The perceptions and experience of developing patient (version of) guidelines: a descriptive qualitative study with Chinese guideline developers.

OBJECTIVE: To understand developers' perception of patient (versions of) guidelines (PVGs), and identify challenges during the PVG development, with the aim to inform methodological guidance for future PVG development. METHODS: We used a descriptive qualitative design. Semi-structured interviews were conducted virtually from December 2021 to April 2022, with a purposive sampling of 12 PVG developers from nine teams in China. Conventional and directed content analysis was used for data analysis. RESULTS: The interviews identified PVG developers' understanding of PVGs, their current practice experience, and the challenges of developing PVGs. Participants believed PVGs were a type of health education material for patients; therefore, it should be based on patient needs and be understandable and accessible. Participants suggested that PVGs could be translated/adapted from one or several clinical practice guidelines (CPG), or developed de novo (i.e., the creation of an entirely new PVG with its own set of research questions that are independent of existing CPGs). Participants perceived those existing methodological guidelines for PVG development might not provide clear instructions for PVGs developed from multiple CPGs and from de novo development. Challenges to PVG development include (1) a lack of standardized and native guidance on developing PVGs; (2) a lack of standardized guidance on patient engagement; (3) other challenges: no publicly known and trusted platform that could disseminate PVGs; concerns about the conflicting interests with health professionals. CONCLUSIONS AND PRACTICE IMPLICATIONS: Our study suggests clarifying the concept of PVG is the primary task to develop PVGs and carry out related research. There is a need to make PVG developers realize the roles of PVGs, especially in helping decision-making, to maximize the effect of PVG. It is necessary to develop native consensus-based guidance considering developers' perspectives regarding PVGs.

Rural population's preferences matter: a value set for the EQ-5D-3L health states for China's rural population.

PURPOSE: To develop an EQ-5D-3L social value set based on Chinese rural population's preferences using the time trade-off (TTO) method, and to compare the differences in preferences on health states between China urban and rural population. METHODS: Between Sep 2013 and Nov 2013, a total of 1201 participants were recruited from rural areas of five Chinese cities (Beijing, Chengdu, Guiyang, Nanjing, and Shenyang) using a quota sampling method. Each respondent valued 13 health states using the TTO, and a total of 97 EQ-5D-3L health states were directly valued for estimating the value set. Various models with different specifications were explored at both aggregate and individual levels. The final model was determined by a set of predefined selection criteria. FINDINGS: An ordinary least square model at the aggregate level included 10 dummy variables for specifying the level 2 and 3 for each dimension and an N3 term presenting any dimension on level 3 was selected as the final model. The final model provides a value set ranges from - 0.218 to 0.859. The predicted utility values were highly correlated with but consistently lower than that of the published Chinese EQ-5D-3L value set (for urban population). CONCLUSION: The availability of the China rural value set provides a set of social preferences weights for researchers and policy decision-makers for use in China rural area.

Mapping the Edmonton Symptom Assessment System-Revised: Renal to the EQ-5D-5L in patients with chronic kidney disease.

PURPOSE: The Edmonton Symptom Assessment System-Revised: Renal (ESAS-r: Renal) is a disease-specific patient-reported outcome measure (PROM) that assesses symptoms common in chronic kidney disease (CKD). There is no preference-based scoring system for the ESAS-r: Renal or a mapping algorithm to predict health utility values. We aimed to develop a mapping algorithm from the ESAS-r: Renal to the Canadian EQ-5D-5L index scores. METHODS: We used data from a multi-centre cluster randomized-controlled trial of the routine measurement and reporting of PROMs in hemodialysis units in Northern Alberta, Canada. In two arms of the trial, both the ESAS-r: Renal and the EQ-5D-5L were administered to CKD patients undergoing hemodialysis. We used data from one arm for model estimation, and data from the other for validation. We explored direct and indirect mapping models; model selection was based on statistical fit and predictive power. RESULTS: Complete data were available for 506 patient records in the estimation sample and 242 in the validation sample. All models tended to perform better in patients with good health, and worse in those with poor health. Generalized estimating equations (GEE) and generalized linear model (GLM) on selected ESAS-r: Renal items were selected as final models as they fitted the best in estimation and validation sample. CONCLUSION: When only ESAS-r: Renal data are available, one could use GEE and GLM to predict EQ-5D-5L index scores for use in economic evaluation. External validation on populations with different characteristics is warranted, especially where renal-specific symptoms are more prevalent.

Natural-Product-Mediated Autophagy in the Treatment of Various Liver Diseases.

Autophagy is essential for the maintenance of hepatic homeostasis, and autophagic malfunction has been linked to the pathogenesis of substantial liver diseases. As a popular source of drug discovery, natural products have been used for centuries to effectively prevent the progression of various liver diseases. Emerging evidence has suggested that autophagy regulation is a critical mechanism underlying the therapeutic effects of these natural products. In this review, relevant studies are retrieved from scientific databases published between 2011 and 2022, and a novel scoring system was established to critically evaluate the completeness and scientific significance of the reviewed literature. We observed that numerous natural products were suggested to regulate autophagic flux. Depending on the therapeutic or pathogenic role autophagy plays in different liver diseases, autophagy-regulative natural products exhibit different therapeutic effects. According to our novel scoring system, in a considerable amount of the involved studies, convincing and reasonable evidence to elucidate the regulatory effects and underlying mechanisms of natural-product-mediated autophagy regulation was missing and needed further illustration. We highlight that autophagy-regulative natural products are valuable drug candidates with promising prospects for the treatment of liver diseases and deserve more attention in the future.

Follicle stimulating hormone, its association with glucose and lipid metabolism during the menopausal transition.

AIM: Accumulative evidence shows that follicle stimulating hormone (FSH) is associated with metabolic disorders. We aimed to ascertain the relationship between FSH, blood glucose and lipid metabolism in general perimenopausal women. METHODS: This cross-sectional study analyzed 2121 perimenopausal women aged 40-54 years in Zhejiang Province from January 2016 to December 2018. Regression analysis was performed to assess the relationship between FSH and metabolic parameters. RESULTS: Serum FSH had a significant inverse association with fasting plasma glucose (P < 0.05) and triglycerides (TG) (P < 0.01) in perimenopausal women. However, after adjusting for body mass index, there was no significant association between FSH and fasting plasma glucose. In a model fully adjusted for demographic variables, estradiol, body mass index, high-density lipoprotein, low-density lipoprotein, homocysteine, systolic blood pressure and blood viscosity, a significant association still existed between FSH and TG (standardized ß = -0.095; R2 = 0.155; P = 0.002). CONCLUSION: Overall, FSH is negatively associated with metabolic parameters, especially TG, in perimenopausal women. These results indicated that FSH might be a biomarker for the primary prevention of disorders with lipid metabolism during the menopausal period.

Responsiveness of the EQ-5D-3L and EQ-5D-5L in patients following total hip or knee replacement.

PURPOSE: To examine the responsiveness of the EQ-5D-3L and EQ-5D-5L among total hip/knee replacement (THR/TKR) patients. METHODS: The EQ-5D (3L or 5L) and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) have been routinely administered to all THR/TKR patients before and at 3 months after surgery in Alberta, Canada, since 2010. Patients were included in this analysis if they completed the WOMAC and the same version of EQ-5D at baseline and 3-month follow-up. The WOMAC was used as an anchor to categorize patients into 9 subgroups according to the relative change from baseline, i.e., no change, and 4 categories each for the amount of deterioration or improvement: large (≥ 70%), moderate (50% ≤ change < 70%), small but important (20% ≤ change < 50%), and very mild (0 < change ≤ 20%). The responsiveness of the EQ-5D-3L and EQ-5D-5L for each subgroup was assessed using effect size, standardized response mean, and Guyatt's Responsiveness Index. RESULTS: A total of 1594 patients completed the EQ-5D-3L and WOMAC (60% females, mean age 66 years, N = 646 [41%] THR), and 3180 completed the EQ-5D-5L and WOMAC (60% females, mean age 66 years, N = 1352 [43.2%] THR) at baseline and 3-month follow-up. For both THR and TKR patients with "small but important" improvement, the EQ-5D-5L was consistently more responsive than the EQ-5D-3L. CONCLUSION: Our study demonstrated that the EQ-5D-5L is more responsive than the EQ-5D-3L in identifying health-related quality of life changes in THR/TKR patients. We recommend using the EQ-5D-5L in longitudinal studies in this patient population.

The EQ-5D-5L Is Superior to the -3L Version in Measuring Health-related Quality of Life in Patients Awaiting THA or TKA.

BACKGROUND: As a generic measure of health-related quality of life among patients awaiting THA or TKA, the three-level version of the EQ-5D (EQ-5D-3L), which has three response levels of severity (no problems, some problems, and extreme problems/unable) to five questions, is widely used. Previous studies indicated that the ceiling effect of the EQ-5D-3L limits its application. The five-level version of the EQ-5D (EQ-5D-5L) was developed to enhance the measurement properties of the tool by adding two levels: slight problems and severe problems. However, only a few small studies have compared the EQ-5D-3L and EQ-5D-5L in patients awaiting THA and TKA. QUESTIONS/PURPOSES: The purpose of this study was to examine the performance of the EQ-5D-3L and EQ-5D-5L among patients awaiting THA or TKA in terms of (1) response patterns, (2) convergent construct validity, (3) known-group validity, and (4) informativity and discriminatory power. METHODS: This is a retrospective analysis of the Alberta Bone and Joint Health Data Repository, which recorded information on all patients receiving hip or knee arthroplasties between April 2010 and March 2017 in Alberta, Canada (n = 37,377). Patients receiving THA or TKA and who completed the EQ-5D and WOMAC at baseline (presurgery) were included in this study (n = 24,766). The EQ-5D-3L was administered to all patients in 2010, and was gradually replaced by the EQ-5D-5L between 2013 and 2016; the EQ-5D-5L reached full application in all clinics by 2017.A propensity score was used to match patients 1:1 who completed either the EQ-5D-3L or EQ-5D-5L before surgery. Response patterns have been explored using ceiling and floor effects and distribution across severity levels of each dimension. Convergent construct validity was examined using Spearman's correlation (rho) against the WOMAC. Known-group validity was examined by gender, preoperative risk factors, mental health, obesity, and WOMAC physical function score. Informativity and discriminatory power were examined using the Shannon (H') and Shannon evenness (J') indices. A total of 3446 pairs of patients awaiting THA (55% women; mean age, 66 years) and 5428 pairs of patients awaiting TKA (59% women; mean age 67 years) were included in this analysis; the study group included all patients who were kept in the propensity score matching. RESULTS: Ceiling and floor effects were comparable and small (less than 0.5%) for both versions; the responses across severity levels for each dimension were more evenly distributed for the EQ-5D-5L. Convergent construct validity was stronger for the EQ-5D-5L as it consistently had stronger correlations with the WOMAC overall and domain scores than the EQ-5D-3L (rho(3L-THA), -0.77 to -0.31; rho(3L-TKA), -0.71 to -0.24; rho(5L-THA), -0.71 to -0.17; rho(5L-TKA), -0.64 to -0.17; all p values < 0.001). The hypotheses of known-group analyses were confirmed for both versions. The EQ-5D-5L demonstrated stronger informativity and discriminatory power than the EQ-5D-3L, particularly for the mobility dimension (THA, H'(5L/3L)=1.66/0.37, J'(5L/3L)=0.72/0.23; TKA, H'(5L/3L)=1.66/0.41, J'(5L/3L)=0.71/0.26). CONCLUSIONS: This study demonstrates the superior construct validity, and informativity and discriminatory power of the EQ-5D-5L compared with the EQ-5D-3L among patients awaiting THA or TKA. CLINICAL RELEVANCE: Compared with the three-level version, the five-level version of the EQ-5D differentiates between patients awaiting THA and TKA much better based on their mobility, which is a key health aspect or outcome in these patients. Our findings suggest that the EQ-5D-5L is more appropriate for this population.

Minimally important difference and predictors of change in quality of life in type 2 diabetes: A community-based survey in China.

BACKGROUND: To identify the minimally important difference (MID) of the EQ-5D-3L and determinants of change in quality of life (QoL) as measured by the EQ-5D-3L over 1 year for Chinese type 2 diabetic patients (T2DPs). METHODS: Clinically diagnosed T2DPs were recruited from 66 community health centres in five Chinese cities using a multistage quota sampling method between December 2010 and October 2011. Demographics, diabetes-related information, and health-related behaviours were collected at baseline. The EQ-5D-3L was administered at baseline and at 12 months. Anchor-based and distribution-based approaches were employed to estimate MIDs. Using the MIDs as cut-points, we identified the change in EQ-5D-3L-measured QoL into "worsening," "no change," and "bettering." Logistic and ordered logistic regressions were conducted for those who reported best possible EQ-5D health state ("best possible HS") and impaired EQ-5D health states ("impaired HS") at baseline, respectively. Explanatory variables included demographics, diabetes-related information, and health-related behaviours. RESULTS: A total of 1958 patients (54.9% female, mean age 61.2 years, mean diabetes duration 7.9 years) were included in our analysis. MIDs of the EQ-5D-3L for deterioration and improvement were estimated as -0.066 to -0.003, and 0.049 to 0.077, respectively. For the impaired HS group, older age, lower education, and less exercise were significant predictors for worsening in QoL; whereas, those predictors were older age, female gender, and lower income for the best possible HS group. CONCLUSIONS: Minimally important differences for deterioration and improvement were estimated for the EQ-5D-3L. Age, gender, education, income, and exercise were significant determinants of QoL change for Chinese T2DPs.

Item reduction and validation of the Chinese version of diabetes quality-of-life measure (DQOL).

BACKGROUND: The Diabetes Quality-of-Life (DQOL) Measure is a 46-item diabetes-specific quality of life instrument. The original English version of the DQOL has been translated into Chinese after cultural adaption, and the Chinese DQOL has been validated in the Chinese diabetic patient population and used in diabetes-related studies. There are two recognized problems with the Chinese DQOL: 1) the instrument is too long, and 2) the non-response rate of certain items is relatively high. This study aimed to develop and validate a short version for the Chinese DQOL. METHODS: Item reduction was conducted based on the classical test theory (CTT) and item response theory (IRT), each combined with exploratory factor analysis (EFA). The confirmatory factor analysis (CFA) and Spearman correlation coefficient were employed in validating the short versions. RESULTS: Both the study sample (n = 2,886) and the validation sample (n = 2,286) were from a longitudinal observation study of Chinese type 2 diabetic patients. The CTT kept 32 items, and the IRT kept 24 items from the original 46-item version. The two short versions were comparable in psychometric properties. CONCLUSION: The 24-item IRT-based short version of the Chinese DQOL was selected as the preferred short version because it imposes a lower burden on patients without compromising the psychometric properties of the instrument.

Estimating an EQ-5D-5L Value Set for China.

OBJECTIVES: To estimate a five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) value set for China using the health preferences of residents living in the urban areas of the country. METHODS: The values of a subset of the EQ-5D-5L-defined health states (n = 86) were elicited using the time trade-off (TTO) technique from a sample of urban residents (n = 1271) recruited from five Chinese cities. In computer-assisted personal interviews, participants each completed 10 TTO tasks. Two additive and two multiplicative regression models were evaluated for their performance in describing the relationship between TTO values and health state characteristics using a cross-validation approach. Final values were generated using the best-performed model and a rescaling method. RESULTS: The 8- and 9-parameter multiplicative models unanimously outperformed the 20-parameter additive model using a random or fixed intercept in predicting values for out-of-sample health states in the cross-validation analysis and their coefficients were estimated with lower standard errors. The prediction accuracies of the two multiplicative models measured by the mean absolute error and the intraclass correlation coefficient were very similar, thus favoring the more parsimonious model. CONCLUSIONS: The 8-parameter multiplicative model performed the best in the study and therefore was used to generate the EQ-5D-5L value set for China. We recommend using rescaled values whereby 1 represents the value of instrument-defined full health in economic evaluation of health technologies in China whenever the EQ-5D-5L data are available.

Is bad living better than good death? Impact of demographic and cultural factors on health state preference.

PURPOSE: The aim of this study was to examine the impact of demographic and cultural factors on health preferences among Chinese general population. METHODS: The Chinese EQ-5D-5L valuation study was conducted between December 2012 and January 2013. A total of 1296 participants were recruited from the general public at Beijing, Chengdu, Guiyang, Nanjing, and Shenyang. Each participant was interviewed to measure preferences for ten EQ-5D-5L health states using composite time trade-off and seven pairs of states using discrete choice experiment (data were not included in this study). At the end of the interview, each participant was also asked to provide their demographic information and answers to two questions about their attitudes towards whether bad living is better than good death (LBD) and whether they believe in an afterlife. Generalized linear model and random effects logistic models were used to examine the impact of demographic and cultural factors on health preferences. RESULTS: Participants who had serious illness experience received college or higher education, or agree with LBD were more likely to value health states positively and have a narrower score range. Participants at Beijing were more likely to be non-traders, value health states positively, less likely to reach the lowest possible score, and have narrower score range compared with all other four cities after controlling for all other demographic and culture factors. CONCLUSIONS: Health state preference is significantly affected by factors beyond demographics. These factors should be considered in achieving a representative sample in valuation studies in China.

Spontaneous Ectopic Tubal Pregnancy After Partial Salpingectomy.

Objective: To report a rare case of spontaneous ectopic pregnancy (EP) after partial salpingectomy treated by laparoscopy. Case Report: A 30-year-old gravida 1 para 0 woman with a history of left adnexectomy, due to left ovarian torsion 13 years ago, was referred to our hospital. She had experienced lower abdominal pain for 1 day and amenorrhea for 1 week. Transvaginal ultrasonography did not reveal an intrauterine pregnancy, but showed a suspected extrauterine gestational sac on the left adnexal area. The patient was diagnosed with ectopic pregnancy, and laparoscopy was performed. During the operation, we found a gestational sac on the left fallopian tube stump. Conclusion: The most significant risk factors for ectopic pregnancy (EP) are previous procedures and conditions that cause tubal injury. Therefore, it is necessary to be alert to the occurrence of the disease even if there is a history of tubal resection and ensure no part of the fallopian tube is left behind during removal.

Immediate and delayed placement of the intrauterine device after abortion: a systematic review and meta-analysis.

This article aims to report the comprehensive and up-to-date analysis and evidence of the insertion rate, expulsion rate, removal rate, and utilization rate of immediate placement of intrauterine devices (IUDs) versus delayed placement after artificial abortion. PubMed, Embase, Cochrane, Web of Science, CNKI, and Wanfang databases were comprehensively searched up to January 12, 2024 for studies that compared immediate versus delayed insertion of IUDs after abortion. The evaluation metrics included the number of IUD insertion after surgical or medical abortions, the frequency of expulsion and removal at 6 months or 1 year, the number of continued usage, pain intensity scores, the number of infections, the duration of bleeding, and instances of uterine perforation during or after IUD insertion. Ten randomized controlled articles were eligible, comprising 11 research projects, of which 3 projects involved the placement of an IUD after surgical abortion, and 8 projects involved the placement of an IUD after medical abortion. This included 2025 patients (977 in the immediate insertion group and 1,048 in the delayed insertion group). We summarized all the extracted evidence. The meta-analysis results indicated that for post-surgical abortions, the immediate insertion group exhibited a higher IUD placement rate than the delayed insertion group. After medical abortions, the immediate insertion group showed higher rates of IUD placement, utilization, and expulsion at 6 months or 1 year. The two groups showed no statistically significant differences in the removal rate, post-insertion infection rate, pain scores during insertion, and days of bleeding during the follow-up period. Compared to delayed placement, immediate insertion of IUDs can not only increase the usage rate at 6 months or 1 year but also enhance the placement rate.

Trophoblastic microcirculation occlusion as an adjunct to electric vacuum aspiration for the treatment of endogenous cesarean scar pregnancy.

OBJECTIVE: To describe a simple adjunct treatment option, trophoblastic microcirculation occlusion (TMO), which could change subsequent high-risk electric vacuum aspiration in patients with an endogenous cesarean scar pregnancy (CSP) into a routine conventional surgical procedure. Electric vacuum aspiration for the treatment of CSP may be associated with several significant complications, including hemorrhage and tissue remnants. Consequently, a second intervention, such as uterine artery embolization, resectoscopy, or methotrexate, may be required, thus complicating the surgical treatment of CSP. DESIGN: We demonstrate the principle and detailed technique of TMO treatment using animations, video clips, and slides. The study was approved by the institutional review board of Hangzhou Women's Hospital. SETTING: Tertiary maternity hospital. PATIENT(S): The video shows a 30-year-old woman with a 5-week endogenous CSP. The procedural steps were repeated in another 6 patients suffering from endogenous CSP (Table 1). Written informed consent was obtained from each patient. INTERVENTION(S): In patients with a CSP, the syncytiotrophoblastic cells erode the helicine arteries in the inner uterine myometrium. The cytotrophoblastic cells extend as villi tissue into the syncytiotrophoblast. Maternal blood enters the intervillous space between the cytotrophoblast and syncytiotrophoblast. The syncytiotrophoblast, cytotrophoblast, and intervillous space constitute the trophoblastic microcirculation, which subsequently becomes the main blood supply to the gestational sac (Fig. 1). During TMO treatment, the trophoblastic microcirculation is identified by contrast-enhanced ultrasound with the cubital vein injected with sulfur hexafluoride microbubbles (Bracco, Switzerland). A 21-gauge needle (200 mm long) was punctured vaginally into the uterine myometrium surrounding the syncytiotrophoblast at 3 different points, and a total of 8 mL sclerosant was injected directly to seal the trophoblastic microcirculation. Complete compression of the helicine arteries for trophoblastic blood supply is the key to TMO treatment (Fig. 2, see video interpretation for detailed information). A repeat contrast-enhanced ultrasound was performed after injection to confirm a significant reduction of blood flow in the trophoblast. An electric vacuum aspiration was performed 24 hours after TMO treatment to remove the products of conception completely. Surgical safety was enhanced by deep sedation and concurrent transabdominal ultrasound guidance. The levels of ß-human chorionic gonadotropin (ß-hCG) were measured weekly until a nonpregnant level was achieved. A follow-up ultrasound then was performed to confirm that the treatment was complete. MAIN OUTCOME MEASURE(S): The clinical value and feasibility of TMO treatment as an adjunct before high-risk electric vacuum aspiration for the management of endogenous CSP. RESULT(S): The TMO treatment was performed successfully in all 7 patients; the clinical outcomes are presented in Table 2. The TMO treatment significantly reduced the risk of hemorrhage during electric vacuum aspiration. No complications were detected perioperatively. Patients were discharged on day 1 postoperatively. Follow-up ultrasound, performed when the levels of ß-hCG had fallen to normal, failed to identify any remnants of the uterine corpus. One patient achieved an intrauterine pregnancy 7 months postoperatively and gave birth to a live baby at 39 weeks of gestation via repeat cesarean section. No cesarean scar dehiscence was observed. CONCLUSION(S): Surgical abortion of an endogenous CSP, with a high risk of intraoperative hemorrhage, can be performed with minimal blood loss in a single electric vacuum aspiration when assisted by TMO treatment. This technique provides good results in terms of bleeding reduction that are comparable to those in conventional patients. The TMO treatment can be accomplished via ultrasound-guided needle puncture, a technique that is available widely in the practice of reproductive medicine with a reduced need for consumable resources. The use of a simple adjunct treatment option, TMO, expands the indications of electric vacuum aspiration. This sequential treatment allows for completion of clinical management without the need for uterine artery embolization, resectoscopy, or methotrexate, thus simplifying the originally complicated form of surgical treatment for CSP.

Economic and Humanistic Burden of Osteoarthritis: An Updated Systematic Review of Large Sample Studies.

OBJECTIVE: A previous systematic literature review demonstrated a significant economic and humanistic burden on patients with osteoarthritis (OA). The aim of this study was to systematically review and update the burden of OA reported by large sample studies since 2016. METHODS: We searched Medline (via Ovid) and Embase using the updated search strategy based on the previous review. Those studies with a sample size ≥ 1000 and measuring the cost (direct or indirect) or health-related quality of life (HRQL) of OA were included. Pairs of reviewers worked independently and in duplicate. An arbitrator was consulted to resolve discrepancies between reviewers. The Kappa value was calculated to examine the agreement between reviewers. All costs were converted to 2021 US dollars according to inflation rates and exchange rates. RESULTS: A total of 1230 studies were screened by title and abstract and 159 by full text, and 54 studies were included in the review. The Kappa value for the full-text screening was 0.71. Total annual OA-related direct costs ranged from US$326 in Japan to US$19,530 in the US. Total annual all-cause direct costs varied from US$173 in Italy to US$41,433 in the US. The annual indirect costs ranged from US$736 in the US to US$18,884 in the Netherlands. Thirty-four studies reported HRQL, with EQ-5D (13, 38%) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) (6, 18%) being the most frequently used instruments. The EQ-VAS and utility scores ranged from 41.5 to 81.7 and 0.3 to 0.9, respectively. The ranges of WOMAC pain (range 0-20, higher score for worse health), stiffness (range 0-8), and physical functioning (range 0-68) were 2.0-3.0, 1.0-5.0, and 5.8-42.8, respectively. CONCLUSION: Since 2016, the ranges of direct costs of OA became wider, while the HRQL of patients remained poor. More countries outside the US have published OA-related disease burden using registry databases.

Systemic Inflammation Markers Associated with Bone Mineral Density in perimenopausal and Postmenopausal Women.

Objective: The aim of this research was to determine whether systemic inflammatory indicators, including aggregate index of systemic inflammation (AISI), neutrophils lymphocyte to platelet ratio (NLPR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI), are related to bone mineral density (BMD) in perimenopausal and postmenopausal women. Methods: One hundred and eighty-one perimenopausal and 390 postmenopausal women were enrolled in this cross-sectional study. Continuous variables by analysis of variance and Kruskal Wallis test for comparing the clinical characteristics. Linear regression analysis was conducted to investigate the associations between inflammatory indicators with BMD. The comparison between the subgroups was performed using the nonparametric test and the T-test. Results: AISI, NLPR, SII, and SIRI quartile values were inversely associated with BMD in menopausal women (P = 0.021; P = 0.047; P < 0.001; P < 0.001, respectively). After adjusting for confounding factors, four inflammatory indicators remained significantly associated with BMD (all P for trend <0.001). Analysis according to menopausal status demonstrated that AISI, SII, and SIRI were significantly correlated with mean femoral neck BMD in postmenopausal women (P for trend = 0.015, 0.004, and 0.001), but not significantly associated with BMD in perimenopausal women (P for trend = 0.248, 0.054, and 0.352) after adjustment for covariates. Conclusion: The quartile values of AISI, SII, and SIRI were inversely associated with BMD in postmenopausal women, following adjustment for individual variables, hormone profiles and glucolipid metabolism profiles. AISI, SII, and SIRI have potential to be important tools for screening and prevention of bone loss in menopausal women in future clinical practice.

Health-related quality of life of children with Williams syndrome and caregivers in China.

Introduction: Williams syndrome (WS) is a rare genetic disorder that impacts multiple systems and may cause developmental delays. These medical and developmental issues impose a heavy burden on affected children and their families. However, there was no study on children's health-related quality of life (HRQoL) with WS and only two studies about family quality of life globally. Therefore, the primary purpose of this study was to assess the HRQoL of children with WS and their caregivers in China, and the secondary purpose was to identify the potential determinants of children's and caregivers' HRQoL. Methods: In total, 101 children and caregivers were included. We applied the proxy-reported PedsQL 4.0 Generic Core Module (PedsQL GCM) and PedsQL 3.0 Family Impact Module (FIM) to measure the HRQoL of children and caregivers. Additionally, we collected information on a comprehensive set of social demographic and clinical characteristics. Differences in HRQoL scores across subgroups were assessed by two-independent-samples t-tests, one-way ANOVA, and post hoc tests. We also calculated effect sizes to indicate clinical relevance. Multivariate linear regression models were applied to assess the potential determinants of HRQoL. Results: We found that the HRQoL of children with WS and their caregivers was dramatically worse than the norm average scores of the healthy controls of children published in previous studies. Paternal educational level, household income, and the perceived financial burden significantly influenced the HRQoL of both children and families (p-values < 0.05). Multivariate linear regression analysis showed that the perceived financial burden was independently associated with family quality of life (p-values < 0.05)., and the presence of sleeping problem was independently associated with children's HRQoL (p-value = 0.01). Conclusion: We call for attention from policymakers and other stakeholders on the health status and well-being of children with WS and their families. Supports are needed to relieve psychosocial distress and financial burden.

Effect of different timing of letrozole initiation on pregnancy outcome in polycystic ovary syndrome.

Objective: To investigate the efficacy of oral letrozole (LE) starting on day 3 or 5 of the menstrual cycle in patients with polycystic ovary syndrome (PCOS). Design: Retrospective cohort study. Setting: Reproductive Endocrinology Department of Hangzhou Women's Hospital. Methods: In this retrospective analysis, we analyzed patients who received oral LE for ovulation induction (OI) at the Hangzhou Women's Hospital from January 2016 to January 2021. In total, 539 PCOS patients with fertility requirements were classified into the D3 group and D5 group according to the different starting times of oral LE, that is, from the 3rd or 5th day of the menstrual cycle or LE is taken orally for 5 days starting on day 3 or 5 of progesterone withdrawal bleeding. Treatment started with one tablet (LE 2.5 mg), continue the regimen from the previous cycle in non-responders and continued until pregnancy or for up to three ovulatory cycles, with visits to determine ovulation and pregnancy, followed by tracking of pregnancies. The primary outcome was to compare ovulation rates, conception rates, live birth rates, pregnancy complications, and pregnancy outcomes at different initiation times. Results: Women who started LE on the 5th day of their menstrual cycle had more cumulative conception rates than those who started LE on the 3rd day(173 of 228[75.9%]vs. 201 of 311[64.6%], P= 0.005; rate ratio for conception, 1.174; 95% confidence interval,1.052 to 1.311) without significant differences in overall live birth rate, though there were 142 of 228[62.3%] in the D5 group versus 172 of 311[55.3%] in the D3 group (P= 0.105). The median (IQR) endometrial thickness was significantly (P = 0.013) greater during the D5 group treatment compared to the D3 group, which may be related to higher conception and clinical pregnancy rates. The median (IQR) maximum follicle diameter was not statistically (P = 0.073) different between the two groups. The cumulative ovulation per cycle rate was higher with D5 than with D3 (287 of 405 treatment cycles [70.9%] vs. 388 of 640 treatment cycles [60.6%], P=0.001). There were no significant between-group differences in pregnancy loss (31 of 173 conceptions in the D5 group [17.9%] and 29 of 201 conceptions in the D3 group [14.4%]) or multiples pregnancy (8.2% and 10.5%, respectively). Rates of other adverse events during pregnancy were similar in the two treatment groups. Conclusion: As compared with D3 group, D5 group was associated with higher ovulation and conception rates, shorter time-to-pregnancy among infertile women with the PCOS.

SKAP2 is downregulated in the villous tissues of patients with missed abortion and regulates growth and migration in trophoblasts through the WAVE2-ARP2/3 signaling pathway.

INTRODUCTION: Abnormal placental trophoblast function is the main cause of missed abortion (MA). Src kinase-associated phosphoprotein 2 (SKAP2) indirectly affects actin reunion, which is significantly associated with cell migration. METHODS: Twenty women with MA and 20 healthy women who underwent voluntarily induced abortion were included in this study. Immunohistochemistry, qRT-PCR, and western blotting were used to determine SKAP2, WAVE2, and ARP2 expression in the villous tissues. We investigated the effects of SKAP2 and the W336K mutant (blocked SKAP2 Src homology 3 function) on growth and migration in HTR8/SVneo cells using the CCK8 assay, flow cytometry, and transwell assay. The effects of SKAP2 on the WAVE2-ARP2/3 signaling pathway in HTR8/SVneo cells were evaluated by western blotting and immunofluorescence. RESULTS: Compared to the women in the voluntary abortion group, SKAP2 and WAVE2 expression levels were downregulated in the villous of patients with MA. In HTR8/SVneo cells, SKAP2 siRNA silencing regulated the growth and migration, while SKAP2 overexpression promoted growth and migration, and inhibited apoptosis. Additionally, SKAP2 regulated the expression of WAVE2 and ARP2, as well as the colocalization of actin with WAVE2. The SKAP2 W336K mutant could not alter WAVE2 and ARP2 expression, nor HTR8/SVneo cell growth and migration, with or without SKAP2 siRNA transfection. DISCUSSION: SKAP2 could activate the WAVE2-ARP2/3 pathway resulting in an increase of growth and migration in trophoblasts. SKAP2 probably played an important role in MA by affecting the growth and migration of trophoblasts.