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Objective: The weight-adjusted-waist index (WWI) is a novel obesity measurement indicator, and this study aims to determine the relationship between WWI and Familial hypercholesterolemia (FH)., Methods: Using data from the National Health and Nutrition Examination Survey (NHANES) from 2017 to March 2020, cross-sectional data from 3698 participants were analyzed. The study examined the correlation between WWI and FH using multivariate logistic regression and smooth curve fitting, and conducted subgroup analysis and interaction tests., Results: The study sample consisted of 3698 subjects for whom the overall probable prevalence of FH was 5.43% and increased with WWI tertile (quantile 1: 4.00%; quantile 2: 4.94%; quantile 3: 7.34%); individuals with the highest WWI tertile were significantly more likely to have FH than those with the lowest tertile (OR = 4.60,95% CI: 2.00-10.60). Subgroup analysis and interaction tests showed significant significance between WWI and personal history of early Atherosclerotic cardiovascular disease (ASCVD), family history of early ASCVD and probable prevalence of FH (p < 0.05)., Conclusion: This study demonstrates a nonlinear positive correlation between WWI and FH. This may provide new ideas for the prevention and treatment of FH in the future., Competing Interests: Declarations Ethics approval and consent to participate The portions of this study involving human participants, human materials, or human data were conducted in accordance with the Declaration of Helsinki and were approved by the National Center for Health Statistics (NCHS) Ethics Review Board. The patients/participants provided their written informed consent to participate in this study. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: The platelet to high-density lipoprotein cholesterol ratio (PHR) is a novel biomarker for inflammation and hypercoagulability. This study aimed to explore the potential association between PHR and prevalence of chronic obstructive pulmonary disease (COPD)., Methods: Participants aged between 40 and 85 years from the 1999-2018 US National Health and Nutrition Examination Survey with COPD were included. Multivariable logistic regression and restricted cubic spline analysis were applied to evaluate the associations between PHR and COPD. Propensity score matching (PSM) was performed to reduce the impact of potential confounding factors., Results: A total of 25751 participants, including 753 with COPD, at a mean age of 57.19 years and 47.83% men, were included. The multivariable-adjusted model showed that the odds ratio (OR) and 95% confidence interval (CI) for PHR to predict COPD was 1.002 (1.001-1.003). Compared with the lowest quartile, the ORs and 95% CIs for the Q2, Q3, and Q4 PHR quartile were 1.162 (0.874-1.546), 1.225 (0.924-1.625), and 1.510 (1.102-2.069), respectively (P for trend = 0.012). Restricted cubic spline analysis demonstrated a linear association between PHR and COPD prevalence both before and after PSM. Significant association between PHR and COPD prevalence was observed only in participants without hypertension. Receiver-operating characteristic curves showed significantly higher area under the curve for distinguishing COPD from non-COPD by PHR than platelet count and high-density lipoprotein cholesterol., Conclusion: PHR is significantly associated with COPD prevalence in US adults aged 40 to 85 years without hypertension, supporting the effectiveness of PHR as a potential biomarker for COPD., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Wang et al.)

Previous studies on the relationship between vitamin D, sleep quality, and osteoarthritis (OA) have been controversial and the aim of this study is to analyze the association. In this study, relevant data from 2 survey cycles (2009-2010 with 2011-2012) are downloaded from the CDC's NHANES project to analyze the relationship between vitamin D, sleep quality, and osteoarthritis, as well as other related risk factors. The analysis of statistics in this study is performed using t-tests and chi-square tests, modeling is performed using logistic regression based on NHANES weights, and other risk factors are analyzed using forest plots. In association models between serum vitamin D, sleep quality, and OA is statistically significant during the stepwise inclusion of covariates. In model 1, Q3 (OR = 1.83; 95% CI: 1.05, 3.23) and Q4 (OR = 2.22; 95% CI: 1.27, 3.94) are significant. Neither model 2 nor model 3 is statistically significant and P for trend is more than .05 in all 3 models. After the inclusion of all covariates, forest plot showed that sleep deprivation (OR = 1.64; 95% CI: 1.05, 2.56), advanced age (OR = 1.03; 95% CI: 1.01, 1.04), female (OR = 1.79; 95% CI: 1.14, 2.85), overweight (25 ≤ BMI < 30) (OR = 1.92; 95% CI: 1.05, 3.61), and obesity (≥30) (OR = 2.06; 95% CI: 1.11, 3.93) are risk factors for OA. This study is based on a larger sample and a stepwise logistic regression of multiple covariates. We concluded that vitamin D may not influence OA. However other risk factors for OA are confirmed, including advanced age, female and high BMI, especially bad sleep quality., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Ethylene oxide (EO) is a volatile compound positively correlated with respiratory and cardiovascular diseases. Currently, evidence suggests that environmental exposure may contribute to depressive symptoms. This study evaluated the correlation between EO exposure and depressive symptoms and investigated whether inflammatory indicators had a mediation effect on this correlation., Methods: Patients were enrolled from the National Health and Nutrition Examination Survey during 2013-2016, and 2,764 (49.67% male and 50.33% female) participants were ultimately included. EO exposure was determined by measuring hemoglobin-EO adduct (Hb-EO) concentration due to its long half-life, which was log 2 -transformed. Depressive symptoms were assessed using the Patient Health Questionnaire-9. Multivariable logistic regression analysis was performed to identify any correlations before and after covariate adjustment. Sensitivity analysis, subgroup analyses, and interaction tests were performed to further evaluate identified correlations. Mediation analysis was conducted to reveal whether specific inflammatory indicators mediated the correlation., Results: A high prevalence of depressive symptoms was observed in quartiles with increased levels of EO exposure, and male individuals exhibiting higher Hb-EO levels than female individuals. A positive correlation was observed between EO exposure and depressive symptoms (odds ratio [OR]: 1.439, 95% confidence interval [CI]: 1.310, 1.581), which remained stable even after covariate adjustment (OR: 1.332, 95% CI: 1.148, 1.545). Interaction tests showed significant effects of sex ( p  < 0.001) and thyroid diseases ( p = 0.048) on this correlation. In the mediation analysis, white blood cell ( p = 0.010) and neutrophil counts ( p = 0.010) exerted a mediating effect, accounting for 13.6 and 11.9%, respectively., Conclusion: Increased exposure to EO is associated with an elevated risk of depressive symptoms, where white blood cell and neutrophil counts exert a significant mediating effect. Further prospective studies are required to investigate the potential link among EO, other environmental pollutants, and human mental health., Competing Interests: 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., (Copyright © 2024 Du, Yuan, Guan, Xie and Dong.)

Background: Early intervention and diagnosis of Metabolic Syndrome (MetS) are crucial for preventing adult cardiovascular disease. However, the optimal indicator for identifying MetS in adolescent remains controversial., Methods: In total,1408 Chinese adolescents and 3550 American adolescents aged 12-17 years were included. MetS was defined according to the modified version for adolescents based on Adult Treatment Panel III (NCEP-ATP III) criteria. Areas under the curve (AUC) and corresponding 95% confidence interval (95% CI) of 8 anthropometric/metabolic indexes, such as waist circumference (WC), body mass index (BMI), a body shape index (ABSI), waist triglyceride index (WTI), were calculated to illustrate their ability to differentiate MetS. Sensitivity analysis using the other MetS criteria was performed., Results: Under the modified NCEP-ATP III criteria, WTI had the best discriminating ability in overall adolescents, with AUC of 0.922 (95% CI: 0.900-0.945) in Chinese and 0.959 (95% CI: 0.949-0.969) in American. In contrast, ABSI had the lowest AUCs. Results of sensitivity analysis were generally consistent for the whole Chinese and American population, with the AUC for WC being the highest under some criteria, but it was not statistically different from that of WTI., Conclusions: WTI had relatively high discriminatory power for MetS detection in Chinese and American adolescents, but the performance of ABSI was poor., Impact: While many studies have compared the discriminatory power of some anthropometric indicators for MetS, there are few focused on pediatrics. The current study is the first to compare the discriminating ability of anthropometric/metabolic indicators (WC, BMI, TMI, ABSI, WHtR, VAI, WTI, and TyG) for MetS in adolescents. WTI remains the optimal indicator in screening for MetS in adolescents. WC was also a simple and reliable indicator when screening for MetS in adolescents, but the performance of ABSI was poor. This study provides a theoretical basis for the early identification of MetS in adolescents by adopting effective indicators., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Objective: Few studies have examined the relationship between systemic oxidative stress and prostate cancer (PCa) risk. This study aimed to explore potential correlations between PCa and oxidative balance score (OBS), which measures systemic oxidative stress., Design: A cross-sectional study., Setting: The National Health and Nutrition Examination Survey., Participants: A total of 8156 individuals were included in this study., Primary and Secondary Outcome Measures: Weighted logistic regression with multivariable adjustment and restricted cubic splines (RCS) were used to assess the correlation between PCa and OBS. A sensitivity analysis was conducted specifically on patients with PCa to verify the results., Results: The prevalence of PCa was 2.55%. The multivariable logistic regression model revealed no correlation between OBS, dietary OBS, lifestyle OBS and PCa. Compared with the lowest quartile of OBS, the adjusted ORs for the highest quartile of OBS, dietary OBS and lifestyle OBS were 1.852 (95% CI 1.028-3.339), 1.565 (95% CI 0.841-2.913) and 1.575 (95% CI 0.915-2.710), respectively. Additionally, all p values for trend were greater than 0.05. Subgroup analysis revealed a consistent lack of association between OBS and PCa across various population settings. Furthermore, analysis using RCS confirmed this absence of association, indicating no significant relationship in either a linear or non-linear context. A sensitivity analysis focusing exclusively on patients with PCa showed a strong association (OR=2.737, p=0.008)., Conclusion: This cross-sectional study reveals no significant association between systemic oxidative stress, measured by OBS, and PCa risk. Notably, a sensitivity analysis focusing solely on PCa patients suggested a potential link, warranting further investigation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Basic research shows that flavonoids have anti-inflammatory effects that influence rheumatoid arthritis (RA) in rats. Investigating potential dietary interventions for RA helps prevent the onset and progression of the disease. Clinical evidence on the association of flavonoid and subclass intake with RA is lacking. Using three survey cycles of 2007-2008, 2009-2010, and 2017-2018 from the National Health and Nutrition Survey and the United States Department of Agriculture's Food and Nutrient Database for Dietary Studies (FNDDS), we analyzed 7,419 American adults (≥20 years old). The values of flavonoid and subclass intake were calculated using FNDDS. The status questions for self-reported RA were from the NHANES codebook. Weighted analyses, revealed that among the 7,419 participants included in this study (mean age of 44.69 years [standard error, 0.40] and 3,584 [48.31%] were female), 408 met the classification criteria for RA. According to the multivariable logistic regression model, compared with the risk of RA in the first quartile (Q1), the risks of RA in the second quartile (Q2), the third quartile (Q3) and the fourth quartile (Q4) were lower (Q2: OR=0.55, 95% CI: 0.38-0.80; Q3: OR=0.66, 95% CI: 0.44-0.97; Q4: OR=0.64, 95% CI: 0.46-0.89; trend: P=.03). The association between total flavonoids and RA remained significant after full consideration of confounding factors. With regard to the subclasses of flavonoids, high flavanones intake was associated with low RA prevalence in Model 3 (Q3: OR= 0.60, 95% CI:0.39-0.92; Q4: OR = 0.56, 95% CI: 0.32-0.99, trend: P=.02), but no such association was found in the other subclasses. Total flavonoids intake protected against RA, and the risk of developing RA decreased significantly with increasing intake of total flavonoids. Total flavonoids and flavanones were significantly associated with reduced RA risk for the American adult population. We highlighted the importance of employing diverse methodologies to assess the health effects of flavonoids., Competing Interests: Declaration of competing interest The authors declare that the research was conducted without any commercial or financial conflict and competing interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Politicization and misinformation or disinformation of unproven COVID-19 therapies have resulted in communication challenges in presenting science to the public, especially in times of heightened public trepidation and uncertainty., Objective: This study aims to examine how scientific evidence and uncertainty were portrayed in US news on 3 unproven COVID-19 therapeutics, prior to the development of proven therapeutics and vaccines., Methods: We conducted a media analysis of unproven COVID-19 therapeutics in early 2020. A total of 479 discussions of unproven COVID-19 therapeutics (hydroxychloroquine, remdesivir, and convalescent plasma) in traditional and online US news reports from January 1, 2020, to July 30, 2020, were systematically analyzed for theme, scientific evidence, evidence details and limitations, safety, efficacy, and sources of authority., Results: The majority of discussions included scientific evidence (n=322, 67%) although only 24% (n=116) of them mentioned publications. "Government" was the most frequently named source of authority for safety and efficacy claims on remdesivir (n=43, 35%) while "expert" claims were mostly mentioned for convalescent plasma (n=22, 38%). Most claims on hydroxychloroquine (n=236, 79%) were offered by a "prominent person," of which 97% (n=230) were from former US President Trump. Despite the inclusion of scientific evidence, many claims of the safety and efficacy were made by nonexperts. Few news reports expressed scientific uncertainty in discussions of unproven COVID-19 therapeutics as limitations of evidence were infrequently included in the body of news reports (n=125, 26%) and rarely found in headlines (n=2, 2%) or lead paragraphs (n=9, 9%; P<.001)., Conclusions: These results highlight that while scientific evidence is discussed relatively frequently in news reports, scientific uncertainty is infrequently reported and rarely found in prominent headlines and lead paragraphs., (©Sara Watson, Tyler J Benning, Alessandro R Marcon, Xuan Zhu, Timothy Caulfield, Richard R Sharp, Zubin Master. Originally published in JMIR Infodemiology (https://infodemiology.jmir.org), 29.08.2024.)

One of the justifiable criticisms of human genetic studies is the underrepresentation of participants from diverse populations. Lack of inclusion must be addressed at-scale to identify causal disease factors and understand the genetic causes of health disparities. We present genome-wide associations for 2068 traits from 635,969 participants in the Department of Veterans Affairs Million Veteran Program, a longitudinal study of diverse United States Veterans. Systematic analysis revealed 13,672 genomic risk loci; 1608 were only significant after including non-European populations. Fine-mapping identified causal variants at 6318 signals across 613 traits. One-third ( n = 2069) were identified in participants from non-European populations. This reveals a broadly similar genetic architecture across populations, highlights genetic insights gained from underrepresented groups, and presents an extensive atlas of genetic associations.

To explore complex biological questions, it is often necessary to access various data types from public data repositories. As the volume and complexity of biological sequence data grow, public repositories face significant challenges in ensuring that the data is easily discoverable and usable by the biological research community. To address these challenges, the National Center for Biotechnology Information (NCBI) has created NCBI Datasets. This resource provides straightforward, comprehensive, and scalable access to biological sequences, annotations, and metadata for a wide range of taxa. Following the FAIR (Findable, Accessible, Interoperable, and Reusable) data management principles, NCBI Datasets offers user-friendly web interfaces, command-line tools, and documented APIs, empowering researchers to access NCBI data seamlessly. The data is delivered as packages of sequences and metadata, thus facilitating improved data retrieval, sharing, and usability in research. Moreover, this data delivery method fosters effective data attribution and promotes its further reuse. This paper outlines the current scope of data accessible through NCBI Datasets and explains various options for exploring and downloading the data., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Exposure to a mixture of environmental chemicals may cause gallstone, but the evidence remains equivocal. The current study aims to investigate the association between phthalate metabolites and gallstones, and to explore their mediators., Methods: Data from the National Health and Nutrition Examination Survey 2017-2018 on U.S. adults (≥20 years) were analyzed to explore the association between phthalate metabolites and gallstones by employed survey-weighted logistic regression, restricted cubic spline (RCS), weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR). Mediation analyses examined the role of oxidative stress markers, inflammatory markers, metabolic syndrome, body composition, diabetes, and insulin., Results: The current study included 1,384 participants, representing 200.6 million U.S. adults. Our results indicated a significant association between phthalate metabolites, particularly high molecular weight metabolites such as Di(2-ethylhexyl) phthalate (DEHP) and 1,2-Cyclohexane dicarboxylic acid diisononyl ester (DINCH), and gallstones. Furthermore, mediation analyses indicated that phthalate metabolites may play a role in the development of gallstones by influencing insulin secretion. Subgroup analyses did not reveal significant interaction., Conclusion: The association between exposure to phthalates and the occurrence of gallstones, potentially mediated by hyperinsulinemia from a nationally representative epidemiological perspective. These insights contribute to a better understanding of the potential health implications of plasticizers, emphasizing the need for proactive management measures., Competing Interests: 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., (Copyright © 2024 Tang, Zhang, Huang, Luo, Chen, Yang, Lin and Hua.)

Objective: The escalating prevalence of chronic pain poses a substantial socio-economic burden. Chronic pain primarily stems from musculoskeletal and nervous system impairments. Given cadmium's known toxicity to these systems, our study sought to investigate the correlation between blood cadmium levels and chronic pain., Methods: The cross-sectional study was conducted from the National Health and Nutrition Examination Survey (NHANES, 1999-2004), and comprised US adults who participated in a chronic pain interview. We employed logistic regression models and smooth curve fitting to elucidate the relationship between blood cadmium levels and chronic pain., Results: Our findings revealed a linear association between blood cadmium levels and chronic pain. Compared to the lower blood cadmium tertile 1 (<0.3 ug/dL), the adjusted odds ratios (ORs) for tertile 2 (0.3-0.4 ug/dL), and tertile 3 (≥0.5 ug/dL), were 1.11 (0.96-1.29) and 1.2 (1.03-1.39), respectively. Sensitivity analyses corroborated these results., Conclusion: Elevated levels of blood cadmium are associated with a heightened risk of chronic pain among adults in the United States. Mitigating cadmium exposure could potentially decrease the risk of chronic pain, thereby enhancing strategies for chronic pain prevention and management., Competing Interests: 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., (Copyright © 2024 Mi, Dong, Chen, Gao, Cao, Liu, Wang and Fan.)

Objectives: To explore the association between palbociclib and related adverse events (AEs) in the real world through U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database., Methods: The signal strength of palbociclib-related AEs was done by disproportionality analysis. Clinical priority of palbociclib-related AEs was scored and ranked by assessing five different features. Outcome analysis, time to onset analysis, dose-report /AEs number analysis, and stratification analysis were all performed., Results: There were 61,821 'primary suspected (PS)' reports of palbociclib and 195,616 AEs associated with palbociclib. The four algorithms simultaneously detected 18 positive signals at the SOC level, and 65 positive signals at the PT level. Bone marrow failure, neuropathy, peripheral, pleural effusion, myelosuppression, pulmonary edema, and pulmonary thrombosis were also found to have positive signals. Gender (female vs male, χ 2  = 5.287, p  = 0.022) and age showed significant differences in serious and non-serious reports. Palbociclib-related AEs had a median onset time of 79 days (interquartile range [IQR] 20-264 days)., Conclusions: The study identified potential Palbociclib-related AEs and offered warnings for special AEs, providing further data for palbociclib safety studies in breast cancer patients. Nonetheless, prospective clinical trials are needed to validate these results and explain their relationship.

Background: The Metabolic Score for Insulin Resistance (METS-IR) offers a promising and reliable non-insulin-based approach to assess insulin resistance and evaluate cardiometabolic risk. However, evidence for the association between METS-IR and hypertension was still limited., Methods: Participants from the National Health and Nutrition Examination Survey (NHANES) database from 2007-2016 were selected for weighted multivariable regression analyses, subgroup analyses and restricted cubic spline (RCS) modeling to assess the association between the METS-IR and hypertension, as well as systolic blood pressure (SBP) and diastolic blood pressure (DBP)., Results: This study enrolled 7,721 adults aged ≥20 years, 2,926 (34.03%) of whom was diagnosed as hypertension. After adjusting for all potential covariates, an increased METS-IR (log 2 conversion, denoted as log 2 METS-IR) was independently associated with a higher prevalence of hypertension (odd ratio [OR] 3.99, 95% confidence interval [CI] 3.19~5.01). The OR for hypertension in subjects with the highest quartile of METS-IR was 3.89-fold (OR 3.89, 95% CI 3.06~4.94) higher than that in those with the lowest quartile of METS-IR. This positive correlation became more significant as METS-IR increased ( p for trend < 0.001). Log 2 METS-IR was significantly correlated with increase in SBP (β 6.75, 95% CI 5.65~7.85) and DBP (β 5.59, 95% CI 4.75~6.43) in a fully adjusted model. Consistent results were obtained in subgroup analyses. Hypertension, SBP and DBP all exhibited a non-linear increase with the rise in METS-IR. The minimal threshold for the beneficial association of METS-IR with hypertension, SBP and DBP were all identified to be 46.88., Conclusion: The findings of this study revealed a significant positive association between METS-IR and hypertension among US adults, suggesting METS-IR as a potential tool for assessing hypertension risk., Competing Interests: 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., (Copyright © 2024 Zeng, Zhang, Yang, Wang, Zheng, Hou, Tong, Fan, Wang and Fang.)

Study Objectives: The aims of this study were to characterize obstructive sleep apnea (OSA) care pathways among commercially insured individuals in the United States and to investigate between-groups differences in population, care delivery, and economic aspects., Methods: We identified adults with OSA using a large, national administrative claims database (January 1, 2016-February 28, 2020). Inclusion criteria included a diagnostic sleep test on or within ≤ 12 months of OSA diagnosis (index date) and 12 months of continuous enrollment before and after the index date. Exclusion criteria included prior OSA treatment or central sleep apnea. OSA care pathways were identified using sleep testing health care procedural health care common procedure coding system/current procedural terminology codes then selected for analysis if they were experienced by ≥ 3% of the population and assessed for baseline demographic/clinical characteristics that were also used for model adjustment. Primary outcome was positive airway pressure initiation rate; secondary outcomes were time from first sleep test to initiation of positive airway pressure, sleep test costs, and health care resource utilization. Associations between pathway type and time to treatment initiation were assessed using generalized linear models., Results: Of 86,827 adults with OSA, 92.1% received care in 1 of 5 care pathways that met criteria: home sleep apnea testing (HSAT; 30.8%), polysomnography (PSG; 23.6%), PSG-Titration (19.8%), Split-night (14.8%), and HSAT-Titration (3.2%). Pathways had significantly different demographic and clinical characteristics. HSAT-Titration had the highest positive airway pressure initiation rate (84.6%) and PSG the lowest (34.4%). After adjustments, time to treatment initiation was significantly associated with pathway ( P < .0001); Split-night had shortest duration (median, 28 days), followed by HSAT (36), PSG (37), PSG-Titration (58), and HSAT-Titration (75). HSAT had the lowest sleep test costs and health care resource utilization., Conclusions: Distinct OSA care pathways exist and are associated with differences in population, care delivery, and economic aspects., Citation: Wickwire EM, Zhang X, Munson SH, et al. The OSA patient journey: pathways for diagnosis and treatment among commercially insured individuals in the United States. J Clin Sleep Med . 2024;20(4):505-514., (© 2024 American Academy of Sleep Medicine.)

Background: Anti-IL-5 monoclonal antibodies (mAbs) targeting IL-5 or IL-5 R α (including mepolizumab, benralizumab, and reslizumab) are widely used for inflammatory diseases such as asthma, eosinophilia, and polyangiitis. However, real-world data regarding its safety in a large sample population are incomplete. So, we evaluated the safety of anti-IL-5 mAbs by pharmacovigilance analyzes based on related adverse events (AEs) from the FDA Adverse Event Reporting System (FAERS)., Methods: In disproportionality analysis, four algorithms were employed to detect the signals of anti-IL-5 mAbs from the FAERS between 2016 and 2022. In addition, we also used MYSQL 8.0, Navicat Premium 15, and Microsoft EXCEL 2019 to analyze the signals of anti-IL-5 mAbs systematically., Results: There are 9,476,351 reports collected from the FAERS database, of which 22,174 reports listed anti-IL-5 mAbs as the 'primary suspected (PS)' drug. A total of 59 (20 new signals, mepolizumab) and 62 (19 new signals, benralizumab) significant disproportionality preferred terms (PTs) conforming to the four algorithms were retained synchronously. Finally, we detected that the anti-IL-5 mAbs-induced AEs occurred in 31 organ systems (mepolizumab) and 30 organ systems (benralizumab). For mepolizumab and reslizumab, unexpected and new significant PTs of AEs were found, such as asthmatic crisis, chronic obstructive pulmonary disease (COPD), pneumonia, COVID-19, pneumothorax, adrenal insufficiency and so on. Notably, the risk signal of asthmatic crisis for mepolizumab was stronger than benralizumab (ROR 108.04 [95%CI, 96.09-121.47] vs 26.83 [95%CI, 18.91-38.06]). Comparing with mepolizumab and benralizumab, we found the proportion of serious adverse events in mepolizumab was both greater than benralizumab in each age group (≤20, 20-65, and ≥ 65). The median onset time of mepolizumab was 280 days (interquartile range [IQR] 1-367 days)., Conclusion: Analysis of FAERS data identified anti-IL-5 mAbs-associated AEs, and our findings supported continuous clinical monitoring, pharmacovigilance, and further studies of anti-IL-5 mAbs. In addition, clinicians may be more aware of the limitations of use in package inserts of anti-IL-5 mAbs: Not for relief of acute bronchospasm or status asthmaticus. Because of some limitations in the FAERS such as self-reports from patients and other confounding factors, the safety of anti-IL-5 mAbs needed more studies in different dimensions, especially the risk of cancer.

Objectives: Systematic reviews (SRs) are becoming essential evidence in the decision-making process within the field of social sciences. This study aimed to investigate how Campbell SRs were cited and explore their specific application roles., Study Design and Setting: We included Campbell SRs published between 2016 and 2020 by searching the Wiley online library, and retrieved the articles and documents citing Campbell SRs from the Web of Science and Google Scholar by December 31, 2021. We described the characteristics of the SRs and citations, and formulated a set of application roles by analyzing the sentences or paragraphs where the SRs were cited., Results: Sixty nine Campbell SRs were published between 2016 and 2020; they were cited in 641 articles or documents a total of 1,289 times. The primary types of articles that cited Campbell SRs were cross-sectional studies (n = 226, 35.3%), SRs (n = 112, 17.5%), randomized controlled trials (n = 77, 12.0%), and policy reports (n = 57, 8.8%). Articles utilizing Campbell SRs were predominantly led by authors from the United States (n = 184, 28.7%), the United Kingdom (n = 98, 15.3%), and Australia (n = 51, 8.0%). We formulated a set of 10 application roles for the Campbell SRs, of which the most frequent were: describing the current status in the field of interest (n = 691, 53.6%), corroboration of the results (n = 140, 10.9%), identifying research gaps (n = 130, 10.1%), and providing methodological references (n = 126, 9.8%); the role of supporting policy recommendations or decisions accounted for 6.0% (n = 77) of the citations. Approximately 12% of Campbell SRs were used to support policy recommendations or decisions., Conclusion: Campbell SRs are widely applied, particularly in scientific research, to describe the current status in the field of interest. Although the current application of Campbell SRs in supporting policy recommendations and decisions may not be predominant, there is a growing recognition of their value in using Campbell SRs to inform decision-making., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2023. Published by Elsevier Inc.)

Background: Child flourishing includes healthy social and emotional development and an open, engaged approach to learning. However, there remains a significant knowledge gap concerning a minority of children with ADHD who may demonstrate flourishing in one or more areas of functioning. This study investigated the association between positive childhood experiences (PCEs) and flourishing among children with ADHD., Method: Data were derived from the 2021 National Survey of Children's Health in the United States. The analysis included a final sample of 3727 children with ADHD. Logistic regression, restricted cubic splines, and random forest were used to examine the associations between seven PCEs and flourishing., Results: The adjusted odds of flourishing were 72% lower (odds ratio [OR] = 0.28,95% confidence interval [CI] = 0.21, 0.38) among children with PCE scores of 0-2 compared to those with scores of 3-5. In addition, the adjusted odds of flourishing were 2.45 times (95%CI = 2.00, 2.99) greater for children with PCE scores of 6-7 compared to those with scores of 3-5. These associations were consistent regardless of the level of adverse childhood experiences. Having a "connected caregiver" was the PCE most closely related to flourishing (unweighted OR = 3.24, 95%CI = 2.72, 3.89)., Conclusions: Our findings revealed a positive association between higher levels of PCEs and greater flourishing among children with ADHD, regardless of the level of childhood adversity they experienced. These results highlight the importance of positive experiences in the lives of children with ADHD, with a specific focus on nurturing supportive relationships within families., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest with regard to the study design, data collection, analysis, interpretation, or publication of the findings. Data analysis in this study was supported by the Fundamental Research Funds for the Central Universities, China (Grant 2022JC018)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aims: To examine the prevalence and associated factors of chemotherapy-related cognitive impairment (CRCI) in older breast cancer survivors (BCS)., Design: Systematic review., Data Sources: We searched EMBASE, PubMed, PsychInfo, CINAHL, Cochrance Library, Web of Science, CNKI and SinoMed, without language restrictions, for studies published from the establishment of the database to September 2022., Review Methods: Two researchers independently examined the full texts, data extraction and quality assessment, and any discrepancies were resolved through discussion with a third reviewer. Quality of evidence was assessed using the Newcastle-Ottawa Scale and the Agency for Healthcare Research and Quality Scale., Results: The seven included studies showed that the estimated prevalence of CRCI in older BCS ranged from 18.6% to 27% on objective neuropsychological tests and from 7.6% to 49% on subjective cognitive assessments. The areas most affected were attention, memory, executive functioning and processing speed. CRCI was associated with 10 factors in six categories, including sociodemographic (e.g. age, education level), physiological (e.g. sleep disorders, fatigue and comorbidities), psychological (e.g. anxiety, depression), treatment modalities (e.g. chemotherapy cycles, chemotherapy regimens), genetic (e.g. APOE2, APOE4) and lifestyle factor (e.g. physical inactivity)., Conclusion: CRCI is multifactorial and has a relatively high prevalence. However, the results of subjective and objective cognitive examinations were inconsistent, possibly due to variations in tools used to evaluate different definitions of CRCI. Nevertheless, as there are few published studies of older BCS, this conclusion still require verification by well-designed studies in the future., Impact: We found that the prevalence of CRCI in older adults is relatively high and multifactorial, providing evidence for further health care for this population., No Patient or Public Contribution: There was no patient or public involvement., (© 2023 John Wiley & Sons Ltd.)

Abortion is a controversial topic that has long been debated in the US. With the recent Supreme Court decision to overturn Roe v. Wade, access to safe and legal reproductive care is once again in the national spotlight. A key issue central to this debate is patient privacy, as in the post-HITECH Act era it has become easier for medical records to be electronically accessed and shared. This study analyzed a large Twitter dataset from May to December 2022 to examine the public's reactions to Roe v. Wade's overruling and its implications for privacy. Using a mixed-methods approach consisting of computational and qualitative content analysis, we found a wide range of concerns voiced from the confidentiality of patient-physician information exchange to medical records being shared without patient consent. These findings may inform policy making and healthcare industry practices concerning medical privacy related to reproductive rights and women's health., (©2023 AMIA - All rights reserved.)

Background: Bivalent mRNA COVID-19 vaccines were developed to provide protection against the original SARS-CoV-2 strain and Omicron BA.4/BA.5 variants, but uptake in the United States has been low. Sociodemographic disparities in COVID-19 vaccine uptake have been documented, but it is unclear if similar disparities persist among individuals who previously completed a primary series of monovalent COVID-19 vaccine., Methods: We conducted a retrospective cohort study at Kaiser Permanente Southern California (KPSC) including youth aged 5-17 years and adults aged ≥18 years who were KPSC members and had completed a primary series of monovalent COVID-19 vaccine. Individuals were followed from index date (date of eligibility for bivalent vaccine) to 03/31/2023 to ascertain receipt of any dose of bivalent mRNA COVID-19 vaccine or until disenrollment from KPSC or death. Multivariable robust Poisson regression was conducted to assess the adjusted relative risk and 95 % confidence intervals of factors associated with receipt of bivalent vaccine., Results: The final cohorts included 305,339 youth and 2,534,619 adults, of whom 19.5 % and 30.7 %, respectively, had received bivalent COVID-19 vaccine. Factors associated with being more likely to receive bivalent COVID-19 vaccine included older age, Asian race, more prior year outpatient and virtual visits, Charlson score ≥1, and immunocompromised status. Factors associated with being less likely to receive a bivalent COVID-19 vaccine included age 12-17 vs 5-11 years, Hispanic and non-Hispanic Black race/ethnicity, ≥1 prior year inpatient or emergency department visits, prior history of SARS-CoV-2 infection (adults only), Medicaid insurance, and higher neighborhood deprivation index., Conclusion: Even among youth and adults who had previously received a primary series of monovalent COVID-19 vaccine, sociodemographic and clinical disparities were observed in receipt of bivalent COVID-19 vaccine. These findings are critical to inform equitable strategies for the implementation of the updated monovalent COVID-19 vaccine targeting the Omicron XBB strain., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: KJB reports research support from Moderna for a COVID-19 vaccine effectiveness study and Dynavax, Gilead, GlaxoSmithKline, and Pfizer for research unrelated to this study. LSS reports research support from Moderna for a COVID-19 vaccine effectiveness study and GlaxoSmithKline, Dynavax, and Moderna for unrelated studies. LQ reports research support from Moderna for a COVID-19 vaccine effectiveness study and GlaxoSmithKline and Dynavax for unrelated studies., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Babesia gibsoni is mainly transmitted by hard ticks of the genus Rhipicephalus (R. sanguineus) and Haemaphysalis (H. longicornis), and causes canine babesiosis. Clinical manifestations of B. gibsoni infection include fever, hemoglobinemia, hemoglobinuria, and progressive anemia. Traditional antibabesial therapy, such as imidocarb dipropionate or diminazene aceturate, can only alleviate severe clinical manifestations and cannot eliminate parasites in the host. Food and Drug Administration (FDA)-approved drugs are a solid starting point for researching novel therapy strategies for canine babesiosis. In this work, we screened 640 FDA-approved drugs against the growth of B. gibsoni in vitro. Among them, 13 compounds (at 10 μM) exhibited high growth inhibition (>60%), and two compounds, namely idarubicin hydrochloride (idamycin) and vorinostat, were chosen for further investigation. The half-maximal inhibitory concentration (IC 50 ) values of idamycin and vorinostat were determined to be 0.044 ± 0.008 μM and 0.591 ± 0.107 μM, respectively. Viability results indicated that a concentration of 4 × IC 50 of vorinostat prevented the regrowth of treated B. gibsoni, whereas parasites treated with 4 × IC 50 concentration of idamycin remained viable. The B. gibsoni parasites treated with vorinostat exhibited degeneration within erythrocytes and merozoites, in contrast to the oval or signet-ring shape of normal B. gibsoni parasites. In conclusion, FDA-approved drugs offer a valuable platform for drug repositioning in antibabesiosis research. Particularly, vorinostat demonstrated promising inhibitory effects against B. gibsoni in vitro, and further studies on vorinostat are necessary to elucidate its mechanism as a novel treatment in infected animal models., Competing Interests: Conflict of interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Hepatitis B virus (HBV) infection is a global health concern that can potentially affect bone health. However, the specific association between resolved HBV infection and bone mineral density (BMD) remains unclear. This cross-sectional study aimed to investigate the potential association between resolved HBV infection and femoral and spinal BMD in adults in the United States., Methods: This cross-sectional study included participants aged 20-79 years with negative HBV surface antigen (HBsAg) from the 2005-2010, 2013-2014, and 2017-2018 cycles of the National Health and Nutrition Examination Survey. Resolved HBV infection was defined as negative HBsAg with positive HBV core antibody. BMD was measured using dual-energy X-ray absorptiometry. Propensity score matching (PSM) was performed to balance baseline characteristics., Results: A total of 10,333 eligible participants were identified and matched, of whom 737 (7.1%) had resolved HBV infection. Men with resolved HBV infection had significantly lower femoral and spinal BMD compared to those with no HBV infection, both before and after PSM. In the matched population, resolved HBV infection in men was negatively associated with femoral BMD (β= -0.024, 95% CI: -0.047 to -0.002, p = 0.0332) and spinal BMD (β= -0.025, 95% CI: -0.048 to -0.002, p = 0.0339). Postmenopausal women exhibited similar trends to men, while premenopausal women showed a tendency towards higher BMD, although statistical significance was not consistently achieved. Subgroup and sensitivity analyses supported the robustness of the findings., Conclusion: The study suggests a negative association between resolved HBV infection and femoral and spinal BMD in adult men in the United States. It highlights the importance of routine bone density assessments and the consideration of anti-osteoporotic therapy, if necessary, in individuals with resolved HBV infection., Competing Interests: 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., (Copyright © 2023 Yang, Zeng, Zhang, Wang, Fan, Wang, Wang, Qi and Fang.)

Objective: Widespread electronic health information exchange (HIE) across hospitals remains an important policy goal for reducing costs and improving the quality of care. Meanwhile, cybersecurity incidents are a growing threat to hospitals. The relationship between the electronic sharing of health information and cybersecurity incidents is not well understood. The objective of this study was to empirically examine the impact of hospitals' HIE engagement on their data breach risk., Materials and Methods: A balanced panel dataset included 4,936 US community hospitals spanning the period 2010-2017, which was assembled by linking the American Hospital Association annual survey database and the Information Technology (IT) supplement, and the Department of Health and Human Services reports of health data breaches. The relationship between HIE engagement and hospital data breaches was modeled using a difference-in-differences specification controlling for time-varying hospital characteristics., Results: The percentage of hospitals electronically exchanging information has more than tripled (from 18% to 68%) from 2010 to 2017. Hospital data breaches increased concurrently, largely due to the rise in hacking and unauthorized access. HIE engagement was associated with a 0.672 percentage point increase in the probability of an IT breach three years after the engagement. Hospitals actively engaging in a health information organization and exchanging data with outside providers were associated with a higher risk of IT related breaches in the long run; however, hospitals actively engaging in HIE and exchanging data with inside providers were not associated with any significant risk of IT related breaches., Discussion: Over time, the increasing amount and complexity of patient information being exchanged can create challenges for cybersecurity if data protection is not up to date. Additionally, data security depends on the weakest link of HIE, and providers with fewer resources for data governance and infrastructure are more vulnerable to data breaches., Conclusion: Moving toward widespread health information exchange has important cybersecurity implications that can significantly impact both patients and healthcare organizations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The American Heart Association recently released a new cardiovascular health (CVH) metric, Life's Essential 8 (LE8), for health promotion. However, the association between levels of LE8 and the risk of cardiovascular disease (CVD) outcomes is not known from a large prospective cohort. We aim to analyze the relationship between CVH, indicated by LE8, and risks of coronary heart disease (CHD), stroke, and CVD. Moreover, we sought to test whether the genetic susceptibility to CHD or stroke could be modified by LE8., Methods: A total of 137 794 participants free of CVD from the UK Biobank were included. CVH was scored using LE8 and categorized as low, moderate, and high., Results: During a median of 10 years, 8595 CVD cases (6968 CHDs and 1948 strokes) were documented. A higher LE8 score was associated with remarkably lower risks of CHD, stroke, and CVD ( P <0.001 for all). Comparing the high CVH to the low CVH, the hazard ratios (95% CI) were 0.34 (0.30-0.38) for CHD, 0.45 (0.37-0.54) for stroke, and 0.36 (0.33-0.40) for CVD. Moreover, the model with LE8 achieved higher accuracy and outperformed the model with Life's Simple 7 for CHD, stroke, and CVD ( P <0.001 for all). The protective associations of the LE8 score with CVD outcomes were more pronounced among women ( P interaction, <0.001 for CHD and 0.0013 for CVD, respectively) and among younger adults ( P interaction, <0.001, 0.007, and <0.001 for CHD, stroke, and CVD, respectively). In addition, a significant interaction was found between the genetic risk of CHD and the LE8 score ( P interaction, <0.001). The inverse association was stronger among those with a lower genetic risk of CHD., Conclusions: High level of CVH, defined by LE8, was associated with significantly lower risks of CHD, stroke, and CVD., Competing Interests: Disclosures None.

Objective: To compare the diagnostic efficacy of the Chinese Thyroid Imaging Reporting and Data Systems (C-TIRADS) with the well-accepted ACR-TIRADS guidelines in identifying benign from malignant thyroid nodules., Methods: A total of 2064 nodules were collected from 1627 patients undergoing thyroid ultrasonography in our center between October 2019 and November 2021. Nodules were divided into two groups: "≥1 cm" and "<1 cm". Ultrasound features of each nodule were observed and recorded by two physicians with more than 15 years of experience and classified according to the ACR-TIRADS and C-TIRADS guidelines, respectively., Results: The area under the curve of the ACR-TIRADS guideline was higher than that of the C-TIRADS guideline (0.922, P = 0.017), the specificity and positive predictive value of the C-TIRADS guideline were higher (81.64%, 88.72%, all P < 0.05), which was more significant in the subgroup of nodules <1 cm (P = 0.001). In addition, there was no statistical difference between the two guidelines in the diagnostic efficacy indicators for nodules ≥1 cm. The ACR-TIRADS effectively reduced unnecessary biopsies compared with the C-TIRADS (P < 0.05)., Conclusions: There was high agreement between the two guidelines for the diagnosis of thyroid nodules, C-TIRADS guidelines had a higher specificity and simplicity while were inferior to the ACR-TIRADS guidelines in terms of reducing the number of biopsies., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Cardiovascular disease may be the main reason for stagnant growth in life expectancy in the United States since 2010. The American Heart Association recently released an updated algorithm for evaluating cardiovascular health (CVH)-Life's Essential 8 (LE8) score. We aimed to quantify the associations of CVH levels, estimated by the LE8 score, with life expectancy in a nationally representative sample of US adults., Methods: We included 23 003 nonpregnant, noninstitutionalized participants aged 20 to 79 years who participated in the National Health and Nutrition Examination Survey from 2005 to 2018 and whose mortality was identified through linkage to the National Death Index through December 31, 2019. The overall CVH was evaluated by the LE8 score (range, 0-100), as well as the score for each component of diet, physical activity, tobacco/nicotine exposure, sleep duration, body mass index, non-high-density lipoprotein cholesterol, blood glucose, and blood pressure. Life table method was used to estimate life expectancy by levels of the CVH., Results: During a median of 7.8 years of follow-up, 1359 total deaths occurred. The estimated life expectancy at age 50 years was 27.3 years (95% CI, 26.1-28.4), 32.9 years (95% CI, 32.3-33.4), and 36.2 years (95% CI, 34.2-38.2) in participants with low (LE8 score <50), moderate (50≤ LE8 score <80), and high (LE8 score ≥80) CVH, respectively. Equivalently, participants with high CVH had an average 8.9 (95% CI, 6.2-11.5) more years of life expectancy at age 50 years compared with those with low CVH. On average, 42.6% of the gained life expectancy at age 50 years from adhering to high CVH was attributable to reduced cardiovascular disease death. Similarly significant associations of CVH with life expectancy were observed in men and women, respectively. Similarly significant associations of CVH with life expectancy were observed in White participants and Black participants but not in Mexican participants., Conclusions: Adhering to a high CVH, defined as the LE8 score, is related to a considerably increased life expectancy in US adults, but more research needs to be done in other races and ethnicities (eg, Hispanic and Asian).

Importance: The average life expectancy has increased substantially in the past few decades in most industrialized countries; however, not all of the increased life expectancy is being spent in optimal health, especially among individuals with low socioeconomic status., Objective: To quantify the associations between levels of cardiovascular health (CVH), estimated by the American Heart Association's Life's Essential 8 (LE8) metrics, with life expectancy free of major chronic disease, including cardiovascular disease (CVD), diabetes, cancer, and dementia, in UK adults., Design, Setting, and Participants: This cohort study included 135 199 adults in the UK Biobank study who were initially free of major chronic disease and had complete data on LE8 metrics. Data analyses were performed in August 2022., Exposures: Cardiovascular health levels, as estimated by LE8 score. The LE8 score, which consists of 8 components: (1) diet, (2) physical activity, (3) tobacco/nicotine exposure, (4) sleep, (5) body mass index, (6) non-high-density lipoprotein cholesterol, (7) blood glucose, and (8) blood pressure. The CVH level was evaluated at baseline and categorized into low (LE8 score <50), moderate (LE8 score ≥50 but <80), and high (LE8 score ≥80) levels., Main Outcomes and Measures: The primary outcome was the life expectancy free of 4 major chronic diseases (CVD, diabetes, cancer, and dementia)., Results: Of the 135 199 adults (44.7% men; mean [SD] age, 55.4 [7.9] years) included in the study, a total of 4712, 48 955, and 6748 men had low, moderate, and high CVH levels, respectively, and the corresponding numbers for women were 3661, 52 192, and 18 931. At age 50 years, the estimated disease-free years were 21.5 (95% CI, 21.0-22.0), 25.5 (95% CI, 25.4-25.6), and 28.4 (95% CI, 27.8-29.0) for men with low, moderate, and high CVH levels, respectively; the corresponding estimated disease-free years at age 50 years for women were 24.2 (95% CI, 23.5-24.8), 30.5 (95% CI, 30.4-30.6), and 33.6 (95% CI, 33.1-34.0). Equivalently, men with moderate or high CVH levels lived on average 4.0 (95% CI, 3.4-4.5) or 6.9 (95% CI, 6.1-7.7) longer years free of chronic disease, respectively, at age 50 years, compared with men with low CVH levels. The corresponding longer years lived free of disease for women were 6.3 (95% CI, 5.6-7.0) or 9.4 (95% CI, 8.5-10.2). For participants with high CVH level, there was not a statistically significant difference in disease-free life expectancy between participants with low and other socioeconomic status., Conclusions and Relevance: In this cohort study, a high level of CVH, evaluated using the LE8 metrics, was associated with longer life expectancy free of major chronic diseases and may contribute to narrowing socioeconomic health inequalities in both men and women.

Objective: The utilization of image-guided navigation during endoscopic sinus surgery (ESS) has increased significantly since its introduction. However, the most common associated complications are still unknown. This study describes and analyzes adverse events related to image-guided ESS., Study Design: Cross-sectional analysis., Setting: The Food and Drug Administration's 2018-2022 MAUDE database (Manufacturer and User Facility Device Experience)., Methods: The MAUDE database was searched for all reports on adverse events involving sinus navigation systems used in ESS from 2018 to 2022. Reported events were reviewed and categorized., Results: During the study period, there were 1857 adverse events from 1565 reports, which were divided into device-related (n = 1834, 98.8%) and patient-related (n = 23, 1.2%) complications. The most common device-related complications were nonfunctionality of the system (n = 512, 27.9%), device imprecision (n = 427, 23.3%), and device sensing problems (n = 277, 15.1%). The most common patient-related complications were cerebrospinal fluid (CSF) leak (n = 14, 60.9%), intracranial injury (n = 4, 17.4%), and bleeding/hemorrhage (n = 3, 13.1%). Imprecision was associated with increased risk of navigation abortion by the surgeon (odds ratio, 1.50 [95% CI, 1.38-1.65]; P < .001) and increased risk of CSF leak (odds ratio, 16.5 [95% CI, 3.66-74.0]; P < .001) as compared with other device-related complications., Conclusions: The most commonly reported device- and patient-related adverse events associated with image-guided sinus navigation systems were device nonfunction, imprecision, device sensing difficulties, and CSF leak. When imprecise navigation occurred, there was an increased likelihood of CSF leak and navigation abortion by the surgeon. Health care providers should be mindful of these possible complications when electing to use image-guided sinus navigation during ESS., (© 2022 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

The complexity and privacy issues inherent in social science research data makes research data management (RDM) an essential skill for future researchers. Data management training has not fully addressed the needs of graduate students in the social sciences. To address this gap, this study used a mixed methods design to investigate the RDM awareness, preparation, confidence, and challenges of social science graduate students. A survey measuring RDM preparedness and training needs was completed by 98 graduate students in a school of education at a research university in the southern United States. Then, interviews exploring data awareness, knowledge of RDM, and challenges related to RDM were conducted with 10 randomly selected graduate students. All participants had low confidence in using RDM, but United States citizens had higher confidence than international graduate students. Most participants were not aware of on-campus RDM services, and were not familiar with data repositories or data sharing. Training needs identified for social science graduate students included support with data documentation and organization when collaborating, using naming procedures to track versions, data analysis using open access software, and data preservation and security. These findings are significant in highlighting the topics to cover in RDM training for social science graduate students. Additionally, RDM confidence and preparation differ between populations so being aware of the backgrounds of students taking the training will be essential for designing student-centered instruction., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Zhou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: A reliable risk prediction model is critically important for identifying individuals with high risk of developing lung cancer as candidates for low-dose chest computed tomography (LDCT) screening. Leveraging a cutting-edge machine learning technique that accommodates a wide list of questionnaire-based predictors, we sought to optimize and validate a lung cancer prediction model., Methods: We developed an Optimized early Warning model for Lung cancer risk (OWL) using the XGBoost algorithm with 323,344 participants from the England area in UK Biobank (training set), and independently validated it with 93,227 participants from UKB Scotland and Wales area (validation set 1), as well as 70,605 and 66,231 participants in the Prostate, Lung, Colorectal, and Ovarian cancer screening trial (PLCO) control and intervention subpopulations, respectively (validation sets 2 & 3) and 23,138 and 18,669 participants in the United States National Lung Screening Trial (NLST) control and intervention subpopulations, respectively (validation sets 4 & 5). By comparing with three competitive prediction models, i.e., PLCO modified 2012 (PLCO m2012 ), PLCO modified 2014 (PLCO all2014 ), and the Liverpool Lung cancer Project risk model version 3 (LLPv3), we assessed the discrimination of OWL by the area under receiver operating characteristic curve (AUC) at the designed time point. We further evaluated the calibration using relative improvement in the ratio of expected to observed lung cancer cases (RI EO ), and illustrated the clinical utility by the decision curve analysis., Findings: For general population, with validation set 1, OWL (AUC = 0.855, 95% CI: 0.829-0.880) presented a better discriminative capability than PLCO all2014 (AUC = 0.821, 95% CI: 0.794-0.848) (p < 0.001); with validation sets 2 & 3, AUC of OWL was comparable to PLCO all2014 (AUC PLCOall2014 -AUC OWL < 1%). For ever-smokers, OWL outperformed PLCO m2012 and PLCO all2014 among ever-smokers in validation set 1 (AUC OWL  = 0.842, 95% CI: 0.814-0.871; AUC PLCOm2012  = 0.792, 95% CI: 0.760-0.823; AUC PLCOall2014  = 0.791, 95% CI: 0.760-0.822, all p < 0.001). OWL remained comparable to PLCO m2012 and PLCO all2014 in discrimination (AUC difference from -0.014 to 0.008) among the ever-smokers in validation sets 2 to 5. In all the validation sets, OWL outperformed LLPv3 among the general population and the ever-smokers. Of note, OWL showed significantly better calibration than PLCO m2012 , PLCO all2014 (RI EO from 43.1% to 92.3%, all p < 0.001), and LLPv3 (RI EO from 41.4% to 98.7%, all p < 0.001) in most cases. For clinical utility, OWL exhibited significant improvement in average net benefits (NB) over PLCO all2014 in validation set 1 (NB improvement: 32, p < 0.001); among ever smokers of validation set 1, OWL (average NB = 289) retained significant improvement over PLCO m2012 (average NB = 213) (p < 0.001). OWL had equivalent NBs with PLCO m2012 and PLCO all2014 in PLCO and NLST populations, while outperforming LLPv3 in the three populations., Interpretation: OWL, with a high degree of predictive accuracy and robustness, is a general framework with scientific justifications and clinical utility that can aid in screening individuals with high risks of lung cancer., Funding: National Natural Science Foundation of China, the US NIH., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: BRAF and MEK inhibitor combination therapy have significantly improved the outcome of several BRAF-mutation tumors, but it also confers the risk of drug-induced ocular adverse events (oAEs). However, very few studies focused on this risk., Methods: The United States Food and Drug Administration Adverse Event Reporting System (FAERS) data from Quarter 1-2011 to Quarter 2-2022 were searched to detect signs of oAEs of three marketed BRAF and MEK inhibitor combination therapies: vemurafenib plus cobimetinib (V + C), dabrafenib plus trametinib (D + T), and encorafenib plus binimetinib (E + B). Disproportionality analyses were performed by calculating the proportional reporting ratio (PRR), χ2 (chi-square), and reporting odds ratios (RORs) with a 95% confidence interval (CI)., Results: A series of oAEs were identified, including 42 preferred terms, which could be classified into 8 aspects. In addition to previously reported oAEs, several unexpected oAE signals were detected. Moreover, differences in oAE profiles were found among three combination therapies (V + C, D + T, and E + B)., Conclusions: Our findings support an association between several oAEs and BRAF and MEK inhibitor combination therapies, including several new oAEs. In addition, oAEs profiles may vary across the treatment regimens. Further studies are needed to better quantify these oAEs.

Background: The key to effective stroke management is timely diagnosis and triage. Machine learning (ML) methods developed to assist in detecting stroke have focused on interpreting detailed clinical data such as clinical notes and diagnostic imaging results. However, such information may not be readily available when patients are initially triaged, particularly in rural and underserved communities., Objective: This study aimed to develop an ML stroke prediction algorithm based on data widely available at the time of patients' hospital presentations and assess the added value of social determinants of health (SDoH) in stroke prediction., Methods: We conducted a retrospective study of the emergency department and hospitalization records from 2012 to 2014 from all the acute care hospitals in the state of Florida, merged with the SDoH data from the American Community Survey. A case-control design was adopted to construct stroke and stroke mimic cohorts. We compared the algorithm performance and feature importance measures of the ML models (ie, gradient boosting machine and random forest) with those of the logistic regression model based on 3 sets of predictors. To provide insights into the prediction and ultimately assist care providers in decision-making, we used TreeSHAP for tree-based ML models to explain the stroke prediction., Results: Our analysis included 143,203 hospital visits of unique patients, and it was confirmed based on the principal diagnosis at discharge that 73% (n=104,662) of these patients had a stroke. The approach proposed in this study has high sensitivity and is particularly effective at reducing the misdiagnosis of dangerous stroke chameleons (false-negative rate <4%). ML classifiers consistently outperformed the benchmark logistic regression in all 3 input combinations. We found significant consistency across the models in the features that explain their performance. The most important features are age, the number of chronic conditions on admission, and primary payer (eg, Medicare or private insurance). Although both the individual- and community-level SDoH features helped improve the predictive performance of the models, the inclusion of the individual-level SDoH features led to a much larger improvement (area under the receiver operating characteristic curve increased from 0.694 to 0.823) than the inclusion of the community-level SDoH features (area under the receiver operating characteristic curve increased from 0.823 to 0.829)., Conclusions: Using data widely available at the time of patients' hospital presentations, we developed a stroke prediction model with high sensitivity and reasonable specificity. The prediction algorithm uses variables that are routinely collected by providers and payers and might be useful in underresourced hospitals with limited availability of sensitive diagnostic tools or incomplete data-gathering capabilities., (©Min Chen, Xuan Tan, Rema Padman. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 30.01.2023.)

Introduction: The current prevalence of chronic kidney disease (CKD) is substantial, and CKD individuals face a heightened risk of mortality, encompassing both all-cause and cause-specific outcomes. The current study aims to investigate the potential impact of adhering to Life's Essential 8 (LE8) on reducing mortality among CKD individuals., Methods: Using the National Health and Nutrition Survey (NHANES) data from 2005 to 2018, we analyzed 22,420 US adults (≥20 years old). CKD is defined by urinary albumin-to-creatinine ratio (≥30 mg/g or 3 mg/mmol) and estimated glomerular filtration rate (&lt;60 mL/min/1.73 m2). The components of LE8, including diet, physical activity (PA), nicotine exposure, sleep, body mass index, blood lipids, blood glucose, and blood pressure (BP), were measured and given a score of 0-100. The total LE8 score was the unweighted average of all components and was divided into low cardiovascular health (CVH) (0-49), moderate CVH (50-79), and high CVH (80-100). A Cox proportional hazards regression model was used to explore the associations of LE8 with all-cause, cardiovascular disease (CVD), and cancer mortality, which were followed prospectively by the National Center for Health Statistics until December 31, 2019., Results: In the overall population, individuals with moderate CVH had a 47% lower risk of CKD, while high CVH was linked to a 55% lower risk compared to low CVH. During a median follow-up of 7.58 years, CKD individuals had a 93% higher all-cause mortality rate and a 149% higher CVD mortality rate compared to those without CKD. Among the CKD individuals, every 10-point increase in the LE8 score was associated with reduced risks of 17% for all-cause mortality (especially PA, nicotine exposure, blood glucose, and BP), 18% for CVD mortality (especially PA), and 12% for cancer mortality (especially PA and sleep health). In additional and sensitivity analysis, the results remained significant after further consideration of potential confounding of renal function. Additionally, LE8 demonstrated superior risk stratification for CVD mortality among CKD patients compared with LS7. Interaction was observed between LE8 and age, education level, marital status, and drinking status., Conclusion: The current study demonstrates that adherence to higher LE8 levels within CKD individuals is associated with a reduced risk of both all-cause and cause-specific mortality., (© 2023 S. Karger AG, Basel.)

Introduction: Lung cancer mortality is higher among rural United States populations compared with nonrural ones. Little is known about screening low-dose chest computed tomography (LDCT) outcomes in rural settings., Materials and Methods: This retrospective cohort study examined all patients (n=1805) who underwent screening LDCT in a prospective registry from March 1, 2015, through December 31, 2019, in a majority-rural health care system. We assessed the proportion of early-stage lung cancers (American Joint Committee on Cancer stage I-II) diagnosed among LDCT-screened patients, and analyzed overall survival after early-stage lung cancer diagnosis according to residency location., Results: The screening cohort had a median age of 63 and median 40-pack-year smoking history; 62.4% had a rural residence, 51.2% were female, and 62.7% completed only 1 LDCT scan. Thirty-eight patients were diagnosed with lung cancer (2.1% of the cohort), of which 65.8% were early-stage. On multivariable analysis, rural (vs nonrural) residency was not associated with a lung cancer diagnosis (adjusted hazard ratio 1.59; 95% CI, 0.74-3.40; P =0.24). At a median follow-up of 37.1 months (range, 3.3 to 67.2 months), 88.2% of rural versus 87.5% of nonrural patients with screen-diagnosed early-stage lung cancer were alive ( P =0.93)., Conclusions: In a majority-rural United States population undergoing LDCT, most screen-detected lung cancers were early-stage. There were no significant differences observed between rural and nonrural patients in lung cancer diagnosis rate or early-stage lung cancer survival. Increased implementation of LDCT might blunt the historical association between rural United States populations and worse lung cancer outcomes., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Context: Sleep quality has been related to the risk of diabetes; however, little is known about the prevalence of diabetes in the United States according to the levels of sleep quality., Objective: To examine the joint secular trends of the overall sleep quality and diabetes among US adults from 2005-2006 to 2017-2018., Methods: Seven cycles of cross-sectional National Health and Nutrition Examination Survey (NHANES) data between 2005-2006 and 2017-2018 were included. Nonpregnant adults aged 20 years or older were eligible for the study. A healthy sleep score was calculated to represent overall sleep quality. The prevalence of diabetes was estimated and mean levels of fasting plasma glucose (FPG), glycated hemoglobin, and insulin resistance were calculated., Results: Both the estimated age-standardized prevalence of diabetes and changing trend in prevalence of diabetes varied by the overall sleep quality groups. The highest prevalence of diabetes was consistently observed in the low sleep quality group in each cycle, in which a significantly increasing trend was also noted across cycles (P for trend = .004). In contrast, the lowest prevalence of diabetes was consistently observed in the high sleep quality group in each cycle, in which no increasing trend over time was observed (P for trend = .346)., Conclusions: Overall sleep quality decreased significantly between 2005-2006 and 2017-2018 among US adults. The estimated prevalence of diabetes and related measures only increased in participants with low or medium overall sleep quality but remained stable in participants with high sleep quality., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Numerous studies have covered exercise-induced muscle damage (EIMD) topics, ranging from nutritional strategies to recovery methods, but few attempts have adequately explored and analyzed large volumes of scientific output. The purpose of this study was to assess the scientific output and research activity regarding EIMD and protein intake by conducting a bibliometric and visual analysis. Relevant publications from 1975-2022 were retrieved from the Web of Science Core Collection database. Quantitative and qualitative variables were collected, including the number of publications and citations, H-indexes, journals of citation reports, co-authorship, co-citation, and the co-occurrence of keywords. There were 351 total publications, with the number of annual publications steadily increasing. The United States has the highest total number of publications (26.21% of total publications, centrality 0.44). Institutional cooperation is mostly geographically limited, with few transnational cooperation links. EIMD and protein intake research is concentrated in high-quality journals in the disciplines of Sport Science, Physiology, Nutrition, and Biochemistry & Molecular Biology. The top ten journals in the number of publications are mostly high-quality printed journals, and the top ten journals in centrality have an average impact factor of 13.845. The findings of the co-citation clusters and major keyword co-occurrence reveal that the most discussed research topics are "exercise mode", "nutritional strategies", "beneficial outcomes", and "proposed mechanisms". Finally, we identified the following research frontiers and research directions: developing a comprehensive understanding of new exercise or training models, nutritional strategies, and recovery techniques to alleviate EIMD symptoms and accelerate recovery; applying the concept of hormesis in EIMD to induce muscle hypertrophy; and investigating the underlying mechanisms of muscle fiber and membrane damage.

Introduction: The adverse effects of neuromuscular junction dysfunctions caused by immune checkpoint inhibitor (ICI) drugs have not been thoroughly assessed in the clinics., Objective: To assess the neuromuscular junction dysfunctions in cancer patients with adverse events caused by ICI therapy by searching the Food and Drug Administration Adverse Event Reporting System (FAERS) database., Methods: The FAERS data from January 2004 to December 2020 were collected to analyze the association between neuromuscular connection dysfunction and ICI use. Disproportionate analysis and Bayesian analysis were used to quantify the association between the neuromuscular junction dysfunctions and ICIs. The onset time and outcome of neuromuscular junction dysfunctions in different ICI regimens were also compared., Results: Out of 88,617 adverse event reports, 557 neuromuscular junction dysfunction reports (0.63%) were analyzed. Marketed ICI drugs, including ipilimumab, nivolumab, pembrolizumab, atezolizumab, durvalumab, cemiplimab, avelumab, as well as their combinations, showed positive associations with four detection methods. Most of the adverse event reports were associated with the use of nivolumab (53.32%) and pembrolizumab (31.96%). However, nivolumab-related neuromuscular junction dysfunctions were similar with pembrolizumab (33.33% vs 33.14%, p > 0.05). The onset time of neuromuscular junction dysfunctions showed no significant difference among different ICIs (p > 0.05)., Conclusions: Analysis of FAERS data identified that over 30% (32.85%) of reports of neuromuscular junction dysfunctions resulted in death. Ongoing monitoring, risk evaluations, and further comparative studies of ICIs should be considered., Competing Interests: 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., (Copyright © 2022 Zhang, Lao, Chen, Zhao, Du, Zhai, Ye and Yu.)

Background: Colorectal cancer (CRC) screening is underutilized despite evidence that screening improves survival. Since healthcare provider recommendation is a strong predictor of CRC screening completion, providers are encouraged to engage eligible patients in collaborative decision-making that attends to patients' values, needs, and preferences for guideline-concordant screening modalities., Methods: This three-arm randomized controlled trial is testing the effectiveness of an evidence-based video intervention informing patients of screening choices delivered in a clinic prior to a healthcare appointment. We hypothesize that participants randomized to watch a basic video describing CRC and screening in addition to an informed choice video showing the advantages and disadvantages of fecal immunochemical test (FIT), stool DNA FIT (s-DNA FIT), and colonoscopy (Arm 3) will exhibit a greater proportion of time adherent to CRC screening guidelines after 1, 3 and 6 years than those who only watch the basic video (Arm 2) or no video at all (Arm 1). Primary care and Obstetrician/Gynecology clinics across the United States are recruiting 5280 patients, half who have never been screened and half who previously screened but are currently not guideline adherent. Participants complete surveys prior to and following an index appointment to self-report personal, cognitive, and environmental factors potentially associated with screening. Proportion of time adherent to screening guidelines will be assessed using medical record data and supplemented with annual surveys self-reporting screening., Conclusion: Results will provide evidence on the effectiveness of informational and motivational videos to encourage CRC screening that can be easily integrated into clinical practice., Clinicaltrials: gov #NCT05246839., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Colorectal cancer (CRC) screening among average-risk patients is underused in the US. Clinician recommendation is strongly associated with CRC screening completion. To inform interventions that improve CRC screening uptake among average-risk patients, we examined clinicians' routine recommendations of 7 guideline-recommended screening methods and factors associated with these recommendations., Methods: We conducted an online survey in November and December 2019 among a sample of primary care clinicians (PCCs) and gastroenterologists (GIs) from a panel of US clinicians. Clinicians reported whether they routinely recommend each screening method, screening method intervals, and patient age at which they stop recommending screening. We also measured the influence of various factors on screening recommendations., Results: Nearly all 814 PCCs (99%) and all 159 GIs (100%) reported that they routinely recommend colonoscopy for average-risk patients, followed by stool-based tests (more than two-thirds of PCCs and GIs). Recommendation of other visualization-based methods was less frequent (PCCs, 26%-35%; GIs, 30%-41%). A sizable proportion of clinicians reported guideline-discordant screening intervals and age to stop screening. Guidelines and clinical evidence were most frequently reported as very influential to clinician recommendations. Factors associated with routine recommendation of each screening method included clinician-perceived effectiveness of the method, clinician familiarity with the method, Medicare coverage, clinical capacity, and patient adherence., Conclusion: Clinician education is needed to improve knowledge, familiarity, and experience with guideline-recommended screening methods with the goal of effectively engaging patients in informed decision making for CRC screening.

Importance: Studies have shown that delayed initiation of surgery and adjuvant chemotherapy is associated with lower rates of breast cancer survival. However, it remains unclear whether delayed initiation of adjuvant hormone therapy (AHT) is associated with survival., Objective: To assess the association of time to adjuvant hormone therapy (TTH) with breast cancer survival and evaluate the factors associated with AHT., Design, Setting, and Participants: This cohort study examined data from the National Cancer Database from 2004 through 2014 to assess the association of TTH (stratified as ≤150 and >150 days) with cancer survival. All patients included were diagnosed with stage I to stage III hormone receptor-positive, human epidermal growth factor receptor-2 (ERBB2; formerly HER2)-negative invasive breast cancer and underwent AHT without chemotherapy. Data were analyzed from April 2019 to May 2020., Exposures: AHT was administered at different time points following surgical procedures for breast cancer treatment., Main Outcomes and Measures: An inverse probability of treatment weighting (IPTW) model was constructed to evaluate overall survival by adjusting for treatment facility, patient demographics, tumor characteristics, and treatment; multivariable logistic regression was conducted to assess factors associated with delayed treatment., Results: A total of 144 103 patients (median [IQR] follow-up, 36.6 months [25.5-49.2 months]; mean [SD] age, 63.7 [11.6] years) were identified, which included 142 916 (99.2%) women, 11 574 (8.0%) Black patients, and 126 013 (87.4%) White patients. Of these, 134 873 patients (93.6%) had a TTH of 150 days or less and 9230 patients (6.4%) had a TTH longer than 150 days. The IPTW-based Cox model demonstrated that patients with delayed AHT (ie, a TTH past 150 days) were associated with decreased survival (hazard ratio [HR], 1.31; 95% CI, 1.26-1.35; P < .001) compared with those receiving the timely treatment (TTH ≤150 days). Several sensitivity analyses (including IPTW with stabilized weight [HR, 1.31; 95% CI, 1.19-1.45; P < .001], propensity score matching [HR, 1.41; 1.13-1.76; P = .002], and propensity score regression adjustment [HR, 1.29; 95% CI, 1.16-1.43; P < .001]) and exploratory subgroup analyses yielded similar trends. Factors associated with delayed AHT included Black racial identity (OR, 1.66; 95% CI, 1.55-1.77), nonprivate insurance (eg, no insurance: OR, 1.46; 95% CI, 1.26-1.70), living in large metropolitan or metropolitan areas (reference vs urban, less urban, or rural: OR, 0.82; 95% CI, 0.76-0.87), treatment in a community hospital (reference vs academic or research: OR, 0.91; 95% CI, 0.84-0.98), Charlson-Deyo Comorbidity Index score 2 or higher (OR, 1.17; 95% CI, 1.04-1.32), poor grade differentiation (OR, 1.42; 95% CI, 1.32-1.53), II and III pathological stage (stage III: OR, 3.13; 95% CI, 2.76-3.54), estrogen receptor-positive (ER+)/progesterone receptor-negative (PR-) or ER-/PR+ (OR, 1.22; 95% CI, 1.13-1.31), receiving breast conservation surgery (reference vs mastectomy: OR, 0.87; 95% CI, 0.79-0.94), and radiotherapy (reference vs no radiotherapy: OR, 0.56; 95% CI, 0.52-0.61)., Conclusions and Relevance: The delay of the initiation of AHT past 150 days was associated with diminished survival in hormone receptor-positive, ERBB2-negative patients with breast cancer who did not receive chemotherapy. Efforts should be made to address factors associated with delayed treatment to improve survival.

Objective: This study aimed to analyze the progression and trends of multimorbidity in the elderly in China and internationally from a bibliometric perspective, and compare their differences on hotspots and research fronts., Methods: Publications between January 2001 and August 2021 were retrieved from WOS and CNKI databases. Endnote 20 and VOSviewer 1.6.8 were used to summarize bibliometric features, including publication years, journals, and keywords, and the co-occurrence map of countries, institutions, and keywords was drawn., Results: 3857 research papers in English and 664 research papers in Chinese were included in this study. The development trends of multimorbidity in the elderly are fully synchronized in China and other countries. They were divided into germination period, development period, and prosperity period. Research literature in English was found to be mainly focused on public health, and the IF of the literature is high; In China, however, most research papers are in general medicine and geriatrics with fewer core journals. Co-occurrence analysis based on countries and institutions showed that the most productive areas were the United States, Canada, the United Kingdom, and Australia, while the Chinese researchers have made little contribution. The clustering analysis of high-frequency keywords in China and around the globe shows that the hotspots have shifted from individual multimorbidity to group multimorbidity management. Sorting out the top 10 highly cited articles and highly cited authors, Barnett, K's article published in Lancet in 2012 is regarded as a milestone in the field., Conclusion: Multimorbidity in the elderly leads to more attention in the world. Although China lags behind global research the research fronts from disease-centered to patient-centered, and individual management to population management is consistent.

Background: Chronic obstructive pulmonary disease (COPD) is an age-related condition that has been associated with early telomere attrition; the clinical implications of telomere shortening in COPD are not well known. In this study we aimed to determine the relationship of the epigenetic regulation of telomeric length in peripheral blood with the risk of exacerbations and hospitalization in patients with COPD., Methods: Blood DNA methylation profiles were obtained from 292 patients with COPD enrolled in the placebo arm of the Macrolide Azithromycin to Prevent Rapid Worsening of Symptoms Associated with Chronic Obstructive Pulmonary Disease (MACRO) Study and who were followed for 1-year. We calculated telomere length based on DNA methylation markers (DNAmTL) and related this biomarker to the risk of exacerbation and hospitalization and health status (St. George Respiratory Questionnaire [SGRQ]) score over time using a Cox proportional hazards model. We also used linear models to investigate the associations of DNAmTL with the rates of exacerbation and hospitalization (adjusted for chronological age, lung function, race, sex, smoking, body mass index and cell composition)., Results: Participants with short DNAmTL demonstrated increased risk of exacerbation (P = 0.02) and hospitalization (P = 0.03) compared to those with longer DNAmTL. DNAmTL age acceleration was associated with higher rates of exacerbation (P = 1.35 × 10 -04 ) and hospitalization (P = 5.21 × 10 -03 ) and poor health status (lower SGRQ scores) independent of chronological age (P = 0.03)., Conclusion: Telomeric age based on blood DNA methylation is associated with COPD exacerbation and hospitalization and thus a promising biomarker for poor outcomes in COPD., (© 2021. The Author(s).)

Importance: Assumption of a well-mixed population during modeling is often erroneously made without due analysis of its validity. Ignoring the importance of the geo-spatial granularity at which the data is collected could have significant implications on the quality of forecasts and the actionable clinical recommendations that are based on it., Objective: This paper's primary objective is to test the hypothesis that the characteristic dynamics defining the trajectory of the pandemic in a region is lost when the data is aggregated and modeled at higher geo-spatial levels., Design: We use publicly available confirmed SARS-CoV-2 cases and deaths from January 1st, 2020 to August 3rd, 2020 in the United States at different geo-spatial granularities to conduct our experiments. To understand the impact of this hypothesis, the output of this study was implemented in Tampa General Hospital (TGH) to provide resource demand forecast., Results: The Mean Absolute Percentage Error (MAPE) in the forecast confirmed cases can be 30% higher for modeling at the state-level than aggregating model results at the scale of counties or clusters of counties. Similarly, modeling at a state-level and crafting policy decisions based on them may not be effective - county-level forecasts made by partitioning state-level forecasts are 3x worse for confirmed cases and 20x worse for deaths relative to the same model at the county level. By leveraging these results, TGH was able to accurately allocate clinical resources to tackle COVID-19 cases, continue elective surgical procedures largely uninterrupted and avoid costly construction of overflow capacity in the first two epidemic waves., Conclusions and Relevance: Accurate forecasting at the county level requires hyper-local modeling with county resolution. State-level modeling does not accurately predict community spread in smaller sub-regions because state populations are not well mixed, resulting in large prediction errors. Actionable decisions such as deciding whether to cancel planned surgeries or construct overflow capacity require models with local specificity., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Influenza vaccination is the most effective way to prevent influenza and influenza-associated complications including those leading to hospitalization. Resources otherwise used for influenza could support caring for patients with coronavirus disease 2019 (COVID-19). The Health Resources and Services Administration (HRSA) Health Center Program serves 30 million people annually by providing comprehensive primary healthcare, including influenza vaccination, to demographically diverse and historically underserved communities. Because racial and ethnic minority groups have been disproportionately affected by COVID-19, the objective of this analysis was to assess disparities in influenza vaccination at HRSA-funded health centers during the COVID-19 pandemic., Methods: The Centers for Disease Control and Prevention and HRSA analyzed cross-sectional data on influenza vaccinations from a weekly, voluntary health center COVID-19 survey after addition of an influenza-related question covering 7-11 November 2020., Results: During the 3-week period, 1126 of 1385 health centers (81%) responded to the survey. Most of the 811 738 influenza vaccinations took place in urban areas and in the Western US region. There were disproportionately more health center influenza vaccinations among racial and ethnic minorities in comparison with county demographics, except among non-Hispanic blacks and American Indian/Alaska Natives., Conclusions: HRSA-funded health centers were able to quickly vaccinate large numbers of mostly racial or ethnic minority populations, disproportionately more than county demographics. However, additional efforts might be needed to reach specific racial populations and persons in rural areas. Success in influenza vaccination efforts can support success in severe acute respiratory syndrome coronavirus 2 vaccination efforts., (Published by Oxford University Press for the Infectious Diseases Society of America 2021.)

Objectives: Major depressive disorder (MDD) is a common and serious disorder with significant impact on patients and families. The goal of this retrospective cohort study was to determine the economic burden among patients with MDD stratified by number of treatment lines needed for episode resolution., Methods: Truven Health Analytics MarketScan ® claims data were used to identify US patients (≥ 18 years) who were diagnosed with MDD and started on an antidepressant between 2013 and 2017. A generalized linear model estimated direct and employment-related costs for the first 12 months following initiation of treatment across cohorts with increasing number of lines of MDD pharmacotherapy. Analyses were adjusted for demographics and clinical factors., Results: A total of 73,597 patients with MDD comprising the commercial (n = 66,459) and Medicare (n = 7138) populations met selection criteria. Patients who completed treatment for their episode with a single line of antidepressant had the lowest total adjusted direct costs (commercial $9975; Medicare $14,628) followed by those who completed with two lines (commercial $11,723; Medicare $15,526) and those treated with three or more lines of antidepressant regimens (commercial $21,259; Medicare $20,964). Patients who completed treatment with two lines as opposed to one incurred significantly higher direct costs (commercial +$1748, p < 0.0001; Medicare +$898, p = 0.0092). Patients who completed treatment with one line had the lowest employment-related costs compared to other groups., Conclusions: There was an increased economic burden associated with delay of episode resolution as early as the second line compared to the first line in MDD.

Recommended colorectal cancer screening modalities vary with respect to safety, efficacy, and cost. Better understanding of the factors that influence patient preference is, therefore, critical for improving population adherence to colorectal cancer screening. To address this knowledge gap, we conducted a panel survey focused on three commonly utilized colorectal cancer screening options [fecal immunochemical test or guaiac-based fecal occult blood test (FIT/gFOBT), multi-target stool DNA (mt-sDNA) test, and colonoscopy] with a national sample of U.S. adults, ages 40-75 years and at average risk of colorectal cancer, in November 2019. Of 5,097 panelists invited to participate, 1,595 completed the survey (completion rate, 31.3%). Our results showed that when presented a choice between two colorectal cancer screening modalities, more respondents preferred mt-sDNA (65.4%) over colonoscopy, FIT/gFOBT (61%) over colonoscopy, and mt-sDNA (66.9%) over FIT/gFOBT. Certain demographic characteristics and awareness of and/or experience with various screening modalities influenced preferences. For example, uninsured people were more likely to prefer stool-based tests over colonoscopy [OR, 2.53; 95% confidence interval (CI), 1.22-5.65 and OR, 2.73; 95% CI, 1.13-7.47]. People who had heard of stool-based screening were more likely to prefer mt-sDNA over FIT/gFOBT (OR, 2.07; 95% CI, 1.26-3.40). People who previously had a stool-based test were more likely to prefer FIT/gFOBT over colonoscopy (OR, 2.75; 95% CI, 1.74-4.41), while people who previously had a colonoscopy were less likely to prefer mt-sDNA or FIT/gFOBT over colonoscopy (OR, 0.39; 95% CI, 0.24-0.63 and OR, 0.40; 95% CI, 0.26-0.62). Our survey demonstrated broad patient preference for stool-based tests over colonoscopy, contrasting the heavy reliance on colonoscopy for colorectal cancer screening in clinical practice and highlighting the importance of considering patient preference in colorectal cancer screening recommendations. PREVENTION RELEVANCE: Our national survey demonstrated broad patient preference for stool-based tests over colonoscopy, contrasting the heavy reliance on colonoscopy for colorectal cancer screening in clinical practice and highlighting the importance of considering patient preference in colorectal screening recommendations., (©2021 American Association for Cancer Research.)

The Protecting Access to Medicare Act (PAMA) mandates clinical decision support mechanism (CDSM) consultation for all advanced imaging. There are a growing number of studies examining the association of CDSM use with imaging appropriateness, but a paucity of multicenter data. This observational study evaluates the association between changes in advanced imaging appropriateness scores with increasing provider exposure to CDSM. Each provider's first 200 consecutive anonymized requisitions for advanced imaging (CT, MRI, ultrasound, nuclear medicine) using a single CDSM (CareSelect, Change Healthcare) between January 1, 2017 and December 31, 2019 were collected from 288 US institutions. Changes in imaging requisition proportions among four appropriateness categories ("usually appropriate" [green], "may be appropriate" [yellow], "usually not appropriate" [red], and unmapped [gray]) were evaluated in relation to the chronological order of the requisition for each provider and total provider exposure to CDSM using logistic regression fits and Wald tests. The number of providers and requisitions included was 244,158 and 7,345,437, respectively. For 10,123 providers with ≥ 200 requisitions (2,024,600 total requisitions), the fraction of green, yellow, and red requisitions among the last 10 requisitions changed by +3.0% (95% confidence interval +2.6% to +3.4%), -0.8% (95% CI -0.5% to -1.1%), and -3.0% (95% CI 3.3% to -2.7%) in comparison with the first 10, respectively. Providers with > 190 requisitions had 8.5% (95% CI 6.3% to 10.7%) more green requisitions, 2.3% (0.7% to 3.9%) fewer yellow requisitions, and 0.5% (95% CI -1.0% to 2.0%) fewer red (not statistically significant) requisitions relative to providers with ≤ 10 requisitions. Increasing provider exposure to CDSM is associated with improved appropriateness scores for advanced imaging requisitions., (© 2021. The Author(s).)