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Objectives: This study aimed to examine the relationship between measures of kidney function and impaired lung function in individuals with diabetes and to assess all-cause mortality risk associated with having chronic kidney disease (CKD) and or impaired lung function., Design: Cross-sectional and retrospective cohort study., Setting: The National Health and Nutrition Examination Survey 2007-2012., Participants: A total of 10 809 participants aged over 20 years were included in this study: 9503 with normal spirometry, 951 with preserved ratio impaired spirometry (PRISm) and 355 with variable obstruction (VO)., Exposure and Outcome Measures: Kidney function measures, including estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (UACR), were considered exposure variables. PRISm and VO were outcome variables. PRISm was defined as a forced expiratory volume in 1 s (FEV1)<80% predicted and an FEV1/forced vital capacity (FVC) ratio≥0.7, while VO was defined as an FEV1/FVC ratio <0.7 prebronchodilator and ≥0.7 postbronchodilator. In the cross-sectional analysis, multivariate logistic regression models were used to assess the relationship between kidney function measures and spirometry findings. In the retrospective cohort analysis, Cox proportional hazards models were employed to evaluate the impact of having PRISm or VO, combined with CKD, on all-cause mortality., Results: An increase in UACR was significantly associated with higher odds of PRISm (OR (95% CI)=1.10 (1.01, 1.21), p=0.03). Additionally, eGFR <60 was associated with the odds of variable obstructive lung function (OR (95% CI)=1.72 (1.07, 2.74), p=0.03) compared with eGFR >60. After adjustments, an increase in UACR was associated with higher odds of PRISm in individuals with diabetes (OR (95% CI)=1.21 (1.08, 1.36), p=0.002), and UACR ≥300 mg/g significantly increased odds of having PRISm in idividuals with diabetes (OR (95% CI)=2.34 (1.23, 4.47), p=0.01). During a mean follow-up of 12.3 years, 10 500 deaths occurred. In the diabetic group, compared with normal spirometry without CKD, those with both PRISm and CKD had a significantly increased risk of all-cause mortality (HR (95% CI)=3.46 (1.94, 6.16), p<0.0001)., Conclusion: An elevated UACR and albuminuria were linked to a higher risk of PRISm. Our study emphasises that kidney and lung function are correlated. Further research is necessary to confirm our findings., 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.)

Propofol is an ultra-fast-acting intravenous anesthetic, which is rapidly metabolized primarily into inactive compounds in the live and then excreted in the urine. The purpose of this study is to explore the risk signals of propofol based on the US FDA Adverse Event Reporting System database. The risk signals of propofol-related adverse reactions in adverse event (AE) reports from 2004 to 2021 in the US FAERS were mined using ratio-report method (ROR) and the ratio-report ratio method (PRR) methods. We screened out 1651 pairs AE reports using propofol as primary suspect (PS) drugs. ROR, PRR, BCPNN and MGPS methods were used to calculate respectively, there are 363 positive preferred terms (PT) signals with 9549 cases. Among them, the top 3 adverse reactions associated with using propofol from the FAERS database were anaphylactic shock, hypotension and propofol infusion syndrome. The top 3 systems of the body associated with adverse reaction of propofol from the FAERS database were General disorders, Cardiac disorders and administration site conditions and Respiratory, thoracic and mediastinal disorders. The top 4 indication of using propofol from the FAERS database, including anaesthesia, induction of anaesthesia, sedation, general anaesthesia. There are many adverse reactions that are not included in the drug insert of propofol and involve a wide range of organs and/or systems. Caution should be exercised in the clinical use of propofol.

Aim: This study aims to explore the relationship between niacin intake and the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) within a large, multi-ethnic cohort., Methods: A total of 2946 participants from the National Health and Nutrition Examination Survey (NHANES) were carefully selected based on strict inclusion and exclusion criteria. Participants meeting the eligibility criteria underwent two dietary recall interviews, and niacin intake was calculated using the USDA's Food and Nutrient Database for Dietary Studies (FNDDS). Liver steatosis was diagnosed using a Controlled Attenuation Parameter (CAP) of 248 dB/m, and MASLD diagnosis was based on metabolic indicators. Weighted multivariate logistic regression was utilized to analyze the correlation between niacin intake and MASLD prevalence, with potential nonlinear relationships explored through restricted cubic spline (RCS) regression., Results: Analysis of baseline data revealed that MASLD patients had lower niacin intake levels and poorer metabolic biomarker profiles. Both RCS analysis and multivariate logistic regression indicated a U-shaped association between niacin intake and MASLD prevalence. Specifically, there was a non-linear dose-response relationship, with the odds of MASLD gradually decreasing with increasing niacin intake until reaching a threshold of 23.6 mg, beyond which the odds of MASLD began to increase., Conclusion: This study confirms a U-shaped nonlinear relationship between niacin intake and MASLD prevalence within the diverse American population., (© 2024. The Author(s).)

Background: Implantable cardioverter-defibrillators are used globally and are reliable, but complications related to transvenous leads remain a concern. Evidence related to the incidence and costs of those complications is heterogeneous with respect to scope and healthcare system. This analysis aims to create estimates of the incidence and costs of tricuspid valve (TV) complications, lead failures, and lead extractions from a single large real-world data set., Methods and Results: This retrospective longitudinal cohort study used the deidentified Medicare Fee for Service administrative claims database. A total of 116 036 patients with de novo transvenous ICD implant were analyzed. Mean hospital costs were $26 903 for tricuspid valve complications, $20 851 for lead failures, and $22 278 for lead extractions., Conclusions: Transvenous ICD lead complications incur significant costs to patients, hospitals, and payers when they occur. Advancements in lead technology that reduce these complications could bring significant clinical and economic value., (© 2024 The Author(s). Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

Objective: The purpose of this study was to investigate the association between depressive symptoms and second primary cancer (SPC) in U.S. cancer survivors., Methods: Cancer survivors from the 2005-2018 National Health and Nutrition Examination Survey (NHANES) were included in this cross-sectional study, and depressive symptoms were defined by the Patient Health Questionnaire 9 (PHQ-9). The association between depressive symptoms and SPC was assessed via multiple logistic regression, restricted cubic spline (RCS), sensitivity, and subgroup analyses., Results: This study involved 2315 participants representing >15 million noninstitutionalized U.S. residents. Multivariate logistic regression fully adjusted for confounders revealed that cancer survivors with a PHQ-9 score ≥ 10 had a greater risk of developing SPC than those with a PHQ-9 score of 0-4 ([OR] = 1.88, 95% [CI] = 1.20-2.89, p = 0.005). The RCS showed a linear positive correlation between the PHQ-9 score and SPC (p for overall = 0.017). The robustness of this association was subsequently confirmed via multiple interpolation of missing data and different cluster-level methods (namely weighted linear regression) as sensitivity analyses. Furthermore, subgroup analyses confirmed this correlation was stronger in participants with sleep duration <7 h (p for interaction = 0.036)., Conclusion: Moderate to severe depressive symptoms in cancer survivors were associated with an increased risk of developing SPC, especially at <7 h of sleep., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

People with long COVID are those who still have symptoms, signs, and conditions after the initial phase of infection of SARS-CoV-2. The incidence of long COVID varies among regions-31% in North America, 44% in Europe, and 51% in Asia, which is challenging the healthcare system, but there is limited guidelines for its treatment. With more and more nationwide projects funded by the government such as the RECOVER initiative in the United States and National Institute for Health Research funding in the United Kingdom, an increasing number of ongoing clinical trials are investigating the efficacy of diverse therapies on reversing long COVID. After searching the World Health Organization International Clinical Trial Registry Platform, 587 clinical studies are identified as long COVID studies. Among these, 312 studies (53.2%) are testing potential therapies. Most of the long COVID trials were conducted in the United States (58 trials [18.6%]), followed by India (55 trials [17.6%]), and Spain (20 trials [6.4%]). Interventions in these clinical trials include physical exercise, rehabilitation therapy, behavioral therapy, and pharmacological therapies including herbs, paxlovid, and fluvoxamine. These trials are aiming to deal with these long COVID symptoms and signs including fatigue, decreased pulmonary function, reduced cognitive function, and others. To date, only 11 of these 312 studies have published their results that were not confirmative, unfortunately. Future studies should be designed to address sleep disorders which were seldomly included in registered clinical studies. Moreover, interventions aimed at treating the underlying pathophysiology of long COVID are also necessary but currently lacking., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Current estimates of atrial fibrillation (AF)-associated mortality rely on claims- or clinical-derived diagnoses of AF, limit AF to a binary entity, or are confounded by comorbidities. The objective of the present study is to assess the association between device-recognized AF and mortality among patients with cardiac implantable electronic devices capable of sensitive and continuous atrial arrhythmia detection. Secondary outcomes include relative mortality among cohorts with no AF, paroxysmal AF, persistent AF, and permanent AF., Methods: Using the deidentified Optum Clinformatics US claims database (2015 to 2020) linked to the Medtronic CareLink database, we identified individuals with a cardiac implantable electronic device who transmitted data ≥6 months after implantation. AF burden was assessed during the first 6 months after implantation (baseline period). Subsequent mortality, assessed from claims data, was compared between patients with and without AF, with adjustment for age, geographic region, insurance type, Charlson Comorbidity Index, and implantation year., Results: Of 21 391 patients (age, 72.9±10.9 years; 56.3% male) analyzed, 7798 (36.5%) had device-recognized AF. During a mean of 22.4±12.9 months (median, 20.1 [12.8-29.7] months) of follow-up, the overall incidence of mortality was 13.5%. Patients with AF had higher adjusted all-cause mortality than patients without AF (hazard ratio, 1.29 [95% CI, 1.20-1.39]; P <0.001). Among those with AF, patients with nonparoxysmal AF had the greatest risk of mortality (persistent AF versus paroxysmal AF: hazard ratio, 1.36 [95% CI, 1.18-1.58]; P <.001; permanent AF versus paroxysmal AF: hazard ratio, 1.23 [95% CI, 1.14-1.34]; P <.001)., Conclusions: After adjustment for potential confounding factors, the presence of AF was associated with higher mortality in our cohort of patients with cardiac implantable electronic devices. Among those with AF, nonparoxysmal AF was associated with the greatest risk of mortality., Competing Interests: Dr Passman received research support from the American Heart Association (No. 18SFRN34250013) and the National Institutes of Health (UG3HL165065); research support and speaker fees from Medtronic; research support from Abbott; and royalties from UpToDate. Dr Zhou, S.C. Rosemas, and Drs Soderlund and Longacre are employees and shareholders of Medtronic. A.I. Roberts is a contractor with Medtronic. Northwestern University receives fellowship support from Medtronic. The remaining authors report no conflicts.

Stereotactic body radiation therapy (SBRT) and hypofractionation using pencil-beam scanning (PBS) proton therapy (PBSPT) is an attractive option for thoracic malignancies. Combining the advantages of target coverage conformity and critical organ sparing from both PBSPT and SBRT, this new delivery technique has great potential to improve the therapeutic ratio, particularly for tumors near critical organs. Safe and effective implementation of PBSPT SBRT/hypofractionation to treat thoracic malignancies is more challenging than the conventionally fractionated PBSPT because of concerns of amplified uncertainties at the larger dose per fraction. The NRG Oncology and Particle Therapy Cooperative Group Thoracic Subcommittee surveyed proton centers in the United States to identify practice patterns of thoracic PBSPT SBRT/hypofractionation. From these patterns, we present recommendations for future technical development of proton SBRT/hypofractionation for thoracic treatment. Among other points, the recommendations highlight the need for volumetric image guidance and multiple computed tomography-based robust optimization and robustness tools to minimize further the effect of uncertainties associated with respiratory motion. Advances in direct motion analysis techniques are urgently needed to supplement current motion management techniques., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Brominated Flame Retardants (BFRs) have attracted widespread concern due to their environmental persistence and potential toxicity. This study aims to examine the association between BFRs exposure and hypertension., Methods: We used data from the National Health and Nutrition Examination Survey (NHANES) spanning 2005 to 2016 for the cross-sectional analysis. To evaluate the individual and combined impacts of BFRs exposure on hypertension, we utilized multivariate models, including generalized additive models, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models., Results: 9882 individuals (48% male) aged ≥ 20 were included in the final analysis, of whom 4114 had hypertension. After controlling for potential covariates, higher serum concentrations of PBDE100 (OR: 1.26; 95% CI: 1.01, 1.57) and PBDE153 (OR: 1.50; 95% CI: 1.18, 1.88) were significantly associated with hypertension. A nonlinear relationship between PBDE28 and hypertension was observed (P = 0.03). Moreover, BFRs mixture were positively associated with the prevalence of hypertension in both the WQS (β:1.09; 95% CI: 1.02, 1.17; P = 0.02) and BKMR models., Conclusion: Our study suggested that BFRs exposure is positively associated with hypertension in the general population. To confirm this association and elucidate the mechanisms, further research is required., (© 2024. The Author(s).)

Aims: Cardiac implantable electronic device (CIED) infections are a burden to hospitals and costly for healthcare systems. Chronic kidney disease (CKD) increases the risk of CIED infections, but its differential impact on healthcare utilization, costs, and outcomes is not known., Methods and Results: This retrospective analysis used de-identified Medicare Fee-for-Service claims to identify patients implanted with a CIED from July 2016 to December 2020. Outcomes were defined as hospital days and costs within 12 months post-implant, post-infection CKD progression, and mortality. Generalized linear models were used to calculate results by CKD and infection status while controlling for other comorbidities, with differences between cohorts representing the incremental effect associated with CKD. A total of 584 543 patients had a CIED implant, of which 26% had CKD and 1.4% had a device infection. The average total days in hospital for infected patients was 23.5 days with CKD vs. 14.5 days (P < 0.001) without. The average cost of infection was $121 756 with CKD vs. $55 366 without (P < 0.001), leading to an incremental cost associated with CKD of $66 390. Infected patients with CKD were more likely to have septicaemia or severe sepsis than those without CKD (11.0 vs. 4.6%, P < 0.001). After infection, CKD patients were more likely to experience CKD progression (hazard ratio 1.26, P < 0.001) and mortality (hazard ratio 1.89, P < 0.001)., Conclusion: Cardiac implantable electronic device infection in patients with CKD was associated with more healthcare utilization, higher cost, greater disease progression, and greater mortality compared to patients without CKD., Competing Interests: Conflict of interest: D.J.W. has received research grants and consultancy fees from Medtronic and Boston Scientific and educational fees from Abbot. M.E.T. has received speaker’s fees from Abbot, Biotronik, Boston Scientific, Medtronic, and Microport CRM. J.Z., C.W., R.H., and J.M. are employees of Medtronic, Inc. M.F.E.-C. has received consultant fees from Medtronic and Boston Scientific., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: A reliable, user-friendly, and multidimensional prediction tool can help to identify children at high risk for ADHD and facilitate early recognition and family management of ADHD. We aimed to develop and validate a risk nomogram for ADHD in children aged 3-17 years in the United States based on clinical manifestations and complex environments., Methods: A total of 141,356 cases were collected for the prediction model. Another 54,444 cases from a new data set were utilized for performing independent external validation. The LASSO regression was used to control possible variables. A final risk nomogram for ADHD was established based on logistic regression, and the discrimination and calibration of the established nomogram were evaluated by bootstrapping with 1000 resamples., Results: A final risk nomogram for ADHD was established based on 13 independent predictors, including behavioral problems, learning disabilities, age, intellectual disabilities, anxiety symptoms, gender, premature birth, maternal age at childbirth, parent-child interaction patterns, etc. The C-index of this model was 0.887 in the training set, and 0.862 in the validation set. Internal and external validation proved that the model was reliable., Conclusions: A nomogram, a statistical prediction tool that assesses individualized ADHD risk for children is helpful for the early identification of children at high risk for ADHD and the construction of a conceptual model of society-family-school collaborative diagnosis, treatment, and management of ADHD., Competing Interests: Declaration of competing interest All authors disclosed that there was no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The study aimed to examine the association between the systemic immune-inflammation index (SII), a contemporary metric of systemic inflammatory response, and biological aging, which are closely interconnected processes., Methods: This cross-sectional study utilized 10 cycles of data from the NHANES database spanning from 1990 to 2018. The study examined the relationship between the SII index, calculated as P * N/L, where P represents preoperative peripheral platelet count, N represents neutrophil count, and L represents lymphocyte count, and biological aging. Biological aging was assessed through various methods, such as phenotypic age, phenotypic age acceleration (PhenoAgeAccel), biological age, and biological age acceleration (BioAgeAccel). Correlations were analyzed using weighted linear regression and subgroup analysis., Results: Among the 7,491 participants analyzed, the average age was 45.26 ± 0.34 years, with 52.16% being female. The average phenotypic and biological ages were 40.06 ± 0.36 and 45.89 ± 0.32 years, respectively. Following adjustment for potential confounders, elevated SII scores were linked to increased phenotypic age, biological age, Phenotypic age acceleration, and Biological age acceleration. Positive correlations were observed between health behavior and health factor scores and biological aging, with stronger associations seen for health factors. In health factor-specific analyses, the β coefficient was notably higher for high BMI. The robust positive associations between SII scores and both phenotypic age and biological age in the stratified analyses were consistently observed across all strata., Conclusion: The evidence from the NHANES data indicate that SII may serve as a valuable marker for assessing different facets of aging and health outcomes, such as mortality and the aging process. Additional research is warranted to comprehensively elucidate the implications of SII in the aging process and its utility as a clinical instrument for evaluating and addressing age-related ailments., 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 Wang, Ren, Li, Hu, Zhou, Sun, Pei, Li, Peng, Yu, Zhao, Huang, Chen and Huang.)

Background: With cardiovascular diseases standing as a leading cause of mortality worldwide, the interplay between diet-induced inflammation, as quantified by the Dietary Inflammatory Index (DII), and heart failure biomarker NT-proBNP has not been investigated in the general population., Methods: This study analyzed data from the National Health and Nutrition Examination Survey (NHANES) 1999-2004, encompassing 10,766 individuals. The relationship between the DII and NT-proBNP levels was evaluated through multivariable-adjusted regression models. To pinpoint crucial dietary components influencing NT-proBNP levels, the LASSO regression model was utilized. Stratified analyses were then conducted to examine the associations within specific subgroups to identify differential effects of the DII on NT-proBNP levels across diverse populations., Results: In individuals without heart failure, a unit increase in the DII was significantly associated with an increase in NT-proBNP levels. Specifically, NT-proBNP levels rose by 9.69 pg/mL (95% CI: 6.47, 12.91; p < 0.001) without adjustments, 8.57 pg/mL (95% CI: 4.97, 12.17; p < 0.001) after adjusting for demographic factors, and 5.54 pg/mL (95% CI: 1.75, 9.32; p = 0.001) with further adjustments for health variables. In participants with a history of heart failure, those in the second and third DII quartile showed a trend towards higher NT-proBNP levels compared to those in the lowest quartile, with increases of 717.06 pg/mL (95% CI: 76.49-1357.63, p = 0.030) and 855.49 pg/mL (95% CI: 156.57-1554.41, p = 0.018). Significant interactions were observed in subgroup analyses by age (<50: β = 3.63, p = 0.141; 50-75: β = 18.4, p<0.001; >75: β = 56.09, p<0.001), gender (men: β = 17.82, p<0.001; women: β = 7.43, p = 0.061),hypertension (β = 25.73, p<0.001) and diabetes (β = 38.94, p<0.001)., Conclusion: This study identified a positive correlation between the DII and NT-proBNP levels, suggesting a robust link between pro-inflammatory diets and increased heart failure biomarkers, with implications for dietary modifications in cardiovascular risk management., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ma 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.)

Objective: This report presents an overview of the objectives, design, and analytic strategy of the Child Maltreatment in Military Families Life Course Study , an investigation of factors associated with child maltreatment in active duty military families., Method: The study uses a case-control retrospective research design and discrete-time survival methodology to examine service member demographic characteristics, family characteristics, military-related characteristics, and military family life events associated with child maltreatment incidents that meet the Department of Defense definition of child abuse or neglect. The sample includes all active duty families with a first occurrence of child maltreatment anytime between Fiscal Year (FY) 2009 and FY 2018 ( n  = 28,684), and a representative sample of control families with children under age of 18 during the same period ( n  = 589,417). Analyses include child maltreatment and domestic abuse data from the Family Advocacy Program Central Registry; sponsor socio-demographic, military-related, and family data from the Active Duty Military Personnel Master and Defense Enrollment Eligibility Reporting System data files; deployment data from the Contingency Tracking System; and mental health data from the Medical Data Repository., Results and Conclusions: Study results identify risk and protective factors associated with child maltreatment in military families, subgroups at elevated risk of child maltreatment, and periods of heightened risk during the military family life course. These results are expected to improve the ability to identify families most at-risk for particular types of child maltreatment and inform prevention strategies that promote the health and safety of military families.

In this paper, we present findings from four separate studies using different data sources and methods to examine Chinese attitudes toward the United States amid the COVID-19 pandemic. The empirical results consistently indicate a marked and significant decline in Chinese attitudes toward the US between late 2019 and the end of 2022. Using a quasi-experimental design and granular survey data that exploit daily variations in public opinion, we offer additional evidence that the decline in Chinese attitudes toward the United States followed a distinct pattern not true for Chinese attitudes toward other countries. Specifically, the rise in Chinese unfavorability toward the United States closely corresponded to the heightened Chinese attention to the pandemic's progression in the United States. These results collectively suggest a causal effect of COVID-19, shedding light on how public health crises, international relations, and media jointly shape the increasing enmity between the two great powers., Competing Interests: Competing interests statement:The authors declare no competing interest.

Objectives: Low-value care is associated with increased healthcare costs and direct harm to patients. We sought to develop and validate a simple diagnostic intensity index (DII) to quantify hospital-level diagnostic intensity, defined by the prevalence of advanced imaging among patients with selected clinical diagnoses that may not require imaging, and to describe hospital characteristics associated with high diagnostic intensity., Methods: We utilized State Inpatient Database data for inpatient hospitalizations with one or more pre-defined discharge diagnoses at acute care hospitals. We measured receipt of advanced imaging for an associated diagnosis. Candidate metrics were defined by the proportion of inpatients at a hospital with a given diagnosis who underwent associated imaging. Candidate metrics exhibiting temporal stability and internal consistency were included in the final DII. Hospitals were stratified according to the DII, and the relationship between hospital characteristics and DII score was described. Multilevel regression was used to externally validate the index using pre-specified Medicare county-level cost measures, a Dartmouth Atlas measure, and a previously developed hospital-level utilization index., Results: This novel DII, comprised of eight metrics, correlated in a dose-dependent fashion with four of these five measures. The strongest relationship was with imaging costs (odds ratio of 3.41 of being in a higher DII tertile when comparing tertiles three and one of imaging costs (95 % CI 2.02-5.75))., Conclusions: A small set of medical conditions and related imaging can be used to draw meaningful inferences more broadly on hospital diagnostic intensity. This could be used to better understand hospital characteristics associated with low-value care., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Integrating patient-specific cardiac implantable electronic device (CIED)-detected atrial fibrillation (AF) burden with measures of health care cost and utilization allows for an accurate assessment of the AF-related impact on health care use., Objectives: The goal of this study was to assess the incremental cost of device-recognized AF vs no AF; compare relative costs of paroxysmal atrial fibrillation (pAF), persistent atrial fibrillation (PeAF), and permanent atrial fibrillation (PermAF) AF; and evaluate rates and sources of health care utilization between cohorts., Methods: Using the de-identified Optum Clinformatics U.S. claims database (2015-2020) linked with the Medtronic CareLink database, CIED patients were identified who transmitted data ≥6 months postimplantation. Annualized per-patient costs in follow-up were analyzed from insurance claims and adjusted to 2020 U.S. dollars. Costs and rates of health care utilization were compared between patients with no AF and those with device-recognized pAF, PeAF, and PermAF. Analyses were adjusted for geographical region, insurance type, CHA 2 DS 2 -VASc score, and implantation year., Results: Of 21,391 patients (mean age 72.9 ± 10.9 years; 56.3% male) analyzed, 7,798 (36.5%) had device-recognized AF. The incremental annualized increased cost in those with AF was $12,789 ± $161,749 per patient, driven by increased rates of health care encounters, adverse clinical events associated with AF, and AF-specific interventions. Among those with AF, PeAF was associated with the highest cost, driven by increased rates of inpatient and outpatient hospitalization encounters, heart failure hospitalizations, and AF-specific interventions., Conclusions: Presence of device-recognized AF was associated with increased health care cost. Among those with AF, patients with PeAF had the highest health care costs. Mechanisms for cost differentials include both disease-specific consequences and physician-directed interventions., Competing Interests: Funding Support and Author Disclosures Dr Passman has received research support from the American Heart Association (#18SFRN34250013) and the National Institutes of Health (UG3HL165065); has received research support and speaker fees from Medtronic; has received research support from Abbott; and has received royalties from UpToDate. Ms. Zhou, Rosemas, Soderlund, and Longacre are employees and shareholders of Medtronic. Mr Roberts is a contractor with Medtronic. Northwestern University has received fellowship support from Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The United States is a nation of diverse racial and ethnic origins. Athletes represent the full spectrum of the nation's population. However, the orthopedic surgeons who serve as team physicians are Caucasian and male with staggeringly few exceptions. This manuscript provides an overview of the current status and barriers to diversity among orthopedic team physicians, along with strategies to address the issue. Specifically, pipeline initiatives implemented at one academic medical school and orthopedic surgery department are summarized as potential models that can be further developed by other institutions to enhance diversity in orthopedic surgery., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. Due to the complexity of the disorder and the presence of the blood-brain barrier (BBB), its drug discovery and development are facing enormous challenges, especially after several failures of monoclonal antibody (mAb) trials. Nevertheless, the Food and Drug Administration's approval of the mAb aducanumab has ushered in a new day. As we better understand the disease's pathogenesis and identify novel intracerebral therapeutic targets, antibody-based therapies have advanced over the past few years. The mAb drugs targeting β-amyloid or hyperphosphorylated tau protein are the focus of the current research. Massive neuronal loss and glial cell-mediated inflammation are also the vital pathological hallmarks of AD, signaling a new direction for research on mAb drugs. We have elucidated the mechanisms by which AD-specific mAbs cross the BBB to bind to targets. In order to investigate therapeutic approaches to treat AD, this review focuses on the promising mAbs targeting intracerebral dysfunction and related strategies to cross the BBB.

Decitabine's early successful therapeutic outcomes in hematologic malignancies have led to regulatory approvals from the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for addressing myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). These approvals have sparked keen interest in exploring the potential of decitabine for treating solid tumors. Continuous preclinical and clinical trials have proved that low doses of decitabine also bring benefits in treating solid tumors, and various proposed mechanisms attempt to explain the potential efficacy. It is important to note that the application of decitabine in solid tumors is still considered investigational. This article reviews the application mechanism and current status of decitabine in the treatment of solid tumors., 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 © 2024 Elsevier B.V. All rights reserved.)

Fluorine continues to show its potential applications in drug discovery and development, as reflected by twelve drugs being fluorinated out of the fifty-five approved by the FDA in 2023. This concise review highlights the discovery of each of these fluorine-containing drugs in the past year, including its brand name, date of approval, composition, sponsors, indication, and mechanism of action. The relevant future trend is also briefly discussed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Risk stratification systems for thyroid nodules are limited by low specificity. The fine-needle aspiration (FNA) biopsy size thresholds and stratification criteria are based on evidence from the literature and expert consensus. Our aims were to investigate the optimal FNA biopsy size thresholds in the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) and artificial intelligence (AI) TI-RADS and to revise the stratification criteria in AI TI-RADS. Methods: A total of 2596 thyroid nodules (in 2511 patients) on ultrasound examination with definite pathological diagnoses were retrospectively identified from January 2017 to September 2021 in 6 participating Chinese hospitals. The modified criteria for ACR TI-RADS were as follows: (1) no FNA for TR3; (2) FNA threshold for TR4 increased to 2.5 cm. The modified criteria for AI TI-RADS were as follows: (1) 6-point nodules upgraded to TR5; (2) no FNA for TR3; (3) FNA threshold for TR4 increased to 2.5 cm. The diagnostic performance and the unnecessary FNA rate (UFR) of modified versions were compared with the original ACR TI-RADS. Results: Compared with the original ACR TI-RADS, the modified ACR (mACR) TI-RADS yielded higher specificity (73% vs. 46%), accuracy (74% vs. 51%), area under the receiver operating characteristic curve (AUC; 0.80 vs. 0.70), and lower UFR (25% vs. 48%; all p  < 0.001), although the sensitivity was slightly decreased (87% vs. 93%, p  = 0.057). Compared with the original ACR TI-RADS, the modified AI (mAI) TI-RADS yielded higher specificity (73% vs. 46%), accuracy (75% vs. 51%), AUC (0.81 vs. 0.70), and lower UFR (24% vs. 48%; all p  < 0.001), although the sensitivity tended to be slightly decreased (89% vs. 93%, p  = 0.13). There was no significant difference between the mACR TI-RADS and mAI TI-RADS in the diagnostic performance and UFR (all p  > 0.05). Conclusions: The revised FNA thresholds and the stratification criteria of the mACR TI-RADS and mAI TI-RADS may be associated with improvements in specificity and accuracy, without significantly sacrificing sensitivity for malignancy detection.

Background: Many studies have shown that both elevated serum uric acid (SUA) levels and hyperhomocysteinemia are risk factors for atherosclerosis. However, the relationship between the two has not been thoroughly investigated., Objective: This study aimed to explore the possible link between SUA levels and homocysteine (Hcy) levels., Methods: In this cross-sectional study, 17,692 adults aged > 19 years in National Health and Nutrition Examination Survey from 1999 to 2006 were analyzed. Multivariable linear regression analysis was performed to assess the association between SUA and Hcy levels. In addition, smooth curve fitting (penalized spline method) and threshold effect analysis were performed., Results: Multivariable linear analysis showed that Hcy levels increased by 0.48 µmol/L (β = 0.48, 95%CI: 0.43-0.53) for every 1 mg/dL increase in SUA levels. We found a nonlinear relationship between SUA and Hcy levels. The results of threshold effect analysis showed that the inflection point for SUA levels was 7.1 mg/dL (β = 0.29, 95% CI: 0.23-0.36 and β = 1.05, 95% CI: 0.67-1.43 on the left and right sides of the inflection point, respectively). The p-values was less than 0.001 when using the log likelihood ratio test. This nonlinear relationship was also found in both sexes. The inflection point for SUA levels was 5.4 mg/dL in males and 7.3 mg/dL in females, respectively., Conclusions: This cross-sectional study showed that the SUA levels were positively correlated with Hcy levels. And we found a nonlinear relationship between SUA and Hcy levels., (© 2023. The Author(s).)

The triglyceride-glucose (TyG) index is an accessible and reliable surrogate indicator of insulin resistance and is strongly associated with diabetes. However, its relationship with diabetic retinopathy (DR) remains controversial. This meta-analysis aimed to assess the relationship between the TyG index and the prevalence of DR. Initial studies were searched from PubMed, Embase, Web of Science, and China National Knowledge Infrastructure (CNKI) electronic databases. The retrieval time range was from the establishment of the database to June 2023. Pooled estimates were derived using a random-effects model and reported as odds ratio (OR) with 95% confidence intervals (CIs). Two researchers independently assessed the methodological quality of the included studies. The Newcastle-Ottawa Quality Scale (NOS) was utilized to assess cohort studies or case-control studies. The Agency for Healthcare Research and Quality (AHRQ) methodology checklist was applied to assess cross-sectional studies. Ten observational studies encompassing 13716 patients with type 2 diabetes were included in the meta-analysis. The results showed that a higher TyG index increased the risk of DR compared with a low TyG index (OR: 2.34, 95% CI: 1.31-4.19, P < 0.05). When the index was analyzed as a continuous variable, consistent results were observed (OR: 1.48, 95% CI: 1.12-1.97, P < 0.005). There was no significant effect on the results of the sensitivity analyses excluding one study at a time (P all < 0.05). A higher TyG index may be associated with an increased prevalence of DR in patients with type 2 diabetes. However, high-quality cohort or case-control studies are needed to further substantiate this evidence., Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023432747., 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 Zhou, Zhu and Li.)

Background: Infigratinib is a fibroblast growth factor receptor (FGFR)-specifc tyrosine kinase inhibitor indicated for the treatment of patients with previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma. However, few studies have been conducted to evaluated the safety of infigratinib in the real world. In this study, we conducted a pharmacovigilance study to evaluate the adverse events (AEs) of infigratinib by using the Food and Drug Administration Adverse Event Reporting System (FAERS) database., Methods: OpenVigil 2.1 was employed to extract the FAERS database. Descriptive analysis was used to describe the characteristics of infigratinib-associated AE reports. Disproportionality analysis was performed by calculating the proportional reporting ratio (PRR), reporting odds ratios (ROR), and Bayesian analysis confidence propagation neural network (BCPNN) to detect positive signals., Results: Our findings revealed 149 AE reports, among which 36 significant signals were identified. These significant AE signals were mainly observed in gastrointestinal disorders (N = 26, ROR = 26.03, PRR = 8.44, information component [IC] = 3.08) and skin and subcutaneous tissue disorders (N = 21, ROR = 92.13, PRR = 40.41, IC = 5.34). Notably, dehydration and skin exfoliation were unexpected AEs, but had relatively high signal intensities (ROR = 29.75, PRR = 26.64, IC = 4.74; ROR = 50.61, PRR = 45.24, IC = 5.50, respectively) despite not being listed on the drug label. Furthermore, our analysis showed that infigratinib dose differed statistically between severe and non-severe reports (113.82 ± 16.13 mg vs 125 ± 0.00 mg, t = - 4.28; p < 0.001). However, there were no significant differences in sex, age, and types of AEs between the two groups (p  = 0.06, p  = 0.86, and p = 0.93, respectively)., Conclusions: These findings suggest that gastrointestinal and skin toxicities are the most common adverse reactions for infigratinib. It is important to recognize skin exfoliation and dehydration in clinical practice, as they are unexpected AEs. Additionally, our study indicates that infigratinib dose may correlate with an increased risk of AE severity, highlighting the need for dose adjustment of infigratinib when exposure to the drug is increased due to internal or external factors., (© 2023. The Author(s).)

Aims: Patients with epilepsy often require long-term use of antiseizure medications (ASMs) to control their seizures. However, movement disorders (MDs) related to ASMs can significantly impact their quality of life. This study aims to analyse MDs related to ASMs in the Food and Drug Administration Adverse Event Reporting System database to provide recommendations for safe medication., Methods: All adverse drug reactions associated with 26 marketed ASMs in Food and Drug Administration Adverse Event Reporting System were extracted for analysis. Disproportionality analyses were used to assess the association between ASMs and MDs, and signal colour scale maps were created to identify potential ASM-MD safety signals., Results: A total of 1921 cases experienced MDs while taking ASMs were included. A higher prevalence of MDs was observed in females compared to males. The association between specific MDs with ASMs was revealed, including known and unknown MDs such as tremors, Parkinson and paralysis. Lamotrigine and carbamazepine exhibited multiple significant MDs, while levetiracetam and pregabalin were linked to the earlier onset of MDs. Generally, higher doses were linked to a higher incidence of MDs., Conclusion: MDs were the most obvious adverse drug reactions in the nervous system triggered by using ASMs. Fourteen drugs exhibited positive signals for MDs, including some not previously reported. Conversely, 12 ASMs were deemed to have a lower possibility of inducing MDs. The incidence of MDs can be mitigated by selecting appropriate ASMs for epileptic patients. These findings enhance our understanding of the relationship between ASMs and MDs., (© 2023 British Pharmacological Society.)

Lenvatinib is a medication that targets multiple tyrosine kinases and is commonly used to treat various types of cancer. With its frequent usage, monitoring and assessing its potential adverse effects has become crucial. This study utilizes the US Food and Drug Administration Adverse Event Reporting System (FAERS) database to analyze the possible link between lenvatinib and gastrointestinal perforation. FAERS was used to analyze adverse drug reactions (ADRs) linked with lenvatinib from the first quarter of 2015 to the last quarter of 2022. The association between lenvatinib and gastrointestinal perforation was evaluated using disproportionality analyses. This study included 464 patients who developed gastrointestinal perforation after using lenvatinib. Perforation involved the entire digestive tract, with the colon among the most commonly affected perforation sites, and previously undetected esophageal perforation was frequently observed. Patients with uterine and liver cancer were at a higher risk of developing gastrointestinal perforation; patients with liver cancer experienced a shorter onset time, whereas patients with endometrial cancer had a slower onset time. Middle-aged and elderly patients exhibited a higher propensity for developing gastrointestinal perforation than younger adults. Patients with gastrointestinal perforation were found to have a significantly higher mortality rate than patients without gastrointestinal perforation. This study has identified several gastrointestinal perforation events not included in the drug instructions. It has also described the perforation site and clinical characteristics based on various types of cancer. These results could provide valuable insights for developing safer and more effective regulatory strategies concerning the use of lenvatinib., (© 2023, The American College of Clinical Pharmacology.)

The objective of this review is to provide an update on the fluorine-containing drugs approved by U.S. Food and Drug Administration in the span of past five years (2018-2022). The agency accepted a total of fifty-eight fluorinated entities to diagnose, mitigate and treat a plethora of diseases. Among them, thirty drugs are for therapy of various types of cancers, twelve for infectious diseases, eleven for CNS disorders, and six for some other diseases. These are categorized and briefly discussed based on their therapeutic areas. In addition, this review gives a glimpse about their trade name, date of approval, active ingredients, company developers, indications, and drug mechanisms. We anticipate that this review may inspire the drug discovery and medicinal chemistry community in both industrial and academic settings to explore the fluorinated molecules leading to the discovery of new drugs in the near future., Competing Interests: Declaration of competing interest The authors are partially supported by the pharmaceutical industry MapLight Therapeutics, Inc. through an industry-funded collaborative research project, which might be relevant, but not directly related to this manuscript., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Objective: To externally validate the performance of the 2019 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for IgG4-related disease (IgG4-RD) within a cohort from China and to compare the criteria with the 2020 revised comprehensive diagnostic (RCD) criteria for IgG4-RD., Methods: This study included 875 IgG4-RD and 302 non-IgG4-RD cases (213 mimickers and 89 patients with other diseases). Using expert clinical judgment as the gold standard for diagnosis of IgG4-RD, the performance (sensitivity, specificity, area under the curve (AUC) of the 2019 ACR/EULAR criteria for IgG4-RD was evaluated. We also compared it with the 2020 RCD criteria., Results: The 2019 ACR/EULAR classification criteria had a sensitivity of 76.6% (95% CI: 73.8% to 79.4%) and a specificity of 98.0% (96.0%-99.4%), an AUC of 0.873 (0.857-0.889) in the overall cohort. Those false negative cases under the 2019 ACR/EULAR classification criteria had significantly lower levels of serum IgG4, and fewer had pathological information, with a higher frequency in the involvement of those uncommon organs compared with the true positive cases. The cases judged as negative by the 2019 ACR/EULAR classification criteria yet judged as "definite" by the 2020 RCD criteria had more involvement of uncommon organs., Conclusions: The 2019 ACR/EULAR classification criteria for IgG4-RD show outstanding specificity and good sensitivity in real-world clinical practice. The 2020 RCD criteria are helpful for the diagnosis of IgG4-RD in clinical scenarios where IgG4-RD presents as involving an isolated organ, especially the unusual sites., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier Inc.)

Aim: To assess the association of mental health burden with diabetes-related self-care behaviors and healthcare utilization among older adults., Method: This cross-sectional 2019 Behavioral Risk Factor Surveillance System (BRFSS) study included ≥ 65 years old adults with self-reported diabetes. Three groups were used based on the number of days in the past month affected by mental health: 0 days (no burden), 1-13 days (occasional burden), and 14-30 days (frequent burden). Primary outcome was performing ≥ 3 of 5 diabetes-related self-care behaviors. Secondary outcome was performing ≥ 3 of 5 healthcare utilization behaviors. Multivariable logistic regression was used in Stata/SE 15.1., Results: Of 14,217 included individuals, 10.2 % reported frequent mental health burden. Compared to 'no burden', 'occasional' and 'frequent burden' groups included more female, obese, not married persons with younger age of diabetes diagnosis, and reported more comorbidities, insulin use, cost-related barriers to see doctors, and diabetes-related eye issues (p < 0.05). 'Occasional/frequent burden' groups reported less self-care and healthcare utilization behaviors, except 30 % higher healthcare utilization was observed in the 'occasional burden' group compared to no burden (aOR 1.30, 95 %CI 1.08-1.58, p = 0.006)., Conclusions: Overall, mental health burden was associated with reduced participation in diabetes-related self-care and healthcare utilization behaviors in a stepwise manner, except occasional burden was associated with higher healthcare utilization., 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 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Background: Rates of early mortality and complications after catheter ablation (CA) of atrial fibrillation (AF) vary across health care settings., Objective: The purpose of this study was to identify the rate and predictors of early mortality (within 30 days) after CA in the inpatient and outpatient settings., Methods: Using the Medicare Fee for Service database, we analyzed 122,289 patients who underwent CA for treatment of AF between 2016 and 2019 to define 30-day mortality in both inpatients and outpatients. Odds of adjusted mortality were assessed with several methods, including inverse probability of treatment weighting., Results: Mean age was 71.9 ± 6.7 years, 44% were women, and mean CHA 2 DS 2 -VASc score was 3.2 ± 1.7. Overall, 82% underwent AF ablation as an outpatient. Mortality rate 30 days after CA was 0.6%, with inpatients accounting for 71.5% of deaths (P <.001). Early mortality rates were 0.2% for outpatient procedures and 2.4% for inpatient procedures. The prevalence of comorbidities was significantly higher in patients with early mortality. Patients with early mortality had significantly higher rates of postprocedural complications. After adjustment, inpatient ablation was significantly associated with early mortality (adjusted odds ratio [aOR] 3.81; 95% confidence interval [CI] 2.87-5.08; P <.001). Hospitals with high overall ablation volume had 31% lower odds of early mortality (highest vs lowest tertile: aOR 0.69; 95% CI 0.56-0.86; P <.001)., Conclusion: AF ablation conducted in the inpatient setting is associated with a higher rate of early mortality compared with outpatient AF ablation. Comorbidities are associated with enhanced risk of early mortality. High overall ablation volume is associated with a lower risk of early mortality., (Copyright © 2023. Published by Elsevier Inc.)

Background: US attributable Clostridioides difficile infection (CDI) mortality and cost data are primarily from Medicare fee-for-service populations, and little is known about Medicare Advantage Enrollees (MAEs). This study evaluated CDI incidence among MAEs from 2012 to 2019 and determined attributable mortality and costs by comparing MAEs with and without CDI occurring in 2018., Methods: This retrospective cohort study assessed CDI incidence and associated mortality and costs for eligible MAEs ≥65 years of age using the de-identified Optum Clinformatics Data Mart database (Optum; Eden Prairie, Minnesota, USA). Outcomes included mortality, healthcare utilization, and costs, which were assessed via a propensity score-matched cohort using 2018 as the index year. Outcome analyses were stratified by infection acquisition and hospitalization status., Results: From 2012 to 2019, overall annual CDI incidence declined from 609 to 442 per 100 000 person-years. Although the incidence of healthcare-associated CDI declined overall (2012, 53.2%; 2019, 47.2%), community-associated CDI increased (2012, 46.8%; 2019, 52.8%). The 1-year attributable mortality was 7.9% (CDI cases, 26.3%; non-CDI controls, 18.4%). At the 2-month follow-up, CDI-associated excess mean total healthcare and out-of-pocket costs were $13 476 and $396, respectively. Total excess mean healthcare costs were greater among hospitalized (healthcare-associated, $28 762; community-associated, $28 330) than nonhospitalized CDI patients ($5704 and $2320, respectively), whereas total excess mean out-of-pocket cost was highest among community-associated hospitalized CDI patients ($970)., Conclusions: CDI represents an important public health burden in the MAE population. Preventive strategies and treatments are needed to improve outcomes and reduce costs for healthcare systems and this growing population of older US adults., Competing Interests: Potential conflicts of interest. H. Y., T. A., J. L. N., and J. Z. are employees of Pfizer Inc, and may hold stock or stock options, and Pfizer pays for conference attendance. M. A. O. reports grant funding and consulting work funded by Pfizer Inc. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objectives: To investigate whether intravenous thrombolysis (IVT) with alteplase (a recombinant tissue plasminogen activator, rt-PA) before endovascular treatment (EVT) is beneficial for acute ischemic stroke (AIS) patients in different periods., Methods: This study enrolled a total of 140 patients hospitalized between 2019 and 2022 with AIS from large vessel occlusion (LVO) in the anterior circulation. Those patients were divided into the EVT alone group and IVT + EVT group, in which EVT was preceded by intravenous rt-PA. According to the time from onset to femoral artery puncture, the above two groups were divided into the following subgroups: < 4.5 h, between 4.5 and 6 h, between 6 and 8 h, and between 8 and 10 h. There were 78 patients in the EVT alone group and 62 patients in the IVT + EVT group., Results: There was no statistically significant difference in functional independence, recanalization rate, favorable outcome rate, or mortality between the EVT and IVT + EVT groups (P > 0.05). After adjusting for confounding factors, a lower incidence of intracerebral hemorrhage was observed in the EVT group (P < 0.05). A comparison of time-dependent efficacy between the two groups showed that within 6-8 h, there were statistically significant differences between admission and postoperation in the National Institutes of Health Stroke Scale scores at 24 h (P = 0.01) or 7 days (P = 0.02)., Conclusions: Although there was no difference in clinical efficacy and safety between the abovementioned two groups, treatment with IVT + EVT could increase the risk of bleeding compared to EVT. Moreover, in the 6-8 h subgroup, the efficacy of EVT alone was better than that of IVT + EVT., (© 2023. The Author(s).)

Purpose: Many patients with actionable driver oncogenes (ADOs) are never identified and thus never receive targeted treatment. This study evaluated the economic impact and the potential life-years gained (LYG) that can be attributed to the extent of next-generation sequencing (NGS) testing in the United States compared with single-gene testing (SGT) in patients with metastatic nonsquamous non-small-cell lung cancer in the United States., Methods: A model was developed to evaluate incremental rates of SGT or NSG testing on the basis of LYG and cost per LYG. ADOs included for NGS included EGFR , ALK , ROS1 , BRAF , RET , MET , and NTRK . SGT included EGFR and ALK . Assumptions were made for expected incidence of ADOs. Survival distributions were fit to published trial averages of median and 5-year overall survival. Treatment costs were estimated from drug cost averages. Reimbursement costs were based on data from the Center for Medicare and Medicaid Services., Results: Each incremental 10% increase in NGS testing produces an average of 2,627.4 additional LYG, with an average cost savings per LYG of $75 US dollars (USD). Replacing SGT at the current rate of 80% with NGS testing would result in an average additional 21,09.6 LYG and reduce cost per LYG by an average of $599 USD. If 100% of eligible patients were tested with NGS and each identified patient had matched treatment, the total average cost per LYG would be $16,641.57 USD., Conclusion: On the basis of current evidence, population-level simulations demonstrate that clinically relevant gains in survival with non-negligible reduction in costs are obtainable from widespread adoption of NGS testing and appropriate treatment matching for patients with advanced nonsquamous non-small-cell lung cancer.

Background: Healthy Eating Index-2015 (HEI-2015), a healthy eating pattern proposed by Dietary Guidelines for Americans, is proven to be protective against various diseases. However, whether it is associated with age-related cataracts is unknown., Methods: This population-based cross-sectional study included 6395 participants from the National Health and Nutrition Examination Survey (NHANES) in the cycles from 2005 to 2008. HEI-2015 was calculated from 24-h dietary recall interviews, ranging from 0 to 100, and higher HEI-2015 represents better diet quality. Age-related cataract was generated from the questionnaire. The association between HEI-2015 and cataract was assessed with logistic regression models. Propensity score weighting, restricted cubic spline, and subgroup analysis were conducted to further explore the relationship., Results: 6395 participants were included in the study, with a mean [standard deviation (SD)] age of 48.7 (15.3) years and 3115 (48.7%) being male. HEI-2015 was negatively associated with cataracts after adjusting all covariates included, both as a continuous variable [odds ratio (OR): 0.991, 95% confidence interval (CI): 0.984-0.997, p = 0.006] and quartiles with the highest quartile compared to the lowest (OR: 0.739, 95% CI: 0.559-0.980, p = 0.035). After propensity score weighting, the association remained significant. Restricted cubic spline revealed no non-linear relationship ( p for non-linearity 0.085). Subgroup analysis showed that there were no interaction effects., Conclusions: Adherence to the healthy eating pattern, HEI-2015, was associated with a lower risk of age-related cataracts.

Life's Simple 7 (LS7) is the American Heart Association's (AHA) proposal for a healthy lifestyle, also known as cardiovascular health (CVH) metrics. However, the association between CVH metrics and the severity of hepatic steatosis and liver fibrosis detected by transient elastography is unknown. We performed a cross-sectional study using the data from the 2017-2018 National Health and Nutrition Examination Survey (NHANES) cycle. The controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) were used to evaluate the severity of hepatic steatosis and liver fibrosis and to define NAFLD, advanced liver fibrosis, and cirrhosis. A total of 2679 participants were included. Multivariate linear regression analysis revealed that per 1-unit increase in the CVH metric, CAP and LSM decreased by 8.565 units and 0.274 units, respectively. In the multivariate logistic regression analysis, the risk of NAFLD, advanced liver fibrosis, and cirrhosis were 7, 10, and 6 times higher in the poor CVH group than in the ideal CVH group. Subgroup analysis indicated that CVD patients and non-Hispanic whites could benefit more from ideal CVH. In conclusion, adherence to ideal CVH metrics, as proposed by the AHA, can significantly reduce the risk of hepatic steatosis and liver fibrosis.

Background: Proprotein convertase subtilisin/kexin type (PCSK9) inhibitor is a new drug class approved for treating dyslipidemias. Herein, we aimed to investigate the safety profiles of PCSK9 inhibitors (alirocumab and evolocumab) using the Food and Drug Administration Adverse Event Reporting System (FAERS)., Methods: We included adverse event (AE) reports regarding alirocumab and evolocumab submitted to the FAERs between 2015Q3 to 2021Q1. Disproportionality analyses, including reporting odds ratio (ROR), were performed to detect risk signals from the FAERs data to identify potential drug-AE associations. A signal was considered when the lower limit of the 95% confidence interval of ROR exceeded 1 and ≥3 AEs were reported. The definition relied on system organ class and preferred terms established by the Medical Dictionary for Regulatory Activities., Results: The FAERS database documented 31 475 reports regarding PCSK9 inhibitors (alirocumab and evolocumab) from July 1, 2015, to March 31, 2021. Although some differences were detected, alirocumab and evolocumab shared considerably similar safety profiles. The most significant RORs and most common reports were injection-site reactions (eg, injection-site pain, bruising, haemorrhage, erythema), muscle-related AEs (eg, myalgia, back pain, arthralgia, muscle spasms), influenza-like illness, pain and headache., Conclusion: Data mining of the FAERs is useful for examining PCSK9 inhibitor-induced AEs. Herein, our findings were largely consistent with clinical experience and could help clinicians improve the safety of PCSK9 inhibitors in clinical practice., (© 2022 British Pharmacological Society.)

Background: Over the past 30 years, treatments from different disciplines have been applied to spastic cerebral palsy (SCP). However, few bibliometric studies have been conducted to date. This study explored the knowledge base, emerging hotspots, and future trends related to SCP treatment research using bibliometric analysis., Methods: Publications on SCP treatment included in the Web of Science Core Collection database between 1990 and 2020 were retrieved, and Medical Subject Headings terms were extracted from PubMed. Online bibliometric analysis website (http://bibliometric.com/), 2 pieces of software called "CiteSpace" and "VOSViewer" were used for quantitative analysis and knowledge map establishment., Results: A total of 1668 papers were retrieved from 1990 to 2020. The number of publications has increased annually. Developmental Medicine and Child Neurology is the most productive and the highest co-cited journal. The United States has been the largest contributor. Vrije Universiteit Amsterdam ranked first in the number of papers published among institutions that have conducted correlational research. Becher JG and Graham HK should be considered scholars who have made outstanding contributions. The knowledge base of the SCP treatment research field is thoughtfully constructed to promote understanding of the field., Conclusion: This bibliometric study identified global achievements, research hotspots, and trends of SCP treatment. They provide insights into the research field and valuable information for future scientific research and clinical treatment., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Both COVID-19 infection and COVID-19 vaccines have been associated with the development of myopericarditis. The objective of this study is to (1) analyse the rates of myopericarditis after COVID-19 infection and COVID-19 vaccination in Hong Kong, (2) compared to the background rates, and (3) compare the rates of myopericarditis after COVID-19 vaccination to those reported in other countries., Methods: This was a population-based cohort study from Hong Kong, China. Patients with positive RT-PCR test for COVID-19 between 1st January 2020 and 30th June 2021 or individuals who received COVID-19 vaccination until 31st August were included. The main exposures were COVID-19 positivity or COVID-19 vaccination. The primary outcome was myopericarditis., Results: This study included 11,441 COVID-19 patients from Hong Kong, four of whom suffered from myopericarditis (rate per million: 326; 95% confidence interval [CI] 127-838). The rate was higher than the pre-COVID-19 background rate in 2019 (rate per million: 5.5, 95% CI 4.1-7.4) with a rate ratio of 55.0 (95% CI 21.4-141). Compared to the background rate, the rate of myopericarditis among vaccinated subjects in Hong Kong was similar (rate per million: 5.5; 95% CI 4.1-7.4) with a rate ratio of 0.93 (95% CI 0.69-1.26). The rates of myocarditis after vaccination in Hong Kong were comparable to those vaccinated in the United States, Israel, and the United Kingdom., Conclusions: COVID-19 infection was associated with significantly higher rate of myopericarditis compared to the vaccine-associated myopericarditis., (© 2022. The Author(s).)

Abstract: Although nonsteroidal anti inflammatory drugs are superior to opioids in dental pain management, opioids are still prescribed for dental pain in the United States. Little is known about the serious adverse outcomes of short-acting opioids within the context of dental prescribing. The objective of this study was to evaluate adverse outcomes and persistent opioid use (POU) after opioid prescriptions by dentists, based on whether opioids were overprescribed or within recommendations. A cross-sectional analysis of adults with a dental visit and corresponding opioid prescription (index) from 2011 to 2018 within a nationwide commercial claims database was conducted. Opioid overprescribing was defined as >120 morphine milligram equivalents per Centers for Disease Control and Prevention guidelines. Generalized estimating equation models were used to assess adverse outcomes (emergency department visits, hospitalizations, newly diagnosed substance use disorder, naloxone administration, or death within 30 days from index) and POU (≥1 prescription 4-90 days postindex). Predicted probabilities are reported. Of 633,387 visits, 2.6% experienced an adverse outcome and 16.6% had POU. Adverse outcome risk was not different whether opioids were overprescribed or within recommendations (predicted probability 9.0%, confidence interval [CI]: 8.0%-10.2% vs 9.1%, CI: 8.1-10.3), but POU was higher when opioids were overprescribed (predicted probability 27.4%, CI: 26.1%-28.8% vs 25.2%, CI: 24.0%-26.5%). Visits associated with mild pain and those with substance use disorders had the highest risk of both outcomes. Findings from this study demonstrate that dental prescribing of opioids was associated with adverse outcomes and POU, even when prescriptions were concordant with guidelines. Additional efforts are required to improve analgesic prescribing in dentistry, especially in groups at high risk of opioid-related adverse outcomes., (Copyright © 2022 International Association for the Study of Pain.)

In January 2021, the U.S. Food and Drug Administration (FDA) approved crizotinib for pediatric patients 1 year and older and young adults with relapsed or refractory systemic anaplastic large cell lymphoma (sALCL). This is the first approval for pediatric sALCL. Approval was based on a single-arm trial of crizotinib monotherapy that included 26 patients, aged 1-20 years, with previously treated sALCL. Efficacy was based on centrally assessed objective response rate (88%) and duration of response. Herein, we highlight unique aspects of the regulatory review, including extension of the indication to young adults, postmarketing safety, and dose optimization strategies., (Published 2022. This article is a U.S. Government work and is in the public domain in the USA.)

Background: Identifying factors associated with transitioning from mild cognitive impairment (MCI) to dementia due to Alzheimer's disease (AD dementia) or dementia due to any cause (all-cause dementia) may inform economic assessments of disease and early care planning., Research Design and Methods: A multivariate logistic regression approach identified potential predictors of progression to AD dementia or all-cause dementia in individuals with MCI or cognitive impairment (CI). Eligible patients and variables of interest were identified using claims data from the Medicare Advantage Patient Database, by Optum., Results: Predictors of an AD dementia diagnosis included age (odds ratio [OR], 1.71) and use of antipsychotics (OR, 2.50) and hypertension medication (OR, 1.25). Medication use for comorbid conditions was a better indicator of risk than comorbidity coding. Diagnosis of CI by a neurologist increased the odds of an AD dementia diagnosis. Possible protective factors for progression included the use of anxiolytics (OR, 0.76), inpatient status at time of diagnosis (OR, 0.49), and a history of stroke (OR, 0.87). None of these factors differentiated AD dementia from all-cause dementia., Conclusions: Identifying patients at risk for AD dementia allows for improved system-level planning to guide policy and optimize economic and clinical outcomes for patients, caregivers, and society.

Land conversion for intensive agriculture produces unfavorable changes to soil ecosystems, causing global concern. Soil bacterial communities mediate essential terrestrial ecosystem processes, making it imperative to understand their responses to agricultural perturbations. Here, we used high-throughput sequencing coupled with a functional gene array to study temporal dynamics of soil bacterial communities over 1 year under different disturbance intensities across a U.S. Southern Plains agroecosystem, including tallgrass prairie, Old World bluestem pasture, no-tillage (NT) canola, and conventional tillage (CT) wheat. Land use had the greatest impact on bacterial taxonomic diversity, whereas sampling time and its interaction with land use were central to functional diversity differences. The main drivers of taxonomic diversity were tillage > sampling time > temperature, while all measured factors explained similar amounts of variations in functional diversity. Temporal differences had the strongest correlation with total nitrogen > rainfall > nitrate. Within land uses, community variations for CT wheat were attributed to nitrogen levels, whereas soil organic matter and soil water content explained community variations for NT canola. In comparison, all measured factors contributed almost equally to variations in grassland bacterial communities. Finally, functional diversity had a stronger relationship with taxonomic diversity for CT wheat compared to phylogenetic diversity in the prairie. These findings reinforce that tillage management has the greatest impact on bacterial community diversity, with sampling time also critical. Hence, our study highlights the importance of the interaction between temporal dynamics and land use in influencing soil microbiomes, providing support for reducing agricultural disturbance to conserve soil biodiversity. IMPORTANCE Agricultural sustainability relies on healthy soils and microbial diversity. Agricultural management alters soil conditions and further influences the temporal dynamics of soil microbial communities essential to ecosystem functions, including organic matter dynamics, nutrient cycling, and plant nutrient availability. Yet, the responses to agricultural management are also dependent on soil type and climatic region, emphasizing the importance of assessing sustainability at local scales. To evaluate the impact of agricultural management practices, we examined bacterial communities across a management disturbance gradient over 1 year in a U.S. Southern Plains agroecosystem and determined that intensive management disturbance and sampling time critically impacted bacterial structural diversity, while their interactive effect influenced functional diversity and other soil health indicators. Overall, this study provides insights into how reducing soil disturbance can positively impact microbial community diversity and soil properties in the U.S. Southern Plains.

The FDA's Accelerated Approval program (AA) is a regulatory program to expedite availability of products to treat serious or life-threatening illnesses that lack effective treatment alternatives. Ideally, all of the many stakeholders such as patients, physicians, regulators, and health technology assessment [HTA] agencies that are affected by AA should benefit from it. In practice, however, there is intense debate over whether evidence supporting AA is sufficient to meet the needs of the stakeholders who collectively bring an approved product into routine clinical care. As AAs have become more common, it becomes essential to be able to determine their impact objectively and reproducibly in a way that provides for consistent evaluation of therapeutic decision alternatives. We describe the basic features of an approach for evaluating AA impact that accommodates stakeholder-specific views about potential benefits, risks, and costs. The approach is based on a formal decision-analytic framework combining predictive distributions for therapeutic outcomes (efficacy and safety) based on statistical models that incorporate findings from AA trials with stakeholder assessments of various actions that might be taken. The framework described here provides a starting point for communicating the value of a treatment granted AA in the context of what is important to various stakeholders., Competing Interests: The authors have declared that no competing interests exist.

Importance: Racial and ethnic disparities in postpartum care access have been well identified in the United States. Such disparities could be exacerbated by the COVID-19 pandemic because of amplified economic distress and compromised social capital among pregnant women who belong to racial or ethnic minority groups., Objective: To examine whether the COVID-19 pandemic is associated with an increase in the existing racial and ethnic disparity in postpartum care access., Design, Setting, and Participants: This was a retrospective cohort study using electronic health records data. Multinomial logistic regressions in an interrupted time series approach were used to assess monthly changes in postpartum care access across Asian, Hispanic, non-Hispanic Black (hereafter, Black), non-Hispanic White (hereafter, White) women, and women of other racial groups, controlling for maternal demographic and clinical characteristics. Eligible participants were women who gave live birth at 8 hospitals in the greater Boston, Massachusetts, area from January 1, 2019, to November 30, 2021, allowing for tracking 90-day postpartum access until March 1, 2022., Exposures: Delivery period: prepandemic (January to December 2019), early pandemic (January to March 2020), and late pandemic (April 2020 to November 2021)., Main Outcomes and Measures: Postpartum care within 90 days after childbirth was categorized into 3 groups: attended, canceled, and nonscheduled., Results: A total of 45 588 women were included. Participants were racially and ethnically diverse (4735 [10.4%] Asian women, 3399 [7.5%] Black women, 6950 [15.2%] Hispanic women, 28 529 [62.6%] White women, and 1269 [2.8%] women of other race or ethnicity). The majority were between 25 and 34 years of age and married and had a full-term pregnancy, vaginal delivery, and no clinical conditions. In the prepandemic period, the overall postpartum care attendance rate was 75.2%, dropping to 41.7% during the early pandemic period, and rebounding back to 60.9% in the late pandemic period. During the months in the late pandemic, the probability of not scheduling postpartum care among Black (average marginal effect [AME], 1.1; 95% CI, 0.6-1.6) and Hispanic women (AME, 1.3; 95% CI, 0.9-1.6) increased more than among their White counterparts., Conclusions and Relevance: In this cohort study of postpartum care access before and during the COVID-19 pandemic, racial and ethnic disparities in postpartum care were exacerbated following the onset of the COVID-19 pandemic, when postpartum care access recovered more slowly among Black and Hispanic women than White women. These disparities require swift attention and amelioration to address barriers for these women to obtain much needed postpartum care during this pandemic.

Dyslipidaemia, a significant risk factor of CVD, is threatening human health worldwide. PUFA are crucial long-chain fatty acids for TAG synthesis and removal, potentially decreasing dyslipidaemia risk. We examined dyslipidaemia prevalence among 15 244 adults aged ≥ 20 years from National Health and Nutrition Examination Survey 2009-2016. Dyslipidaemia was defined as total cholesterol ≥ 240 mg/dl, or HDL-cholesterol < 40 mg/dl/50 mg/dl for males/females, respectively, or LDL-cholesterol ≥ 160 mg/dl, or TAG ≥ 200 mg/dl, or taking lipid-modifying medications. We measured the daily PUFA intake using a 24-h dietary recall. Demographics, social economics, and lifestyle factors were collected using questionnaires/interviews. Additionally, we measured Se and Hg levels in the whole blood. Logistic regression models were used to examine the association between PUFA and dyslipidaemia. The unweighted and weighted dyslipidaemia prevalences were 72·4% and 71·0 %, respectively. When grouped into tertiles, PUFA intake above 19·524 g/d was associated with an independent 19 % decrease in dyslipidaemia risk (OR = 0·81 (95 % CI 0·71, 0·94)) compared with the lowest tertile (PUFA intake ≤ 12·349 g/d). A threshold inverse association was further determined by the restricted cubic spline analysis. When PUFA intake was increased to its turning point, that is, 19 g/d, the lower nadir risk for dyslipidaemia was obtained (OR = 0·72 (95 % CI 0·56, 0·89)). When the exposure was the sum of α -linolenic acid and octadecatetraenoic acid, the inverse linear association remained. Dietary PUFA intake is a beneficial factor for dyslipidaemia among American adults, independent of many potential confounders, including Hg and Se.

Objective: To operationalize an intersectionality framework using a novel statistical approach and with these efforts, improve the estimation of disparities in access (i.e., wait time to treatment entry) to opioid use disorder (OUD) treatment beyond race., Data Source: Sample of 941,286 treatment episodes collected in 2015-2017 in the United States from the Treatment Episodes Data Survey (TEDS-A) and a subset from California (n = 188,637) and Maryland (n = 184,276), states with the largest sample of episodes., Study Design: This retrospective subgroup analysis used a two-step approach called virtual twins. In Step 1, we trained a classification model that gives the probability of waiting (1 day or more). In Step 2, we identified subgroups with a higher probability of differences due to race. We tested three classification models for Step 1 and identified the model with the best estimation., Data Collection: Client data were collected by states during personal interviews at admission and discharge., Principal Findings: Random forest was the most accurate model for the first step of subgroup analysis. We found large variation across states in racial disparities. Stratified analysis of two states with the largest samples showed critical factors that augmented disparities beyond race. In California, factors such as service setting, referral source, and homelessness defined the subgroup most vulnerable to racial disparities. In Maryland, service setting, prior episodes, receipt of medication-assisted opioid treatment, and primary drug use frequency augmented disparities beyond race. The identified subgroups had significantly larger racial disparities., Conclusions: The methodology used in this study enabled a nuanced understanding of the complexities in disparities research. We found state and service factors that intersected with race and augmented disparities in wait time. Findings can help decision makers target modifiable factors that make subgroups vulnerable to waiting longer to enter treatment., (© 2021 The Authors. Health Services Research published by Wiley Periodicals LLC on behalf of Health Research and Educational Trust.)

Purpose: To explore trial-level and patient-level associations between response (complete remission [CR] and CR + CR with incomplete hematologic [CRi] or platelet [CRp] recovery), event-free survival (EFS), and overall survival (OS) in newly diagnosed acute myeloid leukemia (AML) trials of intensive chemotherapy., Methods: We identified data from eight randomized, active-controlled trials of intensive chemotherapy submitted to the US Food and Drug Administration for treatment of newly diagnosed AML (N = 4,482). Associations between trial-level odds ratios (ORs) for CR and CR + CRi or CRp, and hazard ratios (HRs) for EFS and OS were analyzed using weighted linear regression models. We performed patient-level responder analyses to compare OS by response using pooled data from all studies., Results: In trial-level analyses, association between HR for OS and OR for CR was moderate (R 2 = 0.49; 95% CI, 0.05 to 0.86), as was the association with OR for CR + CRi or CRp (R 2 = 0.48; 95% CI, 0.05 to 0.99). For OS versus EFS, a strong association was observed (R 2 = 0.87; 95% CI, 0.47 to 0.98) when EFS definitions were harmonized across trials using raw data. In the patient-level responder analyses, patients who achieved CR had better OS compared with CRi or CRp responders (0.73; 95% CI, 0.64 to 0.84) and nonresponders (HR, 0.33; 95% CI, 0.31 to 0.37)., Conclusion: On a trial level, there is a moderate association between OS and CR rate. A strong association between EFS and OS was observed. However, CIs were wide, and results became moderate using alternative definitions for EFS. Patient-level analyses showed CR responders have better OS compared with CRi or CRp responders and nonresponders. A therapy in newly diagnosed AML with benefit in EFS or substantial benefit in CR rate would be likely to have an OS effect., Competing Interests: Yutao GongEmployment: BeiGeneStock and Other Ownership Interests: BeiGene Jonathon VallejoEmployment: AstraZeneca (I) Gideon M. BlumenthalEmployment: MerckStock and Other Ownership Interests: MerckNo other potential conflicts of interest were reported.