medical history including symptoms and blood examination from February 2014 to September 2021. These patients were clinically diagnosed with ankylosing spondylitis, psoriatic arthritis, reactive arthritis, and osteoarthritis by a professional rheumatologist and respectively fulfilled the 2009 update of spondyloarthritis international society classification criteria for axial spondyloarthritis , classifAny of the following situations were excluded to control bias. (1) Patients with other rheumatic diseases. (2) Patients with severe nephropathy, hepatopathy, and hemopathy, which may relate to the generation and excretion of albumin and fibrinogen. (3) Patients with acute infection.The selection of patients was based on the following rules. (1) All PsA, ReA, and OA inpatients were included without selection. (2) AS patients were randomly selected from all AS inpatients. Gender-age matching between PsA, ReA and AS was not adopted because it could increase the risk of bias. For example, if AS patients were matched to ReA, the average course of these matched AS patients would be longer than that of all AS patients. Increased average course could lead to severe disease activity and introduce additional bias.(3) Healthy controls were from health examination data and were matched to SpA patients in age, gender and white blood cell (WBC) counts.The basic data was composed of basic information (age and gender), infection indicators (white blood cell counts (× 10^9/L) and lymphocytes counts(× 10^9/L)), inflammation indicators (CRP (mg/L) and ESR (mm/L)), HLA-B27 status, and the focused indicators , fibrinogen(g/L), and FAR). ESR and HLA-B27 were absent in healthy controls because the tests were not necessary in a basic medical examination.In the study, a hyper-inflammatory state was defined as CRP > 33.88 mg/L or ESR > 52 mm/h. The standard was calculated by ASDAS-CRP and ASDAS-ESR when a subjective assessment was valued as 4 and a total score > 3.5, which suggested high disease activity . A slighP-value < 0.0001 in univariate regression were selected as possible predictors, which included WBC, ALB, FIB and FAR. Then multi-factor linear regression and stepwise regression were reported to confirm the significance of possible indicators. Because FAR is the ratio of FIB to ALB, the multivariate regression and stepwise regression were separately applied to FAR and to FIB, ALB. Receiver operating characteristics (ROC) analysis was used to estimate the ability of FAR in reflecting hyper-inflammatory state and identifying cut-off values of FAR in overall consideration of sensitivity and specificity. The choice of cut-off value was based on Youden Index. In the study, FAR was calculated by FAR = fibrinogen/albumin× 100 to keep more effective digits. Multiple imputation and regression imputation were adopted to fill in the missing data to keep as many samples as possible while avoiding miscalculation. P-value < 0.05 was considered significant. Groups were matched by SPSS. Multigroup analysis was corrected by SNK test before being reported.Quantitative variables were reported as mean ± standard deviation (SD), and categorical variables were described as ratios and percentages. Basic data were analyzed by Mann–Whitney U test for abnormally quantitative data  and chi-square test for categorical data (gender and HLA-B27 status). Correlation analyses between albumin, fibrinogen, FAR and ESR, CRP were evaluated by Spearman’s correlation test. Univariate linear regression was used to screen for possible predictors from a series of indicators. The series of indicators were chosen by a rheumatologist according to clinical practice. Factors with p < 0.05), which supported that SpA patients undergone more serious inflammatory reactions. Though the HC group was matched to the SpA group by gender, age and WBC counts, still revealed divergence in CRP, ESR, FIB, ALB, and FAR (p < 0.05). Within SpA patients, three subgroups  showed discrepancies in basic information and inflammatory biomarkers. The ReA group was characterized by advanced age, a high incidence in women, and serious inflammatory reactions. AS, just as reverse, occurred more frequently in young men with lower CRP, ESR and FAR levels (p < 0.05). The PsA group, with the lowest mean value in ESR, FIB, and FAR, had no significant difference from the AS group.Finally, 196 patients with SpA, 66 patients with OA, and 81 healthy controls were collected in this retrospective study. The SpA group included 69 patients with PsA, 47 patients with ReA, and 80 patients with AS. The highest percentage of missing data was in lymphocyte counts, which was 7.8%. The missing percentages of CRP, ESR, ALB, FIB, and FAR were less than 5%. The basic characteristics of the SpA group, OA group, and HC group are shown in Table p = 0.0083). After CRP matching, FAR level was also higher in the SpA group but not significant (p = 0.1266). FAR showed no significant difference within SpA subgroups after ESR and CRP matching. More information is exhibited in Fig. For deeper analysis, ESR and CRP matching were imported to investigate whether there was a distinction between SpA group and OA group as well as within SpA subgroups when ESR or CRP was at the same level. Results came out that after ESR matching, FAR was still significantly higher in SpA group than OA group  of 0.95, but the AUC of ALB was just 0.67. A recommended cut-off value was 9.44 for FAR and 3.98 g/L for FIB, with the sensitivity of 0.91(FAR)&0.85(FIB) and specificity of 0.88(FAR)&0.94(FIB). Besides, a similar ROC analysis for ESR and CRP was also applied to show the ability of ESR and CRP compared to FIB and FAR. The AUC of ESR and CRP was 0.94, which was slightly less than FIB and FAR. A graphical representation of ROC analysis was displayed in Fig. p < 0.05). Considering the consistency of CRP, ESR and FAR, the distinction can be explained by the fact that inflammation levels in spondyloarthritis patients are higher than in osteoarthritis patients and healthy controls. In previous studies, FAR or AFR  was proved to be related to a systemic inflammatory response in various malignant tumors, including but not limited to gastric, esophageal, lung and cervical cancers [The first part of the study came out that FAR increased in the SpA group but remained lower in the OA and HC groups. In addition, the ReA group owned the highest FAR level among SpA subgroups  of FAR is higher than FIB under the same sensitivity. In contrast, FIB performs better when sensitivity is less than 0.9. For example, at a sensitivity of 0.91, the LR+ of FAR is 7.58 and the LR+ of FIB is 5.95. However, at a sensitivity of 0.85, the LR+ of FAR is 8.39 and the LR+ of FIB is 14.17. This phenomenon suggests that FAR was a better choice when high sensitivity is required.The necessity of introducing a new inflammatory biomarker lies in the complicated situation in clinical practice: some patients present low ESR levels but show high CRP levels, or vice versa. In the study, 59 out of 196 patients with discordant for CRP and ESR were observed (details are provided in the supplementary document). The fact that the AUC of CRP and ESR was only 0.94 meant an inconsistency between CRP and ESR, which supported the situation. In comparison of CRP and ESR, FAR showed a similar ability to identify serious inflammation, which denoted that the ability of FAR is not inferior to the now widely used inflammatory indicators. Moreover, the application of FAR in assessing inflammation in spondyloarthritis can be cost-effective, as the detecting techniques of ALB and FIB are well developed and widely accepted in clinical practice. Compared to a brand new biomarker, FAR can be brought into use promptly.In fact, the application of FAR in autoimmune diseases has been investigated in many previous studies. FAR was notably elevated in rheumatoid arthritis patients than in systemic lupus erythematosus patients, which could be proof that FAR is related to arthritis . A studyThis study expanded the target population to spondyloarthritis and osteoarthritis patients, which was not mentioned before. The correlation between FAR and traditional inflammatory biomarkers (CRP and ESR) as well as the capacity of FAR in identifying inflammation status supported FAR to be a new indicator in the assessment of inflammation in spondyloarthritis. Moreover, the difference of FAR between the SpA group and OA group after ESR matching suggested the potential of FAR. However, more profound research on the accuracy of CRP, ESR, and FAR in reflecting the disease activity of spondyloarthritis is required.The study is limited to a retrospective and single-center design. Though multiple and regression interpolation has been employed to fill in missing data and healthy controls have been matched to SpA patients in age, gender, and WBC, there may still be an unestimated bias. Another limitation is that the study fails to assess the disease activity directly due to the disparate assessment criteria. In addition, the reliability of FAR may be questioned when a patient develops nephropathy, hepatopathy or hemopathy. Furthermore, according to the current study, FAR did not show more advanced abilities than ESR or CRP in reflecting inflammatory status. Whether FAR can perform better in other areas needs further research.In summary, the study shows the ability of FAR in evaluating inflammation, which is related to ESR&CRP, but not limited to them. Ultimately, FAR is regarded as the most potential indicator, with the recommended cut-off value of 9.44 for serious inflammation and 8.34 for mild conditions compared to ALB and FIB. Further exploration of the direct relationship between FAR and SpA disease activity is expected, and an assessment standard including FAR is worth studying.Additional file 1.