Objectives: Health-related quality-of-life (HRQoL) instruments for cardiovascular diseases (CVD) have been commonly used to measure important patient-reported outcomes (PROs) in clinical trials and practices. This study aimed at systematically identifying and assessing the content validity of CVD-specific HRQoL instruments in clinical studies. Methods: The research team searched Cumulative Index to Nursing and Allied Health Literature, Embase, and PubMed from inception to January 20, 2022. The research team included studies that reported the development and content validity for CVD-specific instruments. Two reviewers independently assessed the methodological quality using the Consensus-based Standards for the Selection of Health Measurement Instruments methods on evaluating content validity of PROs. Content analysis was used to categorize the items included in the instruments. Results: The research team found 69 studies reporting the content validity of 40 instruments specifically developed for CVD. Fourteen (35.0%) were rated "sufficient" with very low to moderate quality of evidence. For PRO development, all instruments were rated "doubtful" or "inadequate." Twenty-eight (70.0%) instruments cover the core concepts of HRQoL. Conclusions: The quality of development and content validity vary among existing CVD-specific instruments. The evidence on the content validity should be considered when choosing HRQoL instrument in CVD clinical studies and health economic evaluations.

Objectives: China Health -Related Outcomes Measures (CHROME) was an initiative aimed at developing a system of preference -based health -related quality of life instruments for China. CHROME -cardiovascular disease (CVD) is a CVD-specific instrument with 14 items developed under this initiative. This study aimed to test the psychometric properties of CHROME-CVD. Methods: This validation study was conducted using cross-sectional questionnaire survey in China. Eligible patients with CVD were recruited and asked to complete the CHROME-CVD, the EQ-5D-5L, and a CVD-specific nonpreference-based healthrelated quality of life instrument selected according to the confirmed diagnosis of the patients. Item evaluation, internal consistency, measurement invariance, test -retest reliability, structural validity, and construct validity were tested using classic test theory. Item response theory was used to evaluate item -level performance. Results: A total of 444 patients with CVD (coronary artery disease, n = 276, heart failure, n = 104, angina, n = 33, and atrial fibrillation, n =16) from 6 provinces in China were enrolled for the validation. Exploratory factor analysis identified 4 factors: chest pain, other symptoms, physical health, and mental and social health. Cronbach 's alpha and intraclass correlation coefficient were .0.8. A total of 20 of 26 (76.9%), and 90 of 95 (94.7%) predefined hypotheses were met for convergent and discriminant validities, respectively. No important difference was identified between subgroups of gender and residency. Response options of 10 items were found overlapped based on categorical response curves, which led to modification to 4 -level response options. Wording of 3 items were modified by referring wordings of reference instruments. Conclusion: The validation of the CHROME-CVD demonstrated generally good psychometric properties. Further validation on the modified CHROME-CVD is needed.

This is the protocol for a Campbell systematic review. The objectives are as follows. The objectives of the present study are to answer the following questions: (1) What types of home-based interventions are currently being studied to prevent child neglect? (2) How effective are the different home-based interventions for preventing child neglect? (3) What are the causes of heterogeneity among included studies and their impact on study effects?

Background: Disturbances in immunological responses and modulation lead to implantation and pregnancy failure and might be involved in the pathogenesis of infertility. This project aimed to screen and identify immune-related genes as potential biomarkers for treatment.Methods: Gene expression profiles were obtained from Gene Expression Omnibus (GEO) databases. Differentially expressed genes (DEGs) were screened using GEO 2R to explore potential biomarkers. Protein-protein interaction (PPI) network analysis and functional enrichment analysis were applied to explore possible mechanisms. The deconvolution algorithm [referred to as Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT)] was employed to assess tissue-infiltrating immune cells. Western blot analysis and immunohistochemistry (IHC) were conducted for determination of protein levels.Results: In this research, we identified 24 candidate immune-related DEGs via combined DEGs and functional analysis. We also found that the ratio of M0 macrophages and resting mast cells was higher in infertile group (P<0.05), whereas the amounts of activated natural killer (NK) cells was significantly lower compared with the control group (P<0.05). Furthermore, we evaluated the relationship between immune cells and candidate genes and found that 17 genes were related to M0 macrophages, resting mast cells, or activated NK cells. The genes CD40, PRF1, and EDN3 were chosen based on validation from independent datasets. Finally, our clinical samples confirmed the expression of the 3 genes.Conclusions: The study recognized 3 genes that are signatures and could be potential biomarkers for unexplained infertility. These genes might guide the immunotherapy of these patients and become new treatment targets.

Background: The potential effectiveness of traditional Chinese medicine (TCM) against "epidemic diseases " has highlighted the knowledge gaps associated with TCM in COVID-19 management. This study aimed to map the matrix for rigorously assessing, organizing, and presenting evidence relevant to TCM in COVID-19 management.Methods: In this study, we used the methodology of evidence mapping (EM). Nine electronic databases, the WHO International Clinical Trials Registry Platform (ICTRP) Search Portal, , gray literature, reference lists of articles, and relevant Chinese conference proceedings, were searched for articles published until 23 March 2022. The EndNote X9, Rayyan, EPPI, and R software were used for data entry and management.Results: In all, 126 studies, including 76 randomized controlled trials (RCTs) and 50 systematic reviews (SRs), met our inclusion criteria. Of these, only nine studies (7.14%) were designated as high quality: four RCTs were assessed as "low risk of bias " and five SRs as "high quality. " Based on the research objectives of these studies, the included studies were classified into treatment (53 RCTs and 50 SRs, 81.75%), rehabilitation (20 RCTs, 15.87%), and prevention (3 RCTs, 2.38%) groups. A total of 76 RCTs included 59 intervention categories and 57 efficacy outcomes. All relevant trials consistently demonstrated that TCM significantly improved 22 outcomes (i.e., consistent positive outcomes) without significantly affecting four (i.e., consistent negative outcomes). Further, 50 SRs included nine intervention categories and 27 efficacy outcomes, two of which reported consistent positive outcomes and two reported consistent negative outcomes. Moreover, 45 RCTs and 38 SRs investigated adverse events; 39 RCTs and 30 SRs showed no serious adverse events or significant differences between groups.Conclusion: This study provides evidence matrix mapping of TCM against COVID-19, demonstrating the potential efficacy and safety of TCM in the treatment and prevention of COVID-19 and rehabilitation of COVID-19 patients, and also addresses evidence gaps. Given the limited number and poor quality of available studies and potential concerns regarding the applicability of the current clinical evaluation standards to TCM, the effect of specific interventions on individual outcomes needs further evaluation.

AimsWe aimed to determine the effects of different exercise modalities in patients with type 2 diabetes mellitus (T2DM). MethodsWe searched PubMed, Embase, and the Cochrane Library from their inception until July 2020 to identify randomised controlled trials (RCTs) on exercise in adults with T2DM. Paired reviewers independently performed study selection, data extraction, and risk of bias assessment. The certainty of the evidence was assessed using the Confidence in Network Meta-Analysis (CINeMA) framework. ResultsA total of 106 RCTs that enroled eight exercise modalities with 7438 patients were included. Six exercise modalities, except unsupervised aerobic/resistance exercise, significantly reduced glycosylated haemoglobin (HbA1c), with mean differences (MDs) ranging from 0.71 (95% confidence interval [CI]: 0.34-1.08) to 0.34 (95% CI: 0.17-0.52), low to high certainty, in comparison with no exercise. The evidence of low to moderate certainty showed that supervised aerobic/resistance exercise improved glycaemic control, body weight, blood pressure, and blood lipid profiles compared with no exercise. Flexibility exercise may be associated with glycaemic control (HbA1c: MD = 0.71, 95% CI: 0.34-1.08); fasting plasma glucose (MD = 1.48, 95% CI: 0.78-2.17), and weight loss (MD = 1.80, 95% CI: 0.85-2.75) compared with controls, but not blood pressure and lipid profiles. Balance exercise showed the largest benefit in improving total cholesterol (MD = 52.81, 95% CI: 28.47-77.16) and low certainty. We found no significant differences between exercises and the triacylglycerol (TG) level. ConclusionsOverall, our network meta-analyses support the recommendation for exercise in patients with T2DM, especially supervised exercises. Limited evidence supports the benefits of flexibility and balance exercises. The effectiveness of exercise modalities for TG reduction remains unclear.

The abstract should read: This is the protocol for a Campbell systematic review. The objectives are as follows: (1) Which formal HBC services for people with dementia have been tested in an RCT? (2) How effective are the different formal HBC services in improving the physical and mental health outcomes of people with dementia? (3) What is the cost and patient's health service usage of different formal HBC services?

Objectives: This study aimed to conduct a systematic review of cost-utility studies of internet-based and face-to-face cognitive behavioral therapy (CBT) for depression from childhood to adulthood and to examine their reporting and methodological quality. Methods: A structured search for cost-utility studies concerning CBT for depression was performed in 7 comprehensive databases from their inception to July 2020. Two reviewers independently screened the literature, abstracted data, and assessed quality using the Consolidated Health Economic Evaluation Reporting Standards and Quality of Health Economic Studies checklists. The primary outcome was the incremental cost-effectiveness ratio (ICER) across all studies. To make a relevant comparison of the ICERs across the identified studies, cost data were inflated to the year 2020 and converted into US dollars. Results: Thirty-eight studies were included in this review, of which 26 studies (68%) were deemed of high methodological quality and 12 studies (32%) of fair quality. Despite differences in study designs and settings, the conclusions of most included studies for adult depression were general agreement; they showed that face-to-face CBT monotherapy or combination therapy compared with antidepressants and usual care for adult depression were cost-effective from the societal, health system, or payer perspective (ICER $241 212.4/quality-adjusted life-year [QALY] to $33 032.47/QALY, time horizon 12-60 months). Internet-based CBT regardless of guided or unguided also has a significant cost-effectiveness advantage (ICER $37 717.52/QALY to $73 841.34/QALY, time horizon 3-36 months). In addition, CBT was cost-effective in preventing depression (ICER $23 932.07/QALY to $26 092.02/QALY, time horizon 9-60 months). Nevertheless, the evidence for the cost-effectiveness of CBT for children and adolescents was still ambiguous. Conclusions: Fair or high-quality evidence showed that CBT monotherapy or combination therapy for adult depression was cost-effective; whether CBT-related therapy was cost-effective for children and adolescents depression remains inconclusive.

For patients with recurrent implantation failure (RIF), immune system imbalances have become the focus of research. The effects of different classes of immunotherapies on improving pregnancy outcomes have not been fully established. This network meta-analysis was performed to assess the impact of popular immunotherapies in women with RIF. We systematically searched the Cochrane Central Register of Controlled Trials, PubMed, Embase, and Web of Science databases as well as clinical trial registration websites. Randomized controlled trials comparing immunotherapeutic outcomes were included. We performed the random-effects network metaanalysis to compare efficacy measures. A total of 21 trials involving 2277 participants and 8 immunotherapies were eligible for this study. Patients that had been administered with PBMCs, G-CSF, PRP, and sirolimus exhibited higher CPR than those administered with the placebo (2.63, 1.71-4.06; 2.03, 1.35-3.05; 1.98, 1.02-3.84; 2.55, 1.36-4.79; and 3.95, 1.33-11.72, respectively). For IR, only PBMCs and G-CSF were significantly more effective than the placebo (2.92, 1.39-6.12; 2.66, 1.16-6.06, respectively). In terms of LBR, PBMCs (2.96, 1.67-5.27) and sirolimus (3.55, 1.18-10.64) were effective. However, r-hLIF (0.25, 0.10-0.62) had a reduced risk of LBR. No therapeutic regimen was found to have significantly decreased MR, but PBMCs exhibited the lowest rank among all interventions (0.28, 0.06-1.44). To improve clinical pregnancy while reducing miscarriage outcomes, PBMCs might be a beneficent therapeutic option for RIF in the future.

Objectives: To assess the reporting and methodological quality of COVID-19 systematic reviews, and to analyze trends and gaps in the quality, clinical topics, author countries, and populations of the reviews using an evidence mapping approach. Study Design and Setting: A structured search for systematic reviews concerning COVID-19 was performed using PubMed, Embase, Cochrane Library, Campbell Library, Web of Science, CBM, WanFang Data, CNKI, and CQVIP from inception until June 2020. The quality of each review was assessed using the Assessment of Multiple Systematic Reviews 2 (AMSTAR 2) checklist and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Results: In total, 243 systematic reviews met the inclusion criteria, over 50% of which (128, 52.7%) were from 14 developing countries, with China contributing the most reviews (76, 31.3%). In terms of methodological quality of the studies, 30 (12.3%) were of moderate quality, 63 (25.9%) were of low quality, and 150 (61.7%) were of critically low quality. In terms of reporting quality, the median (interquartile range) PRISMA score was 14 (10-18). Regarding the topics of the reviews, 24 (9.9%) focused on the prevalence of COVID-19, 69 (28.4%) focused on the clinical manifestations, 30 (12.3%) focused on etiology, 43 (17.7%) focused on diagnosis, 65 (26.7%) focused on treatment, 104 (42.8%) focused on prognosis, and 25 (10.3%) focused on prevention. These studies mainly focused on general patients with COVID-19 (161, 66.3%), followed by children (22, 9.1%) and pregnant patients (18, 7.4%). Conclusion: This study systematically evaluated the methodological and reporting quality of systematic reviews of COVID-19, summarizing and analyzing trends in their clinical topics, author countries, and study populations. (c) 2021 Elsevier Inc. All rights reserved.

Purpose: This study aimed to review the association between antidepressive agent (AD) use and the incidence risk of breast cancer. Methods: CBM, WOS, Embase, PubMed and Cochrane Library were systematically searched in July 2019. The methodological quality of the studies was assessed through the Newcastle–Ottawa Scale. Results: We included 19 studies from six countries or regions with relationships between breast cancer and ADs. Subgroup analysis showed no significant association in nested case–control or case–control studies; however, cohort studies revealed a significant association (odds ratio = 1.11; 95% CI: 1.04–1.17). Conclusions: This meta-analysis indicates that breast cancer was not associated with the use of ADs when considering all types of studies, but an association was observed if we considered cohort studies.

Hepatocellular carcinoma (HCC) is a malignant primary liver cancer with poor prognosis. Most previous studies on anti-HCC effects of traditional Chinese medicines (TCM) have focused on the mechanism of direct action and few researchers considered that TCM can inhibit tumor progression and improve prognosis of HCC patients through regulating tumor microenvironment (TME). In this study, network pharmacology combined bioinformatics methods were employed to analysis mechanism of Bombyx batryticatus (B. batryticatus, one of the most frequently used traditional Chinese animal medicines, has been used in some Asian countries for centuries as an anticancer agent, anti-inflammatory agent, and antioxidant.) in regulating TME of HCC. The results showed that 24 core targets and 2 compounds were identified from overlapping between differential expression genes related to HCC in the cancer genome atlas (TCGA) database and targets of B. batryticatus in TCMSP database. For further analyzing the role of TME heterogeneity of HCC on anti-HCC mechanism of B. batryticatus, the correlation of core targets related with overall survival of HCC with TME cells in hepatitis C or hepatitis B virus-associated hepatocellular carcinoma (VIR) and non-hepatitis C or hepatitis B virus-associated hepatocellular carcinoma (NVIR) were calculated, respectively. The results showed that AKR1C3, SPP1 were significantly related with macrophages in VIR and other targets including NR1I2, CYP1A2 and CYP3A4 were significantly associated with macrophages in NVIR; the target protein AKR1C3 was significantly negative correlated with macrophages M1 in VIR (cor=-0.35, P-value0.05). In conclusion, the molecular mechanism of anti-HCC of B. batryticatus can be related to the tumor microenvironment to some extent. B. batryticatus may exert its anti-cancer effects and improve prognosis of patients by regulating macrophages M1 in VIR and NVIR through acting on different targets.

Aims We aim to systematically review the existing guidelines on physical activity for T2DM and assess the consistency of their recommendations, methodological quality, and reporting quality. Methods We performed a literature search on PubMed, China Biology Medicine disc, and four main guideline databases in order to identify existing T2DM guidelines. We then evaluated the methodological and reporting qualities of the guidelines using the AGREE II instrument and the RIGHT checklist. Fifteen guidelines were included in total, with eight of these (53.33%) assessed being "recommended" and five graded as having good reporting quality. Result A total of 30 physical activity recommendations were extracted. Fifteen recommendations reported the levels of evidence, and of these, five were found to be based on a high quality of evidence. Aerobic exercise at least 3 days per week was recommended by most guidelines (10/15, 66.67%). Eight guidelines (53.33%) recommended resistance exercise, while combined aerobic and resistance exercise was recommended in three of the guidelines (20.0%). Only two guidelines recommended supervised exercise, and one recommended flexibility exercise. Four of the guidelines (26.67%) solely recommended physical activity or exercise, but with no added details. Conclusions The quality of the guidelines concerning physical activity for T2DM was found to be moderate to low and varied substantially. Recommendations regarding physical activity for T2DM are not very specific or clear and remain incompletely consistent, while the level of evidence and the strength of the recommendations were seldom reported. Our findings suggest a need for guidelines for diabetes based on high levels of evidence.

Background: Artificial intelligence (AI) has been extensively used in a range of medical fields to promote therapeutic development. The development of diverse AI techniques has also contributed to early detections, disease diagnoses, and referral management. However, concerns about the value of advanced AI in disease diagnosis have been raised by health care professionals, medical service providers, and health policy decision makers. Objective: This review aimed to systematically examine the literature, in particular, focusing on the performance comparison between advanced AI and human clinicians to provide an up-to-date summary regarding the extent of the application of AI to disease diagnoses. By doing so, this review discussed the relationship between the current advanced AI development and clinicians with respect to disease diagnosis and thus therapeutic development in the long run. Methods: We systematically searched articles published between January 2000 and March 2019 following the Preferred Reporting Items for Systematic reviews and Meta-Analysis in the following databases: Scopus, PubMed, CINAHL, Web of Science, and the Cochrane Library. According to the preset inclusion and exclusion criteria, only articles comparing the medical performance between advanced AI and human experts were considered. Results: A total of 9 articles were identified. A convolutional neural network was the commonly applied advanced AI technology. Owing to the variation in medical fields, there is a distinction between individual studies in terms of classification, labeling, training process, dataset size, and algorithm validation of AI. Performance indices reported in articles included diagnostic accuracy, weighted errors, false-positive rate, sensitivity, specificity, and the area under the receiver operating characteristic curve. The results showed that the performance of AI was at par with that of clinicians and exceeded that of clinicians with less experience. Conclusions: Current AI development has a diagnostic performance that is comparable with medical experts, especially in image recognition-related fields. Further studies can be extended to other types of medical imaging such as magnetic resonance imaging and other medical practices unrelated to images. With the continued development of AI-assisted technologies, the clinical implications underpinned by clinicians' experience and guided by patient-centered health care principle should be constantly considered in future AI-related and other technology-based medical research.

The study aims to evaluate the effectiveness of different durations of aerobic exercise on hypertensive patients. Four electronic databases (PubMed, Embase, Cochrane Library, and Web of Science) were searched from their inception until July 2018. English publications and randomized controlled trials involving aerobic exercise treatment for hypertensive population were included. Two reviewers independently extracted the data. The Cochrane's Risk of Bias tool was used to assess the quality of included studies. In this systematic review, a total of 14 articles were included, involving 860 participants. The quality of the included studies ranged from moderate to high. The results of the meta-analysis showed that compared with the control group, significant effects of aerobic exercise were observed on reducing systolic blood pressure (SBP) (mean difference [MD] = -12.26 mm Hg, 95% confidence interval [CI] = -15.17 to -9.34, P < 0.05), diastolic blood pressure (DBP; MD = -6.12 mm Hg, 95% CI = -7.76 to -4.48, P < 0.05), and heart rate (MD = -4.96 bpm, 95% CI = -6.46 to -3.43, P < 0.05). In addition, significant reductions were observed in ambulatory DBP (MD = -4.90 mm Hg, 95% CI = -8.55 to -1.25, P < 0.05) and ambulatory SBP (MD = -8.77mm Hg, 95% CI = -13.97 to -3.57, P < 0.05). Therefore, aerobic exercise might be an effective treatment for blood pressure improvement in hypertensive patients. However, the effectiveness between the duration of different treatment needs to be well-designed and rigorous studies will be required to verify the dataset.