Long-term distress throughout one's life: health-related quality of life, economic and caregiver burden of patients with neurofibromatosis type 1 in China.

Introduction: Neurofibromatosis type 1 (NF1) is a rare genetic disorder, with lack of evidence of disease burden in China. We aimed to describe the economic burden, health-related quality of life (HRQL), and caregiver burden of NF1 patients in China. Methods: We conducted an online cross-sectional survey employing the China Cloud Platform for Rare Diseases, with 223 caregivers of NF1 pediatric patients (patients under 18), and 226 adult patients. Economic burden was estimated using direct and indirect costs related to NF1 in 2021, and the Work Productivity and Activity Impairment Questionnaire: General Health V2.0 (WPAI-GH). HRQL measures included EQ-5D-Y proxy version and PedsQL™ 4.0 Generic Core Scales (PedsQL GCS) proxy version for pediatric patients, and EQ-5D-5L and PedsQL™ 3.0 Neurofibromatosis Module (PedsQL NFM) for adult patients. Caregiver burden was estimated by Zarit Burden Interview (ZBI). Results: For pediatric patients, the average direct cost in 2021 was CNY 33,614 (USD 4,879), and employed caregivers' annual productivity loss was 81 days. EQ-5D-Y utility was 0.880 ± 0.13 and VAS score was 75.38 ± 20.67, with 52.6% patients reporting having problems in "pain/discomfort" and 42.9% in "anxiety/depression." PedsQL GCS total score was 68.47 ± 19.42. ZBI score demonstrated that 39.5% of caregivers had moderate-to-severe or severe burden. For adult patients, average direct cost in 2021 was CNY 24,531 (USD 3,560). Patients in employment reported an absenteeism of 8.5% and presenteeism of 21.6% according to the results of WPAI-GH. EQ-5D-5L utility was 0.843 ± 0.17 and VAS score was 72.32 ± 23.49, with more than half of patients reporting having problems in "pain/discomfort" and "anxiety/depression" dimensions. PedsQL NFM total score was 68.40 ± 15.57. Conclusion: Both pediatric and adult NF1 patients in China had a wide-ranging economic burden and low HRQL, especially in the psychological dimension. Caregivers for NF1 pediatric patients experienced considerable caregiver burden. More attention and support from policymakers and stakeholders are required to relieve NF1 patients' and caregivers' distress.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Estimating an EQ-5D-Y-3L Value Set for China.

INTRODUCTION: The standard EQ-5D-Y-3L valuation protocol applies DCE data as the primary preference source to model the relative importance of dimensions while cTTO data served to anchor the DCE coefficients onto the QALY scale. This study aims to estimate an EQ-5D-Y-3L value set for China following this protocol, but with a larger cTTO design to better understand the role of cTTO data in estimating EQ-5D-Y-3L value sets. METHODS: In total, 150 choice sets and 28 EQ-5D-Y-3L health states were valued using DCE and cTTO methods with two independent samples, respectively. General public from 14 different regions were recruited using quota sampling method to achieve representativeness. We compared two modelling strategies: (1) fit the DCE data with mixed logit model with correlated coefficients and a subsequent mapping procedure for anchoring; (2) fit the DCE and TTO data jointly in a hybrid model. Two evaluation criteria (1) coefficient significance and monotonicity; (2) prediction accuracy of the observed cTTO values were used to select the value set. RESULTS: In total, 1476 individuals participated in the study, with 1058 participated the DCE interview and 418 participated the cTTO interview. The highest mean TTO value was 0.924 for state 11112 and the lowest mean TTO value was - 0.088 for state 33333. The hybrid model with an A3 term performed the best and was selected as the value set. DISCUSSION: Following the international protocol and using a larger cTTO design, this study established the EQ-5D-Y-3L value set using a hybrid model for China. Future EQ-5D-Y-3L valuation study could consider using a larger cTTO design for estimating the value set.

Clinical characteristics and in silico analysis of congenital pseudarthrosis of the tibia combined with neurofibromatosis type 1 caused by a novel NF1 mutation.

Congenital pseudarthrosis of the tibia (CPT) is a rare congenital bone malformation, which has a strong relationship with Neurofibromatosis type 1 (NF1). NF1 is an autosomal dominant disease leading to multisystem disorders. Here, we presented the genotypic and phenotypic characteristics of one unique case of a five-generation Chinese family. The proband was CPT accompanied with NF1 due to NF1 mutation. The proband developed severe early-onset CPT combined with NF1 after birth. Appearance photos and X-ray images of the left limb of the proband showed significant bone malformation. Slit-lamp examination showed Lisch nodules in both eyes of the proband. Whole-exome sequencing (WES) and Sanger sequencing confirmed the truncation variant of NF1 (c.871G>T, p. E291*). Sequence conservative and evolutionary conservation analysis indicated that the novel mutation (p.E291*) was highly conserved. The truncated mutation led to the loss of functional domains, including CSRD, GRD, TBD, SEC14-PH, CTD, and NLS. It may explain why the mutation led to a severe clinical feature. Our report expands the genotypic spectrum of NF1 mutations and the phenotypic spectrum of CPT combined with NF1.

Insulin-like peptide 5 (INSL5) positively correlates with anti-Müllerian hormone (AMH) in women with the polycystic ovary syndrome: a case-control study.

BACKGROUND: Insulin-like peptide 5 (INSL5) is involved in both reproductive and metabolic processes in polycystic ovary syndrome (PCOS). This study aimed to evaluate the relationship between INSL5 and anti-Müllerian hormone (AMH). METHODS: A retrospective case-control study was conducted in a university-based reproductive centre between December 2019 and January 2021. We included 117 women with PCOS and 100 healthy subjects from Zhejiang Province. All subjects were divided into four groups (1st-4th) based on quartiles of serum INSL5 levels. Serum INSL5 concentration was assayed using an enzyme-linked immunosorbent assay. RESULTS: A significant direct association was observed between serum INSL5 and AMH levels in women with PCOS. The mean AMH level in the 1st-4th INSL5 level quartiles were 4.64, 5.20, 6.46, and 9.48 ng/ml, respectively (P < 0.001). After adjusting for age, body mass index, metabolic indices, and serum levels of oestradiol and total testosterone, AMH levels remained positively and significantly associated with INSL5 levels (P for trend < 0.001). The diagnostic value of AMH was better than that of INSL5. CONCLUSIONS: INSL5 and AMH levels were significantly correlated and elevated in women with PCOS. INSL5 and AMH might be associated with increased androgen secretion and chronic anovulation in PCOS.

Si-Wu-Tang ameliorates bile duct ligation-induced liver fibrosis via modulating immune environment.

Si-Wu-Tang (SWT), a traditional Chinese medicine formula firstly recorded from the Tang dynasty, has been reported to alleviate gynecological and liver diseases. We preliminarily demonstrated that SWT could improve liver fibrosis via modulating intestinal microbiota, but little was known about the mechanisms linking its therapeutic effects to the reshaped immune microenvironment within fibrotic livers. Thus, we established a bile duct ligation (BDL)-induced liver fibrosis murine model to evaluate the hepatoprotective effects and potential mechanisms of SWT. The high-performance liquid chromatography, RNA sequencing and other molecular biological techniques were also performed in our study. Our data demonstrated that SWT significantly improved BDL-induced liver fibrosis and inflammatory responses by inhibiting the expression of genes associated with extracellular matrix synthesis and degradation. Combined with the analysis of immune cell infiltration and gene set enrichment analysis (GSEA), we found that SWT remarkably repaired the unbalanced immune microenvironment by modulating the biological functions of different immune cells, especially for macrophages, neutrophils and CD8+ T cells. In addition, SWT significantly inhibited the activation of M2-like macrophages to reduce the release of profibrotic-cytokines and prevented the activation of neutrophils to suppress neutrophil extracellular trap formation. SWT also efficiently promoted the apoptosis of activated hepatic stellate cells via Fas/FasL signaling pathway, which might be mediated by CD8+ tissue-resident memory T cells. In conclusion, our research not only unraveled the intricate mechanisms underlying the hepatoprotective activities of SWT against liver fibrosis but also provided a novel therapeutic strategy for the treatment of liver fibrosis and its relative complications.

Development of patient versions of guidelines in Chinese mainland: A systematic survey of current practices and methods.

OBJECTIVES: To review current practices and methods underlying the development of patient versions of guidelines (PVGs) in Chinese mainland. METHODS: We systematically searched for PVGs created or published between January 2010 and February 2022. We conducted a framework analysis for the development process and assessed the compliance of PVGs using the Reporting Checklist for Public Versions of Guidelines (RIGHT-PVG). RESULTS: We identified 26 PVGs developed by 16 PVG-working teams. In accordance with the Guidelines International Network (GIN), only two PVGs were translated using one clinical practice guideline (CPG) provided by the CPG-working group source. Several CPGs and other information sources were integrated and translated into a single PVG by other PVG teams. Moreover, we identified various practices described by different PVG teams that could be structured into six steps. Out of the 17 RIGHT-PVG items, five items were fully reported in all PVGs, while two items ("Provide a summary of the PVG" and "Provide a list of terms and abbreviations") were not reported in any of the PVGs. CONCLUSIONS AND PRACTICAL IMPLICATIONS: A relatively small number of PVGs were developed in Chinese mainland. The development of a PVG requires comprehensive methodological guidance based on several CPGs and other sources of information as opposed to only using one.

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.

Serious reporting deficiencies exist in minimal important difference studies: current state and suggestions for improvement.

BACKGROUND AND OBJECTIVES: To evaluate reporting of minimal important difference (MID) estimates using anchor-based methods for patient-reported outcome measures (PROMs), and the association with reporting deficiencies on their credibility. METHODS: Systematic survey of primary studies empirically estimating MIDs. We searched Medline, EMBASE, PsycINFO, and the Patient-Reported Outcome and Quality of Life Instruments Database until October 2018. We evaluated study reporting, focusing on participants' demographics, intervention(s), characteristics of PROMs and anchors, and MID estimation method(s). We assessed the impact of reporting issues on credibility of MID estimates. RESULTS: In 585 studies reporting on 5,324 MID estimates for 526 distinct PROMs, authors frequently failed to adequately report key characteristics of PROMs and MIDs, including minimum and maximum values of PROM scale, measure of variability accompanying the MID estimate and number of participants included in the MID calculation. Across MID estimates (n = 5,324), the most serious reporting issues impacting credibility included infrequent reporting of the correlation between the anchor and PROM (66%), inadequate details to judge precision of MID point estimate (13%), and insufficient information about the threshold used to ascertain MIDs (16%). CONCLUSION: Serious issues of incomplete reporting in the MID literature threaten the optimal use of MID estimates to inform the magnitude of effects of interventions on PROMs.

Economic Evaluation of Sucrose Octasulfate Dressing for Treatment of Diabetic Foot Ulcers in Patients with Type 2 Diabetes.

OBJECTIVES: Patients with noninfected neuroischemic diabetic foot ulcers (DFUs) treated with sucrose octasulfate (SOS) dressing have been shown to have improved healing compared with patients wearing a similar type of dressing without SOS. In this study, we aimed to estimate the cost-effectiveness of SOS dressing compared with conventional dressings from a Canadian public payer's perspective. METHODS: We built a Markov model in a hypothetical cohort of 1,000 inpatients with type 2 diabetes with DFUs. The time horizon was 5 years, and the cycle length was 3 months. We incorporated effectiveness data from the Explorer trial and cohort studies, cost data (2020 Canadian dollars) from published Canadian studies and administrative databases, and utility parameters from the Alberta's Caring for Diabetes cohort. We used probabilistic analysis to calculate the incremental cost-effectiveness ratio of SOS dressing compared with conventional dressings. RESULTS: In the comparison with conventional dressings, use of SOS dressing resulted in an expected increase of 0.16 quality-adjusted life-year (QALY) and an expected $5,878 decrease in health-care costs over 5 years. Adding SOS dressing resulted in a cost savings of $37,061 for every QALY gained. The probability that adding SOS dressing is cost-saving and cost-effective compared with conventional dressings was 89% and 86%, respectively, at a $50,000/QALY willingness-to-pay threshold. CONCLUSIONS: SOS dressing accelerates ulcer healing and helps reduce the spending induced by persistent ulcer management and amputation. Therefore, SOS dressing is likely to be cost-effective and cost-saving, which is consistent with previous health technology assessments in other health-care systems.