Waist circumference can be used as an anthropometric measure to assess central obesity and is easier and more convenient than the waist-to-hip ratio in identifying the risk of obesity and medical problems. Most studies showing an association between obesity and infertility in women have used BMI to measure obesity. Our goal was to examine any potential association between waist circumference and infertility.This cross-sectional study, which formed part of the National Health and Nutrition Examination Survey (NHANES), comprised women ages 18 to 45 between 2017 and 2020. Participants without waist circumference data or information on infertility were removed from the study. The independent relationship between waist circumference and infertility was investigated using weighted binary logistic regression and subgroup analysis.p for all interaction tests > 0.05). The inflection point of the positive non-linear relationship between WC and infertility was 116.6 cm.We investigated 1509 participants and discovered that the prevalence of infertility rose as the WC trisection rose. . Multivariate logistic regression showed that after total adjustment, higher WC levels were associated with an increased likelihood of infertility in women , and There was a 2% rise in the incidence of infertility for every unit (cm) increased WC. Subgroup analysis and interaction tests showed no significant dependence of the effects of marital status, diabetes, hypertension, and high cholesterol on the association between WC and infertility (Excessive waist circumference assessment may increase the probability of infertility, and more attention should be paid to the management of waist circumference should be given more attention. Infertility is a condition that has historically been described as the inability to conceive successfully after more than 12 months of regular, unprotected sexual activity or due to a decrease in one’s ability to reproduce either alone or with a partner . Accordi2 (“overweight”) and BMI > 30 kg/m2 (“obese”)  . Numerou“obese”) , 12. In “obese”) , 14.Although measuring the prevalence of obesity by BMI has become a mainstream test, it lacks an adequate benchmark for sensitivity and specificity , 16. AltIn addition, many professionals advocate the inclusion of waist circumference in the analysis of obesity surveillance because of the increasing prevalence of abdominal obesity worldwide . Waist cTherefore, in this cross-sectional study of women in couples having infertility evaluation and treatment, we looked into the relationship between WC and infertility prevalence to further our understanding of this field.https://www.cdc.gov/nchs/nhanes/. The sample used for the NHANES is fairly representative because of the stratified multistage probability sampling technique used in the research design. NHANES data are made available on a two-year cycle to the general public. Women who participated in the NHANES during the March 2017–2020 cycle provided the data for this cross-sectional research. Women aged 18-45 answered: ‘Have you ever tried to get pregnant for at least one year without getting pregnant?’ (n = 1857) were included in the study. Women who underwent hysterectomy (n = 70), underwent bilateral oophorectomy (n = 3), and lacked information on waist circumference (n = 69) and household income to poverty ratio (n = 206) were excluded. Finally, 1509 women qualified for analysis  oversees that attempts to assess the health and nutritional status of the population in the United States. The public may access all NHANES data at In this study, waist circumference was considered an exposure variable, and WC data were obtained from the NHANES 2017-March 2020 Pre-Pandemic Examination Data (P BMX). Detailed measurements of WC are shown on the NHANES website.Self-reported infertility data were obtained from the NHANES Reproductive Health Questionnaire (RHQ). The presence of infertility was assessed based on the following question: “Have you ever tried to get pregnant for at least one year without getting pregnant? Women who answered “yes” were considered to be infertile, and those who answered “no” were considered to be fertile.https://www.cdc.gov/nchs/nhanes/.Covariates that may affect the connection between waist circumference and infertility were also included in our investigation. Continuous variables included Age (years), Ratio of family income to poverty, Minutes of sedentary activity, and Meals from fast food or pizza place. Total Cholesterol, Direct HDL-Cholesterol. Categorical variables included Race (Mexican American/Other Hispanic/Non-Hispanic White/Non-Hispanic Black/Other Races), Marital status (Married with Partner/Divorced/Never married), Educational level (Less than 9th grade/9th-11th grade/High school or GED/Some college or AA degree/College graduate or above), Diabetes. Hypertension, and high cholesterol level, all of these variables were extracted from NHANES demographics, screening data, questionnaires, and laboratory measurements. All of their detailed measurement procedures are publicly available at http://www.r-project.org) and EmpowerStats (http://www.empowerstats.com), with the statistical significance threshold set at p < 0.05. The NCHS analysis criteria produced all estimates, and the sample weights were created to satisfy the NHANES objectives. The specific weighting strategy was to use waist circumference as a continuous variable to delineate the tertiles. The composition of percentages represents categorical variables, while the mean of standard deviations is used to describe continuous variables. Differences between groups divided by WC triads were assessed using weighted Student’s t-tests (for continuous variables) or weighted chi-square tests . The independent connection between WC and infertility was investigated in three distinct models using multifactorial logistic regression. Covariate adjustments were not applied in model 1 at all. Race and age adjustments were made to Model 2. Age, race, educational level, Ratio of family income to poverty, marital status, Minutes of sedentary activity, Meals from fast food or pizza place, Total Cholesterol, Direct HDL-Cholesterol, hypertension, and diabetes adjustments were made to Model 3. In addition to subgroup studies stratified by marital status, diabetes, hypertension, and high cholesterol levels, smoothed curve fitting and threshold effects analysis were performed to investigate the nonlinear association between WC and infertility.As instructed by the Centers for Disease Control and Prevention (CDC), we conducted all statistical analyses using R (p < 0.05). The prevalence of infertility in tertile 1, tertile 2, and tertile 3 was 7.55%, 10.56%, and 15.28%, respectively, and the majority of infertility increased with increasing WC tertile.A total of 1,509 female participants aged 18-45 years were included in this study, and their weighted demographic baseline characteristics are shown in A positive correlation between WC and infertility prevalence can be observed in Transforming WC from a continuous variable to one stratified by Normal, Overweight, and Obese, comparing waist circumference outside the normal range with that of the normal range revealed that the positive association between WC and infertility prevalence remained stable in the fully adjusted model (model 3) . Women with Obese WC were significantly 127% more likely to develop infertility than women with standard WC (Smoothed curve fitting was used to investigate the nonlinear association between WC and infertility. Our findings show that WC and infertility have a positive non-linear connection (p < 0.05) by examining the threshold effect of WC on infertility prevalence, and we found that the inflection point for infertility prevalence was 116.6 cm. The adjusted OR for infertility prevalence increased by 3% for each 1-unit increase in waist circumference level when the waist circumference range was less than 116.6 cm . When the waist circumference range was greater than 116.6 cm, there was no association with infertility prevalence   and without hypertension , each unit increase in WC was associated with a 2% increase in the likelihood of infertility. Among those without diabetes  and without high cholesterol , each unit increase in WC was associated with a 1% increase in the likelihood of infertility .The interaction term did not report the effect of marital status, diabetes, hypertension, and high cholesterol on the association between WC and infertility . The likelihood of infertility was positively correlated. In contrast, the association on the right side of the inflection point was not statistically significant. Marital status, diabetes, hypertension, and high cholesterol did not have a considerable dependence on this association, suggesting that increased waist circumference could raise the risk of infertility. The findings of this investigation indicate that controlling waist circumference levels can help reduce the risk of infertility.This is the first study to assess the correlation between WC and female infertility directly. Previous studies have shown that obesity negatively affects reproductive health, mainly regarding reduced fertility and infertility; obese women are more prone than normal-weight women to experience spontaneous abortions and congenital defects in the early stages of pregnancy , 26. ObeIn a recent clinical trial, obese and infertile women received a six-month lifestyle modification from Vincent Wekker et al. Women in the intervention group had improved sexual function and more vaginal lubrication than women in the control group, according to the findings of a five-year RCT. That weight loss was also beneficial for cardiovascular health, improved body mass, and infertility ; AnotherWaist circumference (WC) is a measurement that is highly correlated with adiposity and has been associated with a variety of adverse pregnancy outcomes, including assisted reproduction failure, gestational diabetes mellitus, gestational hypertension, and preeclampsia; According to a prospective study by Li et al, waist circumference was found to be inversely related to the likelihood of live birth in women undergoing assisted reproductive technology, independent of body mass index . AccordiOur research concentrated on the link between female infertility and waist circumference. We observed a positive association between increased waist circumference and increased prevalence of infertility in both the crude and adjusted models. A sensitivity analysis using WC as a tertile also demonstrated a positive association between WC and infertility prevalence. In addition, we found a nonlinear relationship between WC and infertility prevalence by threshold effect analysis with an inflection point of 116.6, with a positive correlation to the left and no correlation to the right of the inflection point. In conclusion, WC has been widely reported as an indicator of obesity events and reproductive disorders, also recognized in our study. According to the study’s findings, It is important for women of reproductive age to be aware of their WC and can find out about this data by consulting their healthcare provider.There are several advantages of our study. First, our study is based on the NHANES database, and all analyses were considered to select appropriate NHANES sampling weights so the results are more representative. Second, we found for the first time a positive association between WC and the prevalence of infertility in a cross-sectional study of women in the U.S. Through sensitivity analyses, we explored the nonlinear relationship between infertility and WC through smoothed curve-fitting and threshold effect analyses. Third, WC is an easy clinical measure to perform and should be considered to be more routinely incorporated in medical reviews of women of childbearing age to counsel them on their increased risk of infertility. Fourth, our study added two new variables that were strongly associated with obesity and waist circumference, namely Minutes sedentary activity and Meals from fast food or pizza place. Between WC tertile, the individuals with the highest WC tertile compared to other categories were likely to be sedentary women who ate fast food or pizzeria meals frequently.However, there are some limitations to our study. The first is reflected in age and region; the study sample was 1509 women aged 18-45 years in the United States, so the findings are not informative for male or female patients outside the United States and not in that age range. Second, due to our study’s cross-sectional nature, we could not establish a clear causal link between WC and infertility. Third, the information limitations of the NHANES database prohibit a more thorough analysis of other indicators of infertility, such as immune antibodies, reproductive hormones, and ultrasound, as well as further determining the infertility history and duration of the patients. In addition, the lack of information regarding the diagnosis of polycystic ovary syndrome (PCOS) is a weakness, as this may be the greatest predictor of infertility.Our research found that WC was associated with an increased prevalence of infertility. Therefore, high waist circumference values may be a potential risk for infertility. This study will provide support for women and their healthcare providers. Nevertheless, further extensive prospective studies are required to support the results of this article.https://www.cdc.gov/nchs/nhanes/.The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: The studies involving human participants were reviewed and approved by the NCHS Ethic Review Board. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.Y-HY and A-HW designed the study. Y-HY, S-YZ, D-FL, and X-PC collected, analyzed the data and drafted the manuscript. X-DH, BL, and SL gave suggestions, and Y-HY and A-HW revised the manuscript. All authors contributed to the article and approved the submitted version.


Sexual satisfaction is tremendously relevant to wellbeing and quality of life. Inversely, hypersexuality may increase the risk of psychological distress, unprotected sex, and marital problems. This study attempts to explore the sociodemographic variables related to hypersexuality and the relationship between hypersexuality and sexual dissatisfaction with psychological inflexibility, cognitive fusion, body awareness, bodily dissociation, and mindfulness skills in the Spanish population. The sample was made up of 530 participants between 18 and 67 years of age. In total, 5.5% displayed hypersexuality, more likely in males, lesbians and gay men, singles, and students. An online survey was conducted including standardized questionnaires as follows: AAQ-II, CFQ, SBC, MAAS, NSSS-S, and HBI. Significant moderate positive correlations were found between hypersexuality and psychological inflexibility, cognitive fusion, and bodily dissociation, and an inverse moderate correlation with mindfulness skills. Moderate negative correlations were found between sexual satisfaction and bodily dissociation. Linear regression showed psychological inflexibility was the variable with the most weight on hypersexuality, while bodily dissociation was the variable with the most influence on sexual dissatisfaction. This study suggests lesbians and gay men, males, and singles may show an increased vulnerability toward engaging in hypersexual behavior and provides justification for interventions focused on psychological inflexibility and mindfulness skills to treat hypersexuality and improve sexual satisfaction. Hypersexuality is the uninhibited or excessive expression of culturally adapted sexual conduct that leads to important adverse consequences Kafka, . It is aSexual satisfaction has been defined as the subjective evaluation a person makes of his/her sexual relationships . Most of them were women (76.6%), Spanish (89.1%), and resided in Madrid (61.5%). In total, 78.9% were heterosexual, 55.1% considered that they were not religious, and 74.5% considered that their political orientation was left-wing or center-left. A total of 84.3% were graduates, 49.2% were employees, and 28.7% were students. In total, 50.6% were single, and 46.4% were married or cohabiting. For those that had a partner, the average length of the relationship was of 7.6 years . For more detail on sociodemographic data, please refer to Acceptance and Action Questionnaire-II (AAQ-II)       being of legal age, (2) being Spanish-speaking, and (3) having engaged in at least one sexual encounter within the last year.t-test) analyses were performed using SPSS v19 to examine the sample distribution, the means and standard deviations, and the interactions between the studied variables. Due to the absence of normality and homoscedasticity, the Kruskal–Wallis test was selected to compare means of sexual satisfaction and hypersexuality in the function of the studied sociodemographic variables. Linear regression analysis was performed to examine the role of PI, CF, body awareness, bodily dissociation, and mindfulness skills in predicting participant's level of hypersexuality and sexual dissatisfaction.Descriptive, correlational (Pearson's and linear regression), and mean difference ; being slightly higher in males  in comparison with women . According to the criteria established by García-Barba et al. , 5.5% ofp = 0.001), reflecting differences between men and women  in a way that gender accounts for 1.9% of the variance in hypersexuality and that men score higher on hypersexuality (M = 32.9) than women (M = 29.1). Moreover, there were differences for the partner cohabiting variable  showing differences among those who lived on their own but had a partner and those who did not have a partner , with those who had a partner displaying lower levels of hypersexuality. Different levels of hypersexuality were also found between those who cohabited with their partner and those who did not have a partner , with those cohabiting with a partner showing lower levels of hypersexuality. Hence, the partner cohabitation variable accounts for 8.7% of the variance within hypersexuality. Furthermore, the analysis showed that those who scored the highest in hypersexuality are those who did not have a partner (M = 35.55) in comparison with those that did have a partner (M = 28.11). On the other hand, p = 0.00) between heterosexuals and bisexuals  so that sexual orientation accounts for 1.5% of the variance within hypersexuality and that lesbians and gay men display higher levels (M = 34.25) than bisexuals (M = 32.31) and heterosexuals (M = 29.29). Finally, concerning the occupation variable, the paired comparisons showed statistically significant differences  between students and businesspersons or self-employed workers  with occupation accounting for 1.7% of the variance in hypersexuality. It is concluded that students score higher (M = 31.84) than businesspersons or self-employed workers (M = 28). For more details, see The analysis of differences in hypersexuality showed differences relative to gender , CF , and BD , a moderate inverse correlation with mindfulness skills , and a low inverse correlation with sexual satisfaction . PI showed a significant high direct correlation with CF  and BD  and a moderate inverse correlation with mindfulness skills . Similarly, CF showed a significant strong direct correlation with BD  and a moderate inverse correlation with mindfulness . Sexual satisfaction showed a significantly low direct correlation with BA  and mindfulness-related skills  and a negative low or moderate correlation with PI , CF , and BD .As can be seen in p < 0.001). As for the linear regression for the dependent variable sexual satisfaction, it can be concluded that BD is the variable with the greatest weight .As for the linear regression for the dependent variable hypersexuality, it emerged from the analysis that PI is the variable with the most weight (β = −0.285, This study has explored the sociodemographic characteristics associated with hypersexuality and the role of some relevant variables in sexual satisfaction and hypersexuality in a Spanish sample. The level of hypersexuality was similar to the one in a previous study in Spain (Ballester-Arnal et al., On the other hand, hypersexuality was positively correlated with PI, CF, and BD and negatively with mindfulness, with being PI the variable with the greatest weight. Sexual satisfaction showed a correlation with lower levels of hypersexuality, PI, CF, and BD, and with higher levels of BA and mindfulness, being BD the variable with the greatest weight. Regarding mindfulness, it has already been found to be a protective factor for compulsive sexual behavior (Reid et al., This study highlights the relevance that PI has as a variable on sexual satisfaction and, especially, on hypersexuality. Previous studies have pointed out a negative association between hypersexuality and anxiety (García-Barba et al., Moreover, this research also points out the importance of training mindfulness skills and reducing body dissociation for sexual satisfaction. Previous studies have already highlighted the need to take into account the role of mindfulness skills on sexual satisfaction improvement (Brotto and Heiman, Some limitations of the present investigation are listed next. Regarding the participants, it is worth pointing out that the sample was somewhat biased, having an over-representation of women, university students, supporters of left-wing politics, and heterosexuals. This could be attributed to the context where the data were obtained and the recruiting method. Hence, there is a need for more studies that meet the aims of this study while using a more diverse and representative sample to achieve more reliable results. In addition, since the data come exclusively from self-reports, it entails a degree of participant subjectivity and, given the low level of control over the conditions in which the questionnaire was answered, some responses could be biased. However, having obtained the data anonymously through the Internet could be beneficial with regard to the truthfulness of the answers given that it was such a sensible topic (Griffiths, In conclusion, and despite the previously mentioned limitations, this study shows the increased vulnerability of lesbians and gay men, males, and singles to engaging in hypersexual behavior. It also justifies the consideration of psychological interventions based on PF when dealing with hypersexuality and highlights the need of taking into account mindfulness skills to increase sexual satisfaction. Future studies based on these results could extend scientific knowledge about this issue and, in particular, emphasize the importance of considering BD and mindfulness in the improvement of sexual satisfaction, as well as mindfulness and PF in more effective management of hypersexual behaviors.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.The studies involving human participants were reviewed and approved by the Comité de ética de la Universidad Europea de Madrid. The patients/participants provided their written informed consent to participate in this study.All authors listed have made a substantial, direct, and intellectual contribution to the study and approved it for publication.


To determine differences in DM in the U.S. population according to demographic characteristics, physical indicators and living habits.2), TCHOL (mg/dL), fasting plasma glucose (mg/dL) and comparison of means and the proportion of participants with DM.23 546 participants in the 2009 to 2018 National Health and Nutrition Examination Survey (NHANES) who were 20 year of age or older and not pregnant. All analyses used weighted samples and considered the stratification and clustering of the design. Specific indicators include length of leg (cm), BMI  to have diabetes: 14.6%  among black participants, 10.6%  among white participants, and 13.5%  among Mexican-American participants. The prevalence of diabetes is increasing with age, males peaked around the 60s, and women around the 70s. The overall mean leg length and TCHOL was lower in diabetics than in non-diabetics , while mean BMI were higher in diabetics than in non-diabetics (4.27 kg/cm2). DM had the greatest effect on decline of TCHOL in white participants (23.6 mg/dL), less of an effect in black participants (9.67 mg/dL), and the least effect in Mexican-American participants (8.25 mg/dL). Notably, smoking had great effect on percent increment of DM in whites (0.2%), and have little effect on black and Mexican-Americans.DM is more common in the general population than might be clinically recognized, and the prevalence of DM was associated to varying degrees with many indicators of demographic characteristics, physical indicators, and living habits. These indicators should be linked with medical resource allocation and scientific treatment methods to comprehensively implement the treatment of DM. Diabetes mellitus (DM) is a chronic metabolic disease with a series of metabolic disorders  and chronic deficiency, or dysfunction of blood glucose level or dysfunction caused by a variety of pathogenic factors, which has been an important public health problem in the whole world . In the Obesity poses a huge risk on diabetes independently in the United States . PreviouThe National Diabetes Data Group (NDDG) established a classification based mainly on diabetes treatment requirements, which was widely recognized and still used today. This classification included insulin dependent diabetes mellitus (IDDM), non-insulin dependent diabetes mellitus (NIDDM), gestational diabetes and diabetes secondary to other diseases like pancreatic cancer and other endocrine diseases . In our Details of NHANES have been described elsewhere . In shorFor the data sources and the selection criteria, three aspects should be explained. Firstly, leg length and BMI data from body measures of NHANES were collected in the Mobile Examination Center (MEC), by trained health technicians, in order to examine the associations between body weight and the health and nutritional status of the U.S. population . The labAll analyses used weighted samples and considered the stratification and clustering of the design to derive estimates that were applicable to the U.S. population , 13. To The 23 546 NHANES participants with valid body measures and TCHOL value represented 308 million non-institutionalized residents of the United States. Among 26 147 participants with missing data, 30% were white, 24% were black, and 20% were Mexican American. Over the past decade, the prevalence of diabetes has been steadily rising, as is the trend in different races, gender, and age groups Figure 2Firstly, the prevalence of diabetes differed by age, sex, and ethnicity  values was also seen across most age ranges in black participants (2). DM had the greatest effect on decline of TCHOL in white participants (23.6 mg/dL), less of an effect in black participants (9.67 mg/dL), and the least effect in Mexican-American participants (8.25 mg/dL).Firstly, mean age-adjusted and sex-adjusted leg length, BMI and TCHOL were compared for diabetics and non-diabetics Figure 42; P=0.11) and apparently higher mean TCHOL . In addition, mean leg length and TCHOL were higher, and BMI were lower in males than in females (p<0.001)  and higher mean TCHOL . Mexican-American participants had lower mean leg length , lower mean BMI  of more than 125 mg/dL. Due to the different criteria for diabetes , 32–35, For physical indicators, our study shows that people with diabetes have shorter legs than those without diabetes, which confirms the findings from a cross-sectional analysis of data about simple-measured leg muscle strength and the prevalence of diabetes among Japanese males . Some stWith regard to living habits, smoking had a modest association with diabetes prevalence. This finding was also seen in a prospective study published . SmokingAs for alcohol, interestingly, heavy and moderate drinkers had lower mean prevalence of DM than mild drinkers and the association of moderate drinking with DM was significantly different from mild drinking. A large meta-analysis illustrated a similar effect that reductions in risk of DM among moderate alcohol drinkers may be confined to women and non-Asian populations .There are some limitations in our study. Firstly, the study focuses mainly on the prevalence of diabetes and did not explore associated complications. Secondly, the data on fasting plasma glucose is relatively limited, resulting in a large reduction in the sample size in the classification of statistics. Thus, the results of the analysis based on these data may be exaggerated. However, the prevalence of diabetes among ethnic groups is probably not affected, because participants with missing data were evenly distributed among all 3 groups. Third, the observed relationships were limited to adults of 3 races in the US and not include other races, particularly Asian-Americans, which may have limited the extrapolation of the results. Given these limitations, a well-designed prospective cohort trial is needed to validate our results.It can be concluded that DM is more common in the general population than might be clinically recognized, and the prevalence of DM was associated to varying degrees with many indicators of demographic characteristics , physical indicators , and living habits . When deciding whether a thorough diagnostic assessment of diabetes is needed, not only the clinical symptoms should be considered, but also these indicators. They should be linked with medical resource allocation and scientific treatment methods to comprehensively implement the treatment of DM.https://www.cdc.gov/nchs/nhanes/index.htm.Publicly available datasets were analyzed in this study. This data can be found here: LF was involved in all parts of the study, design, acquisition of data, analysis, interpretation, drafting of paper, and final approval. HS and YT participated in data analysis and helped to revise the manuscript. QZ coordinated and supervised data collection, and critically reviewed the manuscript for important intellectual content. All authors approved the final version as submitted, and agree to be accountable for all aspects of the work.


People with cancer are at an increased risk of developing blood clots. Both cancer and anti-cancer treatment are responsible for this risk. In some types of cancer, such risk is higher than in others. There are different types of blood thinners also known as anticoagulants. Blood thinners prevent the recurrence of deep venous thrombosis (a blood clot in the limbs) or pulmonary embolism (a blood clot in the lungs) in people with cancer. In some clinical situations and, specifically, in patients with active cancer, injectable blood thinners are safer than tablets to be taken orally and work just as well.Cancer-associated thrombosis (CAT) is a leading cause of death among patients with cancer. CAT can manifest itself as venous thromboembolism (VTE), in the form of deep vein thrombosis or pulmonary embolism, or arterial thromboembolism. The pathophysiology of CAT is complex and depends on cancer-, patient-, treatment- and biomarkers-related factors. Treatment of VTE in patients with cancer is complex and includes three major classes of anticoagulant agents: heparin and its derivatives, e.g., low molecular weight heparins, direct oral anticoagulants (DOACs), and vitamin K inhibitors. Given the tremendous heterogeneity of clinical situations in patients with cancer and the challenges of CAT, there is no single universal treatment option for patients suffering from or at risk of CAT. Initial studies suggested that patients seemed to prefer an anticoagulant that would not interfere with their cancer treatment, suggesting the primacy of cancer over VTE, and favoring efficacy and safety over convenience of route of administration. Recent studies show that when the efficacy and safety aspects are similar, patients prefer the oral route of administration. Despite this, injectables are a valid option for many patients with cancer. Cancer-associated thrombosis (CAT) is a common cardiovascular complication that manifests itself in individuals with a malignancy. CAT may be the first sign prompting the diagnostic workup that leads to the discovery of occult cancer, or more typically, occurs within six months of cancer diagnosis ,2,3.The clinical presentation of CAT includes venous thromboembolism (VTE) and arterial thromboembolism (ATE). VTE is the most frequent clinical presentation of CAT and includes both deep vein thrombosis (DVT) and pulmonary embolism (PE). However, VTE is not limited to DVT and PE and may involve atypical sites such as the upper extremities, splanchnic and cerebral veins. ATE, instead, primarily manifests itself as myocardial infarction, cerebrovascular event, or peripheral artery disease. Importantly, CAT is the second leading cause of death after cancer itself in patients with cancer who have a 47 times higher annualized rate of death from VTE than the general population .CAT has profound consequences for the patient  and for the healthcare systems  . EffectiSeveral therapeutic options are available for the management of CAT, such as unfractionated heparins (UFHs), low molecular weight heparins (LMWHs), fondaparinux, and direct oral anticoagulants (DOACs) ,11,12,13The introduction of targeted therapies together with the increased survival of patients with cancer has broadened the population of patients with cancer at risk of developing CAT . AmongstThe pathophysiology underlying the development of VTE events, regardless of being or not associated with cancer, consists of one or more elements of the triad named after Rudolf Virchow and composed of hypercoagulability, venous stasis, and endothelial damage . PatientDirect activation of coagulation may be secondary to the presence in the circulation of cytokines secreted directly by tumor cells and their interaction with the tumor microenvironment, such as tissue factor (TF) and, membrane microparticles (MPs) bearing TF, cancer procoagulant (CP) and heparinases. These molecules not only shift the hemostatic balance in a pro-coagulant sense but are probably also involved in mechanisms of tumor diffusion. Moreover, molecules responsible for the inhibition of the fibrinolytic system, such as the plasminogen activator inhibitors 1 and 2  are also overexpressed on the surface of the neoplastic cells, which further destabilizes the hemostatic balance .In patients with cancer, platelets are activated by ADP, thrombin, some metalloproteases, and interleukin (IL)-6 produced by tumor cells that induce the expression of adhesion molecules on platelet surface  increasing their tendency to aggregation . PlateleThe role of inflammation in CAT cannot be underestimated. Tumor cells interact with the tumor microenvironment and with cells of the immune system and increase, both locally and systemically, the levels of acute phase proteins and inflammatory mediators. This, in turn, increases the release of TF, von Willebrand factor, PAI-1, vascular endothelial growth factor (VEGF), and a concomitant reduction in protein C levels that together lead to a pro-coagulant state ,24. FurtSurgical interventions cause several structural and humoral modifications promoting the state of hypercoagulability. The origin of these alterations is multifactorial, including an overexpression by the tumor tissue of procoagulant substances, endothelial damage, an increase in platelet activation, and an increased expression of TF by monocytes ,28.Supportive medical therapy can also induce pro-coagulant changes. In particular, the use of erythropoiesis-stimulating agents, transfusions of packed red blood cells, transfusions of platelet concentrates, and granulocyte-stimulating growth factors (G-CSF) correlates with an increased rate of VTE development . Last buRisk factors and biomarkers for the development of CAT are tumor-, patient- and therapy-related and have been extensively reviewed elsewhere e.g., ,30)..30]).As the risk for VTE in cancer is multifactorial, no single biomarker can be used to predict it. Over the years, several risk assessment models (RAMs) have been developed to identify patients with cancer at increased risk of VTE.The Khorana score, currently recommended by guidelines, was the first risk prediction model for VTE in ambulatory patients with cancer . It evalRecently, a simple two-variable model has been proposed by Pabinger et al. . It incoStudies have shown that patients with some cancer types are at an increased risk of VTE compared to other types. These are pancreas, brain, stomach, kidney, uterus, bladder, lung, colon, and hematological malignancies, whereas such risk is lower in breast and prostate cancer ,35,36. TAll therapeutic modalities used to treat cancer are associated with the risk of developing VTE, albeit through diverse mechanisms, some of which are still not fully understood . In the Treatment of VTE in patients with cancer is complex and includes three major classes of anticoagulant agents: LMWHs, DOACs, and vitamin K inhibitors  were excluded [2. An observational study that analyzed the effects of anticoagulant therapy with VKAs or LMWHs in patients with cancer and renal insufficiency showed that patients with stage 4 and 5 renal failure were at the greatest risk of major bleeding when under treatment with LMWHs, advising caution in the use of these molecules as well [Chronic renal failure is frequently encountered in patients with cancer. In fact, between 52.9% and 87% of patients with cancer have a glomerular filtration rate (eGFR) value < 90 mL/min/1.73 mh cancer . From thexcluded . Moreove as well . Guideli as well . For tin as well .Functional impairment of liver function may lead to a reduced ability to metabolize DOACs. All DOACs are metabolized by cytochrome P450 see . When trIn contrast to the newer classes of DOACs, the injectable anticoagulants are administered intravenously or subcutaneously. They include UFH, dalteparin, enoxaparin, tinzaparin, and fondaparinux . DaltepaHistorically, UFH was the standard treatment for the treatment and prophylaxis of VTE. UFH is a mixture of glycosaminoglycans that bind to antithrombin III (AT-III) via a unique pentasaccharide sequence. Such binding enhances antithrombin’s inhibition mainly of factor Xa and factor IIa (thrombin) coagulation factors. UFH also binds cells and other plasma proteins. This ubiquitous binding property is responsible for the unpredictable pharmacodynamics and pharmacokinetics of UFH that can lead to heparin-induced thrombocytopenia or osteoporosis . UFH musA systematic review of the evidence for the relative efficacy and safety of LMWHs and UFH for perioperative thromboprophylaxis in patients with cancer was performed by Matar et al. The authors included 20 randomized clinical trials  that used preoperative prophylactic anticoagulation with UFH or LMWHs. The meta-analysis did not exclude conclusively a beneficial or harmful effect of LMWHs versus UFH on mortality and embolic outcomes in patients with cancer .The treatment with UFH was compared to LMWH or fondaparinux to obtain pharmacologic prophylaxis of VTE in critically ill patients with cancer. The authors assessed whether LMWH was more effective than UFH at reducing in-hospital rates of VTE and improving clinical outcomes. The study included 103,798 patients from the Premier Database; 75,321 (72.6%) of them received LMWH and 28,477 (27.4%) UFH. The results showed that prophylaxis with LMWH did not decrease the incidence of VTE (5.32% versus 5.50%) but reduced the frequency of PE (0.70% versus 0.99%), significant bleeding  and HIT (0.06% versus 0.19%) .p = 0.19), non-major bleeding , as well as major bleeding , respectively, in the bridging and non-bridging with UFH groups, confirmed the possible usefulness of bridging with UFH [In patients with cancer, a non-bridging therapy with UFH may be useful to reduce the risk of VTE before invasive procedures for which DOAC interruption was performed. In a study, 68 patients were treated with UFH and 74 were not. The rates of VTE recurrence  as far as the occurrence of major and minor bleeding, and all-cause mortality were concerned. DOACs, however, were more effective in VTE prophylaxis in a recent systematic review and Bayesian network meta-analysis of 10 RCTs that included 1128 patients with brain cancer who had neurosurgery .LMWHs are a combination of heparin molecules with a considerably lower molecular weight than UFH. Compared to UFH, LMWHs have greater bioavailability, longer half-lives, more predictable dose–response, and safety. LMWHs are obtained through depolymerization of heparin. They are administered subcutaneously and in the majority of patients, no monitoring is necessary. LMWHs inhibit coagulation by activating antithrombin, which binds to and inhibits factor Xa. The inactivation of Xa results in prothrombin not being activated to thrombin, thereby not converting fibrinogen into fibrin for clot formation .Numerous trials have compared LMWHs to VKAs in the treatment of the acute phase of thrombotic complications. In the CLOT trial, 676 patients were randomized to receive dalteparin or warfarin for a duration of 6 months of treatment . A meta-Amongst LMWHs, dalteparin and tinzaparin, and to a lesser extent, enoxaparin, are by far the most studied LMWH in the setting of CAT.p = 0.002), whilst major bleeding occurred in 19 (6%) patients and 12 (4%) patients, in the dalteparin and in the dalteparin plus VKA arms, respectively, which was not statistically significant (p = 0.27). The study demonstrated that dalteparin was more effective, and as safe as conventional anticoagulant therapy in patients with cancer and acute VTE [Dalteparin sodium is an LMWH made up of strongly acidic sulfated polysaccharide chains and has a mean molecular weight of 5 kDa (range 2–9 kDa). Dalteparin has a bioavailability of 87% when injected subcutaneously . Numeroucute VTE . Other scute VTE ,103. Thecute VTE .p = 0.11; RR  =  0.66) [p = 0.07). From a safety perspective, there was no difference in the incidence rate of major bleeds; however, significantly less clinically significant non-major bleeds occurred in the tinzaparin arm during the six months of treatment  [Tinzaparin has an average molecular weight of 6.5 kDa and is safe and efficacious for both short-term and long-term treatment of VTE in patients with cancer ,106. The=  0.66) . Within =  0.66) . This im=  0.66) . The rec40–0.84) .p = 0.21) in the risk of VTE at 3–6 months, increased to 59% at 12 months, bordering on statistical significance in this patient population (RR: 0.41: p = 0.08) [A subsequent meta-analysis by Laporte et al, which included 24% of patients diagnosed with cancer among 1668 analyzed, demonstrated a non-significant reduction of 38% (RR: 0.62:  = 0.08) . Another = 0.08) ) reached = 0.08) .The TiCAT study, instead, analyzed the efficacy and safety of treatment with tinzaparin as a secondary prophylaxis after a 6-month-long initial treatment period. The rate of clinically relevant bleeds was found to be 0.9% of patients in the first 6 months and 0.6% of patients in the period between 7 and 12 months, while the recurrence rate of VTE was 4.5% during the first period and 1.1% in the following 6 months . Also, tp = 0.024) [Long-term therapy with tinzaparin was also tested as a home treatment in the Home-LITE study . In this= 0.024) . It has Tinzaparin has a favorable pharmacokinetic profile in patients with renal insufficiency. A recent meta-analysis reported that patients with renal insufficiency and cancer treated with tinzaparin had a significant reduction in major bleeding events when compared to those treated with warfarin , demonst2, those with metastases, and those who were ex-smokers, and was associated with no safety issues [In a real-world setting, tinzaparin was administered to 407 patients with cancer, and CAT was included in the Greek study of Management of Thrombosis. A dose of tinzaparin of 8000–12,000 Anti-Xa IU was found to potentially be more effective than the prophylactic dose of ≤4500 Anti-Xa IU, both administered once daily. Such an intermediate dose, along with the administration of erythropoietin, was received more often by patients with a body mass index >30 kg/my issues .The validity of the Ottawa score was assessed in 409 patients who were given prophylaxis with tinzaparin for 6 months. In this study, the application of the Ottawa score did not predict the recurrence of VTE; the overall rate of recurrent VTE was 7.3%  .Enoxaparin is an LMWH that was first approved for medical use in 1993. It has a molecular weight of 4 to 5 kDa and a bioavailability of 91% when administered subcutaneously. Enoxaparin is eliminated mainly into the urine thus requiring a dose adjustment in patients with a creatinine clearance < 30 mL/minute .The efficacy and safety of enoxaparin versus VKAs for long-term therapy of VTE in patients with cancer were demonstrated in two albeit relatively small RCTs: CANTHANOX which enrolled 146 patients and ONCENOX which enrolled 102 patients. Both studies included patients with solid or hematological tumors and VTE ,121. In The comprehension of the mechanism of the anticoagulant action of heparin resulted in the creation of synthetic mimetics, which seemed an attractive and less heterogeneous alternative to natural heparins. In 2001, fondaparinux, a synthetic and selective inhibitor of factor Xa, was registered in the United States and Europe as a new antithrombotic drug. It takes more than 50 steps to synthesize fondaparinux and the overall yield of the process is 0.1% . FondapaUnlike heparin and heparan sulfate, there is little binding and inhibition of factor IIa or other circulating proteins by fondaparinux. Moreover, fondaparinux has been successfully used with other therapeutics .Because of the half-life of 17 h, the bleeding risks of fondaparinux should be carefully assessed. The choice of long-acting anticoagulants requires adequate reversibility by an antidote in cases of bleeding. There is limited experience with the reversal of fondaparinux in the case of bleeding .An assessment of the efficacy, safety, and overall survival when treated with fondaparinux compared to standard initial treatment with LMWH in patients with cancer and VTE was completed in two post hoc analyses from two RCTs. Initially, 237 patients with DVT and 240 patients with PE were treated, respectively, with fondaparinux or enoxaparin and with fondaparinux or UFH. All patients went on to receive vitamin K antagonists. In patients with DVT, the 3-month recurrence rate was 5.4% and 12.7%  in the enoxaparin and fondaparinux recipients, respectively. In patients with PE, the recurrence rate was 8.9 % and 17.2%  in patients treated with fondaparinux and those with UFH, respectively. Overall, no differences in bleeding frequency and overall survival were observed .Similar results regarding the safety and efficacy of fondaparinux in comparison with enoxaparin were obtained in a meta-analysis of four multicenter, randomized, double-blind trials . The incHeparins, including UFH, LMWHs, and heparin derivatives, have been reported to have beneficial effects on cancer survival. Heparin affects the fundamental molecular steps involved in cancer progression, i.e., proliferation, angiogenesis, cell migration, adhesion, and invasion. Multiple mechanisms are responsible for the anticancer properties of heparin and derivatives, the main being heparinase inhibition, and blocking the CXCL12-CXCR4 axis .In vitro studies demonstrated that tinzaparin has anti-angiogenic and anti-metastatic properties . Out of CAT is associated with significant morbidity and mortality and its treatment continues to be a challenge. It is important to both identify patients at high risk of VTE who may benefit from primary prophylaxis and to treat the thrombotic events in the most appropriate manner. To do this, different therapeutic strategies are now available: there is evidence for the efficacy and safety of both injectable anticoagulants extensively reviewed here and of DOACs. Injectable anticoagulation, and in particular LMWHs, may be preferred according to the site of cancer, drug–drug interactions, individual bleeding risk, and the presence of renal and/or hepatic insufficiency. Amongst LMWHs, the usefulness of dalteparin, tinzaparin, and to a lesser extent enoxaparin, has been extensively confirmed in patients with malignancies and all three are approved for the acute and extended treatment of VTE in cancer.Given the evolving trends in the use frequency of different anticoagulant classes , the advAs the prevalence of cancer continues to increase because of the aging population and prolonged survival of patients with advanced malignancies, the burden of CAT will remain a serious clinical reality.


Little is known about the longitudinal association between dietary patterns (DPs) and metabolic disorders in people living at high altitude areas, such as Tibetans. We constructed the first open cohort, with 1832 Tibetans, and collected data in 2018 and in 2022. The metabolic syndrome (MetS) prevalence was 30.1% (32.3% in men and 28.3% in women). Three different DPs were identified: modern DP , urban DP , and pastoral DP . Participants within the third tertile of the urban DP had a 3.42-fold (95% CI 1.65–7.10) higher risk of MetS than those with the first tertile. Modern DP was positively associated with elevated blood pressure (BP) and elevated triglycerides (TAG), while it was inversely associated with low HDL-C. The urban DP was associated with a higher risk of low HDL-C, but a lower risk of impaired fasting blood glucose (FBG). The pastoral DP was a risk factor for impaired FBG, but protective for central obesity and elevated BP. Associations of modern DP with elevated BP, and pastoral DP with low HDL-C, were modified by altitude. In conclusion, among Tibetan adults, DPs were associated with MetS and its components, and the associations were modified by altitude among Tibetans. Metabolic syndrome (MetS) is a cluster of metabolic abnormalities that include central obesity, elevated blood pressure (BP), elevated triglycerides (TAG), low high-density lipoprotein cholesterol (HDL-C), and impaired fasting blood glucose (FBG) . MetS haMetS is a multifactorial disease that is influenced by the interactions of genetic, environmental, and lifestyle factors, and among these, the modifiable factors among Tibetans have attracted considerable interest, especially dietary habits. Diet is an important modifiable factor that can affect MetS risk. The western dietary pattern (DP), characterized by a high consumption of unhealthy elements, for example, sweetened drinks, snacks, and desserts, has been shown to be associated with the risk of developing MetS and its components ,10. On tTibetans live on the world’s highest plateau, and the unique geographical locations of their residences have contributed to the distinct and traditional customs associated with their diet, which mainly includes tsamba, yak milk, Tibetan noodles, butter tea, and Qing cha . Due to This study investigated the effects of DPs on MetS and its components in an open cohort of Tibetan adults and examined the modification effects of altitude on the associations.In this community-based, open cohort study, data were collected twice in 2018 and 2022 ,21. The n = 5), under the age of 18 (n = 31), failed to complete the dietary survey (n = 105), or had missing outcome variables (n = 119). Data were collected using questionnaires, anthropometric measurements, and biomarker tests in 2018 and in 2022, accomplished by well-trained investigators and local medical workers.In this study, 1832 participants completed at least one wave of the 2 surveys that included baseline and follow-up data collection, and 522 of the participants completed two waves of the surveys . The surAll participants gave their informed consent for inclusion before they participated in the study. The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of the Medical College, Qinghai University .The anthropometric and biomarker measurements of participants have been previously detailed . A modifDietary intake information was collected using a revised food frequency questionnaire (FFQ) for assessing self-reported food intake over the previous year. This FFQ was constructed based on similarity of nutrition and local dietary culture, and the details have been previously described . Simply,p < 0.001) indicated that the data were suitable for factor analysis. To determine the number of factors to retain, we considered eigenvalues, scree plots, and interpretability . The Kaiser–Meyer–Olkin (KMO) measure of sampling adequacy (KMO = 0.771) and Bartlett’s test of sphericity  (referred to as residence time). Participants were settled in the community before the investigation. Altitude was determined by the participant’s annual residence time in a pasturing area. Participants who lived in pasturing area for more than 6 months per year were classified as living at very high altitude (>4000 m), while those who lived in pasturing areas less than or equal to 6 months per year were classified as living at high altitude (2800 m).In our analysis, potential confounders were selected by directed acyclic graphs  24]. Th. Th24]. n (%) for categorical variables. Student’s t-test or ANOVA was used to compare means; χ2 test was used to compare percentages. A mixed-effect logistic regression analysis was used to evaluate the associations of the three tertiles of DP scores with MetS and its components. The unadjusted and adjusted models included a random intercept to account for intra-subject variability. The results of the stationary effect were presented as odds ratios (ORs) values and 95% confidence intervals (CIs).Descriptive statistics were calculated using the mean ± standard deviation (SD) for continuous variables or Five models were fit: Crude was an unadjusted model; Model 1 was adjusted for age and sex; Model 2 was further adjusted for marital, education, insurance, household income, smoking, alcohol drinking, and physical activity; Model 3 was further adjusted for altitude; Model 4  was the same as Model 3, but only included those who had both baseline and follow-up data. The linear trend was conducted to test the associations between DPs and MetS and its components, in which DPs were modeled as a continuous variable by using the median score of each tertile across the DP tertiles. We also presented an interaction and subgroups analysis between the three tertiles of DP scores and living altitude among participants who completed two waves of surveys.p-values were 2-sided, and statistical significance was defined as p < 0.05. The multiple comparison adjustments were not used since this is an exploratory study based on observational data [Statistical analyses and graphic plotting were conducted using Stata version 17.0 and R version 4.2.1. OR values and 95% CI for T3 of DPs were visualized using ggplot2 , and thenal data .In 2018 and in 2022, a total of 1832 participants were surveyed in our study, with 522 participants completing two waves of surveys and 1310 participants completing one wave of surveys . Most ofThree different DPs were identified by factor analysis . The modIllustration of the demographic and lifestyle characteristics of 1832 participants who completed the first wave of the surveys based on three tertiles of three DP scores . ParticiThe results of the mixed-effect models showed associations among the three tertiles of three DPs with MetS and its components in Tibetan adults . In ModeConsidering gender difference, the urban DP was inversely associated with MetS only in women, and the ORs (95% CI) were 1.00, 1.28 , and 2.91 , respectively, whereas the association of modern DP with MetS and its components was consistent for both men and women. The intriguing results were found in the pastoral DP, i.e., a high score of pastoral DP (T3) was a protective factor for MetS, central obesity, and elevated BP in men . These fpinteraction = 0.028) and altitude, and between pastoral DP (pinteraction = 0.002) and altitude in relation to elevated BP and low HDL-C, respectively  in the urbanized and semi-urbanized Tibetans adults was higher than that in the native pastoral setting (ranging from 3.6% to 17.3%) ,9,28,29 .1% in thThe modern DP contained a broader range of nutrients, with an increased consumption of unhealthy foods such as offal and processed foods, and healthy foods such as pulses, whole grains, and fresh fruit, which was different from the previously identified western DP . The samThe urban DP is distinguished by higher carbohydrate (refined grains) and choline  levels, and dietary choline, which are precursors of trimethylamine N-oxide (TMAO), may play a role in MetS and its components. The evidence for a positive association between eggs, red meat, and refined carbohydrate consumption and MetS has been observed in different populations ,42,43,44The pastoral DP as a traditional DP is dominated by dairy products and prevents several components of MetS. Some Tibetan habitual foods have been identified as protective factors for MetS , for exaEscherichia Coli to take over, resulting in an increase in the amount of choline catabolized into the precursor for TMAO [The modifiable effect of altitude showed that a high score of pastoral diet was a risk factor for lower HDL-C at very high altitudes, but a protective factor at high altitudes. We hypothesize that hypoxia might affect metabolism, resulting in different outcomes for the same DP. Plasma TMAO concentrations increase with increased consumption of milk and other dairy products, and TMAO concentration has been inversely correlated with HDL-C . A high-for TMAO . The relfor TMAO . The proUnderstanding the influence of DPs on MetS and its components is crucial for developing public health interventions. The high prevalence of MetS is a threat to the long-term health of the Tibetan population with a potentially huge burden on local public health systems. Identifying risk factors for MetS would assist in the development of health promotion strategies to reduce morbidity and mortality in this vulnerable population. The Healthy China 2030 national strategy provides a historical opportunity to develop comprehensive strategies for the wellbeing of local Tibetans. Additionally, our study found interaction effects between altitude and DPs in relation to components of MetS in Tibetan adults, which to some extent fills the gap in the field of public health.This study has several limitations. Firstly, dietary data collected using FFQ were only based on the consumption frequency without portion size and may have inaccurate measurements. However, research has indicated consumption frequency was more important than portion size for interpersonal variation . BecauseIn conclusion, three identified DPs are associated with MetS and its components. The modern DP was popular among young people, and its unhealthy elements may have elevated BP. The negative impact of the urban DP on MetS was further strengthened, and the protective effect of the pastoral DP among Tibetans should be given attention. Furthermore, the interaction of altitude and the pastoral DP relative to HDL-C was discovered for the first time. Public health efforts to promote cultural-adapted healthy eating among the target Tibetan adults are needed, and this study provides some evidence for tailored interventions.


Cardiogenic shock (CS) is increasingly recognized as heterogeneous in its severity and response to therapies. This study aimed to identify CS phenotypes and their responses to the use of vasopressors.The current study included patients with CS complicating acute myocardial infarction (AMI) at the time of admission from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Laboratory and clinical variables were collected and used to conduct latent profile (LPA) analysis. Furthermore, we used a multivariable logistic regression (LR) model to explore the independent association between the use of vasopressors and endpoints.n = 259, 37.5%) was considered as the baseline group; profile 2  was characterized by advanced age, more comorbidities, and worse renal function; and profile 3  was characterized by systemic inflammatory response syndrome (SIRS)-related indexes and acid–base balance disturbance. Profile 3 showed the highest all-cause in-hospital mortality rate (45.9%), followed by profile 2 (43.3%), and profile 1 (16.6%). The LR analyses showed that the phenotype of CS was an independent prognostic factor for outcomes, and profiles 2 and 3 were significantly associated with a higher risk of in-hospital mortality  compared with profile 1. Vasopressor use was associated with an improved risk of in-hospital mortality for profile 2  and profile 3 , respectively. The results of vasopressor use showed no significance for profile 1.A total of 630 eligible patients with CS after AMI were enrolled in the study. The LPA identified three profiles of CS: profile 1 (Three phenotypes of CS were identified, which showed different outcomes and responses to vasopressor use. Cardiogenic shock (CS) is defined as a state of reduced cardiac output due to a primary cardiac problem that results in end-organ hypoperfusion . The mosTherefore, individualized patient care is recommended to improve survival outcomes . The goaTo address the above issues and overcome the shortcomings of previous studies, the purpose of the study was to determine whether phenotypes could be identified using latent profile analysis (LPA) by analyzing routinely collected clinical data. The identified profiles’ responses to widely used vasopressors were also compared.Based on the methods used in our previously published studies –22, we cWe included all critically ill patients with a primary diagnosis of CS after AMI using diagnostic codes of the International Classification of Diseases, 9th revised (ICD-9) and 10th revised (ICD-10) editions . Patients were excluded if they had: (1) the age of less than 18; (2) multiple ICU admissions; (3) a length of stay in the ICU less than 24 h; and (4) incomplete information about study outcome and treatment-related data.Since our goal was to phenotype CS patients based on available data at the time of ICU admission, we only used data that was available within 24 h of ICU admission for further analyses. On the first day of admission, only the initial test results were taken into account for subsequent analyses if patients had received multiple measurements of their vital signs or laboratory tests.aO2), partial pressure of carbon dioxide (PCO2), anion gap, base excess, lactate, activated partial thromboplastin time (aPTT), and international normalized ratio (INR); The eGFR was calculated using the modification of diet in renal disease (MDRD) formula (The extracted variable included: (1) demographics: age, gender, and race; (2) admission type ; (3) vital signs: systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP), heart rate, respiratory rate, temperature, and urine output; (4) laboratory findings: white blood cell (WBC) count, red blood cell (RBC) count, platelet count, red blood cell distribution width (RDW), blood urea nitrogen (BUN), creatinine, estimated glomerular filtration rate (eGFR), glucose, bilirubin, alanine aminotransferase, total calcium, potassium, sodium, chloride, and bicarbonate, pH, arterial oxygen partial pressure  proThe endpoints of our study included all-cause in-hospital and ICU mortality, length of stay (LOS) in ICU and hospital, duration of ventilation, and use of IABP and RRT.Due to the scarcity of the data samples, the missing variables were not simply eliminated. Instead, multiple imputation with chained equations, based on five replications, was used to account for missing data. Variables  have values greater than 20% and were excluded from the study. The remaining variables were subjected to multiple imputation .p values were calculated by BLRT for the k-class model versus (k-1)-class model comparison  or median (interquartile range [IQR]) as appropriate. For categorical variables, the total number (percentage) is presented. Comparisons between groups were made using the Chi-Squared test or Fisher’s exact-test for categorical variables and the analysis of variance for continuous variables as appropriate.After adjusting for some covariates , multivariable logistic regression (LR) was used to determine whether endpoints varied between profiles. Additionally, to investigate the independent influence of CS profile on outcomes, the LR model was also employed to investigate the relationship between vasopressor and outcomes in each profile.p values less than 0.05 were considered statistically significant.All statistical analyses were performed using R software (version 4.1.2). Two-tailed We initially identified 76,540 records of ICU admission from the MIMIC-IV 2.0 database. After the application of inclusion and exclusion criteria, a total of 690 CS patients after AMI were included for analysis . A totalModels with different number of profiles were compared. n = 259, 37.5%) was considered as the baseline profile to compare with other profiles. Profile 2 had the largest proportion of all CS patients  and was characterized by more advanced age, more comorbidities (Charlson comorbidity score), and worse renal function. Profile 3  was characterized by SIRS-related indexes  and acid–base balance disturbance .Clinical features of all three profiles are shown in p < 0.001; profile 3: OR 3.90, 95%CI 2.48–6.13, p < 0.001) and ICU mortality  (Compared with patients in the other two profiles (profiles 1 and 2), patients in profile 3 had the longest length of stay in ICU  and duration of ventilation  .The underlying phenotypes were also verified by using LCA. As shown in p < 0.001) and hospital mortality  (p = 0.015) and profile 3 .Patients in profile 3 showed a high incidence of the use of vasopressors  were, as expected, more prevalent compared to the other two profiles . In the < 0.001) . VasopreCS is a clinical condition that results from ventricular failure due to acute coronary ischemia eventually leading to inadequate peripheral tissue perfusion, tissue and cellular ischemia, end-organ damage and multiorgan system failure . Using rSeveral prognostic classifications or risk stratifications of CS have been reported. For example, based on cardiac output  and volume status , CS patients are typically divided into four phenotypes , 34. AddIn the current study, three distinct profiles of critically ill patients with CS after AMI were determined by using 33 clinical variables obtained from electronic health record (EHR) and the LPA, a kind of unsupervised machine learning technique. The main difference between LPA and other clustering algorithms  is that LPA uses a “model-based clustering” method to derive clusters from a probabilistic model of the data’s distribution , 35–37. Profile 3, characterized by SIRS-related indexes and acid–base balance disturbance, showed the highest all-cause in-hospital and ICU mortality rate. SIRS is frequently observed among patients with AMI or CS and is considered a major pathophysiologic mechanism contributing to worsening shock and organ injury leading to adverse outcomes . JentzerVasopressors are commonly used in the management of patients with CS. This study found that the use of vasopressors was associated with a higher risk of hospital mortality in the whole cohort, profile 2, and profile 3, respectively. However, it was noted that for the patients who did not use vasopressors, the physical signs and laboratory test data are better than those who did. Additionally, vasopressors could increase myocardial oxygen consumption, reduce blood flow to peripheral organs, which might impair microcirculation, and increase cardiac afterload and the risk of arrhythmias. It is important to note that the use of vasopressors can be life-saving in some cases of CS, and their benefits should be weighed against the potential risks on a case-by-case basis. Additionally, other factors such as the timing and dosing of vasopressors may also play a role in their association with increased mortality .The goal of precision medicine is to personalize healthcare with medical decisions, procedures, treatments, or products that are tailored to each patient. A small step toward precision medicine may be the identification of the subphenotypes of ICU patients within a specific diagnostic group. The current research, to the best of our knowledge, is the first to investigate CS subphenotypes using LPA and clinical variables acquired from an electronic health record, which would make it easier to apply the findings to routine clinical practice, and be generalizable to other institutions. In addition, we strictly limited the etiology of CS to avoid the influence of different causes on the research results. Subphenotypes of a disease are usually explored by using genomic information or biomarkers that were not routinely obtained in clinical practice. The identified profiles of CS in the current study may be used and estimated by clinicians in the ICU to quickly assess patients with CS and enhance clinical decision-making, as the key features identified in this study are rapid, easy, and inexpensive laboratory tests. Instead of aiming for a one-size-fits-all solution, these clusters may help clinical trials by developing treatment strategies that are tailored to a CS phenotype. This could pave the way for more individualized health care. Summarily, CS patients exhibit significant heterogeneity, and identification of subphenotypes might help to stratify patients who are most likely to benefit from potential therapies in a clinical trial and facilitate the subsequent randomized controlled trial designs.This study has a few limitations that need to be acknowledged. First, all of the patients who participated in this research came from the MIMIC-III database, so all the data collected in this single-centre retrospective study are not as precise as the dataset analysis collected in prospective cohort study. Second, although it is reasonable to limit the variables used in modeling to those found in clinical practice, this may make it harder to separate profiles. Utilizing genomics and biomarkers together would be preferable. However, the database did not contain any biomarkers that are not typically obtained. Third, this study only discussed three common vasoconstrictor drugs. Other types of vasopressors and their dosages were not discussed because there was limited relevant data in the database. Fourth, instead of providing a definitive profile membership, LPA assigns the profile with the highest posterior probability and provides posterior probabilities for each profile. As a result, the membership status of the profile is unsure. Fifth, our classification tool cannot dynamically evaluate the severity and progression of CS because it only enrolled the CS variable at an early stage. As a result, we will examine the relationship between phenotypes and endpoints within each SCAI stage to characterize the progression of disease severity throughout a hospital stay. Sixth, since the data come mainly from patients in the United States, more clinical analysis is needed to testify whether our results are applicable to the patients with CS in China. Lastly, only the initial test results were taken into account for subsequent analyses if patients had received multiple measurements of their vital signs or laboratory tests, which might not reflect the most serious condition of CS patients.There were three distinct CS phenotypes identified in this study, which showed different mortality outcomes and responses to vasopressor use.The original contributions presented in the study are included in the article/The establishment of the MIMIC-IV database was approved by the Massachusetts Institute of Technology and the Institutional Review Board of Beth Israel Deaconess Medical Center (BIDMC) . Prior tYY, JR, YZ, and ZW conceived the analysis and co-wrote the paper. YY, JX, YZ, and QX extracted all the data. ZW, YY, WX, and PW undertook and refined the inclusion process. YY, JR, JX, and QX undertook the statistical analyses. YY, YZ, and ZW were consulted for clinical issues. All authors contributed to and revised the final manuscript.This work was supported by the National Nature Science Foundation of China (No. 81770244), Medical Science and Technology Youth Cultivation Plan (Nos. 17QNP013 and 20QNPY038), Shanghai Municipal Commission of Science and Technology (No. 17ZR1439100), Shanghai Shenkang Medicine Developing Project (No. SHDC12014107), and Shanghai Science and Technology Committee Medicine Leading Project (No. 15411960100).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


While stroke is one of the most dissected topics in neurology, the primary prevention of PFO-related stroke in young patients is still an unaddressed subject. We present a study concerning clinical, demographic, and laboratory factors associated with stroke and transient ischemic attack in patients with patent foramen ovale (PFO), as well as comparing PFO-patients with and without cerebrovascular ischemic events (CVEs).Consecutive patients with PFO-associated CVEs were included in the study; control group was selected from patients with a PFO and no history of stroke. All participants underwent peripheral routine blood analyses, as well as, on treating physician's recommendations, screening for thrombophilia.p = 0.04). PFO size was similar between patients and controls. Patients with CVEs had more often hypertension , p = 0.007. No significant differences were found between the two groups with regard to routine laboratory tests and thrombophilia status. Hypertension and gender were identified in a binomial logistic regression model as independent predictors for CVEs, but with an area under the ROC curve of 0.531, suggesting a very poor level of discrimination between the two groups.Ninety-five patients with CVEs and 41 controls were included. Females had a significantly lower risk of CVEs than males (There is little difference between patients with PFO with and without CVEs in terms of PFO size and routine laboratory analyses. While still a controversial topic in the specialty literature, classic first-level thrombophilic mutations are not a risk factor for stroke in patients with PFO. Hypertension and male gender were identified as factors associated with a higher risk of stroke in the setting of PFO. Patent foramen ovale (PFO) is one of the most common congenital heart defects in adults  and has Special efforts have been made to standardize the treatment of patients with stroke and PFO and also to detect those suitable for minimally invasive PFO closure , 4. SincNevertheless, while at this moment significant data can be found on the demographic, anatomical, and biological factors of patients with PFO and stroke, there is sparse information concerning the prevalence of these factors in patients with PFO and no cerebral ischemic events. Moreover, although significant data can be found on the selection of patients with PFO at high risk of stroke recurrence, there is little data on primary stroke prevention in persons with PFO.We present a study whose main goal was to find specific clinical, demographic, and laboratory factors that can indicate cerebral ischemic event risk in patients with PFO.The current study was observational and aimed to identify risk factors associated with stroke/TIA in patients with PFO. A secondary goal was to characterize cerebrovascular events in patients with PFO.Participants were selected consecutively from patients hospitalized or referred to the Neurology Department of the University Emergency Hospital of Bucharest, Romania, between October 2019 and May 2022. The main inclusion criterion was a diagnosis of patent foramen ovale (PFO)-associated stroke or transient ischemic attack (TIA), defined as stroke or TIA in patients with a PFO, and no vascular or cardiac disorders predisposing to stroke, except for PFO; patients having lacunar strokes were excluded. All participants had to be between 18 and 65 years of age to be eligible for enrolment. For the purpose of brevity, the history of stroke or TIA will be referred as to a cerebrovascular event (CVE). The control group was selected from patients presenting to the same department, in the same time frame, for headache or vertigo, in whom cerebral vascular events were excluded, and who had no history of stroke/TIA, inflammatory central nervous system (CNS) disorders, or other systemic disorders with possible CNS involvement; they were invited to undergo contrast trans-cranial doppler (c-TCD) with intravenous injection of agitated saline and, in those with a positive test, a subsequent transesophageal echocardiography (TEE).Demographical data, cardio- and cerebrovascular risk factors  were recorded for both groups. For stroke patients, the involved or symptomatic cerebral vascular territory, National Institutes of Health Stroke Scale (NIHSS) score at admission and Modified Rankin Score (mRS) score at discharge were also recorded. Risk of Paradoxical Embolism (RoPE), a score developed to identify which cryptogenic strokes may be attributable to PFO, was also calculated for patients with a history of CVE.For the exclusion of other causes of ischemic stroke, all patients included in the study group had normal cervical and cerebral vascular ultrasonography, computed tomography (CT) or magnetic resonance (MR) angiography, and 24-h cardiac rhythm monitoring.Screening for right-to-left shunt (RLS) was made for both groups using c-TCD with intravenous injection of agitated saline.All participants in the study underwent TEE in different centers by using two types of echo machines and dedicated TEE probes . All patients received oral local anesthesia and additional IV sedation, if needed. They were examined after transesophageal intubation from standard echocardiographic views, according to the ASE guideline for PFO assessment , and INR levels.On treating physician's recommendations, 115 of the patients and controls underwent screening for thrombophilia, with tests including serum homocysteine, protein C, protein S, and lupus anticoagulant levels, the activity of prothrombin and antithrombin III, and factor V Leiden, Plasminogen activator inhibitor-1 (PAI1) and Methylenetetrahydrofolate reductase (MTHFR) mutations. Since thrombophilia testing is not covered by the national insurance plan for patients without a thrombotic event, and due to the fluctuating availability of these tests in our hospital, not all patients had thrombophilia testing. The exact number of patients who were tested for prothrombotic state is depicted in the ® TCD device with DWL® routine software (Doppler-Box™). All examinations were made by the same examiner using a standard protocol, which consisted of insonation of both middle cerebral arteries (MCAs) at 55 mm using 2 MHz PW monitoring probes mounted on a DiaMon® headset, DWL USA, Inc. A 23-gauge cannula was inserted in one of the antecubital veins and one milliliter (mL) of blood was extracted from the patient and mixed with 1 mL of air and 8 mL of 0.9% saline solution. The compound was mixed ten times using two syringes and a three-way stopcock and injected into the intravenous cannula. The patient was asked to perform two Valsalva maneuvers. The total number of microbubbles that passed through both MCAs was counted. The grade of the right-to-left intracardiac shunt was estimated using Spencer's logarithmic scale (SLS)  .t-test was conducted for continuous variables, and the χ2 or Fisher's exact test was used for categorical variables. Outliers were kept in the analysis as they depicted actual clinical scenarios. The homogeneity of variances was assessed by Levene's test of homogeneity of variances. Mann-Whitney U test and Kruskal-Wallis H tests were run to determine if there were differences between two and three or more groups of non-normally distributed variables (via the Box-Tidwell (1962) procedure. To determine the relationships between variables, the Pearson correlation test was performed. In the case of non-linearity, Spearman's rank-order correlation test was run. Binomial logistic regression was run to analyze the effects of clinical variables on the likelihood of a cerebral ischemic event. Variables were selected based on the univariate regression analysis results and introduced in the model using the one-step enter method. Crude and adjusted odds ratios (OR) and their respective 95% confidence intervals (CI) were calculated and reported.For continuous variables, the Shapiro-Wilk test was performed to determine the normality of the data distribution. Continuous variables with normal distribution are presented as mean ± standard deviation, while those with non-normal distribution are presented as median (interquartile range). Categorical variables are reported as the rate (percentage). For comparing differences in demographical, clinical, or laboratory characteristics between PFO patients with cerebral ischemic events and controls, the independent ariables . LineariThe study was approved by the Board of Ethics of the University Emergency Hospital of Bucharest. All patients signed a consent stating their non-opposition to the use of medical data, including its publication. The research was performed in accordance with the Declaration of Helsinki and GDPR standards.n = 53 males, mean age = 42.06 ± 11.05); of those, 73 had a stroke  and 22 had a TIA . For controls, 189 candidates were initially considered; after undergoing c-TCD, patients without RLS were excluded, and 41 participants were finally included .Ninety-five patients fulfilling the inclusion criterion were identified , the OR of CVE in females vs. males being 0.792 .Mean age for CVE patients (42.06 ± 11.05) and controls (42.66 ± 10.73) was not statistically significantly different t(134) = 0.291, n = 59), followed by the posterior circulation , and the anterior cerebral artery (ACA) territory ; in 3.2% (n = 3) of patients, stroke occurred in multiple cerebral vascular territories   = 0.165, p = 0.186.Median NIHSS score at admission of patients having a PFO-associated stroke was 3.5 (IQR = 6). A Spearman's rank-order correlation was run to assess the relationship between PFO shunt size and stroke severity, as assessed by the NIHSS score. There was no statistically significant correlation between PFO shunt size and stroke severity rn = 62, 84.9%), the remaining having mRS score of 3 , and respectively of 4 . Characteristics of PFO-associated stroke depending on PFO shunt size estimated on Spencer's logarithmic scale are depicted in Group comparison section.At discharge, most of the stroke patients had mRS scores between 0–2  =0.633, n = 33, 34.7%) than controls , p = 0.007. It was also noticed that patients with a history of cerebral ischemic events had more frequent chronic kidney disease (CKD) and diabetes mellitus compared to controls but were less often smokers and had a lower smoking index; however, this did not reach statistical significance.When analyzing the differences in laboratory tests and cardiac- and cerebral risk factors between the two groups, patients with CVEs had statistically significant more often hypertension  compared to controls , Of all patients included in the study, 115 underwent screening for classical thrombophilia tests. The exact number of patients having each one of the tests is depicted in the p = 0.014) and gender . Nevertheless, the area under the ROC curve was 0.531, which, according to Hosmer et al.  have no role in PFO-associated stroke. Moreover, thrombophilia and intracardiac shunt size, though highly controversial subjects, have no role in stroke occurrence in patients with PFO. Interestingly, the only two factors associated with a higher risk of stroke in our cohort were hypertension and male gender. The findings of this study represent a cornerstone in the possible primary prevention of stroke in young patients with PFO, and in detangling the unknown factors that contribute to cerebral ischemic events in the large PFO population.These findings, along with the paucity of data concerning primary prevention of stroke in patients with PFO are emphasizing the need for further large sample sized studies.Our study has a major strength. This is one of the first studies to describe the differences between patients with PFO with and without a first ischemic event, thus marking the risk factors that might be involved in the pathogenesis of an ischemic stroke in patients with PFO. However, our study has several limitations. Firstly, the study group was significantly larger than the control group, and the control group comprises a higher ratio of females than the study group. In general, young stroke patients are more frequently males; however, in this particular study, the significance of the statistical association may have been overestimated by choosing a female-predominant control group. A headache-free PFO carriers group should be the ideal control group. While the authors are aware of these major limitations, we believe it reflects the real-life data and the profile of an Emergency Hospital. Another limitation is the absence of data concerning morphological aspects of the PFO, which may have had an important role in differentiating patients with PFO and stroke of those without CVE; while this data is not available at the moment, it will be presented in a future report. Additionally, thrombophilia tests were not available for all patients included in the study and were performed only once, and in the case of patients with ischemic stroke, these results may have been influenced by the acute inflammatory changes that occur in patients with acute stroke. Finally, another limitation is that being a single-center study, the results may limit the generalizability of the study.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Board of Ethics of the University Emergency Hospital of Bucharest. The patients/participants provided their written informed consent to participate in this study.RB, FA, AR, and SB were involved in protocol development and patient recruitment. RB and ET were involved in the data analysis. RB and NG wrote the first draft of the manuscript. CT and BP reviewed and edited the manuscript and approved the definitive version of the manuscript. RB edited and submitted the final paper. All authors contributed to the article and approved the submitted version.


Stair climbing intervention could be suggested to address low occupational physical activity amongst university students and employees. Strong evidence showed the effectiveness of signage intervention in increasing stair use in public areas. However, evidence in worksite settings, including university settings, was inconclusive. This study aimed to evaluate the process and impact of a signage intervention to increase stair use at a university building using the RE-AIM framework.We conducted a non-randomised controlled pretest-posttest study to examine the effect of signage intervention placed in university buildings in Yogyakarta (Indonesia) between September 2019 and March 2020. The process of designing the signage involved the employees in the intervention building. The main outcome was the change in the proportion of stair use to elevator use measured by manual observations of video recordings from closed-circuit television. A linear mixed model examined the intervention effect by controlling the total visitor count as a confounder. RE-AIM framework was used in the process and impact evaluation.The change in the proportion of stair climbing from baseline to the 6th-month phase at the intervention building (+0.067 (95% CI = 0.014–0.120)) was significantly higher than that of the control building. However, the signs did not change the proportion of the stair descending at the intervention building. The signs were potentially viewed 15,077–18,868 times/week by visitors.Signage intervention using portable posters could easily be adopted, implemented, and maintained in similar settings. A co-produced low-cost signage intervention was found to have a good reach, effectiveness, adoption, implementation, and maintenance dimension. Stair cSeveral systematic reviews reported that motivational signage posted near stairs and elevators could increase stair use in public areas . HoweverOur study aimed to examine the effectiveness of motivational signage using a specific message on stair use and to report its process evaluation using the RE-AIM  Framework to improve its external validity and to inform future trials . We exam2.thaiclinicaltrials.org (TCTR20220804005) and was ethically approved by the Medical and Health Research Ethics Committee Faculty of Medicine, Public Health, and Nursing Universitas Gadjah Mada (Ref No: KE/FK/0973/EC). This pragmatic trial was reported in line with the Consolidated Standards of Reporting Trials (CONSORT) statements for pragmatic, pilot, and feasibility trials  has been running since July 2019. The same team supervised health promotion programs at the two sites. They targeted the same fields of intervention, including health literacy, physical activity, nutrition, mental health, zero tolerance for smoking, alcohol consumption, and illicit drug use, zero tolerance for violence, bullying, and sexual harassment, and safe buildings and healthy environments.In choosing the intervention and control buildings, the following characteristics were sought: (1) Two buildings with an almost similar number of occupants, (2) Two buildings with almost similar staircase and elevator design and placement, as well as the numbers of the stories . We did 2.2.W = 0.998, p < 0.001). The daily observations in workdays per 2-h time slot  were written down in a spreadsheet at all locations. The proportion of stair use per time slot was calculated by dividing the number of people taking the stair from the ground floor by the number of people entering the elevator as a proportion of stair climbing and by dividing the number of people taking the stair to the ground floor by the number of people leaving the elevator as a proportion of stair descending.Manual observations from video recordings of closed-circuit television (CCTV) were independently conducted from Monday to Friday in each phase by two observers blinded to the intervention status. Therefore, visitors were not aware of being observed. The speed of the video recordings was accelerated two times to reduce observers’ burden, and the resolution was lowered to protect visitors’ privacy. In addition to counting the visitor journey, whether entering the lift, exiting the lift, climbing the stairs, or descending the stairs, observers also took note of the incidence of stair accidents. The two observers statistically significantly agreed in their counts  Framework . Reach w2.5.We used a co-production approach by involving employees at the end of the value chain to get the optimal benefits of a collaborative approach whilst minimising resource constraints . A surve3.3.1.A total of 93,000 counts from 75 observations resulting from five sessions per day for 5 days during three periods were analysed. There were 28,823 staircases and 64,177 elevator uses on the ground floor of two observed buildings, and no stair accidents occurred. The total visitor counts at the 3rd-month phase were lower than the baseline and 6th-month phases at both buildings . In the p < 0.001), with an unadjusted median of 0.408 (0.12–1.03) and 0.224 (0.03–0.52), respectively. In the 3rd month phase, there were decreases in the stair climbing rate per time slot in both buildings, but there was no significant difference in the change between the two buildings. In the 6th month phase, the stair climbing rate per time slot in the intervention building significantly increased by +0.067 but no change in the control building (p < 0.001) on the proportion of stair climbing per time slot.The stair climbing rate per time slot from the ground floor in the intervention building during the baseline phase was higher than that in the control building  between the stair descending rate to the ground floor per time slot in the intervention building  and the control building  during the baseline phase. There were decreases in descending stair proportion per time slot at the 3rd-month phase and returned to the baseline at the 6th-month phase in both intervention and control buildings. There was no significant difference in the changes between those two buildings (p = 0.312).There was a significant difference (uildings . Total v3.2.Two faculty employees participated in the design and implementation of the stair-use intervention. The implementation of the intervention was described as easy. They found that the stair posters could be easily installed at the point of choice and moved to another place if other posters need to be placed in the same location since the motivational prompts were portable standing posters.3.3.Employees could easily implement the recommended strategy from the research team to introduce the posters at the point of choice without changing the strategy. The intervention cost was 450,000 IDR for each poster and was paid by the research team’s funding. Employees in the intervention building considered the intervention’s cost affordable.3.4.The two stair posters were maintained after the end of the study. Considering the easy-deliver and low cost of the intervention, the employees in the intervention building planned two additional intervention phases to test the effect of different new posters with different messages designed by involving students’ opinions and improving the stairwell’s aesthetic by installing colourful stair stickers. Informal opinions from the HPU units from the other faculties suggested that the intervention will be implemented in their faculties.4.We described the process of designing the stair-use intervention and evaluating the intervention using the RE-AIM framework . A low-cThe 6.7% increase in stair climbing in our study was higher than a previous systematic review reported, which showed a median increase of 0.8% with a motivational sign only . Our resOur study also found that employees easily adopted portable stair posters. This sign might solve overcoming adoption barriers reported by a previous study . PortablOur study had several strengths. It employed a controlled design with two identical buildings and objective monitoring with less burden of observers, less observer bias, and less contamination bias. In addition, we also controlled total visitors as a confounder , 35, 36.5.Our study strengthens previous works on the usefulness of low-cost stair-use interventions at worksites using signage. Based on process evaluation using the RE-AIM framework, co-producing the intervention with employees was associated with the intervention’s effectiveness, adoption, and implementation. Effects of intervention on stair use amongst various genders, ages, and statuses of visitors, as well as effects on health outcomes, need to be elucidated in future studies.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Medical and Health Research Ethics Committee Faculty of Medicine, Public Health, and Nursing Universitas Gadjah Mada. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.ZM: conceptualization, funding acquisition, and supervision. WW: conceptualization, funding acquisition, methodology, and writing–review and editing. MS: methodology, investigation, project administration, funding acquisition, and writing–review and editing. RW: conceptualization, methodology, investigation, formal analysis, writing–original draft, and writing–review and editing. DA: conceptualization, writing–review and editing, and supervision. All authors contributed to the article and approved the submitted version.This work was supported by the Community Empowerment Grant, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada. This funding source had no role in the design of this study and will not have any role during its execution, analyses, interpretation of the data, or decision to submit results.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.