The dietary nutritional status of pregnant women is critical for maintaining the health of both mothers and infants. Food exchange systems have been employed in the nutritional guidance of patients in China, although their application in the dietary guidance of healthy pregnant women is quite limited. This study aimed to develop a novel food exchange system for Chinese pregnant women (NFES-CPW) and evaluate the relative validation of its application.NFES-CPW covers approximately 500 types of food from ten categories and has more elaborate food portion sizes. It established a recommendation index for guiding food selection and used energy, water content, and protein as the exchange basis to balance the supply of energy and important nutrients throughout pregnancy. Furthermore, dietitians used the NFES-CPW and traditional food exchange system to generate new recipes based on the sample recipe. There were 40 derived recipes for each of the two food exchange methods. The food consumption, energy, and key nutrients of each recipe were calculated, and the differences between the two food exchange systems were compared using the Wilcoxon rank sum test or the Chi-square test.P < 0.05), which were more conducive to reaching the recommended range of balanced dietary pagoda. After calculating energy and nutrients, although these two food exchange systems have similar effects on the dietary energy and macronutrient intake of pregnant women, the intake of micronutrients in NFES-CPW derived recipes was significantly higher than that from the traditional food exchange system, which was more conducive to meeting the dietary requirements of pregnant women. The outstanding improvement are primarily vitamin A, vitamin B2, folic acid, vitamin B12, vitamin C, calcium, iron, and iodine (P < 0.05). Moreover, when compared to recipes obtained from the traditional food exchange system, the error ranges of energy and most nutrients were significantly reduced after employing the NFES-CPW.The results revealed that compared to those derived from traditional food exchange system, the NFES-CPW derived recipes had a better dietary structure, as evidenced by the intakes of whole-grain cereals, beans excluding soybeans, potatoes, fruits, fish, shrimp and shellfish, as well as eggs (Therefore, NFES-CPW is an appropriate tool that adheres to Chinese dietary characteristics and can provide suitable dietary guidance to pregnant women.The online version contains supplementary material available at 10.1186/s12937-023-00902-4. The maternal dietary nutrition status throughout pregnancy has long-term consequences on maternal and offspring health . MaternaThe food exchange system is one of the most commonly utilized dietary guidance methods, and its first edition was published in America in 1950 . Up to kThe traditional food exchange systems, which are mainly adopted in China, were designed for the diet management of patients rather than healthy people, considering energy the only basis for food exchange . It is c1 (VB1), vitamin B2 (VB2), vitamin B12 (VB12), and folic acid [The body needs more energy and nutrients during pregnancy . Currentlic acid . Therefolic acid .This study aimed to design a novel food exchange system for Chinese pregnant women (NFES-CPW) based on Chinese traditional dishes, which covered food types from all categories and had elaborate portion sizes and nutrients crucial for pregnant women. Moreover, we investigated the relative validity of the NFES-CPW by comparing the NFES-CPW to the traditional food exchange system when used to generate recipes.China Food Composition Table  [2016 Chinese Balanced Dietary Pagoda for pregnant women [As shown in Table n Table  ” and “20To provide effective guidance to non-professionals and encourage users to select food items with rich nutrition density, the recommendation index was set at 0 − 5 from the perspective of nutrition professionals . A recom2016 Chinese Balanced Dietary Pagoda for pregnant women [2013 Chinese Dietary Reference Intakes (DRIs) [The growth and development of the fetus are relatively slow in the first trimester, and the nutrition required is not significantly different from that before pregnancy. However, beginning in the second trimester, the changes in the fetus and the mother accelerate, and the nutritional needs rise. Therefore, combined with the article’s length limitation, evaluation of the relative validity is limited to the second trimester of pregnancy in this study. A sample one-day recipe for women in their second trimester of pregnancy was developed by us based on the recommended food intake in the “s (DRIs) ”. The foE-mail invitations were sent to the dietitians from the Nutrition Department of a third-level first-class hospital. They were required to have a bachelor’s degree or higher in their major, have worked in dietary management in the Nutrition Department of the hospital for > 3 years, and have clinician or dietitian qualifications. Finally, ten dietitians were recruited, and detailed documents containing recipe samples and NFES-CPW were delivered. In the second trimester of pregnancy, each dietitian was instructed to use the NFES-CPW and traditional food exchange system to derive four new recipes from the sample recipes. There was a standard of creating the recipes and all dietitians received technical training. Traditional food exchange system relies on energy as the basis for food exchange. When using NFES-CPW, the new recipes were created according to the nutritional characteristics of each food category, and the exchange bases are detailed in Table 2016 Chinese Balanced Dietary Pagoda for pregnant women [China Food Composition Table  [2013 Chinese DRIs [1, VB2, folic acid, VB12, vitamin C (VC), calcium, iron, zinc, and iodine. Adequate intake (AI) was used to evaluate insoluble dietary fiber. Furthermore, for carbohydrates and fats, the acceptable macronutrient distribution ranges (AMDR) were used as the lower and upper bounds for the percentage ratio of energy.In the derived recipes, the total daily consumption of each type of food was calculated. Following the calculation of the total daily intake of each food group, the proportion of recipes that meet the recommended intake of each food category is determined using the “n Table  ”. An excese DRIs ”. The enP < 0.05) and expressed in quartiles; median . Categorical variables were expressed as frequency (n) and percentage (%). The Wilcoxon rank sum test and the Chi-square (χ²) test were employed to compare the differences in food, energy, and nutrient intake of the new recipes derived from two exchange systems and those in the proportion of these intakes within the recommended range, respectively.After assessing the normality of the continuous variables, we observed that all continuous variables were non-normally distributed , the percentage of d (d%), the absolute difference (D), and the percentage of D (D%) were calculated:d = data in the derived recipe - data in the sample recipe;D = |data in the derived recipe - data in the sample recipe|;d% = (d/data in the sample recipe) ×100%;D% = (D/data in the sample recipe) ×100%.The Wilcoxon rank sum test was used to analyze the differences in d, d%, D, and D% determined among the new recipes derived from two food exchange systems.P < 0.05 was considered statistically significant. All statistical analyses of this study were performed using the Statistical Package for the Social Sciences version 26.0 .All statistical tests were two-sided, and As presented in Table A similar result was observed in the intake of livestock and poultry meat, fish, shrimp, shellfish, and eggs. The intake of this food category was considerably higher in the new recipes derived from the NFES-CPW than that in the traditional food exchange system. This increase was mainly reflected in an increase in the intake of fish, shrimp, shellfish, and eggs, which leads to a significantly higher proportion of these two food items in the recommended range than that obtained by the traditional food exchange system, with increases of 62.5% and 25%, respectively.There was no statistical difference in the intake of vegetables and milk and its products among the new recipes obtained from the two food exchange systems, and the intakes of vegetables (100%) and milk and its products (97.5%) in almost all recipes were within the recommended range. Based on their low total intake, the intakes of soybean and its products and nuts in the new recipes obtained from the two food exchange systems were not significantly different.The intake of fruit in the new recipes derived from the traditional food exchange system was at a high level, and the proportion of its intake in the recommended range was 51.5%. However, the intake of fruit in the derived recipes based on NFES-CPW decreased significantly, thus, increasing its proportion in the recommended range to 97.5%.P < 0.05). When compared with the relevant indicators in the “2013 Chinese DRIs [As presented in Table ese DRIs ”, it was1, VB2, folic acid, VB12, and VC) and minerals  were selected for further investigation based on the nutritional needs of women during pregnancy. As presented in Table 2013 Chinese DRIs [P ≤ 0.01). Meanwhile, the proportion of the recipes derived from NFES-CPW with the intakes of VA, VB2, folic acid, VB12, VC, calcium, iron, and iodine above the RNI value was higher than that derived from the traditional food exchange system (P < 0.05).Insoluble dietary fiber and representative vitamins , indicating that the intake of these nutrients in recipes derived from NFES-CPW was close to their quantities in the sample recipes. Compared with the recipes derived from the traditional food exchange system, after using the NFES-CPW, the error ranges of these nutrients were reduced by 5.3% (protein), 14% (insoluble dietary fiber), 28.3% (VA), 7.7% (VB1), 45% (folic acid), 40.1% (VB12), 18.8% (VC), 17.3% , 23.3% (iron), and 9.6% (iodine).The absolute value was further calculated, and it was observed that, except for carbohydrates and zinc, the median D-value of energy and nutrients in the recipes derived from NFES-CPW was lower than that derived from the traditional food exchange system. Significant differences were observed in protein, fat, insoluble dietary fiber, VA, VBA healthy and diverse diet remains the preferred means to address the nutritional requirements of pregnant women . The fooTo ensure adequate energy and nutrient intake by pregnant women, NFES-CPW determines the food exchange bases according to the nutritional characteristics of each food category and not just energy. Cereal and their products, potatoes, and beans excluding soybeans were the major sources of the total dietary energy supply , 26. AddThis study simulates the use of the NFES-CPW and traditional food exchange system by dietitians to derive new recipes based on the sample recipe, similar to the use of the food exchange system in real life. The results revealed that the recipes derived from NFES-CPW had better dietary structures compared with those derived from traditional food exchange system. It was primarily reflected in the fact that the proportion of whole-grain cereals, beans excluding soybeans, potatoes, fruits, fish, shrimp and shellfish, and egg intakes within the recommended range in the recipes derived from NFES-CPW were significantly higher than those derived from the traditional food exchange system. However, it is noteworthy that the proportion of nut intake within the recommended range in recipes derived from NFES-CPW was 42.5% less than that in recipes derived from the traditional food exchange system. Considering that nuts are rich in fat and energy, pregnant women should limit their intake . The recEnergy balance was one of the key factors for achieving optimal pregnancy outcomes. Studies have demonstrated that a balanced intake of energy and protein during pregnancy can significantly reduce the risk of stillbirth, small-for-gestational-age, and macrosomia and maintain normal birth weight , 35. NevIn this study, vitamins were further analyzed. Folic acid deficiency in the first trimester can cause stillbirth, abortion , and neuAdditionally, important minerals for pregnant women include calcium and iron. During the second and third trimesters, calcium is gradually deposited in the fetal bones and teeth, and approximately 30 g of calcium is deposited in the newborn . If calcChina Food Composition Table  [Our study does, however, have certain limitations. First, the nutritional data in the “n Table  ” were inNFES-CPW helps to meet the requirements of pregnant women for dietary structure, energy, and key nutrients. It is a simple and effective tool that conforms to Chinese dietary norms and may provide reasonable dietary guidance to pregnant women. We recommend that maternity nutrition clinics employ the NFE-CPW to create flexible meal programs to assist expectant mothers. Furthermore, the NFE-CPW can also be a useful tool for nutritionists to conduct nutritional education and for pregnant women to manage their own diet.Below is the link to the electronic supplementary material.Supplementary Material 1


To systematically evaluate the survival rate and postoperative adverse reactions of patients with hepatocellular carcinoma treated with traditional Chinese medicine combined with TACE by meta-analysis.Four major literature databases  were retrieved to collect published English articles since 2009. After determining the random effect model or fixed utility model based on a heterogeneity test, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.P < .05, I2 = 54.8%), Therefore, the random effect model is used to analyze the data, so as to explore the relationship between CMs combined with TACE treatment and survival rate and postoperative adverse reactions. All the comprehensive test results show that there is a statistical significance between CMs combined with TACE treatment and survival rate. . Then subgroup analysis and sensitivity analysis were carried out. The results indicated that the overall results ranged from 1.12(95% CI = 1.03–1.11) to 1.21(95% CI = 1.22–1.33).This meta-analysis included 8 prospective studies published between 2009 and 2019. Due to moderate heterogeneity (The 1-year survival rate of patients treated with traditional Chinese medicine TACE is a protective factor, and the quality score included in the study affects the evaluation of the effective dose. At the same time, traditional Chinese medicine combined with TACE has nothing to do with the reduction of postoperative complications. HCC is the sixth most common cancer in the world and the second leading cause of cancer death. It is one of the common malignant tumors in China, especially in the southeast coastal areas of China. According to cancer statistics in China, primary liver cancer is the third malignant tumor and the most common cause of death . The main cause of hepatocellular carcinoma is cirrhosis caused by hepatitis virus infection or alcoholism. Early hepatocellular carcinoma  can be treated by surgery. At this stage, patients with non-cirrhosis liver have a good prognosis, but most patients with advanced hepatocellular carcinoma (stage C and D) have lost the opportunity of surgery. These patients are usually treated with transcatheter arterial chemoembolization (TACE), targeted therapy, radiotherapy and liver transplantation. Like most patients with hepatocellular carcinoma, chemoembolization (TACE) is the most commonly used palliative treatment for patients with unresectable hepatocellular carcinoma, because it can improve the survival of patients.Hepatocellular carcinoma (HCC) is the main histological subtype of primary liver cancer, accounting for 70% to 85% of primary liver cancer in the world.–6There are still some risks and shortcomings in TACE, such as the risk of infection after embolization, the embolism staying in the wrong position and losing the blood supply of normal tissues, the contrast agent allergic reaction, kidney damage and the reaction to chemotherapy, which may include nausea, alopecia, leukopenia, thrombocytopenia and anemia.,7TACE is a minimally invasive operation in interventional radiology, which is used to limit the blood supply of tumor. It combines chemotherapy with embolization. Although this kind of surgery can rarely cure liver cancer, research shows that in 70% or more patients, the cancer shrinks and patients may live longer.–10Chinese medicines (CMs) are commonly used in the treatment of HCC, but its side effects are rarely reported. More and more studies have been done to evaluate the influence of CMS on HCC. Studies have confirmed that the chemoprevention and anti-hepatoma properties of CMS are mainly realized by inducing apoptosis and autophagy of cancer cells and cytotoxicity to cancer cells.By searching 4 major literature databases , the open published clinical trials compared the clinical efficacy of Chinese herbal medicine plus TACE versus TACE only in patients with advanced hepatocellular carcinoma were collected.The searching strategy was performed using “hepatocellular carcinoma,” “liver carcinoma,” “hepatocellular carcinoma/cancer” AND “Medicine, Chinese Traditional,” as the Medical Subject Headings (MeSH) and corresponding free text word searching term. The title and abstract of initial identified articles were evaluated for appropriateness to the inclusion criteria. To prevent research from being missed, the references in the studies retrieved from the online databases and previously published systematic reviews were also manually searched to further identify relevant studies.The inclusion criteria of this meta-analysis were: published as an original article; belonged to clinical trial, Including prospective studies, not limited to randomized clinical trials, controlled clinical trial, prospective study; The intervention measures of the treatment group were Chinese medicine combined with TACE, and the control group was TACE alone; provided the number of participants; and The risk estimates were reported with corresponding 95% confidence intervals (95% CIs). Meanwhile, studies were excluded with one or more of the following criteria: review articles; animal trials; conference papers; data unavailable to be extracted; and The treatment group was treated with traditional Chinese medicine combined with other drugs; The control group received TACE combined with other drugs. Data collection was conducted using standardized forms developed by the research team. Data extraction included the following information: study characteristics, such as types, authors, year of publication, number of patients and sample size. An analysis of clinical indicators and data was conducted: case/participants; 1-year survival number; Intervention measures of treatment group; Child-Pugh classification; year; and age. The study quality assessment was performed following the Newcastle-Ottawa Scale. The scoring system assessed 3 aspects of a study: selections (representativeness of cohort and exposure assessment); comparability (confounding determination) and outcomes (assessment of the outcome and follow-up). The studies were rated based on selection, comparability, exposure, and outcome, and scored with a maximum of 6 points. There were 2 categories of papers: high-quality (study score ≥ 6) and low-quality (study score < 6).,14The full text of all articles included was reviewed. Data abstraction and full-text review were carried out independently by 2 authors, and discrepancies were corrected by the third. To remove duplicates, we imported the extracted study into the Endnote Software X9.0, followed by the screening of titles and abstracts by 2 authors. And the MOOSE  guidelines were followed.I2 index and Cochran’s Q tests were employed to quantify incoherence and heterogeneity between studies, respectively. I2 was evaluated as a measure of heterogeneity across studies, which was interpreted as not significant (0–40%), moderate heterogeneity (30–60%), substantial heterogeneity (50–90%), or large heterogeneity (75–100%). If no statistical heterogeneity existed in pooled studies , we adopted a fixed-effect model for Meta-analysis, otherwise, a random-effect model was applied . A sensitivity and subgroup analysis were performed to explore potential causes of heterogeneity. There were several confounding factors, including quality scores, Intervention measures, and study types. We assessed the sources of heterogeneity by analyzing the previously described factors in the subgroups. Meanwhile, analyses of sensitivity were conducted to evaluate the robustness of the main outcomes. Furthermore, Egger’s correlation tests regressed the publication bias, the P value at .05 was considered statistically significant, and the test results were attached to the paper.The meta-analyses were performed using Stata14.0. Since the indices collected in this study were dichotomous variables, the odds ratio (OR) was used as the effect size in the statistical analysis. The All analyses were based on previous published studies, thus no ethical approval and patient consent are required.–24 The process of literature retrieval was shown in Figure A total of 182 relevant studies were retrieved from the initial literature review. Duplicate articles were firstly removed among predefined databases based solely on titles. Additionally, to 67 duplicate articles, the remaining 115 studies were also screened by reviewing titles and abstracts. In addition, 66 studies based on animals, review articles, and case reports were also ruled out from this work. A comprehensive review of 49 studies was conducted. Twenty articles were excluded due to missing results of interest, 13 articles were ruled out because of inaccessible full texts, and 8 with data unavailable. Ultimately 8 articles were included for meta-analysis.A summary of the characteristics of the included studies were presented in Table As shown in Table I2 = 54.8%, and P = .03 < 0.05 in Q test, which indicates that there is slight to moderate heterogeneity among the papers in this study. Further investigation of Labbe diagram indicates that some papers may have strong heterogeneity, and the results are shown in the Figure Eight papers in this study have been tested for heterogeneity, According to the analysis in Figure Z = 3.64, P = .03 < .05).As shown in Figure This study further explored the correlation between the combination of traditional Chinese medicine and TACE and the survival rate of patients at 6 months, 2 years, 3 years, and the adverse reactions of patients after TACE alone. Due to mild heterogeneity between studies, a fixed effects model was used. It was found that there was no statistically significant correlation between the 6-month (7 studies), 2-year (8 studies), and 3-year survival rate (7 studies) of HCC patients treated with traditional Chinese medicine combined with TACE. At the same time, traditional Chinese medicine combined with TACE cannot relieve the fever, leukopenia, nausea, diarrhea, vomiting, fatigue, loss of appetite and stomach upset after TACE. The detailed results are shown in the following table.Potential sources of heterogeneity were investigated using a sensitivity analysis. Following the exclusion of one study, we analyzed the other studies. The results of the sensitivity analysis were shown in Figure P = .03, I2 =54.8%). Subgroup analyses were performed based on Intervention measures, quality score, study type, and year of publication . Conversely, data from the Mixed Chinese medicine treatment combined with TACE subgroup  exhibited opposite results. It is worth noting that, in subgroups of these 4 studies with a quality score of more than 6 , the combination therapy was associated with the prolongation of the 1-year survival rate of patients, which was considered as a protective factor.In subgroup stratified by Intervention measures, data from single medicine subgroup analysis suggested that single Chinese medicine combined with TACE is effective for 1-year survival rate  by Egger’s tests.To detect publication bias in the included studies, Egger tests were conducted and the findings were visualized as well Fig. . Data shAt present, there are many treatments for liver cancer, but due to the lack of effective early screening methods, 70% to 80% of patients are diagnosed at the middle and late stage, resulting in a 5-year overall survival rate of liver cancer of only 14.1%.,26Hepatocellular carcinoma is a multi-factor and multi-stage process, so it is difficult to find a specific drug. Therefore, the combination therapy is most likely to be a new strategy for the treatment of liver cancer in the future, which has reached a broad consensus in academic circles.Marelli et al reviewed the research on combined therapy strategies and found that TACE combined with percutaneous ablation, percutaneous ethanol injection or radiofrequency ablation can improve the survival rate.Primary HCC or HCC is the sixth most common malignant tumor in the world, with 626,000 cases and the third most common cause of cancer death .In this study, we comprehensively evaluated the effect of traditional Chinese medicine combined with TACE on the survival rate of primary liver cancer compared with TACE alone through meta-analysis, and found that from the current data, the combined treatment prolonged the 1-year survival rate of patients. . However, there was no significant difference in the 6-month, 2-year, and 3-year survival rates between this combination therapy and TACE alone. Similarly, the combination therapy did not improve the success rate of patients. Whether the combined treatment can alleviate the postoperative complications of patients, the research shows that there is no obvious difference in postoperative leukopenia, nausea, fever, diarrhea, vomiting, fatigue, loss of appetite and stomach upset , P = .303 > .05); And through sensitivity analysis, it is confirmed that there is no significant heterogeneity or deviation; In addition, the difference of short-term (adverse reaction after TACE) and long-term  effectiveness between traditional Chinese medicine combined with TACE and TACE alone was shown by forest diagram. It must be said that there are still some limitations in this study. First, the current meta-analysis fails to eliminate heterogeneity, whether in overall analysis or subgroup analysis. Second, it was found in this review that the components of CMs prescriptions vary significantly, which may be due to the differences in CMs diagnosis and personal experience in CMs. The third point is that it is currently uncertain whether this combination modality will cause new adverse reactions and/or increase the financial burden on patients because these issues have not been reported in the included literature. Finally, due to the relatively small sample size of some included articles, the statistical strength may be limited, and it is difficult to generalize the results.This analysis recruited 1013 participants. All relevant prospective studies (n = 8) were included in this study, and the risk of publication bias was low . These relationships need to be confirmed by more well-designed large-scale prospective studies and randomized clinical trials.TACE combined with traditional Chinese medicine is a protective factor for prolonging the 1-year survival rate of patients. Compared with mixed Chinese medicine decoction, single medicine is more meaningful for prolonging the survival rate of patients. Combination of TACE with traditional Chinese medicine cannot effectively relieve the postoperative adverse reactions of patients.We appreciate the guidance and support from YWQ on this study.Conceptualization: Chenxia Zhang.Data curation: Yue Shan.Methodology: Yue Shan.Software: Zehua Hong.Supervision: Yuanwang Qiu.Writing – original draft: Jianyuan Xu.Writing – review & editing: Jianyuan Xu.


Background: Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia type. Patients with AF are often administered anticoagulants to reduce the risk of ischemic stroke due to an irregular heartbeat. We evaluated the efficacy and safety of edoxaban versus warfarin in patients with nonvalvular AF by conducting an updated meta-analysis of real-world studies.Methods: In this comprehensive meta-analysis, we searched two databases, PubMed and EMBASE, and included retrospective cohort observational studies that compared edoxaban with warfarin in patients with nonvalvular AF from 1 January 2009, to 30 September 2023. The effectiveness and safety outcomes were ischemic stroke and major bleeding, respectively. In the final analysis, six retrospective observational studies involving 87,236 patients treated with warfarin and 40,933 patients treated with edoxaban were included. To analyze the data, we used a random-effects model to calculate the hazard ratio (HR).Results: Patients treated with edoxaban had a significantly lower risk of ischemic stroke  and major bleeding  than those treated with warfarin. The sensitivity analysis results for ischemic stroke and major bleeding were as follows: HR = 0.66; 95% CI = 0.61–0.70; p < 0.0001 and HR = 0.58; 95% CI = 0.49–0.69; p < 0.0001, respectively.Conclusion: Our findings revealed that edoxaban performed better than warfarin against major bleeding and ischemic stroke. The prevalence of atrial fibrillation (AF) is expected to rise globally in the coming years, with over 12 million cases expected among the population in the United States (US) and Europe by 2030 . In the The ENGAGE AF-TIMI 48 trial showed that both once-daily regimens of edoxaban (60 and 30 mg) were non-inferior to warfarin with respect to the prevention of stroke or systemic embolism and were associated with significantly lower rates of bleeding and death from cardiovascular causes . In a syAnother meta-analysis of real-world studies found that the risk of thromboembolism or stroke associated with apixaban was similar to that associated with dabigatran, rivaroxaban, and edoxaban. The authors also found that apixaban was safer than warfarin in terms of the risk of major bleeding . DabigatIn this study, the systematic review was utilized in accordance with the Preferred Reporting Items for Systematic Review and Meta- Analysis (PRISMA) guidelines . We perfThe study included only retrospective observational cohort studies that compared edoxaban and warfarin in patients diagnosed with NVAF. Randomized clinical trials, reviews, abstracts, editorials, case reports, case series, prospective studies, non-human studies, and cost analyses were excluded. Study outcomes included effectiveness (ischemic stroke) and safety (major bleeding).Two authors independently extracted the articles and any differences between them were addressed by a third author. Data were extracted from included studies. The collected data included the names of the authors of the studies, the year of publication, the locations of these studies, and the sample size of each study .The collected data also included the hazard ratios (HR) and 95% confidence intervals (CI) of edoxaban and warfarin, which were associated with each outcome of effectiveness (ischemic stroke) and safety (major bleeding). The Newcastle-Ottawa scale (NOS) was used to assess the quality of the studies  Table 2Table 2. 2 test was used to evaluate the heterogeneity of the outcomes. A random-effects model was used to calculate the HR in our study. For each outcome, publication bias was measured statistically using the 2-tailed p-value results of Egger’s and Begg’s tests. A sensitivity analysis of excluding one trial at time has been conducted. Further sensitivity analysis was conducted based on the countries (Korea vs other countries) and the study quality (Low vs High). Data were analyzed using the Comprehensive Meta-Analysis Program .The HR and 95% CI were pooled from each study. The IIn our meta-analysis, we identified 774 studies which were retrieved from PubMed and EMBSE. We excluded 424 studies because they were not observational and 350 studies because they did not include the required information. Six retrospective observational studies were included in the final analysis . All incFour studies were conducted in Korea, one in Japan, and one in Taiwan. In all studies, 87, 236 patients received warfarin, and 40,933 patients received edoxaban . The effp < .0001), as shown in 2 was 0% in the analysis, indicating that there was no heterogeneity between the studies.The analysis of the random effects model showed that patients receiving edoxaban had a significantly lower risk of ischemic stroke (IS) compared to warfarin , as presented in 2 is 81.79% in the analysis, which means there is heterogeneity between the studies.Analysis of the random-effects model demonstrated that patients receiving edoxaban had a significant reduction in major bleeding risk compared to those receiving warfarin  and HR = 0.58; 95% CI, 0.49, and 0.69 (P.0001), respectively, as shown in p values for Egger’s and Begg’s tests were >0.05, showing no significant evidence of publication bias for either outcome (ischemic stroke or major bleeding).The 2-tailed versus warfarin by analyzing six real-world studies. We found that edoxaban performed better than warfarin in terms of major bleeding and ischemic stroke, as revealed by the sensitivity analysis.In this updated comprehensive meta-analysis, we evaluated the risk of major bleeding and ischemic stroke in patients with NVAF treated with edoxaban According to a randomized controlled trial, in terms of avoiding strokes, edoxaban has a similar effect as warfarin and considerably decreases the risk of major bleeding and cardiovascular death . MoreoveBai et al. compared the factor Xa inhibitors rivaroxaban and dabigatran with warfarin. In their meta-analysis, the risk of ischemic stroke was lower in the rivaroxaban group than in the warfarin group, which is consistent with the findings of our study, as rivaroxaban and edoxaban belong to the same drug category . HoweverA meta-analysis of RCTs comparing edoxaban with warfarin found a lower risk of major bleeding in edoxaban users than in warfarin users , which iOur study has several strengths. First, since our study was an inclusive, updated, and comprehensive meta-analysis, the total number of patients in all the included studies was 128,169, which is higher than that in other published meta-analyses , thus prIn summary, our updated comprehensive meta-analysis revealed that edoxaban effectively lowered the risk of major bleeding and ischemic stroke in patients with NVAF more effectively than warfarin. Therefore, healthcare professionals should weigh the benefits to their patients in terms of safety and efficacy when deciding between these two medications.


Major trauma is one of the major health care problems facing modern society, trauma systems require careful planning to achieve an ideal level of coverage for the population. The Patient Blood Management Program is an integrated and global strategy to provide patient care that aims to assess and address, when possible, the etiology of blood abnormalities rather than transfuse without treating the underlying cause. We aimed to describe the factors that are associated with the clinical decision to transfuse polytraumatized patients admitted to the Intensive Care Unit (ICU).We performed a cross sectional multicenter study of patients admitted to ICUs for trauma in 14 Spanish hospitals from September 2020 to December 2021.A total of 69 patients were treated in the emergency room due to polytrauma, 46% of them were considered serious in the initial triage. Thirty were caused by a fall from considerable height (43.47%), followed by 39 patients admitted due to trac accidents (56.52%). The location of the trauma was mainly cranioencephalic, followed by thoracic trauma. Of the 69 patients, 25 received a blood transfusion during their ICU stay (36.23%).p = 0.005. In this sense, 92.00% of the transfusions performed were inadequate according to the criteria of Hb in blood prior to the decision to transfuse (Hb < 9). Our data support the need to consider clinical practice guidelines regarding blood transfusion and its practices.No significant differences were observed between transfused and non-transfused patients, except for the severity scales, where transfused patients have a higher score on all the scales assessed in the ICU except for the Revised Trauma Score. As we can see, the incidence of kidney failure was also different between the groups analyzed, reaching 44.00% in transfused patients and 13.64% in the group of patients without blood transfusion,  Major trauma is one of the major health care problems facing modern society, trauma systems require careful planning to achieve an ideal level of coverage for the population . Blood mBlood transfusion is one of the most commonly overused therapeutic interventions in the United States and the rest of the world. World Health Organization (WHO) strongly recommends the implementation of Patient Blood Management (PBM programs), whose main objective to promote adequate transfusion use, in concordance with the recent nationwide intermittent blood shortage, makes PBM more important than ever , 6. To rPBM programs seek a multidisciplinary approach based on the care of patients who need a blood transfusion and to guarantee, at all times, the supply of blood and blood components when needed. Currently, this is a patient-centered approach that addresses such crucial issues as iron deficiency, anemia, coagulopathies, and blood loss, both in surgical and non-surgical patients. Anemia and iron deficiency are recognized as a serious problem global health problems that influence the quality of life . HoweverRestrictive transfusion practice is a key element of PBM, which advocates the principle of administering red blood cell (RBC) transfusions only when the benefits are considered to outweigh the risks, as well as to minimize the use of RBC units . MortaliThis was a cross sectional, prospective and multicenter study of patients admitted to intensive care units (ICUs) for trauma in 14 Spanish hospitals from September 2020 to December 2021. We include all the patients with a diagnosis of trauma admitted into the ICU. Due to movement restrictions imposed by the COVID-19 outbreak, admissions for trauma during the outbreak period were not excessive due to the restrictions traffic established by the government of Spain.The following information was collected through electronic medical records. Epidemiological variables: Age, sex, date of trauma and admission to the ICU, antiplatelet or anticoagulant drugs, and previous comorbidities were registered. We also used the registration of traumatic injuries according to the Abbreviated Injury Scale (AIS)  and the A secondary analysis is done in which the data collection was carried out through the creation of an electronic data collection notebook. The information was treated confidentially and anonymously, since it was dissociated data, following the Regulation of Data Protection (EU) 2016/679 of the European Parliament and the Spanish Law. The study design was approved by the Ethics Committee of La Paz (PI 4155).The convenience sampling was carried out in ICUs located in Madrid (La Paz), Cantabria , Asturias , the Basque Country , Aragón , La Rioja (San Pedro) Balearic Islands  Canary Islands  Murcia  Andalusia  Castille and Leon  Castille-La Mancha  and Catalonia (Germans Trias i Pujol). All patients who met the following inclusion criteria were selected for the study: those over 16 years old who had been admitted to the ICU with a diagnosis of trauma.via their frequency distributions and percentages. To analyze the differences between the categorical variables of the two groups, a chi-square test was used, or Fisher's exact test if the hypotheses of applicability of the former were not met. If the variables were quantitative, we used Student's t-test or the Mann–Whitney U-test according to the normality criteria. Statistical analysis was performed with the STATA/SE v.21.0 program , with any value of p < 0.05 being considered statistically significant.Quantitative variables are described using the mean and standard deviation or median and interquartile range according to the type of distribution. The normality of the distribution was analyzed using the Shapiro–Wilks test. Categorical variables are expressed A total of 69 patients were classified in the emergency room due to polytrauma, 46% of them were considered serious in the initial triage. Thirty caused by fall from considerable height (43.47%), followed by 39 patients admitted due to traffic accidents (56.52%). The location of the trauma was mainly cranioencephalic, followed by thoracic trauma Of the 69 patients, 25 of them received a blood transfusion during their ICU stay (36.23%).p = 0.539).p = 0.026). The incidence of kidney failure was also different between the groups analyzed, reaching 44.00% in transfused patients and 13.64% in the group of patients without blood transfusion, p = 0.005  in the transfused group had orotracheal intubation compared to 19 patients (44.19%) in the non-transfused group, the difference being statistically significant  compared to 38.60 (33.00–42.90) in non-transfused patients, p = 0.025. Significant differences were also found in fibrinogen, with smaller values in the group of patients who received blood transfusion (p = 0.009), pH where the transfused patients had slightly lower values, although statistically significant (p = 0.015), and the value of Glucose we highlight as significative as well (p = 0.005).The values of the biochemical markers in both groups were not very different, as we can see in the following . It shouFactors associated with transfusion practice (adequate vs. inadequate transfusion).The 25 patients who received a blood transfusion were classified into two groups, according to whether or not it was appropriate according guidelines. In this sense, 92.00% of the transfusions performed were inadequate according to the criteria of Hb in the blood before the decision to transfuse (Hb < 9) . There wRegarding comorbidities, significant differences were found in COPD and kidney failure, basically present in patients with adequate transfusion, as we can see in The differences observed in the analytical indices before the transfusion are notable. The patients who underwent an adequate transfusion showed values of Hemoglobin, Hematocrit, and platelet that are significantly lower than patients with inadequate transfusion, and values of leukocytes, urea, and GPT that are significantly higher.Regarding Effect of the transfusion (adequate vs. inadequate) on the patient's analytical values no differences were found in the hemoglobin values in any of the groups; however, we can see in the following table how patients with inappropriate transfusion see their values lowered, from 11.60 (IR: 10.20–13.80) to 11.20 (IR: 9.90–13.70). Conversely in patients with transfusion adequacy, the hemoglobin values slightly increased from 7.25 (IR: 6.90–7.60) to 8.50 (IR: 7.90–9.10), although the difference is not significant, probably due to the sample size of said cluster. It should be noted that leukocytes decreased significantly in the inappropriate group, and values such as fibrinogen or potassium increased after the transfusion in the inappropriate group see .In this work, we have identified the factors that are associated with the practice of transfusing in Spanish ICU services. These factors have worse scores on the scales that measure the patient's clinical status, especially on the SOFA and Apache II scales; and SAPS II, differences in analytical parameters , and the greater presence of kidney failure in transfused patients compared to non-transfused patients.Regarding the factors that are associated with an adequate decision to transfuse, two factors have been identified: renal failure and COPD. By measuring the impact that transfusion produces on patients and analyzing the differences between those who have an adequate indication vs. those who have not found it, which statistically had no significant differences in transfused blood components, fresh frozen plasma, platelets, or red blood cells between the two groups. We found that the only criteria in non-adequate of 92.00% of blood transfusions are related to hemoglobin cut-off criteria, previous to the decision on transfusion (Hb < 9) . TransfuThe indication of transfusions must be carried out according to the references in the current guidelines, and it is necessary to carry out an individual assessment of each patient since blood components are a very scarce resource and their use must be limited to specific indications. Based on this, numerous associations have developed clinical practice guidelines to mitigate the problem of over- transfusion, reducing the number of inappropriate transfusions and optimizing the use of donated blood components , 14.Regarding the adequacy of one transfusion, accumulating evidence suggests a lack of efficacy with red blood cell (RBC), plasma, and platelet transfusion in most critically ill patients. Evidence has also increasingly exposed previously known transfusion risks. A result is a growing number of recommendations for more restrictive, PBM-based red blood cell, plasma, and platelet transfusion strategies. An important exception to a more conservative transfusion practice occurs in patients with major trauma and life-threatening bleeding, such as the patients in our study. In these trauma patients, delaying therapies with red blood cells, plasma, and platelet components in this population can promote the lethal triad of coagulopathy, acidosis, and hypothermia with consequent increased bleeding, increased transfusion needs, and increased mortality .As we can see in our study, one piece of information draws our attention, and it is that the decrease in hemoglobin and hematocrit, after a transfusion, leads us to hypothesize that they are patients with active bleeding. However, the criteria for blood transfusion, especially in trauma patients, are not according to the adoption of guidelines; for this reason, restrictive policies, with the exception of trauma, must be taken into account to avoid over- transfusion. With these policies, more recent studies  show thaSuch programs minimize RBC transfusion and improve patient outcomes worldwide, as shown in their study by Shin et al. , where tLikewise, there were no differences in transfused blood components, fresh frozen plasma, platelets, or red blood cells between both groups (adequate vs. inadequate), nor concerning the drugs administered. Díaz et al. , in a con = 1,474, taking into account the difference in the sample and the limitations of our study, our results could hypothesize that in hospitals there is still an over-transfusion in patients, in concordance with other studies . The patients/participants provided their written informed consent to participate in this study.RJ-V, MQ-D, and JG-E: conceptualization. RV-H: methodology. AR-C: software. JS-S: validation. RJ-V: formal analysis. MG-E: investigation. EG-C: resources. PS-D: data curation. RJ-V and JS-G: writing—original draft preparation. RV-H and RJ-V: writing—review and editing and funding acquisition. CJ: visualization. MQ-D and JG-E: supervision. JLS-G and GG-F: project administration. All authors have read and agreed to the published version of the manuscript.


Helicobacter pylori infection. Our objective was to evaluate the tests used for both the initial diagnosis and the confirmation of eradication after treatment in Europe. Methods: The European Registry on the management of Helicobacter pylori infection is an international, multicentre, prospective, non-interventional registry aiming to evaluate the management of Helicobacter pylori-infected patients in Europe. Countries with at least 100 cases registered from June 2013 to April 2021, and with a validated diagnostic method were analysed. Data were quality reviewed. Results: A total of 34,920 adult patients from 20 countries were included . To establish the initial diagnosis, invasive tests were performed in 19,801 (71%) patients, non-invasive in 11,369 (41%), and both in 3437 (12%). The most frequent were histology , a rapid urease test  and an urea breath test . According to the age, invasive tests were indicated in 11,179 (77%) ≥50 years, and in 8603 (65%) <50 years. Depending on the country, the use of invasive tests ranged from 29–99% in <50 years to 60–99% in ≥50. Most of the tests used to confirm eradication were non-invasive , with the urea breath test being the most frequent . In 2983 (9%) post-treatment tests, histology  or a rapid urease test  were performed. Conclusion: A great heterogeneity was observed for the initial diagnosis and confirmation of the eradication. The reasons for the apparent lack of adherence to the clinical guidelines should be further explored.Background and aims: Several methods are available to diagnose  Helicobacter pylori (H. pylori) [H. pylori infection are at risk of developing various complications, mainly gastroduodenal ulcer, gastric adenocarcinoma and lymphoma [Approximately half of the population worldwide is infected by  pylori) ,2. Its p pylori) . Patientlymphoma . Thus, alymphoma .H. pylori infection [Several tests are indicated to establish the initial diagnosis of nfection . The urenfection . When UBnfection . Serolognfection ,9.H. pylori treatment in routine clinical practice, either as a first-line or as a rescue treatment, is not performed due to the low cost-effectiveness of culture and questionable clinical efficacy compared to empirical highly effective quadruple therapies [Invasive tests are performed by obtaining tissue samples collected with upper gastrointestinal endoscopy. Rapid urease test (RUT) is the first-line diagnostic test. Histology is also recommended as it allows us to assess gastritis and precancerous lesions if suspected . Regardiherapies ,11,12.H. pylori and its subsequent eradication when detected in young (<50 years old) patients with dyspeptic symptoms and the absence of alarm symptoms [The type of test used depends on the characteristics of the patient and the presence or absence of red flags. The “test and treat” strategy is based on the investigation of the presence of symptoms . Howeversymptoms ,14.H. pylori infection has been established and antibiotic treatment prescribed, a confirmatory eradication test should be performed. UBT is generally the test of choice to confirm eradication, but MSAT may be a valid alternative. Serology should not be used to confirm eradication due to its lack of efficacy, and the use of invasive tests is also generally not necessary [Furthermore, once the diagnosis of ecessary .H. pylori, the present study aims to evaluate the type of tests used in Europe for the initial diagnosis of H. pylori infection as well as for the control of eradication after treatment. The aim of the current study was to evaluate the type of tests used pre- and post-treatment in first-line treatment, to assess the type of control tests used to confirm the eradication of the infection both in treatment-naïve and rescue treatment patients, and ultimately to evaluate the evolution in the use of these methods in Europe.Taking into account all these considerations, and since no information is currently available about clinical practice regarding the diagnostic process of Helicobacter pylori management” (Hp-EuReg) brings together information on the real clinical practice of most European countries, including thousands of patients [H. pylori, allowing not only for the continuous assessment of the implementation of clinical recommendations agreed on medical consensus, but also of the possible strategies for improvement. The general aim of the Hp-EuReg was to set up an ongoing database in which a large representative sample of European gastroenterologists would systematically record their routine management of patients infected with H. pylori [The “European Registry on patients . It repr. pylori .www.helicobacter.org accessed on 20 June 2023).This analysis focused on the Hp-EuReg, an international, multicentre, prospective, non-interventional registry that started in 2013 and was promoted by the European Helicobacter and Microbiota Study Group , a non-profit scientific and medical society focused on gastroenterology research [Data were recorded in an electronic case report form using the REDCap collaborative platform hosted at “Asociación Española de Gastroenterología” , encompassing a total of 20 different countries.All The variables analysed included: patient’s characteristics such as age, gender and ethnicity, country of origin, line of treatment, and tests used for diagnosis, and confirmation of eradication. Histology, RUT, culture, or biochemical methods, such as polymerase chain reaction (PCR) or fluorescence in situ hybridization (FISH), were considered as invasive tests, and UBT, serology, monoclonal, and polyclonal stool antigen tests as non-invasive.Data were subjected to monitoring (per country and centre) and were quality-checked to ensure coherence and data reliability. Sub-analyses were conducted depending on a patient’s age, country, and line of treatment, whenever possible. For the bivariate analyses, we selected those patients for whom only one type of test (invasive or non-invasive) was indicated for the initial diagnosis.Continuous variables were summarised using means and standard deviation (SDs) for normal distributions, and medians with the interquartile range for non-normal distributions. Categorical variables were summarised using absolute values together with their relative frequencies (%) and their corresponding 95% confidence intervals (CI).The Chi-square test was used to compare categorical variables or Fisher’s exact test in contingency tables when expected frequencies were less than five. The Mann–Whitney U test was used for non-parametric variables comparisons.Logistic regression was conducted to evaluate the association between the type of test indicated for the initial diagnosis and the patient’s characteristics. Unadjusted odds ratios (OR) and 95% CIs were reported.The evolution in the use of diagnostic tests between 2013 and 2021 was also analysed.In all analyses, a two-sided α-level of 0.05 was considered statistically significant.By April 2021, 34,920 patients from 20 countries were included in the analysis. Patients’ flow-diagram is shown in The patients’ mean age was 51 years (SD ± 14) and most were women  and Caucasian . Further patients’ characteristics are shown in Patients from Spain, Russia, and Italy represented the majority of the data (74%) evaluated. The participation by country including more than 100 patients is shown in H. pylori infection in treatment-naïve patients, non-invasive tests only were performed in 29% (95% CI 0.28–0.29) of cases, invasive tests only in 59% (95% CI 0.58–0.60) and both types of tests in 12% (95% CI 0.11–0.12). The most frequently used diagnostic tests were: histology (43%), RUT (38%), and UBT (28%). Further details are shown in To establish the initial diagnosis of When the invasive tests were analysed, histology was reported as the unique test in 30% of patients and RUT in 26% . The proIn accordance with the age of the patient, an invasive test was used in 77% of those ≥50 years, and in 65% of those <50 years old.Data by country showed that invasive testing in those patients <50 years ranged between 29% and 99% of cases and between 60% and 99.5% in those ≥50 years . There wp < 0.001), male gender , and country of origin (p < 0.01)  .13C-UBT to diagnose the H. pylori infection ranged from 20 to 28% as a minimum and maximum rate over the years, MSAT from 4 to 9%, histology from 35 to 52% and RUT from 18 to 54%. The evolution in the proportions of the type of test used for the initial diagnosis throughout the years in Europe is shown in Between 2013 and 2021, the use of The type of tests used to evaluate the eradication of the bacterial infection were most frequently non-invasive , both after the first-line treatment and after rescue therapies, mainly by means of UBT (78%). In 8.5% (95% CI 0.08–0.09) of the cases, eradication was assessed with an invasive test requiring upper gastrointestinal endoscopy and biopsies for histology in 5.4% and/or RUT in 3.5%.Data on the control tests used both after first-line and rescue treatments are shown in Note that histology was conducted in 4.9%, RUT in 3.1% and both tests in 0.6% to confirm eradication after the first-line treatment . Further13C-UBT (minimum and maximum rate of use over the years ranging from 67 to 86%), followed by MSAT (6–21%) and RUT (1–4%). The evolution of the type of test used for the confirmation of the eradication throughout the years in Europe is shown in Between 2013 and 2021, the most frequently used tests to confirm the eradication were: naïve patients, culture testing was conducted in 10.5%, in 15% of patients receiving a rescue treatment (11% in second-line treatment and 24% in the remaining rescue treatment lines)  .H. pylori infection. The results were obtained by analysing data from over 35,000 patients from 20 different European countries.This is the largest and first study to our knowledge evaluating the tests used for the diagnosis and control of the eradication treatment in the management of H. pylori infection; (2) invasive tests for the initial diagnosis of H. pylori infection were performed probably unnecessarily in the majority of patients, mainly in those <50 years old; (3) a non-negligible number of patients ≥50 years old were only tested with non-invasive tests ; (4) culture was performed in a relatively small number of patients both in first-line and rescue-treatment patients; (5) UBT was by far the most common test used to confirm the eradication of H. pylori infection; however, invasive tests were still used in a low proportion.Our study showed: (1) a great heterogeneity among European countries in the use of invasive and non-invasive tests for the initial diagnosis of H. pylori infection in Europe. The results demonstrated that there is a great heterogeneity between the different European countries when choosing the test for both the initial diagnosis and the control of the H. pylori eradication. These findings suggest that the established recommendations for the correct diagnosis of the infection are probably not correctly followed in a significant number of cases. The same results were previously found in the case of the treatment recommendations [The present study is the first to analyse and perform a mapping review of the diagnostic methods used to detect the ndations .H. pylori infection leads to clinical complications such as peptic ulcers or gastric cancer [H. pylori. However, in patients with alarm symptoms or in those over 50 years old, an upper gastrointestinal endoscopy is recommended in order to exclude potential organic diseases [It is known that chronic c cancer . In ordec cancer ,19,20,21diseases ,14.Our study showed that the “test-and-treat” strategy was not followed in all cases, as an invasive test was performed in over half of the patients under the age of 50. Although a proportion of these patients could have reported alarm symptoms, it has been described that these symptoms are usually present in under 5% , meaningFurthermore, in our cohort, an invasive test was not performed in a non-negligible percentage of patients older than 50; thus, upper gastrointestinal endoscopy was not performed to exclude gastric pathology, mainly neoplastic.The current recommendations state that UBT is the best test to establish the initial diagnosis by non-invasive testing . When UBOur study showed that in most of the cases in which a non-invasive test was indicated, a UBT was performed, but a surprisingly low number of cases were diagnosed by MSAT, despite having good diagnostic accuracy. With regards to serology, our study showed it was performed in approximately the same number of cases as MSAT, and local validation is not frequently performed in most centres. This might mean that serology was used without previous proper validation. Our analyses also showed that in a great number of cases, both invasive and non-invasive tests were indicated to establish the initial diagnosis of the infection. This strategy is not generally recommended due to its high cost, the increased risks of complications , and the discomfort caused to the patient when performing an unnecessary invasive test ,19,21.H. pylori resistance has increased to alarming levels and local surveillance networks should select appropriate, adapted eradication regimens in each region [H. pylori treatment in routine clinical practice, either as first-line or as rescue treatment, is not recommended due to low cost-effectiveness and questionable clinical benefit as compared to empirical highly effective quadruple therapies [Culture-guided tailored treatment remains controversial, as there is scarce evidence supporting this strategy . This aph region . Some sth region ,25; but herapies ,11,26. TH. pylori, non-invasive testing is recommended in the majority of cases, especially UBT, although MSAT can be a valid alternative when the former is not available [Finally, to confirm the eradication of vailable . In somevailable ,19,21.H. pylori status after an eradication treatment.Our study showed that the methods used to evaluate the eradication in Europe were mainly non-invasive, but a significant number of patients had likewise undergone endoscopy for this purpose. Moreover, RUT was the only test performed in a non-negligible number of patients in this group. This is not consistent with the current guidelines which do not recommend using RUT to assess the With regards to the evolution in the use of tests throughout the years, no clear trend could be observed globally or in the countries with more than 1000 patients included. The COVID pandemic may have influenced the number of UBT and MSAT in 2020. However, this is not clearly shown in our data, and solid conclusions cannot therefore be drawn. More specific time-trend studies should be performed in this field.H. pylori-testing including endoscopy ; in educational differences .Finally, our conclusions are based on assuming all investigators followed the recommendations stablished by the Maastricht VI Consensus Report; however, the countries’ reported differences might be certainly due to specific healthcare or socioeconomic burdens of each setting or variability in health insurance accessibilities. All these might result in high-testing vs. low-testing practices ; in the use of other Our study has some limitations. As the patients’ alarm symptoms were not registered, we cannot ensure that those undergoing gastroscopy were properly selected. However, previous investigations support that it can be assumed that the presence of “red flags” is infrequent and, therefore, a maximum prevalence of 5% can be estimated . ConsequH. pylori infection in Europe, and the largest series including over 35,000 patients from 20 different European countries, provided valuable information that can be used to audit and improve our clinical practice.Despite these limitations, our study, the first to analyse the use of diagnostic tests for H. pylori infection. These results suggest that adherence to the main recommendations on H. pylori diagnosis might be able to be improved. The reasons for this apparent lack of adherence to the current clinical practice guidelines should be further clarified and addressed.In summary, a great heterogeneity between European countries was observed, both in the choice of the pre-treatment diagnostic tests and in the evaluation of the post-treatment eradication of


The oral samples from RA patients had higher bacterial diversity than those from non-RA volunteers. The RA samples had a higher relative abundance of Prevotellaceae and Leptotrichiaceae, but a lower content of butyrate and propionate-producing bacteria compared to the control group. The samples from patients in remission had a higher abundance of Treponema sp. and Absconditabacteriales (SR1), whereas those with low disease activity had higher levels of Porphyromonas and those with high RA activity had higher levels of Staphylococcus. A positive correlation was found between the taxa Prevotella_9 and serum levels of antibodies to cyclic citrullinated peptide (ACPA) and rheumatoid factor (RF). The predicted functional pattern of the ACPA+/RF− and ACPA+/RF+ seropositive groups was characterized by increased ascorbate metabolism, degradation of glycosaminoglycans, and reduced biodegradation of xenobiotics. These findings suggest that the functional pattern of the microflora should be considered when selecting a therapeutic strategy for RA in order to provide a personalized approach.This study aimed to identify the oral microbial signature of Kazakh female rheumatoid arthritis (RA) patients. A total of 75 female patients who met the American College of Rheumatology 2010 classification criteria for RA and 114 healthy volunteers were included in the study. Amplicons of the 16S rRNA gene were sequenced to analyze the microbial composition. We identified significant differences in bacterial diversity and abundance between the RA and control groups, as measured by Shannon ( Defluviitaleaceae_UCG-011 and Neisseria oralis species was observed in Chinese patients with RA, while an increase in Prevotella_6 was also seen  bacterium HMT349 was observed in the RA group [Leptotrichia was significantly depleted in patients with Sjögren’s syndrome compared to the control group [Veillonella was elevated in patients with Sjögren’s syndrome according to a study by Singh et al. [However, the data on microbiome markers for RA are conflicting, with some studies reporting that patients ,5, where in mice . This, icontrols . In a Swol group , whereasPrevotella nigrescens and Prevotella intermedi, in the blood serum and the synovial fluid [P. gingivalis, Tannerella forsythia and P. intermedia was found in samples of synovial fluid in patients with RA [Peng et al., analyzing and systematizing the available research data, concluded that the microbial composition of the oral cavity of patients with RA is influenced by the disease . The stual fluid . In addi with RA . This suThe study was approved by the local ethics committee of the National Laboratory Astana Nazarbayev University, Protocol No. 03-2019, Astana, Kazakhstan. Respondents were informed about the aims of the study and signed an informed consent form. Interaction with respondents was carried out in accordance with the general instructions and rules.Patient recruitment was conducted from outpatients No. 10 and No. 12 of Astana city, Kazakhstan, and via an official invitation on social networks in the period from September 2019 to December 2021. Overall, 189 individuals, including 75 RA patients and 114 healthy controls, were included in the study . ConsideAll patients underwent laboratory examination. Blood sampling was carried out strictly in the fasting state after a 12–14 h period of fasting. The inflammatory marker C-reactive protein (CRP) was examined. Immunological parameters such as RF and ACPA were also determined. The diagnosis of RA in the patients under the study was established according to 2010 rheumatoid arthritis classification criteria .Prior to sample collection, respondents were advised not to perform oral hygiene during the last 12 h and not to eat or drink during the last 2 h prior to the study visit. During the visit, scrapings were collected from the surface of the tongue, gums, tonsils, and plaque. Oral scraping samples were collected in a DNA/RNA Shield Collection Tube w/Swab . Genomic DNA from oral samples was extracted using the ZymoBIOMICS DNA Miniprep Kit . A qualitative control of DNA isolation was performed by electrophoresis in a 1% agarose gel. The concentration and purity of each DNA sample were determined using an Invitrogen Qubit 3.0 Fluorometer . Sterile water served as a negative control. Sequencing was performed on the Illumina NovaSeq 6000 platform at the laboratory of Novogene  following the standard Illumina protocols.Clinical examination of the participants was conducted by a dentist, and a thorough collection of complaints and anamnesis of the disease, an examination of the oral cavity, and an index assessment of the condition of the tissues of the periodontal complex were carried out. The survey considered patients’ complaints about bleeding gums, the prescription and conditions of its occurrence, the frequency of abscess formation, the presence of bad breath, and the mobility of teeth, as well as a cosmetic defect associated with the movement of the frontal group of teeth, increased sensitivity of teeth from all types of irritants, and a violation of the function of the dental system. To clarify the diagnosis, if necessary, an X-ray examination was performed. Being periodontally healthy was defined as areas with a probing depth of ≤3 mm and the absence of bleeding during probing . The preThe LotuS2 pipeline (Less OTU Scripts 2)  was usedAlpha diversity (the richness of a sample in terms of the diversity of OTUs observed in it) was estimated using Shannon and Simpson indices. Beta diversity was measured using weighted UniFrac  on HelliFunctional metagenomes were predicted based on the 16S rRNA sequencing data of the oral microbiome using PICRUSt2 (phylogenetic investigation of communities by reconstruction of unobserved states) v2.5.0 with default parameters . Brieflyt-tests or Mann–Whitney U tests, as appropriate, whereas chi-squared tests or Fisher’s exact tests were used to compare discrete parameters. All results were considered statistically significant when p-values were less than 0.05.R v4.2.0  was used for statistical evaluation. For the correlation between bacterial abundance and blood/serological indicators, the Spearman correlation coefficient was used. Continuous data were compared using unpaired The observational study included 189 participants, with 75 diagnosed with rheumatoid arthritis and 114 being healthy individuals . Using distance similarity ≥97%, the sequences were grouped into 2049 OTUs, of which 2042 OTUs belonged to the bacterial kingdom.p < 0.02 and p < 0.001, respectively) (p < 0.05 and α-similarity (dispersion) p > 0.05  detected 473 taxa at 7 taxonomic ranks. Bacterial richness (𝛼-diversity), estimated using the Shannon and Simpson biodiversity indices, showed a significant difference between the two groups (ctively) a. Interep > 0.05 b.Prevotellaceae and Leptotrichiaceae, as well as the persistence of Neisseria, Fusobacteriales, Rothia, Granulicatella, Leptotrichia, Megasphaera micronuciformis, Olsenella, and Erysipelotrichaceae. Conversely, several butyrate- and propionate-producing taxa, including Eubacterium coprostanoligenes, Eubacterium halli, Butyricicoccus, Cutibacterium, Ruminococcus, Subdoligranulum, Faecalibacterium, Blautia, and Roseburia, were depleted in RA patients, but enriched in healthy controls.Since the bacterial diversity (𝛼-diversity) differed between the groups, we carried out the determination of statistically altered bacterial taxa using LEfSe . A histoTreponema sp. (p = 0.01527) and Absconditabacteriales (SR1) (p = 0.03510). Those with moderate disease activity  had an increase in Porphyromonas (p = 0.03213), and those with high disease activity  had an increase in Staphylococcus (p = 0.04127), whereas the moderate stage did not differ in the statistically increased content of any taxa in the studied sample  had an increase in d sample . In addition, we analyzed the relationship between microbial toxins and the presence of autoantibodies (ACPA and RF) and inflammation (measured by CRP) in the blood of these patients. The presence of these autoantibodies is thought to be associated with RA disease severity, and accumulating evidence links certain oral microorganisms to the generation of ACPA and RF . No corrPrevotella_9 was positively correlated in a statistically significant manner with high levels of ACPA and RF in the blood (p < 0.001). Oscillospiraceae UCG-005, Leptotrichia sp. oral taxon 847, Leptotrichia wadei, and Neisseria bacilliformis also had moderate positive correlations with high ACPA levels. On the other hand, Selenomonas sp. and Haemophilus sp. ‘paraurethrae’ were moderately negatively correlated with ACPA levels. A weak positive correlation was further observed between RF and Prevotella_9, and a moderate positive correlation was observed between Treponema sp. canine oral taxon 087 and RF. Streptococcus infantis, on the other hand, had a moderate negative correlation with RF. It is notable that Anaeroglobus geminatus, taxon family Neisseriaceae Dialister sp. Marseille-P5638, Eikenella sp. NML01-A-086), taxon family Spirochaetaceae: Treponema amylovorum, uncultured Treponema sp. all had a moderate positive correlation with CRP. For example, In order to investigate the functional role of the oral microbiome in RA, we used the PICRUSt2 tool to perform functional prediction based on marker sequences of the 16S rRNA gene . This anThe functional pattern of patients with RA showed increased activity in the biosynthesis of vitamins , carbon fixation, carbohydrate metabolism (ascorbate degradation), glycan metabolism , histidine, and lysine metabolism. However, there was decreased activity in pyrimidine metabolism, xenobiotic biodegradation (aromatic degradation), energy metabolism, and overall amino acid metabolism. RA studies have shown that high levels of ACPA and RF in the blood of patients are associated with a more severe and aggressive form of the disease, as well as reduced remission . PatientInterestingly, the ACPA+/RF− and ACPA+/RF+ groups had a higher predicted presence of genes involved in ascorbic acid degradation, energy metabolism such as succinate dehydrogenase and fumarate reductase, and the tricarboxylic acid cycle and respiratory electron transport chain. There was also an increase in the module for lysine and polyamine biosynthesis. The presence of taxa that degrade glycosaminoglycans, such as dermatan, chondroitin, and keratan, was significantly increased and widely distributed in tissues, particularly in the bones and cartilage of vertebrates. These molecules contribute to the gelation of the extracellular matrix in these tissues , which mPrevotellaceae, Leptotrichiaceae and Neisseria, Fusobacteriales, Rothia, Granulicatella, Leptotrichia, Megasphaera micronuciformis, Olsenella, and Erysipelotrichaceae in the oral microbiome of these patients. This is in line with previous research indicating that the oral microbiome plays a role in the development or progression of RA, possibly through dysbiosis of the oral cavity and concomitant periodontal disease [Porphyromonas, particularly Porphyromonas gingivalis, was low in the study group despite the bacterium being linked to systemic autoimmune diseases and the potential to contribute to the development of autoimmunity and clinical RA [In this study, the oral microbiome of Kazakhstani patients with RA was analyzed using 16S rRNA gene sequencing. The results showed an increased presence of  disease . Interesnical RA . Prevotellaceae taxa in RA show a feedback relationship with Bacteroides [P. gingivalis in our RA cohort. Additionally, Kishikawa et al. and other authors have found a higher relative abundance of the Prevotella taxon in the RA group [Prevotella, Veillonella, and Porphyromonas was also reported in samples of patients with early RA and individuals at risk compared with a healthy control group [Previous research has shown that the teroides , which mRA group ,33. A hip = 0.00152) and Shannon index (p = 0.0205) compared to the control group, which may be linked to dysbiosis of the oral cavity and potentially periodontal disease . These opportunistic microorganisms are known to cause periodontal and dental issues [In our study, we observed significant dissimilarity in the microbiota of healthy individuals and RA patients, with higher biodiversity in the RA group. The RA group also had an increase in the average diversity of taxa according to the Simpson index (l issues . WhereasTreponema sp. (p = 0.01527), Absconditabacteriales (SR1) (p = 0.03510), Porphyromonas (p = 0.03213), Staphylococcus (p = 0.04127), Anaeroglobus geminatus, Prevotella/Leptotrichia, Oscillospiraceae UCG-005, and Neisseria bacilliformis (p = 0.05) were all correlated with the activity of the disease. Picchianti Diamanti et al. have previously shown that the relative abundance of intestinal microbial taxa was associated with the DAS28 score [Porphyromonas and Treponema sp., have been previously associated with the active stage of the disease [P. gingivalis is able to aggravate the proinflammatory reaction of the body through the activation of a Toll-like receptor (TLR)2/4 [Treponema sp. taxa in patients with DAS28 scores <2.6 is likely associated with new onset of RA [Streptococcus infantis in the oral microbiota was found to be negatively correlated with the concentration of a certain factor in the blood of patients with arthritis. Overall, these findings suggest that certain bacteria may be involved in the development and progression of the disease.In this study, a relationship was found between the activity of disease and certain taxa of bacteria. Specifically, ) p = 0.010, Porph disease  and are (TLR)2/4 . Anotheret of RA . In addiAnaerglobus geminatus and Prevotella/Leptotrichia has been linked to ACPA seropositivity and clinical RA. Our own research also found correlations between Prevotella/Leptotrichia with the level of clinical RA and ACPA positivity, as well as between taxa such as Oscillospiraceae UCG-005 and Neisseria bacilliformis. Tong et al. observed an increase in Prevotella abundance in Chinese patients associated with RA progression [Prevotella with the level of RF in blood serum. However, the relative abundance of Streptococcus infantis in the oral microbiota was negatively correlated (p < 0.01) with the concentration of RF in patients with arthritis.Brusca et al., in their review , drawinggression . Our stuPrediction of the potential functional profile of the oral microbiota showed a change in some functions in the RA cohort. These changes included a reduction in the metabolism of pyrimidine, the biosynthesis of polyamines and polysaccharides, and the biodegradation of xenobiotics. In addition, the study found an increase in the level of vancomycin resistance genes and virulence factors. Further analysis of the oral microbiota in RA patients revealed differences between subgroups based on the presence of ACPA and RF autoantibodies. The ACPA+/RF− and ACPA+/RF+ subgroups had an increased presence of bacteria that metabolize glycosaminoglycans , which are important components of joint tissue. This suggests that the oral microbiota may contribute to inflammation and joint tissue damage in RA through the transmission of bacterial taxa between the mucous membranes of the oral cavity and the gut , as wellIn this study, we also observed a reduced presence of the lipopolysaccharide metabolism module in certain subgroups of patients with long-standing RA. Our findings are consistent with previous research ,42 showiThere are several limitations to this study. One major limitation is that all of the patients in the study had a long course of RA, which tends to be associated with a less aggressive disease course. Additionally, the patients were receiving treatment at the time of the study , whereas the control group of volunteers did not receive any treatment. In addition, the ACPA+/RF− group included only three patients, which is a small sample size. Finally, the functional repertoire of the microbiome was only evaluated based on 16S rRNA sequence profiles, without determining the functional abundance of the corresponding genes in the microbial community.Prevotellaceae and Leptotrichiaceae. This, in turn, once again, confirms the role of the Prevotella taxon in the development of RA. In addition, an association of the microbial signature with disease activity and ACPA and RF autoantibody profiles was found. These findings suggest that it is important to consider the profile of a patient’s oral microbiome when choosing a treatment strategy for RA, in order to provide a personalized approach.Our study found that patients with RA have a different composition of microbes in their oral cavity compared to non-arthritic individuals. Specifically, the microbial signature in the study cohort was characterized by a decrease in the number of butyrate- and propionate-producing microorganisms, but an increase in overall 𝛼-diversity. The microflora was further distinguished by the enrichment of taxa such as


We tested Goal Management Training (GMT), which has been recommended as an executive training protocol that may improve the deficits in the complex tasks inherent in life role participation experienced by those with chronic mild traumatic brain injury and post-traumatic stress disease (mTBI/PTSD). We assessed, not only cognitive function, but also life role participation .t-test models to explore change, and generated descriptive statistics to inspect given individual patterns of change across measures.We enrolled and treated 14 individuals and administered 10 GMT sessions in-person and provided the use of the Veterans Task Manager (VTM), a Smartphone App, which was designed to serve as a “practice-buddy” device to ensure translation of in-person learning to independent home and community practice of complex tasks. Pre-/post-treatment primary measure was the NIH Examiner, Unstructured Task. Secondary measures were as follows: Tower of London time to complete (cTOL), Community Reintegration of Service Members (CRIS) three subdomains . We analyzed pre-post-treatment, p < .02; effect size = .67) and cTOL . Individuals varied in their treatment response, across measures.There was statistically significant improvement for the NIH EXAMINER Unstructured Task (In Veterans with mTBI/PTSD in response to GMT and the VTM learning support buddy, there was significant improvement in executive cognition processes, sufficiently robust to produce significant improvement in community life role participation. The individual variations support need for precision neurorehabilitation. The positive results occurred in response to treatment advantages afforded by the content of the combined GMT and the employment of the VTM learning support buddy, with advantages including the following: manualized content of the GMT; incremental complex task difficulty; GMT structure and flexibility to incorporate individualized functional goals; and the VTM capability of ensuring translation of in-person instruction to home and community practice, solidifying newly learned executive cognitive processes. Study results support future study, including a potential randomized controlled trial, the manualized GMT and availability of the VTM to ensure future clinical deployment of treatment, as warranted. A miBlast-related mTBI in veterans is often more complicated than mTBI in civilians due to the context of the injury, resulting in both psychological and physical trauma . Thus, cTo date, for veterans with mTBI, there is a lack of evidence to support effectiveness of cognitive treatment. In fact, most published studies were conducted for those with moderate to severe TBI. There are a few cognitive rehabilitation studies that included veterans with mTBI, which reported improvement in symptoms –22; but To address this limitation, Goal Management Training (GMT) was recommended in the past as a training that may produce real-life functional gains . GMT is 2.2.1.This study was a single cohort, pre-/post-treatment design. Veterans reporting cognitive deficits to Speech Services were recruited and treated in two sites  and Durham VA Medical Center (#01887).Subject inclusion criteria were as follows: diagnosis of a blast-related mTBI documented in the medical record by a physician or neuropsychologist; frontal lobe-based cognitive impairment as determined by more than one standard deviation below the mean for the matching age group from the technical manual  on trial2.2.2.2.1.We conducted ten in-person sessions of training  to impro2.2.2.We provided participants with the Veteran's Task Manager, a Smartphone application , which we developed and implemented in order to specifically practice the problem-solving steps taught in GMT. The Veteran's Task Manager provided the following learning-assist features: simplify tasks to small components; estimate time to complete; track and identify each step as completed (check list); and a visual/vibrating alert to stay “On Target”. The Veteran's Task Manager is available in both Apple and Google Smartphone app stores.2.3.2.3.1.p < .005)  .2.4.2.4.1.The cTOL is a measure of the speed of problem-solving required to solve a multiple-step, visual-spatial problem, which demands problem-solving while keeping the final goal in mind , which a2.4.2.The CRIS is a measure of life role participation activities, developed specifically for soldiers with disabilities –41. Each2.4.3.We characterized the sample according to depression, which was measured using the Beck Depression Inventory (BDI-II), a 21-item questionnaire , 44, wit2.5.t-test to obtain p-values for assessing statistical significance, calculated effect sizes, and computed 95% confidence interval using the bias-corrected and accelerated (BCa) bootstrap method ]; demands at school increased (n = 2); moving (n = 1); new baby (n = 1); coming to clinic increased anxiety (n = 3); and no reason given (n = 3). Thus, 14 participants completed GMT (8 at the NF/SG site and 6 at the Durham site). Subject characteristics are given in Forty-eight participants were screened of which 19 did not meet inclusion criteria and 3 declined to participate after testing. Subsequently, there were 12 dropouts [starting a new job . There was no significant relationship between the Unstructured Task and either depression or IQ . There was a relatively higher, but non-significant correlation between the Unstructured Task and PTSD severity . These results should be interpreted with some caution, due to the small sample size of the study.There was no significant relationship between the cTOL and either depression, PTSD symptom severity, or IQ  had improvement in one or more outcome measures, in terms of score change. The NIH Examiner Unstructured Task showed that 67% of the participants showed a gain in score ; in geneThe cTOL showed that 77% had a gain in score . The impFor the CRIS, 89% of participants improved according to the Extent of Participation in life roles , Panel AIn terms of individuals, subject 13 showed the least depression, the least severe PTSD symptomatology, and was in the top quartile of treatment response according to the cTOL  of those with mild TBI). In their analysis, they accepted studies with multiple outcome measures of executive function including the following: Multiple Errands Test, Hotel Task, and BADS Zoo task. From this information, they reported that their meta-analysis showed a small effect size (Hedges' g = 0.297) immediately following training. Their meta-analysis is an important study as a beginning investigation of GMT across patient diagnostic categories. In fairness, our relatively stronger results cannot be directly compared to the meta-analysis described above  neurorehabilitation. A second advantageous feature of GMT is the instruction regarding division of a complex activity into main goal, subgoals, and action steps; this process is guided for success by the therapist, if needed. A third treatment advantage was the use of the VTM app, used for home practice as a memory aid, for keeping in mind the main goal, subgoals, and action steps, during a given activity. Fourth, the VTM provided an alert signal to assist with focus of attention on a given action step. Fifth, the VTM provided a feature that may have improved ability to plan the time for a given task; that is, the VTM timer was used for assessing task completion compared to the prior-predicted time given by the user.Given these strongly supportive features of the GMT itself and the use of the VTM, it is reasonable to consider that they had a strong impact on the gains in response to treatment.4.4.p = .02). The EXAMINER Unstructured Task presents a problem to the user, which is a simulation of a functional task requiring cognitive processes and strategies similar to those cognitive processes and strategies instructed and practiced during GMT task training. These include mindfulness, stating the main goal, generating a plan and evaluating results. In severe TBI, GMT has been offered, with reports of significant improvement in measures, such as the Hotel Task, the Modified Multiple Errands Task and the Zoo Map Test .In the current study, GMT significantly improved cTOL (time to completion), indicating improved efficiency. These prior studies reported varying results, according to TOL variables. One study reported no improvement . The oth4.5.Our descriptive data showed varied results that potentially support the individual nature of treatment response in those with mTBI and PTSD and thus, the need for precision neurorehabilitation. First, for example, for the group, the negative slope of the regression line for the Unstructured Task  shows th4.6.p-value corrections; therefore, these results should be considered in that light. Fourth, we did not acquire follow-up data at a time point following the end of treatment. At the same time, given the need and the promising results, a larger randomized, controlled trial can be justified for GMT with Veterans Task Manager for those with mTBI and PTSD.In this single-cohort study, we would like to note a number of limitations. First, the sample size was small, indicating the standard limitations of generalization of the results. For example, a larger sample size should be studied regarding the influence of individual characteristics on treatment response, including the correlation analyses provided here. Second, given the heterogeneous nature of TBI, there are limitations to generalization of these findings. Third, in this study, we acquired and report two secondary measures, without multiple 5.In Veterans with mTBI/PTSD in response to GMT and the VTM learning support buddy, there was significant improvement in executive cognition processes sufficiently robust to produce significant improvement in community life role participation. There was individual variation in treatment response, indicating the need for precision neurorehabilitation in those with mTBI/PTSD. The positive results occurred likely in response to treatment advantages afforded by the content of the combined GMT and the employment of the VTM learning support buddy, with advantages including the following: manualized content of the GMT; incremental complex task difficulty; GMT structure and flexibility to incorporate individualized functional goals; and the VTM capability of ensuring translation of in-person instruction to home and community practice, solidifying newly learned executive cognitive processes. Study results support future study, including a potential randomized controlled trial. The manualized GMT and availability of the VTM ensure future clinical deployment of treatment, as warranted.