A random-effects model was used to assess the diagnostic efficacy of the above modalities in cases in which a high degree of between-study heterogeneity was noted with respect to their diagnostic efficacies. The database search identified six studies including 578 patients. The pooled sensitivity and specificity of narrow-band imaging were 86%  and 81% , respectively, and the pooled sensitivity and specificity of white-light bronchoscopy were 70%  and 66% , respectively. The pooled relative risks for the sensitivity and specificity of narrow-band imaging vs the sensitivity and specificity of white-light bronchoscopy for the detection of early and invasive lung cancer were 1.33  and 1.09 , respectively, and sensitivity analysis showed that narrow-band imaging exhibited good diagnostic efficacy with respect to detecting early and invasive lung cancer and that the results of the study were stable. Narrow-band imaging was superior to white light bronchoscopy with respect to detecting early and invasive lung cancer; however, the specificities of the two modalities did not differ significantly.This study aimed to compare the ability of narrow-band imaging to detect early and invasive lung cancer with that of conventional pathological analysis and white-light bronchoscopy. We searched the PubMed, EMBASE, Sinomed, and China National Knowledge Infrastructure databases for relevant studies. Meta-disc software was used to perform data analysis, meta-regression analysis, sensitivity analysis, and heterogeneity testing, and STATA software was used to determine if publication bias was present, as well as to calculate the relative risks for the sensitivity and specificity of narrow-band imaging  Trend analyses of high-quality data from 22 registries, including several population-based registries currently available in the National Central Cancer Registry of China, were conducted in 2000–2011 and published in 2016. These analyses suggested that an estimated 4,292,000 new cancer cases and 2,814,000 cancer deaths would occur in China in 2015, and they identified lung cancer as the most common incident cancer and the leading cause of cancer-related death in the country. Lung cancer is considered an important health threat both in China and in other countries around the world and has imposed significant medical and economic burdens on society Surgery offers a relatively good possibility of a cure in patients with early-stage lung cancer, and the 5-year survival rate for patients with stage Ia disease is 73%. However, the 5-year survival rates range from 9% to 46% in patients with more advanced disease (stages II–IV) Endoscopic examination remains the most direct and effective method for detecting lung cancer. Narrow-band imaging (NBI) is a new endoscopic technique designed to detect pathologically altered mucosal and submucosal microvascular patterns that uses the following two narrow light bandwidths: blue light 390–445 nm), which is absorbed by superficial capillaries; and green light (530–550 nm), which is absorbed by blood vessels inside capillary membranes. These narrow bandwidths reduce light scattering  and enable enhanced blood vessel visualization. This approach consequently improves contrast on the mucosal surface, reduces examination times, and eliminates unnecessary biopsies  nm, whicFollowing the successful introduction of NBI in the field of gastroenterology and the confirmation of its diagnostic value for gastrointestinal malignancies, clinicians incorporated this modality into interventional pulmonology. NBI has since been used to diagnose lung diseases, especially early and invasive lung cancer. Several studies have compared the ability of NBI to detect early and invasive lung cancer (defined as moderate and severe dysplasia or carcinoma in situ [CIS]) and invasive lung cancer with that of pathological analysis The simplicity, reproducibility, and straightforward nature of NBI evaluations of the tracheo-bronchial tree ensure that NBI videobronchoscopy will play a significant role in lung cancer detection and staging in the future. However, previous publications have shown that the sensitivity and specificity of NBI for these lesions vary widely . However, most of these studies confirmed that NBI was superior to white-light bronchoscopy (WLB) with respect to detecting both early and invasive lung cancer We searched the PubMed, EMBASE, Sinomed, and China National Knowledge Infrastructure databases for relevant studies published up to September 14, 2015. We focused on English- and Chinese-language publications reporting the diagnostic efficacy of NBI for early and invasive lung cancer. The following search terms were used to ensure the list of studies retrieved via the search was comprehensive:  AND (“Lungs” OR “Lung” OR “Pulmonary”) AND (“Humans” OR “Human”).First, all the records from the database search were imported into Endnote to eliminate duplicate studies. Then, two evaluators (WL and JJZ) independently read the titles and abstracts of the articles identified through the above searches to exclude studies that did not meet the analysis inclusion criteria. Any disagreements were resolved through discussion. Finally, the full texts of the remaining studies were carefully reviewed so that informed final decisions regarding their inclusion in the study could be made. The reference lists of the included records were also screened for relevant articles .The following studies were included in the analysis: (a) studies published in English or Chinese; (b) studies using NBI to diagnose early and invasive lung cancer; (c) studies using histopathological analysis as the reference standard ; (d) studies reporting sufficient data for the construction of 2×2 contingency tables for the true positive (TP), false positive (FP), false negative (FN), and true negative (TN) rates of early or invasive lung cancer, as well as studies reporting “per-lesion” or “per-patient” statistics; and (e) studies including patients who underwent clinical or radiological examinations because they were suspected of having or known to have a lung malignancy or were at high risk for lung cancer. When the same data sets or subsets were presented in more than one article, only the article that provided the greatest detail, was published most recently, or had the highest level of quality was chosen. When abstracts and studies did not report sufficient data, we did not attempt to contact their authors to request additional information.The following studies were excluded from the analysis: (1) studies reporting data pertaining to histologically unconfirmed lesions; (2) studies reporting incomplete data; (3) studies with overlapping data; and (4) letters, editorials, expert opinions, reviews without original data, conference abstracts, meta-analyses, case reports, studies with fewer than 10 cases, and articles for which only the abstract could be obtained.Study quality was evaluated using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool Data pertaining to the numbers of TP, FP, FN, and TN diagnoses were extracted, and histological pathological findings served as the gold standard with which the above modalities were compared. We constructed 2×2 tables containing the number of cases of early or invasive lung cancer. These data were extracted on both a “per-patient” and a “per-lesion” basis when possible. We also extracted data regarding the first author’s name, year of publication, nation of research origin, mean patient age, ratio of men to women, number of lesions, number of patients, pathological results, number of endoscopists and endoscopes, type of NBI system, study design, and other relevant items .2 test and I2 statistic. I2 values of 25%, 50%, and 75% were indicative of low, moderate, and high heterogeneity, respectively. If the I2 value exceeded 50%, or the likelihood ratio χ2 test yielded a p-value <0.05, the data were considered to exhibit significant statistical heterogeneity. Therefore, we pooled the data pertaining to the sensitivity and specificity of the above diagnostic tests using a random-effects model to generate a more conservative estimate.Meta-disc (version 1.4) software was used to test the threshold effect among the included studies by calculating the Spearman correlation coefficient, to combine the indices used to describe the diagnostic efficacy of NBI, and to conduct heterogeneity tests. Study heterogeneity was assessed using the χThe area under the summary receiver operating characteristic curve (AUC) was used to analyse the lung cancer diagnostic efficacy of NBI. If significant heterogeneity was noted, meta-regression was used to identify the sources. Subgroup analysis was conducted to examine the diagnostic value of various statistical indices, and sensitivity analysis was used to assess the stability of the study results.p-value <0.05 was considered significant. An RR >1 indicated that NBI was more sensitive than WLB for the detection of early invasive lung cancer. Publication bias was analysed using a weighted linear regression model and a Deeks funnel plot (STATA software). An asymmetric funnel plot was suggestive of possible publication bias. The significance of the intercept was determined using a t test, and a p-value <0.05 was indicative of statistically significant publication bias. All p-values were two-sided, and all confidence intervals (CIs) had a two-sided probability coverage of 95%.STATA software  was used to calculate the relative risks (RRs) for the sensitivity and specificity of NBI vs the sensitivity and specificity of WLB for the diagnosis of early or invasive lung cancer. For these analyses, a Of the 207 reports retrieved during the database search, 159 remained after the duplicate studies were eliminated, and 28 remained after the titles and abstracts were screened. Twenty-two studies were excluded after a full-text review for the following reasons: (a) their biopsies were performed at sites of abnormal fluorescence, (b) they reported insufficient data with respect to their sensitivity and specificity calculations, (c) they were review articles, (d) their data were presented in more than one article, and (e) their full text was not available .The results of the quality assessment of the eligible studies are shown in p=0.208, indicating that the lack of a definite threshold effect produced heterogeneity. The I2 values for sensitivity and specificity were 94.1% and 88.9%, respectively, indicating that a high level of between-study heterogeneity was present with respect these parameters because of the non-threshold effect. When a random-effects model was used to analyse the sensitivity and specificity of NBI for the detection of early or invasive lung cancer, the pooled effect values for the sensitivity, specificity, and AUC were 86% , 81% , and 0.89  and 81% , respectively, with an AUC of 0.92 (2=90.3%) and 66% , respectively, with an AUC of 0.70 (vs the sensitivity of WLB for the detection of early and invasive cancer was 1.33 (95% CI: 1.07–1.67), and the corresponding pooled RR for the specificity of NBI vs the specificity of WLB for the detection of early or invasive cancer was 1.09 (95% CI: 0.84–1.42) (Four of the included articles  of 0.92 . The poo of 0.70 . The poo84–1.42) . Thus, N2=77.3%) and 58% , respectively, whereas the corresponding values for WLB were 14%  and 69% , respectively. The RR for the sensitivity of NBI vs the sensitivity of WLB for the diagnosis of early lung cancer was 3.86 (95% CI: 1.38–10.75), and the RR for the specificity of NBI vs the specificity of WLB for the diagnosis of early lung cancer was 0.83 (95% CI: 0.45–1.53). Therefore, we concluded that NBI is superior to WLB with respect to detecting early lung cancer. The sensitivity and specificity of NBI were lower in the above studies than in the cumulative results.We also searched for data regarding the ability of NBI to accurately diagnose early lung cancer only 2=0.0%) and 86% , respectively, whereas the corresponding values of AFI were 91%  and 38% , respectively. The RRs for the sensitivity and specificity of NBI for the diagnosis of early and invasive lung cancer were 0.69 (95% CI: 0.60–0.78) and 2.29 (95% CI: 1.61–3.25), respectively.In this study, we also searched for data comparing the ability of NBI to accurately diagnose early and invasive lung cancer with that of autofluorescence imaging (AFI) and NBI + AFI 2=89.3%) and 54% , respectively, and the corresponding RRs were 0.67 (95% CI: 0.59–0.76) and 1.38 (95% CI: 0.49–3.90), respectively. Therefore, we concluded that the sensitivity of NBI for the diagnosis of early and invasive lung cancer was lower than that of AFI + NBI; however the specificity of NBI for the diagnosis of early and invasive lung cancer did not differ significantly from that of AFI, suggesting that NBI and AFI are complementary tests. Unfortunately, only two relevant studies regarding the ability of these tests to diagnosis early and invasive lung cancer were available; thus, additional studies will be needed to confirm the abovementioned findings.The sensitivity and specificity of AFI + NBI for the detection of early and invasive lung cancer were 93% , the Deeks funnel plot suggested that publication bias may have been present among the included studies, and the corresponding nel plot , the angTwo studies reported adverse effects. In one study, all the adverse effects were attributed to bronchoscopy rather than to the NBI devices. The other study reported slight bleeding that was attributed to NBI but described no other NBI-related complications.Diagnosing lung cancer early is essential for effectively treating the disease and optimizing survival. Bronchoscopy is ideal for detecting lung cancer arising from the central airway; however, detecting early and invasive lung cancer and precancerous lesions using WLB remains difficult. According to a previous report, only 29% of CIS and 69% of microinvasive cancer cases are identified by WLB, regardless of the experience level of the bronchoscopist NBI is an optical technique based on the use of narrower blue and green light filters to enhance visualization of the microvascular architecture and microsurface structures. This technique, which offers chromoendoscopy without requiring additional dye sprays, clearly highlights the micromorphology and microvascular structures of mucosal lesions and facilitates the identification of cancerous lesions 2=94.1%) and a specificity 81%  for the detection of early and invasive lung cancer.NBI can distinguish cancer from benign lesions with a high level of accuracy One systematic review The prognoses of patients with lung cancer depend heavily on the stage at which patients are diagnosed with the disease. According to the stepwise progression theory of carcinogenesis, early detection of preinvasive lesions, such as moderate or severe dysplasia or CIS, and subsequent prompt surgical resection or endobronchial treatment will provide the patient with the best chance of survival and lung function conservation. Consistent with this idea, the reported 5-year survival rate for patients treated for preinvasive (stage 0) lung cancer exceeds 90% NBI, a novel observational method, has facilitated pathological diagnoses of lung cancer by allowing mass observation, guiding targeted biopsies, and enabling predictions of pathological type An article p<0.001), these modalities did not differ significantly with regards to sensitivity (p=0.49). Furthermore, although the relative sensitivity for the combination of AFI and NBI vs WLB was 4.0, the combined test did not exhibit improved specificity compared with either AFI alone or NBI alone (p=0.56). The specificity of AFI + NBI was equal to that of AFI and significantly lower than that of NBI; thus, this combination led to a nonsignificant increase in lung cancer diagnostic yield. In summary, this study demonstrated that NBI can be used alone as a first-choice lung cancer diagnostic modality rather than in combination with other diagnostic modalities.In an earlier article, Herth reported that AFI, NBI, and NBI + AFI exhibited sensitivities of 65%, 53%, and 71% and specificities of 40%, 90%, and 40%, respectively, for the diagnosis of early lung cancer p<0.01) but not their sensitivities (p>0.05) for the diagnosis of early and invasive lung cancer, whereas NBI + AFB and NBI alone differed significantly with regards to both their sensitivities and their specificities for the diagnosis of early and invasive lung cancer . Chen concluded that NBI + AFB could diagnose lung cancer with greater specificity than AFB alone, a notable finding that contradicted those reported by Herth. This discrepancy may be attributable to the following factors: 1. The study by Chen addressed obvious bronchial and pulmonary masses and used the above diagnostic techniques only to observe mucosal abnormalities. Moreover, the patients eligible for inclusion in the study were not at high risk for lung cancer. Therefore, that study differed from the study performed by Herth, as it lacked data regarding certain study parameters, as well as data regarding precancerous lesions. 2. The positive diagnosis rate reported by Chen pertained to patients rather than lesions. The discrepancies between these two studies have necessitated additional high quality research to determine whether NBI + AFB is superior to either modality alone with respect to diagnosing cancer.According to Chen Despite these differences, the study by Chen demonstrated the distinct advantages of the above modalities. AFB is used to observe surface mucosal changes, and NBI is used to observe surface mucosal vascular lesions. When used in combination, each modality can compensate for the shortcomings of the other. However, AFI and NBI are not currently integrated into single bronchoscope units. In the future, the combined use of these technologies may reduce inspection times and patient discomfort. In our meta-analysis, which included 578 patients, only one article reported slight bleeding. Therefore, we believe that NBI, which has high diagnostic value and a low complication rate, may be an accurate, safe, and cost-effective tool for diagnosing early lung and invasive lung cancer.Our analysis had some limitations. First, we included only six studies in the analysis. Second, we were unable to identify the sources of heterogeneity among the studies included herein. Although one could argue that heterogeneity is inevitable in a meta-analysis regardless of whether its presence is detectable via statistical analysis, its existence limits the clinical application of the results of the analysis. The heterogeneity noted herein may be attributed to differences in the time spans of the included studies, the use of different types of bronchoscopes, differences in the experience levels of the endoscopists and pathologists who performed the bronchoscopies and biopsies, diagnostic research on small sample sizes, differences in sex ratios and age distributions, and differences in pathological results. Furthermore, in some of the studies included in the analysis, tissue samples biopsied from visually normal areas, as demonstrated by both NBI and WLB, were used as controls; however, other studies included in the analysis did not perform control biopsies. Third, in our subgroup analysis, we compared the diagnostic accuracies of NBI, AFI and AFI + NBI; however, we identified only two studies that performed these comparisons. Therefore, our conclusions regarding the relative efficacies of those modalities require further verification in future studies. Fourth, all the included studies used an earlier bronchoscope model. The newest NBI bronchoscope is the OLYMPUS BF-H290, which produces clearer images than earlier models but is expensive. To date, no published studies have used this bronchoscope. Finally, publication bias was inevitable because we did not search for unpublished data, and data regarding TP, FP, TN, and FN diagnoses could not be extracted from the sensitivity and specificity calculations of two relevant studies NBI is an accurate, safe, and cost-effective tool for diagnosing lung cancer. The current evidence indicates that NBI is more valuable than WLB with respect to diagnosing both early and invasive lung cancer and that it is both feasible and convenient to switch between these two modalities as technologies advance. Our findings indicate that NBI is superior to WLB and that its use may lead to improvements in diagnostic yields, as well as improvements in sensitivity for the diagnosis of cancer that do not compromise specificity. However, additional high-quality prospective studies regarding the ability of NBI to diagnose early and invasive lung cancer remain necessary.Li W designed the study, acquired some of the data, edited the manuscript and critically reviewed the final version of the manuscript. Zhu J acquired some of the data, conducted the statistical analysis, and drafted the manuscript. Chen Y, Zhao C, Zhang T, Peng W, Wang X performed the study and performed the data collection and analysis. All authors read and approved the final version of the manuscript.


Personal health records (PHRs) and mHealth apps are considered essential tools for patient engagement. Mobile PHRs (mPHRs) can be a platform to integrate patient-generated health data (PGHD) and patients’ medical information. However, in previous studies, actual usage data and PGHD from mPHRs have not been able to adequately represent patient engagement.By analyzing 5 years’ PGHD from an mPHR system developed by a tertiary hospital in South Korea, we aimed to evaluate how PGHD were managed and identify issues in PGHD management based on actual usage data. Additionally, we analyzed how to improve patient engagement with mPHRs by analyzing the actively used services and long-term usage patterns.We gathered 5 years (December 2010 to December 2015) of log data from both hospital patients and general users of the app. We gathered data from users who entered PGHD on body weight, blood pressure (BP), blood glucose levels, 10-year cardiovascular disease (CVD) risk, metabolic syndrome risk, medication schedule, insulin, and allergy. We classified users according to whether they were patients or general users based on factors related to continuous use , and analyzed the patients’ characteristics. We compared PGHD entry counts and the proportion of continuous users for each PGHD by user type.P<.001) and BP (P=.03) functions. Continuous use of PGHD in health management  was significantly greater among older users (P<.001) and men (P<.001). In health management , overall chronic disease and continuous use of PGHD were not statistically related (P=.08), but diabetes (P<.001) and cerebrovascular diseases (P=.03) were significant.The total number of mPHR users was 18,265  with 3620 users having entered weight, followed by BP (n=1625), blood glucose (n=1374), CVD (n=764), metabolic syndrome (n=685), medication (n=252), insulin (n=72), and allergy (n=61). Of those 18,256 users, 3812 users had at least one PGHD measurement, of whom 175 used the PGHD functions continuously ; less than 1% of the users had used it for more than 4 years. Except for weight, BP, blood glucose, CVD, and metabolic syndrome, the number of PGHD records declined. General users’ continuous use of PGHD was significantly higher than that of patients in the blood glucose (Although a small portion of users managed PGHD continuously, PGHD has the potential to be useful in monitoring patient health. To realize the potential, specific groups of continuous users must be identified, and the PGHD service must target them. Further evaluations for the clinical application of PGHD, feedback regarding user interfaces, and connections with wearable devices are needed. Patient centeredness and patient engagement are essential characteristics of health care services and provide the greatest benefits to patients . In precPatient information accumulated through mPHRs and wearable devices can help build a personalized baseline . PGHD haPrevious studies have noted the lack of usage data research that analyzes the use of mPHRs from the perspective of PGHD ,10. In pWe conducted this study using data on the 5-year use of an mPHR system distributed by a tertiary hospital in South Korea. The mPHR system, which has been used since 2010, provides several functions through which users can log their health data. Based on actual usage data, we investigated the usage pattern and characteristics of the users of PGHD services. To the best of our knowledge, this is the first study on the long-term use and input of PGHD through mPHRs.We collected the log data of an Android-based mPHR app called My Chart in My Hand (MCMH) at Asan Medical Center (AMC), which is the largest general hospital in South Korea. AMC established the Ubiquitous Health Center in 2009, and the MCMH was implemented on December 27, 2010, after collaboration with a Korean telecommunication company  . The UbiThe items in dashed boxes in To identify the usage pattern of the PGHD functions according to the type of PGHD, user type , and continuous use of the function, we analyzed the logs of all users who signed up and logged in more than once between December 2010 and December 2015. MCMH 1.0 was launched on December 20, 2010, for test users and on December 27, 2010 for all users. It was replaced with MCMH 2.0 on December 31, 2015.As there are no existing criteria for continuous use of PGHD services, this study defined the criteria for each PGHD function. We defined continuous use as follows: weight, BP, and blood glucose entered at least once per week and used for at least 4 weeks (28 days); 10-year CVD risk and metabolic syndrome risk entered at least twice and used for at least 180 days. Because weight, BP, and blood glucose are continuous values that indicate users’ daily health status, 10-year CVD risk or metabolic syndrome risk is a risk-evaluation function that has no definite consensus regarding the evaluation period; we derived these criteria differently through discussion.International Classification of Diseases, 10th Revision.The user logs contained time stamps for each PGHD function, recorded whenever an individual used these functions. We also gathered demographics and medical records for patients, such as age, sex, residence, and health information, including hospital visits and presence of chronic diseases, using our clinical research data warehouse . We condThis study was approved by the AMC’s institutional review board (no. 2017-1128). The ethics committee waived the need for informed consent, as this study used routinely collected log data that were anonymously managed at all stages, including during data cleaning and statistical analyses.We performed a comparative analysis of the continuous use of PGHD services between AMC patients (n=3499) and general app users (n=313). To analyze the demographic and clinical characteristics, we extracted related variables from the clinical data warehouse only for patients. We then analyzed patients’ characteristics according to their continuous use of health management  and risk management (10-year CVD risk and metabolic syndrome risk) functions.t test and chi-square test, respectively. If the observed value was less than 5, we performed Fisher exact test. All reported P values were 2-sided, and P values less than .05 were considered significant. Also, we performed a multiple logistic regression analysis with adjusted age and sex. Data analyses were conducted with the R software, version 3.3.1 (R Foundation).We compared means and of frequencies with the Student Within 5 years of MCMH operation, a total of 18,265 users downloaded the app and logged in more than once. Among these users, 16,729, or 91.59% of the total, were AMC patients. Patients had a statistically significant (1.8 times) longer use of the system (average period of use: 251.86 vs 467.84 days) and a pattern of accessing the app more than 6 times compared with general users (average number of accesses: 8.26 vs 50.96).P=.003), weight (P<.001), and allergy (P=.04). The average number of records per user was also significantly higher in general users: 6.89 (SD 24.79) vs 4.41 (SD 31.46) (P=.009). The median values of 1 for all categories except insulin indicate that more than half of the users made only 1 entry in each category. There was no significant difference in the remaining PGHD items.Among all users, 21.50% (3928) had at least one PGHD record . In the R2=.857), followed by BP , and 10-year CVD risk . In the decreasing pattern, medication showed the steepest decrease .The distribution of total PGHD items was divided into 2 patterns: increasing and decreasing . Items wWe performed a periodic usage analysis of the 3 most recorded PGHD items  among the 9 PGHD items . To deteP<.001) and BP (P=.03). For other PGHD items, there was no statistically significant difference in continuous use between the 2 user types  and risk (at least 180 days for 10-year CVD risk and metabolic syndrome risk) management, and then analyzed the differences between AMC patients and general app users. A total of 175 mPHR users continued to use the PGHD functions. General users were significantly higher than patients in continuous use of PGHD for blood glucose (er types .P<.001). For continuous use of PGHD services, there was no statistically significant difference in overall chronic disease (P=.08), but diabetes (P<.001) and cerebrovascular diseases (P=.03) differed significantly. These characteristics were also significant in age- and sex-adjusted multivariate regression analyses . In those with diabetes, continuous users were younger than noncontinuous users . This is young relative to the average age of continuous users of the entire PGHD group . In those with cerebrovascular disease, continuous users were older than noncontinuous users, which was not statically significant . In each disease group, there was no significant difference between the 2 groups (continuous vs noncontinuous) in sex, distance from the hospital, and type of visit.To identify the characteristics of users who continuously used PGHD functions, we conducted a comparative analysis of the related data on demographics, diagnoses, and hospital visits in the health and risk management menus of MCMH . This anHospital visit experience was not statistically related to continuous use; all continuous users made emergency room and outpatient visits. In risk management, there were no significant differences between continuous and noncontinuous users.The mPHR used in this study was a feasible platform for managing PGHD, for the following reasons. First, it was available not only to patients but also to general users; it was used as a platform to store and refer to general users’ health information. Although the number of users was small, the fact that there were long-term users entering their health information means that this app was used as a suitable tool for storing and referring to health information. Second, there were enough long-term users to show significant differences in usage patterns. Third, the upgraded version, which reflects usage patterns and user needs, of the existing mPHR is expected to improve user satisfaction and to contribute additional data for further research.This study is unique compared with previous studies based on the following characteristics. First, we used actual usage data to investigate long-term use. Meanwhile, research on telecare for chronic disease management lacks enough studies for a sufficient period of time. Second, our analysis was based on users rather than just on patients of AMC. We also compared usage by those who had been in hospital (patients) and those who had not . Third, the mPHR we examined is the first one to provide patient information to patients in Korea, and our study included analysis and consideration of the modifiable factors for long-term use promotion.P=.009). There was a significant difference in blood glucose (P<.001). General users submitted more BP and insulin records, although the differences were not significant. MCMH is not a type of mPHR that mainly aims at chronic disease management; it is a comprehensive platform that includes such services as providing patient information and setting appointments. Therefore, the more frequent use by patients is attributed to the greater number of services available through the mPHR relevant to them than to general users. Nonetheless, general users used it more actively for storing and referring to health information. This result confirms the potency for managing patient health information through an mPHR.Most of the mPHR users were patients (91.59%), and we found them to have significantly longer and more frequent use. However, general users used more of the overall PGHD functions  are more complicated than in other functions. On the other hand, BP, weight, and blood glucose menus required users to input only a few numerical values, and CVD and metabolic syndrome required users to check several boxes for risk evaluation. The user interface problem at the time of data input can be considered to have caused these differences. In addition, while biosignals such as weight, BP, and blood glucose were entered for the purpose of managing health data by the users themselves, the functions that are out of the scope of the users’ management might provide less motivation for continuous use, without rewards such as the feedback of clinicians. Also, the increase in the use of biosignal input functions suggests that automatic input of data through wearable devices, body scales, or blood glucose meters may be helpful for encouraging continuous use. Linking PHR data would reduce the inconvenience to users of inputting data for diseases, insulin, medication, and allergy.General users’ tendency to use the blood glucose and insulin functions longer showed the need for a reliable app service for diabetes management. The mPHR was developed for general care, not only for chronic disease management. Therefore, services for patients with chronic diseases were limited. However, despite the small proportion, there were long-term users for chronic diseases management, especially for diabetes.One of the main reasons for the abandonment of health apps is the mistrust of app developers . AlthougSignificantly, male users, elderly users (mean age 51.81 vs 43.81 years), and users with a diagnosis of diabetes tended to use the health management functions continuously. In the case of cancer, which accounted for more than half of all chronic diseases, the incidence in Korea increased by age beginning with users in their 80s, and the incidence among men was higher than that among women . In addThe main limitation of this study was the lack of a clinical practice application of the PGHD collected in the mPHR; the PGHD in MCMH version 1.0 were used for simple reference without any feedback from a health provider. This aspect is improved in MCMH 2.0, and the PGHD in the mPHR are used clinically in centers for diabetes, cancer, inflammatory bowel diseases, and pediatric and atopic asthma.Another limitation was the definition of continuous use of PGHD services. In this study, we defined our own criteria through discussions among the researchers. Various criteria may be applied when considering the nature of patients’ diseases and hospital visit intervals. The low percentage of those who used the service continuously was also a major drawback of this analysis.Ease of data entry can also affect PGHD service usage. Since wearable devices were not connected to our mPHR, we expected that data input convenience would be poor. Therefore, if wearable devices could be linked to the mPHR, the low compliance may be improved. However, appropriate devices and scenarios need to be considered to collect PGHD effectively. Previously, encouraging results have been reported in cancer and diabetes management. A recent study focused on short-term patient management through wearable devices . FurtherAlthough a small proportion of users managed their PGHD input continuously through the mPHR, we found the mPHR to be a tool for integrating PGHD and patient medical information. Studies examining the factors promoting the continuous use of PGHD functions in mPHRs and the consensus of the continuous use of various PGHD types are needed. Further evaluation for the clinical application of PGHD, feedback regarding user interfaces, and connections with wearable devices are needed as well.


Satisfaction evaluation is widely used in healthcare systems to improve healthcare service quality to obtain better health outcomes. The aim of this study was to measure employee work satisfaction and patient satisfaction status in Wuhan, China. A cross-sectional study was conducted in 14 medical institutions. The final valid sample comprised a total of 696 medical staff and 668 patients. The overall satisfaction levels of medical staff and patients were 58.28 ± 14.60 (10.47–100.00) and 65.82 ± 14.66 (8.62–100.00), respectively. The factors affecting medical staff satisfaction, ranking in sequence from most to least satisfied, were: the work itself, working environment and atmosphere, hospital management, practicing environment, and job rewards. Patient satisfaction factors, from most to least affecting, were ranked as follows: physician-patient relationship and communication, service organization and facilities, continuity and collaboration of medical care, access to relevant information and support, and healthcare and related services, respectively. The overall satisfaction evaluation of medical staff was average. Healthcare policy makers and medical institution management staff should focus on job rewards and working environment. This would allow them to increase their work happiness and sense of belonging, which in turn would allow them to provide better medical services to patients. The overall patient evaluation was satisfactory, with patients satisfied at all levels of the satisfaction evaluation. For a long time, work satisfaction has been a core concept of organizational behavior and has been used to measure the attitudes of proactivity or happiness towards work in employees, based on employees’ evaluation of work characteristics (work experience). Furthermore, work satisfaction is an important marker of whether or not a corporation’s reward mechanism is successful . The worCurrently, there are many tools to measure medical staff satisfaction and patient satisfaction worldwide ,20. EachChina’s “New Medical Reform”, which began in 2009, is currently ongoing. The satisfaction of all parties regarding healthcare reform can directly reflect the implementation and effect of various measures for medical reform. Investigation tools for medical staff work satisfaction and patient satisfaction have not been combined with China’s new healthcare reforms, as the questionnaire items are not focused on investigating satisfaction with healthcare reform policies and cannot be used to directly investigate satisfaction following the healthcare reform. Research tools will often use foreign measurement scales or scales that were developed before 2009. The five reform priorities of the new healthcare reform are as follows: first, to speed up the construction of the basic medical security system, achieve full coverage and gradually raise the level of funding and security; second, to establish a national basic drug system so that the masses can use drugs safely and effectively; third, it is necessary to improve the basic public health service system, achieve full coverage of the network, change the operational mechanism, and improve the service quality; fourth, to promote the equalization of basic public health services, improve the system and the funding guarantee system, and reduce the basic public health services for urban and rural residents; fifth, to promote a pilot reform of public hospitals, strengthen hospital management, optimize service processes, standardize the diagnosis and treatment activities, improve the level of medical services, and facilitate the public in seeking medical treatment. Therefore, there is a need to develop a scale that is focused on patient satisfaction and medical staff work satisfaction following the healthcare reform. A survey on satisfaction with the new healthcare reform was previously carried out in Guangzhou in December 2014 ,35 and tPrevious studies have mostly focused on asking study subjects to describe their level of satisfaction  and thus have segregated medical staff and patients, who should, in fact, be a unified whole and mutually provide feedback and respond to healthcare system operations. This study appropriately expands the research horizons to investigate the status of medical staff work satisfaction and patient satisfaction following China’s healthcare reform in Wuhan  and viewed doctors and patients as a whole in conducting the research.The subjects of this study comprised medical staff and patients in public general hospitals and community healthcare service centers/stations  in Wuhan City, China. The inclusion criteria for medical staff were: 1. specialists, general practitioners, nurses, medical technicians , public health physicians, and hospital management; 2. who have worked at the medical institution for more than half a year; 3. who signed the informed consent form for this study. Exclusion criteria: Medical staff that were in their probation period. Patient inclusion criteria: 1. Patients aged ≥18 years and their relatives; 2. Patients who had attended for diagnosis and treatment in the given medical institution in the past one year ; 3. Inpatient and outpatients were both allowed to participate. Exclusion criteria: 1. Non-patient ; 2. Patients who have just arrived at the hospital and have lost touch with the medical staff access to any diagnosis and treatment.Based on the level of economic development in the administrative region and hospitals that meet a certain scale , we randomly selected four pilot district-level/municipal-level integrated public hospitals  and 10 community healthcare service centers/stations . At this stage, the data collected were mainly used to evaluate patient satisfaction and medical staff work satisfaction in 2016 in Wuhan City following the implementation of the healthcare reforms. This study adopted stratified sampling to ensure maximal consideration of sampling representation. A total of 720 questionnaires were distributed to medical staff and 680 questionnaires to patients, for a total of 1400 questionnaires. A total of 696 medical staff questionnaires and 668 patient questionnaires were deemed valid for analysis. Twenty-four medical staff questionnaires and 12 patient questionnaires were ultimately deemed invalid. Missing responses were those with blank space or vague to see. Response rate: 96.67% for medical staff and 98.23% for patients. Participants were given a small incentive (a piece of soap or a towel per responder) valued at 5 RMB as compensation for their time. Based on our calculation, the sampling error for medical staff and patient is 3.6% and 3.8%, respectively.Trained and qualified investigators conducted this study and distributed unified questionnaires. Self-completion methods were mainly used for the collection of questionnaire data in both the medical staff and patient questionnaires. Once informed consent had been obtained from participants, the investigator distributed a questionnaire to them for completion by themselves. Upon completion, the questionnaires were collected and examined for missing items. Throughout the entire study process, the study subjects could ask the investigators if they had any questions or doubts.To ensure the successful implementation of this study and research quality, rigorous quality control measures were implemented at every stage of the study. A series of measures was used to ensure that differences between the data obtained in this study and the actual situation were kept to a minimum. Quality control was implemented throughout the entire study process: 1. Sampling stage: Comprehensive consideration of sample representativeness and operable design of the sampling protocol, and strict implementation of sampling according to the sampling protocol. 2. Uniform training of investigators and ensuring that the investigators accurately understood the scale dimensions and items. Investigators had to be clear on their roles and responsibilities and have uniform accurate understanding of the questions in the scale and method of answering enquiry questions (non-guided). Medical staff was provided with assistance as needed, including explanation of the meaning of items or skip patterns. 3. Strict implementation of inclusion and exclusion criteria. 4. Establishment of a verification system for survey quality: The investigator must carry out a complete inspection of the content completed by the subject (patient) on site. Investigators would remind the participants that they might forget several items. If the participants suggested they did not wish to answer, then the investigators would respect their decision. 5. To ensure the quality of data entry, a dual entry system was used during the data entry stage, which comprised each questionnaire being independently entered by two investigators. After the data had been verified to ensure no missing items or errors, they were used for statistical analysis. 6. Management of missing values: If missing items were found in some questionnaires during the second review, imputation is necessary. The management method (after discussion with experts) was as follows: If the number of missing values in one questionnaire was >4, the questionnaire was deemed invalid; If the number of missing values in one questionnaire ≤3, such questionnaires were still deemed valid for statistical analysis. Estimates means, standard deviations, covariances, and correlations for different missing value methods: listwise, pairwise, regression, or expectation-maximization (EM). After implementing Little’s MCAR test, it was found that medical staff and patient data belonged to missing at random (MAR) and missing completely at random (MCAR), respectively. Thus, EM and regression method were used for completion of medical staff and patient data, respectively.The study tools comprised two parts:The medical staff satisfaction scale following healthcare reform  and patient satisfaction scale following healthcare reform  ,35 were The medical staff work satisfaction scales include five dimensions and 43 items. The five dimensions are: the work itself (first dimension), job reward (second dimension), hospital management (third dimension), work conditions and atmosphere (fourth dimension), and practicing environment (fifth dimension). Satisfaction from the work itself was used to evaluate the satisfaction status of medical staff towards workload, job autonomy, job stability, job importance, ability utilization, job achievement, and job responsibilities. Job rewards were used to evaluate the satisfaction of medical staff towards material rewards, mental rewards, and reward fairness. Hospital management was used to evaluate the satisfaction status of medical staff towards the organization and management of their medical institution, including hospital leadership ability, process management in the hospital, system management, current development status, industry status and developmental outlook, etc. Work conditions and atmosphere were derived from the internal working environment of medical staff and used to evaluate the satisfaction status of medical staff towards the facilities and equipment, informatization level, logistical support, interpersonal relationships and collaborative atmosphere, etc. Practicing environment was derived from the external environment of practice by medical staff and evaluates the satisfaction level of medical staff in relation to physician-patient relationship, communication, societal opinion, health policies, etc. In addition, a special item, with 0 to 100 points description, was included at the end of the medical staff work satisfaction questionnaires to evaluate the macro-level work satisfaction of the study subject in the past year .The patient satisfaction scales include five dimensions and 29 items. The five dimensions were: physician-patient relationship and communication (first dimension), access to relevant information and support (second dimension), healthcare and related services (third dimension), continuity and collaboration of medical care (fourth dimension), and service organization and facilities (fifth dimension).The physician-patient relationship and communication dimension mainly refer to the level of satisfaction of the patient towards two-way communication during the consultation process. The physician-patient relationship refers to the social interaction process of mutual communication and interaction between physicians and patients. This is a unique interpersonal relationship, with healthcare at its core and maintenance of patient health as its objective. The access to relevant information and support dimension refers to the process by which patients obtain relevant information in relation to medical services and medical insurance from medical staff. The healthcare and related service dimension refers to the services of examination, diagnosis, treatment, recuperation, and preventive healthcare provided by the medical institution to the patients, as well as the drugs, medical equipment, ambulances, and hospital wards that are related to those services. The continuity and collaboration of the medical care dimension refers to the process, design, and implementation of connecting patients to hospital services in order to provide continuous medical services and coordination between medical staff, in order to ensure that the patient’s medical information is transferred when the patient is transferred, to ensure continuous medical services when patients are transferred to another department or hospital, or following discharge. The service organization and facilities dimension refers to access to medical care and evaluation of perception towards environment and facilities. In addition, a special item, with 0 to 100 points description, was included at the end of the patient satisfaction questionnaire to evaluate the macro-level patient satisfaction towards medical services in the previous year .adjSS” and “stdSS” represent the “adjusted satisfaction score” and “standard satisfaction score” respectively.The Likert 5-point evaluation method was used for the response scale of each item, with 1 = extremely dissatisfied, 2 = dissatisfied, 3 = generally satisfied or not, 4 = satisfied, and 5 = extremely satisfied, respectively. Another option 6 was also included, which indicated that the respondent “does not understand” the situation; this was converted into an initial value during statistical analysis. The Likert 5-point scale was converted to 0–100 points. Namely, The five-point value range of the standard satisfaction scale was then converted to 0–100 using the following equation :(1)adjSSUsing a new scoring method, the satisfaction evaluation criteria were developed : “extremely dissatisfied” (adjSS: 0–), “dissatisfied” (20–), “generally satisfied or not” (40–), “satisfied” (60–), and “extremely satisfied” (80–100).The content of the medical staff work satisfaction includes the class of medical institution, gender, age, practice period, educational level, job title, nature of job, employment status, whether at resident/general physician training stage, etc., in the form of multiple choice questions.The content of the patient questionnaire includes the class of medical institution, the gender, age, household registration status, employment status, educational level, average monthly family income, medical insurance type, whether or not they purchased commercial insurance, consultation type, consultation department, and self-perceived disease severity of the patients or relatives, in the form of multiple-choice questions.p < 0.05 or 0.01were deemed statistically significant.Microsoft Excel  and EpiData  were used to create a database for data entry. IBM SPSS Statistics  was used for analysis. Statistical analysis included descriptive analysis, Pearson correlation coefficient, t-test, F-test, multiple linear regression, etc. . Outcome (dependent) variable is actually only the macro-level work satisfaction for the medical staff  and the macro-level patient satisfaction towards medical services for the patient . Before carrying out multiple linear regression analysis, dummy variable quantitation was carried out on independent variables or predictor variables  to avoid collinearity of independent variables. The tests were all two-tailed tests and Before implementing the study, the ethics committee of Wuhan University School of Medicine (WUSM) reviewed it and found it to comply with the Declaration of Helsinki and its revised versions, as well as the relevant regulations of biomedical journals, and approved the research.At the same time, approval was sought from the relevant management departments of the study units and from medical staff and patients. All study subjects signed an informed consent form. Please see the uploaded annex for the ethics approval form.The Cronbach’s alpha of the medical staff work satisfaction scale was 0.973 and the Cronbach’s alpha of each dimension  were 0.880, 0.860, 0.921, 0.892, and 0.963, respectively. The Cronbach’s alpha of the patient satisfaction scale was 0.949 and the Cronbach’s alpha of each dimension  were 0.871, 0.843, 0.888, 0.641, and 0.878, respectively. The overall reliability of the two scales is thus excellent. Besides continuity and collaboration of medical care , the various dimensions and entire scale all showed ideal and extremely ideal quantitative psychometric characteristics ,38. Our p < 0.001). The Special Item-MSSS scoring scored 81.45 ± 13.24 and was evaluated as extremely satisfactory.Medical staff satisfaction ranking, in sequence from most to least satisfied was: work itself, work environment and atmosphere, hospital management, practicing environment, and job rewards. Among samples of medical staff, the highest point is 100.00 and the lowest point is 10.47. The correlation coefficient r of overall work satisfaction and the scoring to evaluate the macro-level work satisfaction in the past one year by a special item  was 0.605 (p < 0.001). The Special Item-PSS scoring has scored 81.18 ± 13.02 and was evaluated as extremely satisfactory. Medical staff and patient overall satisfaction were evaluated as average and satisfied, respectively. Patient satisfaction ranking, in sequence from most to least satisfied was: physician-patient relationship and communication, service organization and facilities, continuity and collaboration of medical care, access to relevant information and support, and healthcare and related services. Among samples of patients, the highest point is 100.00 and the lowest point is 8.62. The correlation coefficient r of overall patient satisfaction and the scoring to evaluate the macro-level patient satisfaction towards medical services in the past 1 year by a special item  was 0.643 (p < 0.05 or 0.01). The class of medical institution approached statistical significance (0.1 > p > 0.05). (p > 0.05). Household registration status, type of medical insurance, and consultation type approached statistical significance (0.1 > p > 0.05). . . There w> 0.05). .p < 0.05 or 0.01), can be included in the regression formula, and explain 39.3% of the variance.In In p < 0.05 or 0.01), can be included in the regression formula, and explain 42.3% of the variance.The multiple linear regression results found that healthcare and related services, service organization and facilities, access to relevant information and support, educational level, average household monthly income, type of medical insurance, self-perceived disease severity, and hospital class showed statistical significance  was extremely satisfactory. For work itself and work environment and atmosphere, the satisfaction evaluation results were satisfactory. For job rewards, hospital management, and practicing environment, the satisfaction evaluation results were average. The above conclusion was consistent with survey results from other provinces in China  ,39,40. AIn terms of demographic characteristics, this study found that the level of satisfaction was relatively higher in females and this was consistent with a number of previous studies in China . HoweverThis study showed that overall patient satisfaction evaluation under the “new healthcare reform” was satisfactory, and that the 5-dimension evaluation was satisfactory. Of the five dimensions, although patients were satisfied with healthcare and related services (barely satisfied), this factor ranked the lowest. The scoring to evaluate the macro-level patient satisfaction towards medical services in the past 1 year by a special item  was also very satisfactory. This reflects the effectiveness of reform initiatives in the “new healthcare reform” policy towards shortcomings that have been present for a long time in the healthcare domain and has reversed the damage in market orientation towards the healthcare domain. The reforms have resulted in a return to fairness and welfare in basic healthcare services , and hasIn terms of demographic information, the levels of medical insurance of inpatients and outpatients in Wuhan City was 94.9%, and this has achieved the goal of the basic medical insurance system, covering 90% of urban and rural residents. This demonstrates that the national public health insurance scheme has gradually taken shape. In recent years, with the continuous expansion of medical insurance coverage, medical insurance payment levels have increased, and the rapid growth of per capita healthcare costs have been controlled to some extent. Government, social, and individual healthcare expenditure are basically balanced and can reasonably share healthcare costs . In addi1The study sample only comprised 14 medical institutions in one major city (Wuhan) in China. We did not include other cities in China to obtain a larger sample because different regions have different economic progress and cultural differences, which may affect satisfaction. We can focus on certain sections of the responder satisfaction in future research, like pre-hospital emergency .2The cross-sectional design of this study limited the inference of causal relationships and was time based. The study tools were only tested in Guangzhou and Wuhan. Although the effectiveness of the tools was initially verified, more samples from different regions and medical institutions are required for continuous measurement and verification in order to optimize and improve the measurement tool.3While the data presented in this study were quantitative, at the same time, qualitative descriptive data were also collected from medical staff and patients . Due to the limitations on manuscript length, we will carry out more in-depth verification and comparison of qualitative data in the further study.Although our investigators have carried out in-depth exploration of satisfaction in medical staff and patients and analyzed several factors, we believe that the study has some shortcomings , with factors that were difficult to estimate excluded from the study . We hope that in the future, we can include more variables (factors) that affect medical staff work satisfaction and patient satisfaction for a further in-depth study:This study has shown that the overall satisfaction of medical staff is affected by many variables, including those found to be statistically significant in the previous sections. However, satisfaction is not only limited to these factors. Although patient satisfaction did not show any statistically significant differences in the demographic data of enrolled patients, some variables still approached statistical significance and deserve further study for verification.On the whole, the overall satisfaction evaluation of medical staff was average. Healthcare policy makers and the management of medical institutions should focus on the aspects of job rewards and practicing environment in order to decrease the risk of dissatisfaction in medical staff and increase their work happiness and sense of belonging so that they can provide better medical services to patients. The overall patient evaluation was satisfactory and patients were satisfied in all levels of the satisfaction evaluation. However, further improvements and enhancements should be made in healthcare and related services.


This study aimed to identify independent associations of sociodemographic, functionality, physical activity, physical and mental health, and osteoarthritis (OA), among older adults.A sample of 1,645 older adults (50+ years) observed by rheumatologists, from EpiReumaPt, a population-based study was analyzed. A structured interview included sociodemographic data, chronic non-communicable disease, and physical activity. Functional ability was assessed by the Health Assessment Questionnaire Disability Index; depression and anxiety were assessed by Hospital Anxiety and Depression Scale. OA (knee OA and/or hip OA and/or hand OA) was defined after medical evaluation by rheumatologists according to expert opinion combined with the fulfillment of the American College of Rheumatology classification criteria.1,059 participants (64.9%) met the OA classification criteria. Statistically significant differences were found between persons with and without OA in all sociodemographic variables, non-communicable diseases, functional status, physical activity, depression, and anxiety. In the unadjusted logistic regression models, all variables were associated with OA. The final adjusted model explained 32% of the variance. Those who are female with higher age, have more than five comorbidities, and lower levels of function and physical activity were more likely to meet the criteria for a diagnosis of OA.We have analyzed data from a population-based study and found that a diagnosis of OA was independently associated with age, female gender, higher number of comorbidities, physical disability, and low levels of physical activity. These results reinforce the usefulness of the development of a multidimensional assessment to design and test effective interventions for this population. Osteoarthritis (OA) is the most prevalent rheumatic disease in the general population , and itsGlobal Burden of Disease Project identify the common causes of years of healthy life lost due to disability in people older than 60 years and identify OA as one of the 10 most relevant causes of disability in this population  to compare people with and without OA with respect to sociodemographic characteristics, functionality, physical activity, non-communicable chronic diseases, and presence of anxiety and depression symptoms; and (2) to identify independent associations between sociodemographic characteristics, functionality, physical activity, physical health and psychological symptoms, and OA.Data from EpiReumaPt project, which is a national, cross-sectional, and population-based study, were used . This stEpiReumaPt involved a three-stage approach. The first stage included the selection of potential participant household/families using a random selection process. In each household, the adult with the most recent birthday was recruited and completed a structured interview , and a screening for rheumatic diseases. In the second stage, all participants who screened positive for at least one rheumatic disease plus 20% of participants with no rheumatic symptoms were invited to be assessed by a rheumatologist. In the last phase, a team of three experienced rheumatologists revised all the clinical, laboratory, and imaging data and confirmed the diagnoses using validated criteria . DetailsIn this study, the sample consisted of adults 50+ years old who participated in the second phase of EpiReumaPt study and were evaluated by a rheumatologist to confirm the presence or absence of OA (knee OA and/or hip OA and/or hand OA). OA was defined by rheumatologists according to expert opinion combined with the fulfillment of the American College of Rheumatology classification criteria for knee OA, hip OA, and hand OA, as described earlier –17.Sociodemographic data, physical function, anxiety and depression symptoms, lifestyle , and chronic non-communicable diseases were collected during the first stage of the EpiReumaPt project.Sociodemographic data included age, gender, marital status, education, and work status. Marital status was categorized in three categories: without partner (single and divorced people), married, and widower. Work status was categorized as employed full time, part-time, not currently employed , and retired.Number of current chronic non-communicable diseases was assessed using a comprehensive list which included the following 14 diseases: high blood pressure, high cholesterol, heart disease, diabetes mellitus, chronic lung disease, problems in the digestive tract, renal colic, neurological disease, allergies, mental or psychiatric illness, cancer, thyroid and parathyroid problems, hypogonadism, hyperuricemia, and other rheumatic diseases (OA was excluded from this list).The Health Assessment Questionnaire Disability Index  was useTo assess physical activity, participants were asked about the amount of time (minutes) per week they dedicated to physical activity. Answers were categorized as <150 or ≥150 min, based on the physical activity recommendations of the WHO  for oldeDepression and anxiety were assessed by Hospital Anxiety and Depression Scale HADS; , 23]. Th. Th23)].EpiReumaPt was approved by the National Committee for Data Protection and by NOVA Medical School Ethics Committee. All participants provided informed consent, and the study was performed according to the principles established by the Declaration of Helsinki.N = 1,645) were divided in two groups: group 1  consisted of participants meeting the OA diagnostic criteria; and group 2 (n = 586) consisted of participants without OA diagnosis or others rheumatic diseases. There were no missing data except for physical activity (n = 485).Participants  and 95% confidence intervals were used to assess the results. All statistical analyses were performed using Statistical Package for the Social Sciences , and α = 0.05 was used to determine significance level.Descriptive analysis was used to describe the main characteristics of the sample, using frequencies (absolute and relative) or means and SDs, depending on the type of the variable. The comparison of groups defined by the presence/absence of OA (group 1: with OA and group 2: without OA) was performed using independent samples n = 1,040) were women. Most of the participants were married  and had 4 years of education . Regarding work status, the majority were retired . With respect to number of self-reported chronic non-communicable diseases, most participants reported 0–2  and 3–4  chronic diseases. Hypertension  and high cholesterol  were the most frequently reported diseases. Among rheumatic diseases, osteoporosis was the most frequently self-reported disease . With respect to functional status, the mean score of HAQ-DI for the total sample was 0.55 (SD = 0.65) out of 3, indicating low levels of limitations. The majority of the sample met the ≥150 min of physical exercises per week . Depressive symptoms were found in 10.6% (n = 174) and anxiety was found in 13.8% (n = 227) of the total sample.The sample comprised 1,645 participants. The mean age of the sample was 65.3 years (SD = 9.3) and 63.2% (n = 132) were classified as having hip OA, 44.7% (n = 473) hand OA, and 68.6% knee OA (n = 726). Among persons with an OA diagnosis, 36.6% (n = 388) reported the presence of other rheumatic diseases. In this sample, the additional rheumatic diseases most commonly reported were osteoporosis  and rheumatoid arthritis .Sample consisted of 1,059 adults with OA diagnosis (64.4%) and 586 without OA diagnosis (35.6%). Among people with OA, 12.5%  was higher than among persons without OA . More participants with OA were married , in comparison to persons without OA . Widowers were the second most common category represented, 263 (24.8%) in participants with OA compared to 71 (12.1%) in those without OA. Regarding work status, the majority of participants in both groups were retired . Among participants with OA, the second most frequent category was “without labor activity” , whereas for persons without OA, the second most common category was “full time employed” . Most persons with OA reported presence 3–4 non-communicable diseases , compared to 0–2 non-communicable diseases  among persons without OA. Individuals with OA were significantly less active  than those without OA . With respect to functional status, participants with OA showed significantly higher levels of functional limitations  than persons without OA . Percentage of depressive symptoms was also higher among individuals with OA  compared to participants without OA . Similar results were found for anxiety, persons with OA showed a higher percentage of anxiety symptoms  than people without OA .Statistically significant differences were found between groups (with and without OA) in all sociodemographic variables , non-communicable diseases, functional status, physical activity, depression, and anxiety Table . Particip = 0.387), work status (p = 0.216), depression (p = 0.512), and anxiety (p = 0.066). In the final adjusted model, age, gender, number of comorbidities, physical disability, and physical activity remained statistically significant and the model explained 32% of the variance. People who were older  and female  were more likely to have OA. People with more than five comorbidities were more likely to report OA than people with 0–2 comorbidities . Functional disability was also associated with OA. Specifically, persons with higher levels functional disability were more likely to report OA than those with lower levels of disability . Physical activity was also associated with OA persons; people with lower levels of physical activity were more likely to report OA than those with higher levels of physical activity .Using OA as the outcome, unadjusted logistic regression models found that all of the variables shown in Table A National Public Health Agenda for Osteoarthritis , disability, physical activity level, and presence of OA; findings that are consistent with previous results reported in the literature on OA. According to rthritis , OA prevd Health  showed an = 554, 52.3%) and had higher levels of physical activity , furthermore, retired people was the oldest group  and had the highest level of disability . Prior studies have analyzed the impact of sociodemographic characteristics in OA, for example, Cleveland et al.  , but verNational Food, Nutrition and Physical Activity Survey Report . This aspect is related to the general objectives of EpiReumaPt that focus on people with rheumatic diseases and with the criteria for sample selection in this study. The amount of variance in OA explained by the model was low (32%), which limits the interpretation of the results. The variance explained could be improved by the inclusion of other biological variables, such as body mass index and muscle strength. Other limitations of the EpiReumaPt initiative were reported by Branco et al. . The maiIn this paper, we have analyzed older adults (+50) from a population-based study and found that a diagnosis of OA was independently associated with age, female gender, higher number of comorbidities, physical disability, and low levels of physical activity. These results reinforce the need to of the develop multidimensional assessments to design and evaluate effective interventions for this population.EpiReumaPt was approved by the National Committee for Data Protection and by NOVA Medical School Ethics Committee. All participants provided informed consent, and the study was performed according to the principles established by the Declaration of Helsinki.ND contributed to the conception, design, analysis, and interpretation of data for the work. She agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. AR, JB, HC, and SH revised the work critically for important intellectual content and approved the final version to be published. CP contributed to the design, analysis, and interpretation of the data for the work; revised the work critically for important intellectual content; and approved the final version to be published.All co-authors have seen and agree with the contents of the manuscript and there is no financial interest to report. We certify that the submission is original work and is not under review at any other publication. No previous data have been reported before. All co-authors confirm the full control of all primary data and we agree to allow the journal to review their data if requested.


A Benjamini-Hochberg multiple testing correction reveled significant SNPs. Corresponding genes were identified using the Bovine Genome UMD 3.1 annotation. Principal Components Analysis (PCA) confirmed differentiation. An analysis of Copy Number Variations (CNVs), obtained from signal intensities, revealed no evidence of association between ovarian pathologies and CNVs. In addition, a haplotype frequency analysis showed no association with ovarian pathologies. Results show that SNP signal intensity, which captures not only information for base-pair genotypes elucidation, but the amount of fluorescence nucleotide synthetization produced in an enzymatic reaction, is a rich source of information that, by itself or in combination with base-pair genotypes, might be used to implement differentiation, prediction and diagnostic procedures, increasing the scope of applications for Genotyping Microarrays.Hypoplasia and ovarian cysts are the most common ovarian pathologies in cattle. In this genome-wide study we analyzed the signal intensity of 648,315 Single Nucleotide Polymorphisms (SNPs) and identified 1338 genes differentiating cows with ovarian pathologies from healthy cows. The sample consisted of six cows presenting an ovarian pathology and six healthy cows. SNP signal intensities were measured with a genotyping process using the Axiom Genome-Wide BOS 1 SNPchip. Statistical tests for equality of variance and mean were applied to SNP intensities, and significance  Hypoplasia and ovarian cysts are two of the most common pathologies in cattle. Ovarian hypoplasia is a congenital malformation that is characterized by the lack of proper growth and development of the ovaries, presenting a decreased or subnormal size. The literature has reported that ovarian hypoplasia can occur in one or both ovaries. However, when it occurs in one ovary of the animal , the remaining one is also affected. Only 9% of females suffer from a bilateral hypoplasia together with an offspring’s womb and an offspring’s mammary gland . On the Single Nucleotide Polymorphism (SNP) Genotyping microarray biotechnology is currently widely used for genome-wide studies, due to its capability of simultaneously measuring the allelic content from a specific position in millions of DNA fragments ,11. By sp-values and cluster visualization allowed us to establish differences between data at the signal intensity level that was not possible at the haplotype level.In this work we present a new application of SNP signal intensities. We performed a genome-wide SNP signal intensity scanning looking for genes differentiating between cows suffering from ovarian pathologies and healthy cows. The data consisted of 648,315 informative SNP markers assayed with the Axiom Genome-Wide Array Bos 1  on 12 cows, from which six were suffering ovarian pathologies. We present a methodology based on the normalized signal intensity that is capable of distinguishing between the two sets of data . The methodology implements a genome-wide scanning, using statistical tests for equality of variance and mean, to vectors of normalized signal intensities, and a PCA clustering analysis for differentiation. Examination of The Autonomous University of Baja California  animal care and use committee deemed it unnecessary to obtain ethical clearance for this study, as all blood samples used for DNA extraction were collected under the directives on animal research of the Institute for Research in Veterinary Science UABC (IICV-UABC) on the basis of the Mexican laws on animal studies (NOM-003-ZOO-1994 and NOM-062-ZOO-1999).®, Franklin Lakes, NJ, USA) with EDTA anticoagulant. DNA extraction and purification was performed using a QIAGEN kit . All DNA samples were analyzed by spectroscopy and agarose gel electrophoresis, and stored at −20 °C for future analysis.None of the animal samples were related to each other. They came from the experimental Holstein cattle herd of the Veterinary Science Research Institute of the Autonomous University of Baja California, in Mexicali . The samples consisted of blood, obtained by venipuncture of the coccygeal vein, using vacutainer tubes . In order to find a possible cause to justify their null reproduction and low milk production, a physical examination was performed following the procedures defined by Sisson et al. . In the 2 ratio. The calculation was made using a Perl script with the following procedure: first, for each marker, a reference was developed using the equation T = A + B, where A and B are the signal intensity values of each allele. For each SNP, a reference is established using M = median . The second step is the estimation of the intensity for each individual sample using the equation log2 (T/M) T, whose mean vector M and covariance C are described by:Given a vector 1, λ2, …, λ3, and the eigenvectors P1, P2, …, dP; arrange them according to their magnitude.Calculate the eigenvalues λd eigenvectors to represent the n variables, d < n. Then, the P1, P2, …, dP are called the principal components [Select mponents . We usedmponents .We estimated the haplotype pair for each sample using PHASE 2.1 algorithm ,28. The p-values in order to control the False Discovery Rate (FDR). The approach was implemented as follows: first, all p-values were ordered from smallest to largest denoting the i-th smallest p-value by P(i), for each i between 1 and m , then, starting from the largest p-value P(m), compare P(m) with 0.05 x i/m. Continue as long as P(i) > 0.05 x i/m. Let k be the first time when P(k) is less than or equal to 0.05 x k/m, and declare the differences corresponding to the smallest k p-values as significant [A Benjamini and Hochberg correction for multiple testing was applied to nificant .F-test for equality of variance and a T-test for equality of means were applied to each of the 4532 selected genes. After applying Benjamini-Hochberg multiple testing correction, only the p-values of 1338 genes resulted significant.We inspected the complete list of autosomal genes  and selected those having at least 15 SNPs within their DNA sequence. As a result, 4532 genes were selected for this study. For each selected gene, two vectors were generated. The first vector included the normalized signal intensity from the six animals suffering the disease. The second vector included the normalized signal intensity from the healthy animals. An RBFOX1 (RNA binding protein fox-1 C. elegans homolog 1) with 970, and had the smallest p-value of 1.57 × 10−16. In addition 55 genes had the lowest number of SNPs within their sequence, with 15. For more details, see From the 1338 significant genes, 729 are the best reference sequences (RefSeq best), 414 are messenger RNA (mRNA), 162 are uncharacterized RNA sequences (maseq), and 33 code for proteins. The chromosomes with the highest number of involved genes were chromosome four, one and two, with 88, 82 and 83 genes, respectively. Chromosomes with the lowest number of involved genes were twenty nine, twenty eight and seven, with 17, 20, and 21 genes respectively. The family groups with more genes involved were zinc finger with 28 genes, solute carrier family with 17, and family with similar sequence with 15 genes. The gene with the greatest number of SNPs within its sequence was FSHR, which is a follicle stimulating-hormone, and the gene LHCGR, which is a luteinizing/choriogonadotropin receptor hormone [LOC537580 known to have no relation to ovarian disease. We obtained a p-value of 0.0002 for the FSHR gene, indicating a highly significant difference between disease and healthy samples. In contrast, an average p-value of 0.44 was obtained for a group of five SNPs to the right, and a group of five SNPs to the left of the FSHR gene location, indicating no difference between disease and healthy samples. Consistently, for the LHCGR gene, we obtained a p-value of 0.0013, while we obtained an average p-value of 0.33 for the surrounding SNP groups. Additionally, we randomly selected a DNA region without encoded genes and with no relationship to ovarian functions in cows. The region start position is at 32,108,743 and an ending position at 32,305,585 in chromosome 20. The total length is 196,842 base-pairs covering 40 SNPs. A p-value of 0.58 was obtained for this region, showing no difference in the mean signal intensity between the two groups.As a measure of accuracy, we inspected the results of the statistical analysis of two genes that are well documented as highly related to ovarian diseases: the gene  hormone ,32,33. Whttp://www.genome.jp/kegg/pathway.html) [FSHR and LHCGR genes are involved in the Calcium Signaling Pathway (bta04020), in the cAMP Signaling Pathway (bta04024) for signal transduction, in the neuroactive ligand-receptor interaction (bta04080) for signaling molecules and interaction in the environmental information processing section, and in the prolactin signaling pathway from endocrine system   for molestem see .In addition to the previous analysis, we conducted a PCA using the initial vectors generated for each animal and each gene. The results show clear differentiation between the two kinds of samples. FSHR. In the plot, bars represent average loading values of normalized signal intensity for every sample. The differentiation appears even clearer when we apply PCA individually to genes we know are strongly related to ovarian pathologies. FSHR gene from this study.In order to identify a possible association between copy number variants (CNVs) and cystic ovarian follicles (COFs), we performed a CNV detection using the signal intensities from the six animals with ovarian pathology. We used two different algorithms, PennCNV and QuantiSNP, with default parameters, and found 84 and 111 CNVs, respectively. None of them showed overlapping with the hormone genes involved in ovarian pathology processes considered in this study. In addition, we performed a review of several studies reporting CNVs, from a total of 6580 samples from different cattle breeds ,22,23,24LHCGR gene. In this example, as in the rest, we found no evidence of haplotype association.In order to discover if there were haplotypes associated to COFs, we obtained the base-pair allele genotypes for all SNPs covered by the genes in the study. We used the files AxiomGT1.Calls.TXT and Axiom_GW_Bos_SNP_1.na32.annot.CSV (provided by the Affymetrix genotyping service) which contain the final cluster of genotypes and annotation for cattle UMD3.1 annotation. For each gene, we inferred haplotype pairs using PHASE 2.1 algorithm ,28, and FSHR and LHCGR were selected for further analysis because it is known they are highly related to ovarian diseases. For differentiation between disease and healthy groups, the normalization of SNP signal intensities allowed us to implement statistical tests for equality of variance and mean, which in turn gave us the first insight of differentiation, based on a measure of data location. From the four differentiation tests , all confirmed the same results. The first two with a clear differentiation and the other two with no differentiation at all, judging by p-values from statistical test. As a complementary technique, PCA allowed us to make differentiation based on data variability. The results presented in  was to verify if the sequences of the genes from the hormones in our study were affected by the recombination process and also if an aberration generates the formation of CNVs. Our results showed that from the 6736 CNVRs previously reported in the literature, only 4.45 × 10The fact that there were no haplotype blocks, or haplotype patterns, consistent just for one group, either healthy or disease, makes clear that this differentiation analysis is not possible at the genotype, or haplotype level. This also shows the missing of important information when mapping from signal intensities to base-pair genotypes information. Therefore, complementing information at the intensity level, with information at the genotype level might increase the power of analysis and the scope of applications for SNP genotyping microarrays.This work presents the first genome-wide SNP signal intensity scanning looking for genes differentiating cows suffering ovarian pathologies from healthy cows. Statistical test for equality of mean and PCA of signal intensity provided by a SNP genotyping microarray revealed a total of 1338 differentiating genes. Differentiation achieved from signal intensity was not possible at the genotype, or haplotype level, which highlighted the missing of important information when mapping from signal intensities to base-pair genotypes information.Finally, our results show that SNP signal intensity, which captures not just information for base-pair genotypes elucidation, but the amount of fluorescence nucleotides synthetization produced in an enzymatic reaction, is a rich source of information that, by itself, or in combination with base-pair genotypes, might be used to implement differentiation, prediction, and diagnostic procedures, increasing the scope of applications for genotyping microarrays.http://www.ebi.ac.uk/arrayexpress.The complete raw data, supporting the results are available in the ArrayExpress repository, under the accession number E-MTAB-4874 in