Advances in the study of the correlation between insulin resistance and infertility.

This is a narrative review of the progress of research on the correlation between insulin resistance and infertility. Insulin resistance (IR) is not only involved in the development of various metabolic diseases, but also affects female reproductive function, and to some extent is closely related to female infertility. IR may increase the risk of female infertility by activating oxidative stress, interfering with energy metabolism, affecting oocyte development, embryo quality and endometrial tolerance, affecting hormone secretion and embryo implantation, as well as affecting assisted conception outcomes in infertile populations and reducing the success rate of assisted reproductive technology treatment in infertile populations. In addition, IR is closely associated with spontaneous abortion, gestational diabetes and other adverse pregnancies, and if not corrected in time, may increase the risk of obesity and metabolic diseases in the offspring in the long term. This article provides a review of the relationship between IR and infertility to provide new ideas for the treatment of infertility.

Lower incidence of new-onset severe conduction disturbances after transcatheter aortic valve implantation with bicuspid aortic valve in patients with no baseline conduction abnormality: a cross-sectional investigation in a single center in China.

Background: With technological advancements, the incidence of most transcatheter aortic valve implantation (TAVI)-related complications, with the exception of conduction disturbances, has decreased. Bicuspid aortic valve (BAV) is also no longer considered a contraindication to TAVI; however, the effect of BAV on postoperative conduction disturbances after TAVI is unknown. Methods: We collected information on patients who met the indications for TAVI and successfully underwent TAVI at our center between January 2018 and January 2021. Patients with preoperative pacemaker implantation status or conduction disturbances (atrioventricular block, bundle branch block, and intraventricular block) were excluded. Based on imaging data, the patients were categorized into the BAV group and the tricuspid aortic valve (TAV) group. The incidence of new perioperative conduction disturbances was compared between the two groups. Results: A total of 187 patients were included in this study, 64 (34.2%) of whom had BAV. The incidence of third-degree block in the BAV group was 1.6%, which was lower than that (13.0%) in the TAV group (P < 0.05). Multivariate logistic regression results showed that the risk of third-degree conduction disturbances was 15-fold smaller in the BAV group than that in the TAV group [relative risk (RR) = 0.067, 95% CI = 0.008-0.596, P < 0.05]. The risk of other blocks in the BAV group was about half of that in the TAV group (RR = 0.498, 95% CI = 0.240-1.032); however, the difference was not statistically significant (P > 0.05). Conclusion: The present study found that patients with BAV had a lower rate of third-degree conduction disturbances after TAVI than patients with TAV.

Innovative use of a self-expanding valve for valve-in-valve transcatheter mitral valve replacement: experience from a four-year single-center study.

Background: Valve-in-valve transcatheter mitral valve replacement (ViV-TMVR) is a minimally invasive option for patients with bioprosthetic mitral valve failure. Since January 2019, our center has been using a new innovative option, J-Valve, to treat patients with bioprosthetic mitral valve failure who were at high risk for open heart surgery. The aim of this study is to explore the effectiveness and safety of J-Valve and report the results from the four-year follow-up period of the innovative application of the transcatheter valve. Methods: Patients who underwent the ViV-TMVR procedure between January 2019 and September 2022 in our center were included in the study. J-Valve™ system (JC Medical Inc., Suzhou, China) with three U-shape grippers was used for ViV-TMVR via transapical approach. Data on survival, complications, transthoracic echocardiographic results, New York Heart Association functional class in heart failure, and patient-reported health-related quality of life according to the Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) were collected during the four-year follow up. Results: Thirty-three patients (mean age 70.1 ± 1.1 years, 13 men) were included and received ViV-TMVR. The surgery success rate was 97%: only one patient was converted to open-heart surgery due to intraoperative valve embolization to the left ventricle. During the first 30 days all-cause mortality was 0%, risk of stroke 2.5% and risk of mild paravalvular leak 15.2%; mitral valve hemodynamics improved (179.7 ± 8.9 at 30 days vs. 269 ± 49 cm/s at baseline, p < 0.0001). Median time from operation to discharge was six days, and there were no readmissions within 30 days from operation. The median and maximum follow-up durations were 28 and 47 months, respectively; during the entire follow-up, all-cause mortality was 6.1%, and the risk of cerebral infarction 6.1%. Cox regression analysis did not identify any variables significantly associated with survival. The New York Heart Association functional class and the KCCQ-12 score improved significantly compared with their preoperative values. Conclusion: The use of J-Valve for ViV-TMVR is safe and effective with a high success rate, low mortality and very few associated complications, representing an alternative surgical strategy for the elderly, high-risk patients with bioprosthetic mitral valve failure.

Comparison of pregnancy outcomes between IVF-ET pregnancies and spontaneous pregnancies in women of advanced maternal age.

AIM: To explore the impact of IVF on pregnancy complications and birth outcomes in women of advanced maternal age. METHODS: In this retrospective study, 3325 women were divided into the ART pregnancy group (n = 241) and the natural pregnancy group (n = 3086). The differences in maternal general conditions, pregnancy complications and birth outcomes were compared between the two groups. RESULTS: The ART group had higher rates of primiparity (78.4% vs 20.4%), cesarean section (90.5% vs 76.2%) and twin births (28.6% vs 2.1%). The risk of gestational hypertension (5.8% vs 2.9%), preeclampsia (5.0% vs 2.3%) and preterm birth [28 ∼ 31 + 6 weeks (2.9% vs 1.1%), 32 ∼ 33 + 6 weeks (5.0% vs 1.4%), 34 ∼ 36 + 6 weeks (15.8% vs 9.4%)] was significantly higher in the ART group than in the natural pregnancy group. Neonates in the ART group had lower birth weights (2882.61 ± 657.70 vs 3223.05 ± 534.28). However, in the singleton-only comparison, only gestational hypertension still showed a statistically significant difference. CONCLUSIONS: For women of advanced maternal age, IVF-ET pregnancies may result in higher rates of pregnancy complications and adverse birth outcomes, but this is likely to be due to increased rates of multiple pregnancies.

Core Outcome Sets in Child Health: A Systematic Review.

Importance: Developing core outcome sets is essential to ensure that results of clinical trials are comparable and useful. A number of core outcome sets in pediatrics have been published, but a comprehensive in-depth understanding of core outcome sets in this field is lacking. Objective: To systematically identify core outcome sets in child health, collate the diseases to which core outcome sets have been applied, describe the methods used for development and stakeholder participation, and evaluate the methodological quality of existing core outcome sets. Evidence Review: MEDLINE, SCOPUS, Cochrane Library, and CINAHL were searched using relevant search terms, such as clinical trials, core outcome, and children, along with relevant websites, such as Core Outcome Measures in Effectiveness Trials (COMET). Four researchers worked in teams of 2, performed literature screening and data extraction, and evaluated the methodological quality of core outcome sets using the Core Outcome Set-Standards for Development (COS-STAD). Findings: A total of 77 pediatric core outcome sets were identified, mainly developed by organizations or researchers in Europe, North America, and Australia and mostly from the UK (22 [29%]) and the US (22 [29%]). A total of 77 conditions were addressed; the most frequent International Classification of Diseases, 11th Revision category was diseases of the digestive system (14 [18%]). Most of the outcomes in pediatric core outcome sets were unordered (34 [44%]) or presented in custom classifications (29 [38%]). Core outcome sets used 1 or more of 8 development methods; the most frequent combination of methods was systematic review/literature review/scoping review, together with the Delphi approach and consensus for decision-making (10 [14%]). Among the 6 main types of stakeholders, clinical experts were the most frequently involved (74 [100%]), while industry representatives were rarely involved (4 [5%]). Only 6 core outcome sets (8%) met the 12 criteria of COS-STAD. Conclusions and Relevance: Future quality of pediatric core outcome sets should be improved based on the standards proposed by the COMET initiative, while core outcome sets methodology and reporting standards should be extended to pediatric populations to help improve the quality of core outcome sets in child health. In addition, the COMET outcome taxonomy should also add items applicable to children.

Management guideline for the off-label use of medicine in China (2021).

BACKGROUND: Off-label drug use embodies a thorough clinical diagnosis and evaluation of treatment needs and should not be confused with unreasonable drug use, but it also faces potential risks with drug safety and legal issues. RESEARCH DESIGN AND METHODS: We first established a guideline working group. Following the guideline development process recommended by the World Health Organization Handbook and the Chinese Medical Association, the key questions were determined through literature searches of PubMed, CNKI (Chinese National Knowledge Infrastructure) and other databases. Both the evidence and the clinicians' diagnosis and treatment workload were considered to formulate the initial recommendations. Finally, two rounds of Delphi surveys and one expert seminar were organized to determine the final recommendations of this guideline. Meanwhile, we graded the recommendations based on the body of evidence. RESULTS: We determined nine questions and proposed a total of 23 recommendations regarding the definition of off-label use of drugs, applicable circumstances, classification of evidence, informed consent, legal basis, adverse drug reaction monitoring and evaluation, management procedure, responsibilities and obligations of different stakeholders, medical insurance reimbursement, and the national approval system. CONCLUSIONS: This guideline standardized clinical off-label drug use and provided suggestions and references for the management of off-label drug use.

Clinical manifestations of COVID-19: An overview of 102 systematic reviews with evidence mapping.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) has rapidly spread worldwide, but there is so far no comprehensive analysis of all known symptoms of the disease. Our study aimed to present a comprehensive picture of the clinical symptoms of COVID-19 using an evidence map. METHODS: We systematically searched MEDLINE via PubMed, Web of Science, Embase, and Cochrane library from their inception to March 16, 2021. We included systematic reviews reporting the clinical manifestations of COVID-19 patients. We followed the PRISMA guidelines, and the study selection, data extraction, and quality assessment were done by two individuals independently. We assessed the methodological quality of the studies using AMSTAR. We visually presented the clinical symptoms of COVID-19 and their prevalence. RESULTS: A total of 102 systematic reviews were included, of which, 68 studies (66.7%) were of high quality, 19 studies (18.6%) of medium quality, and 15 studies (14.7%) of low quality. We identified a total of 74 symptoms including 17 symptoms of the respiratory system, 21 symptoms of the neurological system, 10 symptoms of the gastrointestinal system, 16 cutaneous symptoms, and 10 ocular symptoms. The most common symptoms were fever (67 studies, ranging 16.3%-91.0%, pooled prevalence: 64.6%, 95%CI, 61.3%-67.9%), cough (68 studies, ranging 30.0%-72.2%, pooled prevalence: 53.6%, 95%CI, 52.1%-55.1%), muscle soreness (56 studies, ranging 3.0%-44.0%, pooled prevalence: 18.7%, 95%CI, 16.3%-21.3%), and fatigue (52 studies, ranging 3.3%-58.5%, pooled prevalence: 29.4%, 95%CI, 27.5%-31.3%). The prevalence estimates for COVID-19 symptoms were generally lower in neonates, children and adolescents, and pregnant women than in the general populations. CONCLUSION: At least 74 different clinical manifestations are associated with COVID-19. Fever, cough, muscle soreness, and fatigue are the most common, but attention should also be paid to the rare symptoms that can help in the early diagnosis of the disease.

Guideline for the management of pediatric off-label use of drugs in China (2021).

BACKGROUND: The "Law on Doctors of the People's Republic of China," which was officially implemented on March 1, 2022, emphasizes the requirements for rational drug use and the necessity for appropriate management of off-label drug use. The safety and ethical considerations related to off-label drug use are different in children than in adults. There is so far no management guideline for pediatric off-label use of drugs in China, and the applicability of foreign guidelines is limited. Establishing a localized evidence-based management guideline for pediatric off-label use of drugs to support the national legislation and clinical practice is of critical importance. METHODS: We established a guideline working group, including experts from a broad range of disciplines and developed recommendations following the guidance of the World Health Organization Handbook and the Chinese Medical Association. The following themes were identified by questionnaires and expert interviews to be of great concern in the management of off-label drug use in children: general principles and characteristics of management of pediatric off-label drug use; establishment of expert committees; evidence evaluation; risk-benefit assessment; informed consent; monitoring and assessment of the risk; and monitoring and patient education. Two rounds of Delphi surveys were organized to determine the final recommendations of this guideline. We graded the recommendations based on the body of evidence, referring to the evaluation tool of the Evidence-based management (EBMgt) and the Oxford Center for Evidence-Based Medicine: Level of Evidence (March 2009). RESULTS: We developed the first guideline for the management of pediatric off-label use of drugs in China. CONCLUSIONS: The guideline is to offer guidance for pediatricians, pharmacists, medical managers, policymakers, and primary care physicians on how to manage off-label drug use in pediatrics and to provide recommendations for Chinese healthcare policy in the future.

Publishing clinical prActice GuidelinEs (PAGE): Recommendations from editors and reviewers.

Transparency Ecosystem for Research and Journals in Medicine (TERM) working group summarized the essential recommendations that should be considered to review and publish a high-quality guideline. These recommendations from editors and reviewers included 10 components of essential requirements: systematic review of existing relevant guidelines, guideline registration, guideline protocol, stakeholders, conflicts of interest, clinical questions, systematic reviews, recommendation consensus, guideline reporting and external review. TERM working group abbreviates them as PAGE (essential requirements for Publishing clinical prActice GuidelinEs), and recommends guideline authors, editors, and peer reviewers to use them for high-quality guidelines.

Off-label use of drugs in pediatrics: a scoping review.

To explore the current state of research on off-label drug use in children and identify the existing research gaps in this topic. Six literature databases were searched to identify studies focusing exclusively on off-label drug use in children (aged < 18 years) published in Chinese or English between 2016 and 2021. We also searched clinicaltrials.gov for pediatric clinical trials conducted in the same period and compared the numbers of studies on off-label use and clinical trials for the most commonly reported drugs and drug types. Our search revealed 568 studies on off-label drug use. Almost half of the studies (n = 240) were cross-sectional. A total of 212 specific drugs or drug types were addressed in 361 studies, the most frequent being antipsychotic agents (n = 12), dexmedetomidine (n = 10), and rituximab (n = 8). Antipsychotic agents were also the most common type of drug examined in clinical trials in children. We identified a total of 435 different types of off-label use, the top three being unapproved indication (n = 157), population (n = 96), or age (n = 36). Only about one-third of the studies reported collecting informed consent (n = 195) or having ethics committee approval (n = 166).    Conclusions: Off-label use of antipsychotics in children is widely reported in the literature. We suggest pediatric researchers to consider the number of studies on off-label use and existing clinical trials on different drugs when selecting target drugs for new studies and systematic reviews. What is Known: • There exist a large number of studies on off-label drug use in children. What is New: • This is the first scoping review of studies on off-label drug use in children. • Off-label use of antipsychotic agents is widely reported.

Publishing clinical prActice GuidelinEs (PAGE): Recommendations from editors and reviewers.

Transparency Ecosystem for Research and Journals in Medicine (TERM) Working Group summarized the essential recommendations that should be considered to review and publish a high-quality guideline. These recommendations from editors and reviewers included the ten components of essential requirements: systematic review of existing relevant guidelines, guideline registration, guideline protocol, stakeholders, conflicts of interest, clinical questions, systematic reviews, recommendation consensus, guideline reporting, and external review. TERM Working Group abbreviates them as PAGE (essential requirements for Publishing clinical prActice GuidelinEs), recommends guideline authors, editors, and peer reviewers use them for high-quality guidelines.

Quality appraisal of clinical practice guidelines on physical restraints in ICU: a systematic review.

BACKGROUND: Physical restraint has been regarded as a protective measure in the intensive care unit (ICU) in order to avoid unexpected events. But a great number of researches have proven that physical restraints can cause bad influences on patients' mental health, such as language delays of children, sense of uncertainty, loss of trust, etc. However, it is unclear whether there are currently high-quality clinical practice guidelines (CPGs) to guide clinical practice in physical restraints. So we aim to analyze available CPGs on physical restraints in ICU with Appraisal of Guidelines for Research and Evaluation II (AGREE II) evaluating methodological quality and Reporting Items for Practice Guidelines in Healthcare (RIGHT) evaluating reporting quality. METHODS: We systematically searched PubMed, Embase, Web of Science, CINAHL, CNKI (Chinese database), Wanfang data (Chinese database), relevant websites (GIN, NICE, SIGN, RNAO, AHRQ, AACN), and Google from their inception to Nov 21, 2021. Two reviewers independently use the AGREE II tool and RIGHT checklist to evaluate methodological and reporting quality of included guidelines on physical restraints in ICU. The number and proportion of reported items of RIGHT checklist and the scores of each domain of AGREE II were calculated. We also evaluated the consistency among the reviewers via use of the intragroup correlation coefficient. RESULTS: A total of six guidelines were included. The mean AGREE II score for the included guidelines was 39.56% with a range of 30.27-69.85%. No guideline was "high quality", and only one guideline was "moderate quality" with 69.85% mean AGREE II score. The mean RIGHT reporting score for guidelines was 41.0% with a range of 24.7-77.7%. Only one guideline was "moderate-reported" with a mean reporting score of 77.7%. DISCUSSION: In general, the methodological and reporting quality of physical restraints guidelines is low, and future development or updating of high-quality guidelines to guide clinical practice is needed.

Nurse education to reduce physical restraints use in ICU: A scoping review.

BACKGROUND: Physical restraints are defined as a manual approach to reduce a patient's physical movement and has been regarded as a protective nursing measure in the intensive care unit (ICU) to avoid unplanned extubation, falls, and other unexpected events. However, the limitations and changes associated with physical restraints have been verified by several studies. Restraint minimization has been advocated by studies worldwide; however, the most effective interventions are still being explored. AIM: To identify and map nurse education strategies that reduce the use of physical restraints in the ICU. DESIGN AND METHODS: A systematic literature search that followed the steps of a scoping review was performed in the Cochrane, PubMed, Embase, CINAHL, CNKI, Wan Fang Data, and VIP databases. We included studies that focused on nurse education aiming to reduce the use of physical restraints and/or use physical restraints reasonably. RESULTS: The included studies (n = 12) described a variety of education strategies. Two delivery modes, eight common course durations, 14 main topics, two types of teaching methods with various materials, and two kinds of outcome measurements were identified and compared. CONCLUSION: There are a variety of nurse education activities that could effectively improve ICU nurses' knowledge, attitudes, and behaviours towards physical restraints. However, the strategies of nurse education, such as delivery mode, teaching methods, and outcome measurements, require further study. RELEVANCE TO CLINICAL PRACTICE: Nurse education on physical restraints should be carried out in ICUs. Online courses, practical sessions, and simulated scenarios should be a part of future nurse education. In addition to nurses' knowledge and attitude changes, frequency of physical restraints and other patient-related outcomes should also be considered for outcome evaluation.

Safety, Immunogenicity, and Efficacy of COVID-19 Vaccines in Children and Adolescents: A Systematic Review.

AIM: To identify the safety, immunogenicity, and protective efficacy of COVID-19 vaccines in children and adolescents. METHODS: We conducted a systematic review of published studies and ongoing clinical studies related to the safety, immunogenicity, and efficacy of COVID-19 vaccine in children or adolescents (aged < 18 years). Databases including PubMed, Web of Science, WHO COVID-19 database, and China National Knowledge Infrastructure (CNKI) were searched on 23 July 2021. International Clinical Trials Registry Platform (ICTRP) was also searched to identify ongoing studies. RESULTS: Eight published studies with a total of 2852 children and adolescents and 28 ongoing clinical studies were included. Of the eight published studies, two were RCTs, two case series, and four case reports. The investigated COVID-19 vaccines had good safety profiles in children and adolescents. Injection site pain, fatigue, headache, and chest pain were the most common adverse events. A limited number of cases of myocarditis and pericarditis were reported. The RCTs showed that the immune response to BNT162b2 in adolescents aged 12-15 years was non-inferior to that in young people aged 16-25 years, while with 3 µg CoronaVac injection the immune response was stronger than with 1.5 µg. The efficacy of BNT162b2 was 100% (95% CI: 75.3 to 100), based on one RCT. Of the 28 ongoing clinical studies, twenty-three were interventional studies. The interventional studies were being conducted in fifteen countries, among them, China (10, 43.5%) and United States(9, 39.1%) had the highest number of ongoing trials. BNT162b2 was the most commonly studied vaccine in the ongoing trials. CONCLUSION: Two COVID-19 vaccines have potential protective effects in children and adolescents, but awareness is needed to monitor possible adverse effects after injection. Clinical studies of the COVID-19 vaccination in children and adolescents with longer follow-up time, larger sample size, and a greater variety of vaccines are still urgently needed.