Stratified Analysis Research Articles

#838 Comparison of the incidence of proteinuria and eGFR change between febuxostat and topiroxostat users

Abstract Background and Aims Febuxostat and topiroxostat are novel non-purine selective xanthine oxidoreductase (XOR) inhibitors, commonly available for the treatment of hyperuricemia in Japan. The previous studies suggested that febuxostat and topiroxostat might have renoprotective effects. It is important to compare febuxostat with topiroxostat on the renoprotective effects for the selection of the XOR inhibitors in clinical settings. However, comparative data between febuxostat and topiroxostat on renal function and proteinuria are limited. Therefore, the present study aimed to compare renal function and proteinuria between febuxostat and topiroxostat. Method We conducted a retrospective cohort study using databases provided by DeSC Healthcare Inc. (Tokyo, Japan). We identified 17,446 individuals (11.8% women; mean age 67.4 years) without estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2, a history of cardiovascular disease and proteinuria at baseline. The claims database includes all inpatient, outpatient, and pharmacy claims received from insurers during the study period. The use of febuxostat and topiroxostat was defined as having claims of dispensing (or prescribing) febuxostat and topiroxostat within 1 year before the baseline health check-up, respectively. Analyses were performed for the individuals with eGFR <60 mL/min/1.73 m2 and those with eGFR ≥60 mL/min/1.73 m2 separately. The Cox proportional hazard model was used to assess the adjusted hazard ratio (HR) for the incidence of proteinuria in the topiroxostat users compared with the febuxostat users. We calculated the annual rate of eGFR change as the slope of the linear regression between eGFR and year for each participant. Changes in eGFR were compared between the febuxostat users and the topiroxostat users using multiple regression analysis. We performed stratified analyses according to sex, age (<75 and ≥75 years), body mass index (BMI) (<25 and ≥25 kg/m2), hypertension, and diabetes mellitus. Covariates included sex, age, BMI, current smoker, current drinker, diabetes mellitus, dyslipidemia, systolic blood pressure, use of angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker, dihydropyridine calcium channel blocker, or the other antihypertensive drugs, serum uric acid level, and baseline eGFR. Results During a mean follow-up of 1.79 years, 1,433 participants developed proteinuria. In the non-diabetic individuals with eGFR ≥60 mL/min/1.73 m2, the fully adjusted HRs (95% confidence interval, p-value) for the incidence of proteinuria in the topiroxostat users compared with in the febuxostat users were 0.60 (0.40–0.91, p= 0.016). We found a significant interaction between diabetes mellitus and the use of topiroxostat on the incidence of proteinuria. No significant differences were observed in eGFR change between the two treatment groups with eGFR <60 and ≥60 mL/min/1.73 m2. When we evaluated the eGFR change between the two groups with eGFR <60 and ≥60 mL/min/1.73 m2 using the eGFRCKD-EPI, we found no significant differences in eGFR change between the two groups with eGFR <60 and ≥60 mL/min/1.73 m2. Conclusion The topiroxostat prevalent-users had a lower risk of the incidence of proteinuria than the febuxostat prevalent-users in the non-diabetic individuals with eGFR ≥60 mL/min/1.73 m2. Our findings suggested that topiroxostat might be more effective than febuxostat in preventing proteinuria in non-diabetic individuals with eGFR ≥60 mL/min/1.73 m2.

Association Between Vitamin B12 Intake and Mortality in Patients with Colorectal Cancer: The US National Health and Nutrition Examination Survey, 1999-2018.

Vitamin B12 plays a role in DNA methylation, influencing the 1-carbon cycle; However, its effect on colorectal cancer (CRC) mortality remains uncertain. This study assessed the relationship between vitamin B12 intake and all-cause and cancer-specific mortality among CRC patients. We analyzed data from the NHANES from 1999 to 2018, using multivariable Cox regression, competing risk model, Kaplan-Meier survival curves, and stratified analysis with interaction effects. The studied involved 4,554 cancer patients (mean age 65.8 years, 47.6% males). Results from multivariate Cox regression indicated that each additional 1 mcg/day of dietary vitamin B12 independently increased the risk of all-cause (HR, 1.07; 95% CI: 1.04-1.09, p < 0.001) and cancer-specific mortality (HR, 1.04; 95% CI, 1.02-1.06; p < 0.001). Kaplan-Meier curves indicated a higher risk of all-cause mortality with increased vitamin B12 intake (Log rank p = 0.01). Subgroup analysis suggested that higher vitamin B12 intake correlated with increased all-cause mortality risk, especially in individuals with higher protein (HR, 1.04; 95% CI, 1.02-1.06; p = 0.019) or carbohydrate intake (HR, 1.03; 95% CI, 1.01-1.05; p = 0.04). Thus, higher vitamin B12 intake correlates with increased all-cause and cancer-specific mortality in CRC patients, particularly those with higher protein or carbohydrate intake.

The association between non-alcoholic fatty liver disease and urinary incontinence among adult females in the United States.

Non-alcoholic fatty liver disease (NAFLD) and urinary incontinence (UI) are both highly prevalent and age-related diseases. Nevertheless, the link between NAFLD and UI is unclear. Hence, the study was designed to evaluate the association between the NAFLD and UI (including UI types) in a nationally representative sample of United States (US) female adults. We conducted this study used data from U.S. female adults in the National Health and Nutrition Examination Survey (NHANES) 2017-March 2020 (pre-pandemic) cycles. The diagnosis of NAFLD is based on Vibration controlled transient elastography (VCTE) and absence of know liver diseases and significant alcohol consumption. The diagnosis and types of UI were assessment using a self-report questionnaire. Multivariable logistic regression models were used to analyze the association between NALFD and UI. Stratified analyses based on age, obesity, race, educational level, married status, PIR, and smoking status were conducted. Of the 2149 participants, the mean (95% CI) age was 53.9 (52.7-55.0), 686 (61.1%) were Non-Hispanic White. UI was significantly more common in participants with NAFLD [490 (64.7%)] than those without NAFLD [552 (44.9%)]. Adjusted for age, race/ethnicity, marital status, educational level, family poverty income ratio (PIR) status, alanine aminotransferase (ALT), aspartate aminotransferase (AST), smoking status, obesity, type 2 diabetes mellitus (T2DM), hypertension and insulin resistance (IR) in a multivariable logistic regression model, NALFD were associated with UI [OR: 1.93, 95%CI 1.23-3.02, P = 0.01] and urge UI [OR: 1.55, 95%CI 1.03-2.33, P = 0.03], while patients with NAFLD did not show an increased odds in stress UI and mixed UI when compared with those without NAFLD subject (P > 0.05). In the subgroup analyses, NAFLD remained significantly associated with UI, particularly among those participants without obesity (OR: 2.69, 95% CI 1.84-4.00) and aged ≥ 60 years (OR: 2.20, 95% CI 1.38-3.51). Among US female adults, NAFLD has a strong positive correlation with UI. Given that NAFLD is a modifiable disease, these results may help clinicians to target female patients with NAFLD for treatments and interventions that may help prevent the occurrence of UI and reduce the symptoms of UI.

Association of the triglyceride-glucose index and its related parameters with frailty

BackgroundFrailty is a dynamic geriatric condition. Limited studies have examined the association of the triglyceride-glucose (TyG) index and its related indicators [TyG index, triglyceride glucose-waist to height ratio (TyG-WHtR), triglyceride glucose-waist circumference (TyG-WC), and triglyceride glucose-body mass index (TyG-BMI)] with frailty, and the potential links among them remain unclear. On the basis of data from the National Health and Nutrition Examination Survey (NHANES), this study investigated the potential relationships of the TyG index and its related indices with frailty.MethodsThis research included 7,965 participants from NHANES 2003–2018. The relationship of the TyG index and its related indices with frailty was investigated with binary logistic regression analyses, restricted cubic spline (RCS), and receiver operating characteristic (ROC) curve. Potential influences were further investigated through stratified analyses and interaction tests.ResultsThe prevalence of frailty in the participants of this study was 25.59%, with a average frailty index of 0.16 (0.00). In the three regression analysis models, the continuous TyG index and its associated indices were positively associated with frailty. In addition, quartiles of TyG, TyG-WC, TyG-WHtR, and TyG-BMI were significantly associated with increased frailty prevalence in the fully adjusted models (TyG Q4 vs. Q1, OR = 1.58, 95% CI: 1.19, 2.09, P = 0.002; TyG-WC Q4 vs. Q1, OR = 2.40, 95% CI: 1.90, 3.04, P < 0.001; TyG-WHtR Q4 vs. Q1, OR = 2.26, 95% CI: 1.82, 2.81, P < 0.001; TyG- BMI Q4 vs. Q1, OR = 2.16, 95% CI: 1.76, 2.64, P < 0.001). According to RCS analysis, TyG, TyG-WC, TyG-WHtR, and TyG-BMI were linearly and positively associated with frailty. ROC curves revealed that TyG-WHtR (AUC: 0.654) had greater diagnostic value for frailty than TyG (AUC: 0.604), TyG-BMI (AUC: 0.621), and TyG-WC (AUC: 0.629). All of the stratified analyses and interaction tests showed similar results.ConclusionsElevated TyG and its associaed indices are associated with an increased prevalence of frailty. Reasonable control of blood glucose and blood lipids, and avoidance of obesity, may aid in reducing the occurrence of frailty in middle-aged and older adults.

Serum vitamin D and obesity among US adolescents, NHANES 2011–2018

Background and objectivesChildhood obesity is highly prevalent worldwide. We aimed to assess whether serum 25-hydroxyvitamin D was associated with general/central obesity among US adolescents, and further to explore the mediatory impact of homeostasis model assessment of insulin resistance (HOMA-IR) on this association.MethodsThis study is cross-sectional in design. Study adolescents were enrolled from the National Health and Nutrition Examination Survey (NHANES), 2011–2018. Serum 25-hydroxyvitamin D categories associated with general (indexed by body mass index) and central (indexed by waist circumference to height ratio) obesity were regressed. The possible mediatory effect of HOMA-IR on this association was explored. The nonlinear and dose-response association was examined by restricted cubic spline (RCS) test.ResultsTotal 2,696 adolescents were eligible for inclusion, and the mean age of all adolescents was 15.4 years. Overall, the percentage of general and central obesity was 38.0% and 38.6%, respectively. Compared with adolescents with sufficient vitamin D, adolescent with deficient and insufficient vitamin D intake were associated with general obesity and central obesity; fully-adjusted OR for general obesity was 1.602 (95% CI: 1.161–2.211) and 1.659 (1.385–1.986), and fully-adjusted OR for central obesity was 2.025 (1.445–2.837) and 1.557 (1.287–1.884), respectively, while there was no observable significance in adolescents with possibly harmful vitamin D. The proportion mediated by HOMA-IR was estimated to be 31.7% for global obesity and 50.3% for central obesity (both P &amp;lt; 0.05). More stratified analyses were presented, and identified that the association with general obesity was particularly present among Mexican American, while with central obesity among Non-Hispanic Black adolescents.ConclusionsOur findings indicate that deficient or insufficient 25-hydroxyvitamin D concentrations were associated with the significant risk of general and central obesity among US adolescents, and approximately 30% and 50%, respectively, of these associations were mediated by HOMA-IR.

Relationship between triglyceride-glucose index and blood eosinophils among asthmatic individuals in the USA

BackgroundPresently, the majority of investigations primarily evaluate the correlation between triglyceride-glucose index (TyGI) with lung diseases, such as asthma. However, they did not delve into the correlation between TyGI and inflammatory responses related to the disease. Few studies have explored the association between TyGI and blood eosinophil count (BEOC). Thus, National Health and Nutrition Examination Survey (NHANES) data were used in this study to evaluate the correlation between TyGI and BEOC in individuals with asthma.MethodsThis study investigated 3902 individuals with asthma. Linear regression analysis was performed to investigate the association between TyGI and BEOC in patients with asthma. Subsequently, the GAM and threshold effect models were used to validate the presence of either a nonlinear or linear association between TyGI and BEOC. Finally, stratified analyses were conducted to ascertain the correlations between different subgroups.ResultsFour linear regression models confirmed a positive linear correlation between TyGI and BEOC in patients with asthma. In Model D, which controlled for all covariates, BEOC increased by 12.44 cells/uL for every extra unit of TyGI. The GAM and threshold effect models further verified the positive linear correlation between TyGI and BEOC. The XGBoost model indicated that the six most significant variables influencing BEOC, in order of relative importance, were age, cholesterol level, body mass index (BMI), poverty-to-income ratio (PIR), BNEUC, and TyGI.ConclusionsIn patients with asthma, the study discovered a linear positive correlation between TyGI and BEOC. This indicates a potential connection between TyGI and alterations in the immune status of individuals with asthma, which may help detect abnormalities in a timely manner and provide a reference for clinical decision-making. This study offers fresh insights for the future exploration of the management and treatment of asthma.

U-shaped association between fasting blood glucose and suicide attempts in Chinese patients with first-episode drug-naïve major depressive disorder

BackgroundEvidence regarding the relationship between fasting blood glucose (FBG) and suicide attempts (SA) in patients with major depressive disorder (MDD) was limited. Therefore, the objective of this research was to investigate whether FBG was independently related to SA in Chinese patients with first-episode drug-naïve (FEDN) MDD after adjusting for other covariates.MethodsThe present study was a cross-sectional study. A total of 1718 participants (average age: 34.9 ± 12.4 years, 65.8% females) with FEDN MDD were involved in a hospital in China from September 2016 to December 2018. Multiple logistic regression analysis and smooth curve fitting were used to estimate the association between FBG and the risk of SA. The threshold effect was examined by the two-piecewise linear regression model. Interaction and stratified analyses were conducted according to sex, education, marital status, comorbid anxiety, and psychotic symptoms.ResultsThe prevalence of SA in patients with FEDN MDD was 20.1%. The result of fully adjusted binary logistic regression showed FBG was positively associated with the risk of SA (odds ratio (OR) = 1.62, 95% CI: 1.13–2.32). Smoothing plots also revealed a nonlinear relationship between FBG and SA, with the inflection point of FBG being 5.34 mmol/l. The effect sizes and the confidence intervals on the left and right sides of the inflection point were 0.53 (0.32–0.88, P = 0.014) and 1.48 (1.04–2.10, P = 0.030), respectively.ConclusionsA U-shaped relationship between FBG and SA in FEDN MDD patients was found, with the lowest risk of SA at a FBG of 5.34 mmol/l, indicating that both the lower and higher FBG levels may lead to an increased risk of SA.

Flow cytometry-based peripheral blood analysis as an easily friendly tool for prognostic monitoring of acute ischemic stroke: a multicenter study

Background and objectiveAcute ischemic stroke (AIS) is a leading cause of mortality, severe neurological and long-term disability world-wide. Blood-based indicators may provide valuable information on identified prognostic factors. However, currently, there is still a lack of peripheral blood indicators for the prognosis of AIS. We aimed to identify the most promising prognostic indicators and establish prognostic models for AIS.Methods484 subjects enrolled from four centers were analyzed immunophenotypic indicators of peripheral blood by flow cytometry. Least absolute shrinkage and selection operator (LASSO) regression was applied to minimize the potential collinearity and over-fitting of variables measured from the same subject and over-fitting of variables. Univariate and multivariable Cox survival analysis of differences between and within cohorts was performed by log-rank test. The areas under the receiving operating characteristic (ROC) curves were used to evaluate the selection accuracy of immunophenotypic indicators in identifying AIS subjects with survival risk. The prognostic model was constructed using a multivariate Cox model, consisting of 402 subjects as a training cohort and 82 subjects as a testing cohort.ResultsIn the prospective study, 7 immunophenotypic indicators of distinct significance were screened out of 72 peripheral blood immunophenotypic indicators by LASSO. In multivariate cox regression, CTL (%) [HR: 1.18, 95% CI: 1.03–1.33], monocytes/μl [HR: 1.13, 95% CI: 1.05–1.21], non-classical monocytes/μl [HR: 1.09, 95% CI: 1.02–1.16] and CD56high NK cells/μl [HR: 1.13, 95% CI: 1.05–1.21] were detected to decrease the survival probability of AIS, while Tregs/μl [HR:0.97, 95% CI: 0.95–0.99, p=0.004], BM/μl [HR:0.90, 95% CI: 0.85–0.95, p=0.023] and CD16+NK cells/μl [HR:0.93, 95% CI: 0.88–0.98, p=0.034] may have the protective effect. As for indicators’ discriminative ability, the AUC for CD56highNK cells/μl attained the highest of 0.912. In stratification analysis, the survival probability for AIS subjects with a higher level of Tregs/μl, BM/μl, CD16+NK cells/μl, or lower levels of CD56highNK cells/μl, CTL (%), non-classical monocytes/μl, Monocytes/μl were more likely to survive after AIS. The multivariate Cox model showed an area under the curve (AUC) of 0.805, 0.781 and 0.819 and 0.961, 0.924 and 0.982 in the training and testing cohort, respectively.ConclusionOur study identified 7 immunophenotypic indicators in peripheral blood may have great clinical significance in monitoring the prognosis of AIS and provide a convenient and valuable predictive model for AIS.

When is neoadjuvant chemotherapy indicated in rectal neuroendocrine tumors? An analysis of the National Cancer Database

BackgroundRectal neuroendocrine tumors (rNET) are rare and challenging to manage. While most patients with small rNET can be definitively treated with local excision, the role of chemotherapy in general and neoadjuvant therapy particularly in managing advanced rNET has not been well established. Therefore, this study aimed to determine which patients with rNET may gain a survival benefit from neoadjuvant chemotherapy.MethodsA retrospective cohort analysis of all patients who underwent surgical resection of rNET in the US National Cancer Database (NCDB) (2004–2019) was performed. First, univariate and multivariate Cox regression analyses were performed to determine the independent predictors of poor overall survival (OS) and define the high-risk groups. Afterward, stratified OS analyses were performed for each high-risk group to assess whether neoadjuvant chemotherapy had a survival benefit in each group.ResultsA total of 1837 patients (49.8% female; mean age 56.6 ± 12.3 years) underwent radical resection of a rNET. Tumors > 20 mm in size, clinical T4 tumors, poorly differentiated tumors, and metastatic disease were independent predictors of worse OS and were defined as high-risk groups. Neoadjuvant chemotherapy did not have a significant survival benefit in any of the high-risk groups, except for patients with high-grade rNETs where neoadjuvant therapy significantly improved OS to a mean of 30.9 months compared with 15.9 months when neoadjuvant therapy was not given (p = 0.006).ConclusionsNeoadjuvant chemotherapy improved the OS of patients with high-grade rNET by 15 months and may be indicated for this group.

Circulating trimethylamine N-oxide is correlated with high coronary artery atherosclerotic burden in individuals with newly diagnosed coronary heart disease

BackgroundTrimethylamine N-oxide (TMAO) is a metabolite derived from the gut microbiota and has been reported to be correlated with cardiovascular diseases. Although TMAO is associated with the severity of coronary artery disease in subjects with coronary heart disease (CHD) history. However, the correlation between TMAO and the atherosclerotic burden in newly diagnosed cases of CHD is unknown.MethodsIn this hospital-based study, we enrolled 429 individuals newly diagnosed with CHD undergoing coronary angiography. Plasma TMAO was assessed before coronary angiography. SYNTAX score was computed during coronary angiography to estimate the coronary artery atherosclerotic burden. Both linear and logistic regression analyses were conducted to explore the correlation between plasma TMAO levels and SYNTAX score in newly diagnosed CHD population.ResultsThe TMAO in patients with SYNTAX ≥ 33 and subjects with SYNTAX < 23 were 6.10 (interquartile range [IQR]: 3.53 to 9.15) µmol/L and 4.90 [IQR: 3.25 to 7.68] µmol/L, respectively. Linear regression adjusting for traditional risk factors showed TMAO level was positively correlated with SYNTAX score (β = 0.179; p = 0.006) in CHD population. When TMAO was added to models with traditional risk factors, the predictive value improved significantly, with the receiver operating characteristic curve (AUC) increased from 0.7312 to 0.7502 (p = 0.003). Stratified analysis showed that the correlations did not hold true for subjects who were non-smoker or with histories of diabetes. None of the stratifying factors significantly altered the correlation (all p for interaction < 0.05).ConclusionsWe found a positive linear correlation between plasma TMAO and SYNTAX score among newly diagnosed CHD individuals in Chinese population.

Association between protein intake, serum albumin and blood eosinophil in US asthmatic adults

BackgroundPresently, numerous studies have indicated that protein consumption and levels of blood albumin serve as important biomarkers for a range of respiratory illnesses. However, there have been few investigations into the correlation between protein consumption, serum albumin, and asthma.MethodsOur analysis incorporated 2509 asthmatics from the 2011–2018 NHANES dataset. The investigation employed three linear regression models and XGBoost model to investigate the potential link between protein intake, serum albumin levels, and blood eosinophil counts (BEOC) in patients with asthma. The trend test, generalized additive model (GAM), and threshold effect model were utilized to validate this correlation. As well, we undertook stratified analyses to look at the correlation of serum albumin with BEOC among distinct populations.ResultsIn the univariable regression model, which did not account for any covariates, we observed a positive correlation between protein intake and BEOC. However, univariable and multivariable regression analyses all suggested a negative connection of serum albumin with BEOC in asthma populations. In Model C, which took into account all possible factors, BEOC dropped by 2.82 cells/uL for every unit increase in serum albumin (g/L). Additionally, the GAM and threshold effect model validated that serum albumin and BEOC showed an inverted U-shaped correlation.ConclusionOur investigation discovered there was no independent link between asthmatics’ protein intake and BEOC. However, we observed an inverted U-shaped relationship between serum albumin levels and BEOC, suggesting a possible relationship between the overall nutritional status of asthmatics and immune system changes. Our findings provide new directions for future research in the field of asthma management and therapy.

Metformin use and risk of myeloproliferative neoplasms: a Danish population–based case-control study

AbstractPrevious studies have suggested that metformin has beneficial effects beyond its glucose-lowering properties, particularly in terms of its potential as an antineoplastic and cancer-preventive agent. In this study, we aimed to investigate the association between metformin use and the risk of myeloproliferative neoplasms (MPN). We conducted a population–based case-control study using Danish registers. Cases with MPN diagnosed between 2010 and 2018 were identified, and metformin use before the MPN diagnosis was ascertained. We compared metformin use among cases with MPN and an age- and sex-matched control group from the Danish general population to estimate age- and sex-adjusted odds ratios (ORs) and fully adjusted ORs (aORs) for the association between metformin use and risk of MPN. The study population included 3816 cases and 19 080 controls. Overall, 7.0% of cases and 8.2% of controls were categorized as ever-users of metformin, resulting in an OR for MPN of 0.84 (95% confidence interval [CI], 0.73-0.96) and an aOR of 0.70 (95% CI, 0.61-0.81). Long-term metformin use (≥5 years) was more infrequent and comprised 1.1% of cases and 2.0% of controls, resulting in an OR of 0.57 (95% CI, 0.42-0.79) and an aOR of 0.45 (95% CI, 0.33-0.63). A dose-response relationship was observed when cumulative duration of treatment was analyzed, and this was consistent in stratified analyses of sex, age, and MPN subtypes. In conclusion, metformin use was associated with significantly lower odds of an MPN diagnosis, indicating its potential cancer-preventive effect. Given the retrospective design, causality cannot be inferred.

SARS-CoV-2 infection, vaccination and in vitro fertilization treatment: A prospective cohort study

BackgroundThe impact of COVID-19 on reproductive health is controversial. The association between female SARS-CoV-2 infection and laboratory and pregnancy outcomes following subsequent in vitro fertilization (IVF) treatment remains unclear. This study aimed to investigate the relationship between IVF treatment at different time intervals after SARS-CoV-2 infection and reproductive outcomes. MethodsA prospective cohort study of 920 IVF cycles post-SARS-CoV-2 infection was conducted. Modified Poisson regression and logistic regression models were utilized to evaluate oocyte- and embryo-related outcomes as well as clinical outcomes. Stratified analyses were also performed based on the vaccination status of the female participants. ResultsSARS-CoV-2 infection within three months was associated with reduced available [Adjusted RR (aRR): 0.96, 95 %CI: 0.91–1.00] and top-quality embryos (aRR: 0.90, 95 %CI: 0.83–0.98) in subsequent IVF treatment. Among patients failing to finish the three-dose vaccination, the interval between SARS-CoV-2 infection and cycle initiation of less than 90 days was associated with a lower number of oocytes retrieval (aRR: 8.81, 95 %CI: 8.24–9.41 vs aRR: 9.64, 95 %CI: 9.06–10.25), available embryos (aRR: 0.93, 95 %CI: 0.88–0.99), and top-quality embryos (aRR: 0.81, 95 %CI: 0.72–0.91) rather than among fully vaccinated women. Moreover, COVID-19 infection was not associated with biochemical pregnancy, clinical pregnancy, embryo implantation, and early abortion either in fresh embryo transfer (ET) or frozen ET. ConclusionsThis study indicated that initiating IVF treatment within 90 days of SARS-CoV-2 infection might reduce the likelihood of obtaining available and top-quality embryos, especially among those who had not completed the three-dose vaccination. Nevertheless, female COVID-19 infection did not affect pregnancy or early abortion. Further rigorously designed studies are required to support these findings.

Gender Differences in Authorship and Quality of Anesthesia Clinical Practice Guidelines From 2016 to 2020 Using the Appraisal of Guidelines for Research and Evaluation II Instrument.

Women continue to be underrepresented in academic anesthesiology. This study assessed guidelines in anesthesia journals over the past 5 years, evaluating differences in woman-led versus man-led guidelines in terms of author gender, quality, and changes over time. We hypothesized that anesthesia guidelines would be predominately man-led, and that there would be differences in quality between woman-led versus man-led guidelines. All clinical practice guidelines published in the top 10 anesthesia journals were identified as per Clarivate Analytics Impact Factor between 2016 and 2020. Fifty-one guidelines were included for author, gender, and quality analysis using the Appraisal of Guidelines for Research & Evaluation (AGREE) II instrument. Each guideline was assessed across 6 domains and 23 items and given an overall score, overall quality score, and overall rating/recommendation. Stratified and trend analyses were performed for woman-led versus man-led guidelines. Fifty out of 51 guidelines were included: 1 was excluded due to unidentifiable first-author gender. In total, 255 of 1052 (24%) authors were women, and woman-led guidelines (woman-first author) represented 12 of 50 (24%) overall guidelines. Eighteen percent (9 of 50) of guidelines had all-male authors, and a majority (26 of 50, 52%) had less than one-third of female authors. The overall number and percentage of woman-led guidelines did not change over time. There was a significantly higher percentage of female authors in woman-led versus man-led guidelines, median 39% vs 20% (P = .012), as well as a significantly higher number of female coauthors in guidelines that were woman-led median 3.5 vs 1.0, P = .049. For quality, there was no significant difference in the overall rating or objective quality of woman- versus man-led guidelines. However, there was a significant increase in the overall rating of all the guidelines over time (P = .010), driven by the increase in overall rating among man-led guidelines, P = .002. The overall score of guidelines did not increase over time; however, they increased in man-led but not woman-led guidelines. There was no significant correlation between the percentage of female authors per guideline and either overall score or overall rating. There is a substantial disparity in the number of women leading and contributing to guidelines which has not improved over time. Woman-led guidelines included more women and a higher percentage of women. There was no difference in quality of guidelines by first-author gender or percentage of female authors. Further systematic and quota-driven sponsorship is needed to promote gender equity, diversity, and inclusion in anesthesia guidelines.

Untangling the relationship between smoking and systemic sclerosis: an analysis of the EUSTAR cohort

ObjectivesTo untangle the association between smoking and systemic sclerosis (SSc).MethodsIn the European Scleroderma Trials and Research cohort, the autoantibody status was compared between ever-smokers and never-smokers. Time until disease progression...

Using Power Analysis to Choose the Unit of Randomization, Outcome, and Approach for Subgroup Analysis for a Multilevel Randomized Controlled Clinical Trial to Reduce Disparities in Cardiovascular Health.

We give examples of three features in the design of randomized controlled clinical trials which can increase power and thus decrease sample size and costs. We consider an example multilevel trial with several levels of clustering. For a fixed number of independent sampling units, we show that power can vary widely with the choice of the level of randomization. We demonstrate that power and interpretability can improve by testing a multivariate outcome rather than an unweighted composite outcome. Finally, we show that using a pooled analytic approach, which analyzes data for all subgroups in a single model, improves power for testing the intervention effect compared to a stratified analysis, which analyzes data for each subgroup in a separate model. The power results are computed for a proposed prevention research study. The trial plans to randomize adults to either telehealth (intervention) or in-person treatment (control) to reduce cardiovascular risk factors. The trial outcomes will be measures of the Essential Eight, a set of scores for cardiovascular health developed by the American Heart Association which can be combined into a single composite score. The proposed trial is a multilevel study, with outcomes measured on participants, participants treated by the same provider, providers nested within clinics, and clinics nested within hospitals. Investigators suspect that the intervention effect will be greater in rural participants, who live farther from clinics than urban participants. The results use published, exact analytic methods for power calculations with continuous outcomes. We provide example code for power analyses using validated software.

A dynamic probabilistic model of the onset and interaction of cardio-metabolic comorbidities on an ageing adult population

Comorbidity is widespread in the ageing population, implying multiple and complex medical needs for individuals and a public health burden. Determining risk factors and predicting comorbidity development can help identify at-risk subjects and design prevention strategies. Using socio-demographic and clinical data from approximately 11,000 subjects monitored over 11 years in the English Longitudinal Study of Ageing, we develop a dynamic Bayesian network (DBN) to model the onset and interaction of three cardio-metabolic comorbidities, namely type 2 diabetes (T2D), hypertension, and heart problems. The DBN allows us to identify risk factors for developing each morbidity, simulate ageing progression over time, and stratify the population based on the risk of outcome occurrence. By applying hierarchical agglomerative clustering to the simulated, dynamic risk of experiencing morbidities, we identified patients with similar risk patterns and the variables contributing to their discrimination. The network reveals a direct joint effect of biomarkers and lifestyle on outcomes over time, such as the impact of fasting glucose, HbA1c, and BMI on T2D development. Mediated cross-relationships between comorbidities also emerge, showcasing the interconnected nature of these health issues. The model presents good calibration and discrimination ability, particularly in predicting the onset of T2D (iAUC-ROC = 0.828, iAUC-PR = 0.294) and survival (iAUC-ROC = 0.827, iAUC-PR = 0.311). Stratification analysis unveils two distinct clusters for all comorbidities, effectively discriminated by variables like HbA1c for T2D and age at baseline for heart problems. The developed DBN constitutes an effective, highly-explainable predictive risk tool for simulating and stratifying the dynamic risk of developing cardio-metabolic comorbidities. Its use could help identify the effects of risk factors and develop health policies that prevent the occurrence of comorbidities.

Associations of perfluoroalkyl substances with metabolic-associated fatty liver disease and non-alcoholic fatty liver disease: NHANES 2017-2018.

This study investigated the potential effects of perfluoroalkyl substance (PFAS) in serum on MAFLD, NAFLD, and liver fibrosis. Our sample included 696 participants (≥ 18years) from the 2017-2018 NHANES study with available serum PFASs, covariates, and outcomes. Using the first quartile of PFAS as the reference group, we used weighted binary logistic regression and multiple ordered logistic regression used to analyze the relationship between PFAS and MAFLD, NAFLD, and liver fibrosis and multiple ordinal logistic regression to investigate the relationship between PFAS and MAFLD, NAFLD, and liver fibrosis and calculated the odds ratio (OR) and 95% confidence interval for each chemical. Finally, stratified analysis and sensitivity analysis were performed according to gender, age, BMI, and serum cotinine concentration. A total of 696 study subjects were included, including 212 NAFLD patients (weighted 27.03%) and 253 MAFLD patients (weighted 32.65%). The quartile 2 of serum PFOA was positively correlated with MAFLD and NAFLD (MAFLD, OR 2.29, 95% CI 1.05-4.98; NAFLD, OR 2.37, 95% CI 1.03-5.47). PFAS were not significantly associated with liver fibrosis after adjusting for potential confounders in MAFLD and NAFLD. Stratified analysis showed that PFOA was strongly associated with MAFLD, NAFLD, and liver fibrosis in males and obese subjects. In women over 60years old, PFHxS was also correlated with MAFLD, NAFLD, and liver fibrosis. The serum PFOA was positively associated with MAFLD and NAFLD in US adults. After stratified analysis, the serum PFHxS was correlated with MFALD, NAFLD, and liver fibrosis.

Sleep health among US Navy afloat versus ashore personnel in the Millennium Cohort Study.

Despiteemerging public concern regarding the sleep health of military personnel over the past two decades, there remains a dearth of research examining sleep health among naval personnel assigned to sea duty. This study examined sleep metrics (e.g. fatigue, short sleep duration) and mental (e.g. posttraumatic stress disorder, depression) and physical health (e.g. type 2 diabetes, bodily pain) outcomes among naval personnel with recent sea duty (i.e. afloat) compared with naval personnel with recent shore duty (i.e. ashore). Prevalence ratios and mean differences for all outcomes were estimated and adjusted for demographic and military variables, and subsequently stratified by obesity. Sleep metrics were similar between afloat and ashore sailors except for short sleep duration, while sailors with recent shore duty had poorer physical health compared with those with recent sea duty. Stratified analyses suggested naval personnel with obesity had a higher proportion of nearly all adverse sleep-related health outcomes than those without obesity. Among participants without obesity, afloat personnel were more likely to report very short sleep (≤ 5 hours) and fewer hours of average nightly sleep, but were less likely to report physical health outcomes compared with ashore personnel. These findings suggest potential differences in sleep metrics and sleep-related health outcomes between afloat and ashore naval personnel. Additional research examining sleep outcomes using more objective measures is required to further investigate these findings, which may inform strategies to foster consolidated sleep despite environmental and occupational challenges in order to maintain high-performing naval personnel.

The association between remnant cholesterol and bone mineral density in US adults: the National Health and Nutrition Examination Survey (NHANES) 2013-2018.

Previous evidence showed a possible link of dyslipidemia with bone health. Nevertheless, the correlation of remnant cholesterol (RC) with bone mineral density (BMD) has yet to be well investigated. This study investigated the association of RC with total spine BMD in general Americans. This study explored the relationship of RC with total spine BMD in subjects aged ≥ 20 years from the National Health and Nutrition Examination Survey (NHANES) 2013-2018. After adjusting for covariates, multivariate linear regression and stratified analyses were conducted to determine the correlation of serum RC with total spine BMD in adult Americans. Restricted cubic spline (RCS) was applied to examine the nonlinear association of serum RC with total spine BMD. This study included 3815 individuals ≥ 20 years old, 1905 (49.93%) of whom were men and 1910 (50.07%) of whom were women. After adjusting for all covariates, the results showed a negative relationship of serum RC with total spine BMD (β= -0.024, 95% CI: -0.039, -0.010). The interaction tests of age, sex, race, and BMI showed no statistically significant effects on the association. The RCS also indicated a negative linear correlation of serum RC with total spine BMD (nonlinear P = 0.068, overall P < 0.001). Moreover, RC had a stronger effect on total spine BMD than total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). This study found that serum RC was negatively related to total spine BMD in U.S. adults. These findings emphasized the important role of RC in bone health in American adults.