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This study takes stock of business and economics research on Artificial Intelligence (AI) and provides a dynamic panorama of the overall knowledge structure of this ever-growing body of work ever since its inception in 1966. Our bibliometric analysis based on the full archive of 1024 studies identifies the main trends of and the major intellectual contributors to the extant knowledge of AI in business and economics research. Specifically, our results show that (1) AI-focused business and economics research wintnessed growth over three stages, particularly with a sharp increase after 2017. (2) While this body of research has gained tremendous momentum across the globe, the United States is by far the center of knowledge generation. (3) Research collaborations are still limited in this area. (4) Research topics flourished, ranging from early decision support systems, neural networks, and scheduling methods to more recent machine learning, automation, and big data. This study also identifies fruitful avenues for further business and economics research with an AI focus. [ABSTRACT FROM AUTHOR]

Background: Patients with advanced non-small cell lung cancer (NSCLC) seem to have disparity in prognosis. Accurate prediction of prognosis could be useful in the future to predict individual risk and to develop more aggressive or alternative treatment strategies. Purpose: To evaluate the prognostic value of metabolic tumor volume (MTV) measured by 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in patients with NSCLC. Material and Methods: We retrospectively reviewed 120 patients with pathologically proven NSCLC (61 squamous cell carcinomas and 59 adenocarcinomas) who underwent pretreatment 18F-FDG PET. MTV and maximum standardized uptake value (SUVmax) for the primary tumors were measured by 18F-FDG PET. Pretreatment variables (age, sex, American Joint Committee on Cancer [AJCC] stage, histological type, SUVmax, and MTV) were analyzed to identify their correlation with two-year survival. To further evaluate and compare the predictive value of PET parameters, MTV, and SUVmax, time-dependent receiver-operating characteristic curve (ROC) analysis was used. Results: In the univariate analysis, AJCC stage, histological type, MTV, and SUVmax of primary tumor were significant predictors of survival. On multivariate analysis, independent prognostic factors associated with decreased two-year survival were AJCC stage (hazard ratio [HR] 2.236, P = 0.003), histological type (HR 2.038, P = 0. 004), and MTV (HR 1.016, P = 0.001). SUVmax was not a significant factor (HR 0.96, P = 0.490). On time-dependent ROC analysis, MTV showed good predictive performance for two-year survival consistently better than SUVmax. Conclusion: MTV, a volumetric parameter of 18F-FDG PET, is an important independent prognostic factor for survival and a better predictor of survival than SUVmax for the primary tumor in patients with advanced NSCLC. [ABSTRACT FROM AUTHOR]

Aims: To examine whether an extended lifestyle metrics incorporating sleep quality improves risk stratification for metabolic dysfunction-associated fatty liver disease (MAFLD), at-risk metabolic dysfunction-associated steatohepatitis (MASH) and significant fibrosis., Methods: A total of 5011 participants with abdominal ultrasound from Imaging sub-cohort of South China Cohort (ISSCC) and 3672 participants underwent vibration controlled transient elastography from US National Health and Nutrition Examination Survey (US NHANES) were included. Liver Essential 5 was constructed by incorporating sleep quality into traditional healthy lifestyles (HLS)., Results: A total of 4.66-17.72% of the association between traditional HLS and MAFLD was mediated by sleep quality regardless of the detection techniques, and their joint associations on MAFLD were significant in both cohorts. ORs for individuals with poor sleep and unfavorable HLS were 1.72 (1.29-2.30) in ISSCC and 2.25 (1.55-3.26) in US NHANES, respectively. Around half of the participants previously considered as following a favorable HLS were re-classified by Liver Essential 5 with significantly higher prevalences of MAFLD in both cohorts (P < 0.001). Similar results were also found on at-risk MASH and significant fibrosis in US NHANES. ORs of participants with per one increment increase in Liver Essential 5 were 0.82 (0.77-0.89) and 0.79 (0.70-0.88) for MAFLD in ISSCC and US NHANES, 0.62 (0.48-0.78) for at-risk MASH and 0.78 (0.65-0.93) for significant fibrosis., Conclusions: Liver Essential 5, which incorporates sleep quality and traditional lifestyle factors, provides additional risk stratification for MAFLD-related outcomes., (© 2024. The Author(s).)

Purpose: This investigation seeks to determine the triglyceride glucose (TyG) index's link to stress urinary incontinence (SUI) in American females of adult age., Methods: The investigation relied on data acquired via the National Health and Nutrition Examination Survey (NHANES) conducted over the period from 2011 to 2018. The independent relationship between TyG index and SUI was tested using multivariate logistic regression analysis. We applied a smooth curve fitting approach to analyze the interrelation of them. In addition, subgroup analysis was conducted and interaction experiments were conducted., Results: Among 4459 female participants aged 20 and above, TyG index and SUI demonstrated a favorable correlation. Model 3 indicated that with every single-unit rise in the TyG index, the incidence of SUI increases by 18% [1.18 (1.01, 1.38)]. In contrast to individuals in the lowest tertile, subjects within the highest tertile of the TyG index exhibited a 68% increase in SUI incidence [1.68 (95% CI: 1.26, 2.23), 0.0004]. By using smooth curve fitting, a nonlinear positive evidence of an interconnection of the TyG index to SUI was identified., Conclusions: Women exhibiting increased TyG index levels are at a heightened risk of SUI. TyG index displays a stronger correlation than that observed with BMI. According to our findings, the TyG index is viewed as a potential tool for identifying SUI in women, and monitoring the value of TyG index may be helpful for predicting the occurrence of SUI., (© 2024 Wiley Periodicals LLC.)

Lacosamide was the first approved third-generation antiepileptic drug. However, real-world data regarding its adverse cardiac reactions in large samples still need to be completed. We evaluated the cardiac safety profile of lacosamide using the Food and Drug Administration Adverse Event Reporting System (FAERS). We performed disproportionality analysis computing reporting odds ratio (ROR) as a quantitative metric to assess the signal of lacosamide-related cardiac adverse events (AEs) from 2013 Q1 to 2022 Q4. The signal was considered significant when the lower limit of the 95% confidence interval (CI) of the ROR exceeded 1, and ≥ 5 AEs were reported. Serious and nonserious cases were compared by statistical analysis, and signals were further prioritized using a rating scale. A total of 812 cardiac AEs associated with lacosamide were identified, and 92 signals were detected, of which 17 AEs were significantly associated signals. The median time-to-onset (TTO) for moderate priority signals was 10 days, whereas for weak priority signals, it was 54 days. Notably, all cardiac AEs exhibited an early failing pattern, indicating the risk gradually decreasing. Based on the comprehensive analysis of the FAERS database and prioritization of cardiac AE signals, our research enhances the awareness among healthcare professionals regarding cardiac AEs associated with lacosamide., (© 2024. The Author(s).)

Background: Insulin resistance (IR) is closely linked to cardiometabolic diseases. Preventing and improving IR in nondiabetic populations is critically important. We aimed to investigate the relationship between Life's Essential 8 (LE8), the latest tool from the American Heart Association quantifying cardiovascular health, and IR among nondiabetic populations in the United States., Methods and Results: This cross-sectional study used data on 11 246 nondiabetic adults aged ≥20 years from the 2005 to 2018 the National Health and Nutrition Examination Survey. The LE8 score was classified into 2 subscale scores: health factor score and health behavior score. IR was measured by homeostasis model assessment of insulin resistance (HOMA-IR). Weighted logistic and linear regression models analyzed associations among the LE8 score, health behavior score, health factor score, and IR. Restricted cubic spline models assessed dose-response relationships. Adjusted subgroup analyses and inverse probability of treatment weighting method also evaluated the LE8-IR relationship. Of the 11 246 participants, 4860 (43.2%) had IR. The mean LE8 score was 70.07 (95% CI, 69.57-70.58). In fully adjusted models, higher LE8 scores were associated with lower IR odds (odds ratio per 10-unit increase, 0.57 [95% CI, 0.54-0.61]). Nonlinear LE8-IR dose-response was observed. Similar patterns were seen for health behavior and health factor subscores, with stronger IR correlations for health factors. The inverse LE8-IR association was significantly more pronounced among White participants and those with higher education, higher income, and without hypertension, cardiovascular disease, or chronic kidney disease. Significant negative LE8-IR associations persisted after inverse probability of treatment weighting., Conclusions: LE8 and subscale scores are negatively associated with IR in a nonlinear relationship. Promoting optimal cardiovascular health adherence may improve IR in nondiabetic populations.

Aims: This study aimed to investigate the association between serum levels of common and uncommon unsaturated fatty acids and prediabetes risk., Methods: Data were collected from the National Health and Nutrition Examination Survey for 2003-2004 and 2011-2012. Weighted proportional and multivariate logistic regression analyses were performed to assess the association of serum PUFAs and MUFAs with prediabetes risk after adjusting for potential confounders., Results: A total of 3575 individuals were enrolled in this study. Serum levels of PUFAs EPA (20:5 n3) and GLA (18:3 n6) were associated with increased prediabetes risk (EPA (20:5 n3): OR = 1.878, 95% CI: 1.177-2.996, P trend  = 0.002; GLA (18:3 n6): 1.702, 95% CI: 1.140-2.541, P trend  = 0.016). The MUFAs PA (16:1 n7) and EA (20:1 n9) were associated with the risk of prediabetes (OR in quintile5: PA (16:1 n7): 1.780, 95% CI: 1.056-3.001, P trend  = 0.003; EA (20:1 n9): 0.587, 95% CI: 0.347-0.994, P trend  = 0.010). Moreover, nonlinear analysis revealed that serum levels of EPA (20:5 n3) and EA (20:1 n-9) were nonlinearly associated with prediabetes risk., Conclusion: Some serum n-3 PUFAs are positively associated with prediabetes, several serum n-6 PUFAs are inversely associated with prediabetes. Regulating individual serum USFA levels may help prevent prediabetes, thereby providing evidence for clinical and nutritional practices., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Anemia is common in patients with rheumatoid arthritis (RA), and it is unknown whether the dietary inflammatory index (DII) is linked to anemia. This study aimed to clarify the prevalence of anemia in RA patients and its association with the DII. The data utilized in this study were collected from the National Health and Nutrition Examination Survey database from 1999 to 2018. The prevalence of anemia in RA patients was estimated by ethnicity, sex, and age. Weighted multivariate logistic regression was utilized to explore the correlation between anemia risk and DII. The most crucial dietary factors related to the risk of anemia in RA patients were screened by stepwise regression. A nomogram model was established according to key dietary factors. A total of 10.25% (confidence interval, 8.58-11.92%) of RA patients will develop anemia, with the lowest prevalence around the age of 60. In addition, higher DII levels were discovered in anemic patients than in nonanemic patients. In multivariate regression models, an important positive association was revealed between anemia and growing quartiles of DII (Q4 vs Q1: odds ratio = 1.98; confidence interval, 1.25-3.15). In the subgroup analysis, the adjusted relation of DII with anemia in females, Mexicans, smokers, nondrinkers, and age groups ≥ 60 years was statistically significant. The same association was observed in the sensitivity analysis. A nomogram model based on stepwise regression screening of key dietary factors showed good discriminatory power to identify anemic risk in RA patients (area under the curve: 0.707). In patients with RA, high DII levels were associated with the risk of anemia. More attention should be given to controlling dietary inflammation to better prevent and treat anemia., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Dyslipidemia, which is characterized by an unfavorable lipid profile, is a key risk factor for cardiovascular disease (CVD). Understanding the relationships between epigenetic aging and lipid levels may help guide early prevention and treatment efforts for dyslipidemia., Methods: We used weighted linear regression to cross-sectionally investigate the associations between five measures of epigenetic age acceleration estimated from whole blood DNA methylation (HorvathAge Acceleration, HannumAge Acceleration, PhenoAge Acceleration, GrimAge Acceleration, and DunedinPACE) and four blood lipid measures (total cholesterol (TC), LDL-C, HDL-C, and triglycerides (TG)) in 3,813 participants (mean age = 70 years) from the Health and Retirement Study (HRS). As a sensitivity analysis, we examined the same associations in participants who fasted prior to the blood draw (n = 2,531) and in participants who did not take lipid-lowering medication (n = 1,869). Using interaction models, we also examined whether demographic factors including age, sex, and educational attainment modified the relationships between epigenetic age acceleration and blood lipids., Results: After adjusting for age, race/ethnicity, sex, fasting status, and lipid-lowering medication use, greater epigenetic age acceleration was associated with lower TC, HDL-C, and LDL-C, and higher TG (p < 0.05), although the effect sizes were relatively small (e.g., < 7 mg/dL of TC per standard deviation in epigenetic age acceleration). GrimAge acceleration and DunedinPACE associations with all lipids remained significant after further adjustment for body mass index, smoking status, and educational attainment. These associations were stronger in participants who fasted and who did not use lipid-lowering medication, particularly for LDL-C. We observed the largest number of interactions between DunedinPACE and demographic factors, where the associations with lipids were stronger in younger participants, females, and those with higher educational attainment., Conclusion: Multiple measures of epigenetic age acceleration are associated with blood lipid levels in older adults. A greater understanding of how these associations differ across demographic groups can help shed light on the relationships between aging and downstream cardiovascular diseases. The inverse associations between epigenetic age and TC and LDL-C could be due to sample limitations or non-linear relationships between age and these lipids, as both TC and LDL-C decrease faster at older ages., (© 2024. The Author(s).)

Limited research has explored the relationship between overactive bladder (OAB) and cardiovascular health (CVH). We aim to examine the correlation between OAB and CVH in American adults, utilizing the Life's Essential 8 (LE8). We included 70,190 individuals from the National Health and Nutrition Examination Survey spanning from 2005 to 2018. In our study, the independent variable is LE8 score, where higher scores denote better CVH. The dependent variable is the presence of OAB. We employed multivariable logistic regression along with restricted cubic splines to evaluate the association between LE8 and OAB. Additionally, we performed interaction analyzes on subgroups to validate the findings. There is a significant negative correlation between LE8 scores and OAB. Upon adjusting for all covariates, a 10-point increase in LE8 total score correlated with a 17% decrease in the odds of OAB [0.83 (95% CI 0.78, 0.89)]. Compared to participants with lower LE8 scores, those with higher LE8 scores had a 46% lower probability of developing OAB. Consistent results were also observed in the association between scores of four health behaviors and four health factors and OAB. Furthermore, a notable interaction was observed between LE8 scores and smoking status. This study showed a significant negative correlation between LE8 scores and OAB prevalence., (© 2024. The Author(s).)

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).)

Importance: Realizing the benefits of cancer screening requires testing of eligible individuals and processes to ensure follow-up of abnormal results., Objective: To test interventions to improve timely follow-up of overdue abnormal breast, cervical, colorectal, and lung cancer screening results., Design, Setting, and Participants: Pragmatic, cluster randomized clinical trial conducted at 44 primary care practices within 3 health networks in the US enrolling patients with at least 1 abnormal cancer screening test result not yet followed up between August 24, 2020, and December 13, 2021., Intervention: Automated algorithms developed using data from electronic health records (EHRs) recommended follow-up actions and times for abnormal screening results. Primary care practices were randomized in a 1:1:1:1 ratio to (1) usual care, (2) EHR reminders, (3) EHR reminders and outreach (a patient letter was sent at week 2 and a phone call at week 4), or (4) EHR reminders, outreach, and navigation (a patient letter was sent at week 2 and a navigator outreach phone call at week 4). Patients, physicians, and practices were unblinded to treatment assignment., Main Outcomes and Measures: The primary outcome was completion of recommended follow-up within 120 days of study enrollment. The secondary outcomes included completion of recommended follow-up within 240 days of enrollment and completion of recommended follow-up within 120 days and 240 days for specific cancer types and levels of risk., Results: Among 11 980 patients (median age, 60 years [IQR, 52-69 years]; 64.8% were women; 83.3% were White; and 15.4% were insured through Medicaid) with an abnormal cancer screening test result for colorectal cancer (8245 patients [69%]), cervical cancer (2596 patients [22%]), breast cancer (1005 patients [8%]), or lung cancer (134 patients [1%]) and abnormal test results categorized as low risk (6082 patients [51%]), medium risk (3712 patients [31%]), or high risk (2186 patients [18%]), the adjusted proportion who completed recommended follow-up within 120 days was 31.4% in the EHR reminders, outreach, and navigation group (n = 3455), 31.0% in the EHR reminders and outreach group (n = 2569), 22.7% in the EHR reminders group (n = 3254), and 22.9% in the usual care group (n = 2702) (adjusted absolute difference for comparison of EHR reminders, outreach, and navigation group vs usual care, 8.5% [95% CI, 4.8%-12.0%], P < .001). The secondary outcomes showed similar results for completion of recommended follow-up within 240 days and by subgroups for cancer type and level of risk for the abnormal screening result., Conclusions and Relevance: A multilevel primary care intervention that included EHR reminders and patient outreach with or without patient navigation improved timely follow-up of overdue abnormal cancer screening test results for breast, cervical, colorectal, and lung cancer., Trial Registration: ClinicalTrials.gov Identifier: NCT03979495.

Objective: To identify sociodemographic and clinical factors associated with refusal of gynecologic cancer surgery and to estimate its effect on overall survival., Methods: The National Cancer Database was surveyed for patients with uterine, cervical or ovarian/fallopian tube/primary peritoneal cancer treated between 2004 and 2017. Univariate and multivariate logistic regression were used to assess associations between clinico-demographic variables and refusal of surgery. Overall survival was estimated using the Kaplan-Meier method. Trends in refusal over time were evaluated using joinpoint regression., Results: Of 788,164 women included in our analysis, 5875 (0.75%) patients refused surgery recommended by their treating oncologist. Patients who refused surgery were older at diagnosis (72.4 vs 60.3 years, p < 0.001) and more likely Black (OR 1.77 95% CI 1.62-1.92). Refusal of surgery was associated with uninsured status (OR 2.94 95% CI 2.49-3.46), Medicaid coverage (OR 2.79 95% CI 2.46-3.18), low regional high school graduation (OR 1.18 95% CI 1.05-1.33) and treatment at a community hospital (OR 1.59 95% CI 1.42-1.78). Patients who refused surgery had lower median overall survival (1.0 vs 14.0 years, p < 0.01) and this difference persisted across disease sites. Between 2008 and 2017, there was a significant increase in refusal of surgery annually (annual percent change +1.41%, p < 0.05)., Conclusions: Multiple social determinants of health are independently associated with refusal of surgery for gynecologic cancer. Given that patients who refuse surgery are more likely from vulnerable, underserved populations and have inferior survival, refusal of surgery should be considered a surgical healthcare disparity and tackled as such., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

From 2016 to 2021, the National Institutes of Health Stroke Trials Network funded by National Institutes of Health/National Institute of Neurological Disorders and Stroke initiated ten multicenter randomized controlled clinical trials. Optimal subject randomization designs are demanded with 4 critical properties: (1) protection of treatment assignment randomness, (2) achievement of the desired treatment allocation ratio, (3) balancing of baseline covariates, and (4) ease of implementation. For acute stroke trials, it is necessary to minimize the time between eligibility assessment and treatment initiation. This article reviews the randomization designs for 3 trials currently enrolling in Stroke Trials Network funded by National Institutes of Health/National Institute of Neurological Disorders and Stroke, the SATURN (Statins in Intracerebral Hemorrhage Trial), the MOST (Multiarm Optimization of Stroke Thrombolysis Trial), and the FASTEST (Recombinant Factor VIIa for Hemorrhagic Stroke Trial). Randomization methods utilized in these trials include minimal sufficient balance, block urn design, big stick design, and step-forward randomization. Their advantages and limitations are reviewed and compared with traditional stratified permuted block design and minimization., Competing Interests: Disclosures Dr Zhao reports grants from National Institutes of Health. Dr Yeatts reports other intellectual property licensed to American Stroke Association; compensation from C.R. Bard, Inc & Subsidiaries for data and safety monitoring services; employment by Medical University of South Carolina; grants from National Heart, Lung, and Blood Institute; grants from National Institute of Neurological Disorders and Stroke; and compensation from Emory University for data and safety monitoring services. Dr Selim reports grants from NIH/NIA; compensation from MedRhythms, Inc for consultant services; and grants from NIH/NINDS. Dr Adeoye reports service as Chief Medical Officer for sense diagnostics and compensation from NICO Corporation for data and safety monitoring services. Dr Durkalski-Mauldin reports grants from National Institutes of Health. Dr Elm reports grants from National Institutes of Health.

Background: The prevalence of nonalcoholic fatty liver disease (NAFLD) is rising rapidly in the world. Our aim is to investigate the efficacy and safety of statins in the treatment of NAFLD., Methods: This study was conducted by searching The National Library of Medicine, Cochrane Library, China National Knowledge Infrastructure, Web of Science, and Wanfang Data Knowledge Service Platform databases. Literature data are expressed as mean difference (MD) and 95% confidence intervals (CIs) or relative risk and 95% CI. For I2 > 50% trials, random effect model is used for statistical analysis, otherwise fixed effect model is used., Results: Fourteen studies are selected for this meta-analysis, which includes totally 534 patients in the treatment group and 527 patients in the control group. As a result, 5 studies show that the total effective rate of the treatment group is 17% higher than that of the control group (Z = 2.11, relative risk = 1.17, 95% CI: [1.01-1.35]). Twelve studies show that alanine aminotransferase levels of the experimental group are lower than that of the control group (Z = 2.63, P = .009, MD = -5.53, 95% CI: [-9.64 to -1.41]). Eleven studies show that aspartate transaminase levels of the experimental group are lower than that of the control group (Z = 2.01, P = .04, MD = -3.43, 95% CI: [-6.77 to -0.08]). Six studies show that alkaline phosphatase levels of the experimental group are lower than that of the control group (Z = 0.79, P = .43, MD = -3.46, 95% CI: [-12.08 to 5.16]). Eight studies show that gamma-glutamyl transpeptidase levels of the experimental group are lower than that of the control group (Z = 2.04, P = .04, MD = -4.05, 95% CI: [-7.96 to -0.15]). Thirteen studies show that triglyceride levels of the experimental group are lower than that of the control group (Z = 4.15, P < .0001, MD = -0.94, 95% CI: [-1.39 to -0.50]). Eleven studies show that the total cholesterol levels of the experimental group are lower than that of the control group (Z = 5.42, P < .00001, MD = -1.51, 95% CI: [-2.05 to -0.96]). Seven studies show that low-density lipoprotein-cholesterol levels of the experimental group are lower than that of the control group (Z = 5.00, P < .00001, MD = -0.85, 95% CI: [-1.18 to -0.52])., Conclusion: Statins can significantly reduce liver biochemical indicators in patients with NAFLD., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Cancer, the second largest human disease, has become a major public health problem. The prediction of chemicals' carcinogenicity before their synthesis is crucial. In this paper, seven machine learning algorithms (i.e., Random Forest (RF), Logistic Regression (LR), Support Vector Machines (SVM), Complement Naive Bayes (CNB), K-Nearest Neighbor (KNN), XGBoost, and Multilayer Perceptron (MLP)) were used to construct the carcinogenicity triple classification prediction (TCP) model (i.e., 1A, 1B, Category 2). A total of 1444 descriptors of 118 hazardous organic chemicals were calculated by Discovery Studio 2020, Sybyl X-2.0 and PaDEL-Descriptor software. The constructed carcinogenicity TCP model was evaluated through five model evaluation indicators (i.e., Accuracy, Precision, Recall, F1 Score and AUC). The model evaluation results show that Accuracy, Precision, Recall, F1 Score and AUC evaluation indicators meet requirements (greater than 0.6). The accuracy of RF, LR, XGBoost, and MLP models for predicting carcinogenicity of Category 2 is 91.67%, 79.17%, 100%, and 100%, respectively. In addition, the constructed machine learning model in this study has potential for error correction. Taking XGBoost model as an example, the predicted carcinogenicity level of 1,2,3-Trichloropropane (96-18-4) is Category 2, but the actual carcinogenicity level is 1B. But the difference between Category 2 and 1B is only 0.004, indicating that the XGBoost is one optimum model of the seven constructed machine learning models. Besides, results showed that functional groups like chlorine and benzene ring might influence the prediction of carcinogenic classification. Therefore, considering functional group characteristics of chemicals before constructing the carcinogenicity prediction model of organic chemicals is recommended. The predicted carcinogenicity of the organic chemicals using the optimum machine leaning model (i.e., XGBoost) was also evaluated and verified by the toxicokinetics. The RF and XGBoost TCP models constructed in this paper can be used for carcinogenicity detection before synthesizing new organic substances. It also provides technical support for the subsequent management of organic chemicals., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Nonalcoholic steatohepatitis is regarded as a risk factor of many liver diseases., Methods: Relevant studies were searched from The National Library of Medicine, Cochrane Library, Elsevier, China National Knowledge Infrastructure, Web of Science and WANFANG databases. A total of 15 eligible studies were analyzed in the Reviewer Manager 5.3 software, including 7 English articles and 8 Chinese articles., Results: Fifteen studies are selected for this meta-analysis, which includes totally 623 patients in the treatment group and 594 patients in the control group. As a result, 8 studies show that the total effective rate of the treatment group is higher than that of the control group [Z = 3.64, 95% confidence intervals (CI): 1.78 (1.31-2.43), P = .0003]; eleven studies show that fasting plasma glucose levels of the experimental group are lower than that of the control group [Z = 4.38, 95% CI: -0.95 (-1.38 to -0.53), P < .0001]; ten studies show that glutamic-pyruvic transaminase levels of the experimental group are lower than that of the control group [Z = 3.69, 95% CI: -11.76 (-18.01 to -5.51), P = .0002]; 6 studies show that glutamic oxalacetic transaminase levels of the experimental group are lower than that of the control group [Z = 7.40, 95% CI: -3.01 (-3.81 to -2.22), P < .00001]; 6 studies show that gamma-glutamyl transpeptidase levels of the experimental group are lower than that of the control group [Z = 2.43, 95% CI: -23.77 (-42.98 to -4.57), P = .02]; 9 studies show that triglyceride levels of the experimental group are lower than that of the control group [Z = 3.06, 95% CI: -0.62 (-1.01 to -0.22), P = .002]; 6 studies show that the homeostasis model assessment of insulin resistance of the experimental group is lower than that of the control group [Z = 3.22, 95% CI: -2.33 (-3.75 to -0.91), P = .001]; 6 studies show that the glycated hemoglobin A1c of the experimental group is lower than that of the control group [Z = 4.50, 95% CI: -1.90 (-2.72 to -1.07), P < .00001]; five studies show that the fasting insulin of the experimental group is lower than that of the control group [Z = 3.42, 95% CI: -2.25 (-3.53 to -0.96), P = .0006]., Conclusion: Pioglitazone intake is effective in nonalcoholic steatohepatitis management., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Immune checkpoint inhibitors (ICIs) have been widely used in cancer treatment; however, some case reports suggested that ICIs treatment might result in ileus. This study aims to comprehensively reveal the relationship between ileus and ICIs treatment in real-world cases from Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS)., Methods: Reports from January 1, 2011 to December 31, 2020 were extracted from the FAERS. ICIs-related adverse events in patients were defined as related to use of anti-programmed cell death protein 1 antibodies (PD-1, nivolumab and pembrolizumab), anti-programmed cell death-ligand 1 inhibitors (PD-L1, atezolizumab, durvalumab, avelumab, and cemiplimab), and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4, ipilimumab and tremelimumab). ICIs-related ileus cases were identified to characterize their clinical features. Reporting odds ratios (ROR) and information component (IC) were used to assess the relationship between ICIs and ileus., Results: Among the 105 001 cases related to ICIs, 245 were reported with ICI-related ileus. The affected patients were mainly elderly (median age, 64.5 years) and male (58%, n = 143). The median onset for all cases was 36 (range 0-880) days, and no statistical difference was observed between monotherapy and combination therapy (PD-1 or PD-L1 plus CTLA-4) (p = 0.21). Most patients required drug withdrawal treatment (n = 113, 74%) and can achieve a recovered-resolved state (n = 72, 46%). All ICIs were significantly associated with ileus (ROR = 4.27, 95%Cl: 3.75-4.85; IC = 2.04, 95%Cl: 1.79-2.31). Ileus events were most commonly reported in PD-1 treatment (n = 164, ROR = 3.83, 95%Cl: 3.28-4.48; IC = 1.90, 95%Cl: 1.62-2.21)., Conclusion: This pharmacovigilance database analysis suggested that ICIs are related to ileus. However, combination therapy may not speed up the onset of ileus., (© 2022 John Wiley & Sons Ltd.)

Study Objectives: There is no consensus information on infections associated with nonbenzodiazepines. Knowledge about infections related to newly marketed hypnotics (orexin receptor antagonists and melatonin receptor agonists) is scarce. The study aimed to detect infection signals for nonbenzodiazepines, orexin receptor antagonists, and melatonin receptor agonists by analyzing data from the U.S. Food & Drug Administration adverse event reporting system., Methods: A disproportionality analysis was performed to quantitatively detect infection signals for hypnotics by calculating the reporting odds ratio and the 95% confidence interval. Data registered in the U.S. Food & Drug Administration adverse event reporting system from 2010-2020 were retrieved., Results: A total of 3,092 patients with infection were extracted for the 3 classes of hypnotic drugs. Nonbenzodiazepines were associated with a higher disproportionality of infections (reporting odds ratio: 1.10; 95% confidence interval, 1.06-1.14). The association of infections was not present for melatonin receptor agonists (reporting odds ratio: 0.86; 95% confidence interval, 0.74-1.00) and orexin receptor antagonists (reporting odds ratio: 0.19; 95% confidence interval, 0.15-0.25). Significant reporting associations were identified for nonbenzodiazepines concerning the categories of bone and joint infections, dental and oral soft tissue infections, upper respiratory tract infections, and urinary tract infections., Conclusions: Nonbenzodiazepines had a positive signal for infections, while orexin receptor antagonists and melatonin receptor agonists had a negative signal. More research needs to be conducted to confirm this relationship., Citation: Meng L, Huang J, He Q, et al. Hypnotics and infections: disproportionality analysis of the U.S. Food & Drug Administration adverse event reporting system database. J Clin Sleep Med. 2022;18(9):2229-2235., (© 2022 American Academy of Sleep Medicine.)

The genetic determinants of fasting glucose (FG) and fasting insulin (FI) have been studied mostly through genome arrays, resulting in over 100 associated variants. We extended this work with high-coverage whole genome sequencing analyses from fifteen cohorts in NHLBI's Trans-Omics for Precision Medicine (TOPMed) program. Over 23,000 non-diabetic individuals from five race-ethnicities/populations (African, Asian, European, Hispanic and Samoan) were included. Eight variants were significantly associated with FG or FI across previously identified regions MTNR1B, G6PC2, GCK, GCKR and FOXA2. We additionally characterize suggestive associations with FG or FI near previously identified SLC30A8, TCF7L2, and ADCY5 regions as well as APOB, PTPRT, and ROBO1. Functional annotation resources including the Diabetes Epigenome Atlas were compiled for each signal (chromatin states, annotation principal components, and others) to elucidate variant-to-function hypotheses. We provide a catalog of nucleotide-resolution genomic variation spanning intergenic and intronic regions creating a foundation for future sequencing-based investigations of glycemic traits., (© 2022. The Author(s).)

Objective: This study compares the present status and traits of urology residency programs in the United States and China., Methods: The flow path, structure, curriculum, operative experience, scholarly activities, evaluation systems and other aspects of training were comparatively evaluated between China and the United States., Results: Urology residency training programs are different between China and the United States in many aspects. Admission requirements for the United States urology residency program are more rigorous, and the specialty training program in the United States is more concentrated. Furthermore, residency programs in USA have much more practical clinical and research training, and their evaluation process is more diverse, and it has been designed to assess competencies. Moreover, job opportunities after residency substantially differ between these two countries. Becoming an independent urologic surgeon is not the specific goal of the Urology residency training program in China, and it would require more training time than in the United States., Conclusion: Urology residency training programs in the United States and China have a unique format and characteristics. The training programs in China are focused on general techniques and procedures, while training programs in USA follow a more standardized curriculum. Both USA and China may complement each other to create training programs that would ultimately provide high-quality patient care., (Copyright © 2022. Published by Elsevier España, S.L.U.)

Background: The American Joint Committee on Cancer (AJCC) made improvements for staging pancreatic neuroendocrine tumors (pNETs) in its 8th Edition; however, multicenter studies were not included., Methods: We collected multicenter datasets (n = 1,086, between 2004 and 2018) to validate the value of AJCC 8 and other coexisting staging systems through univariate and multivariate analysis for well-differentiated (G1/G2) pNETs., Results: Compared to other coexisting staging systems, AJCC 7 only included 12 (1.1%) patients with stage III tumors. Patients with European Neuroendocrine Tumor Society (ENETS) stage IIB disease had a higher risk of death than patients with stage IIIA (hazard ratio [HR]: 4.376 vs. 4.322). For the modified ENETS staging system, patients with stage IIB disease had a higher risk of death than patients with stage III (HR: 6.078 vs. 5.341). According to AJCC 8, the proportions of patients with stage I, II, III, and IV were 25.7%, 40.3%, 23.6%, and 10.4%, respectively. As the stage advanced, the median survival time decreased (NA, 144.7, 100.8, 72.0 months, respectively), and the risk of death increased (HR: II = 3.145, III = 5.925, and IV = 8.762)., Conclusion: These findings suggest that AJCC 8 had a more reasonable proportional distribution and the risk of death was better correlated with disease stage., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: To investigate the interaction of hypertension and total plasma homocysteine (tHcy) levels on risk of all-cause and cardiovascular disease (CVD) mortality among middle-aged and older population., Methods: This observational cohort study analyzed data from the National Health and Nutrition Examination Survey database (1999-2002 survey cycle). A generalized additive model (GAM) based on Cox proportional hazards models was applied to estimate the relationship of tHcy level with all-cause and CVD mortality. Stratification analyses by sex and renal function were performed., Results: Among 5724 individuals aged 40-85, 704 (12.3%) died, with 339 CVD deaths after a median follow-up period of 5.58 years. Mean age was 60.7 ± 13.4 years (49.6% men). In the fully adjusted model, we found that per 1 μmol/l increment of plasma tHcy was associated with 8% increased risk of all-cause mortality and 7% increased risk of CVD mortality in hypertensive participants. The adjusted hazard ratio (95% CIs) for all-cause and CVD mortality were 1.08 (1.06-1.10) and 1.07 (1.04-1.10), respectively. There were pronounced interactive effects between hypertension and tHcy levels on risk of all-cause mortality (P for interaction = 0.031)., Conclusion: Hypertension and tHcy levels can interactively affect the risk of all-cause mortality among middle-aged and older population. Conceivably, hypertension may further enhance the ability of elevated tHcy to provoke the risk of all-cause mortality., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Cardiovascular disease (CVD) is the leading cause of mortality among US adults. African Americans have higher burden of CVD morbidity and mortality compared to any other racial group. Identifying biomarkers for clinical risk prediction of CVD offers an opportunity for precision prevention and earlier intervention., Results: Using linear mixed models, we investigated the cross-sectional association between four measures of epigenetic age acceleration (intrinsic (IEAA), extrinsic (EEAA), PhenoAge (PhenoAA), and GrimAge (GrimAA)) and ten cardiometabolic markers of hypertension, insulin resistance, and dyslipidemia in 1,100 primarily hypertensive African Americans from sibships in the Genetic Epidemiology Network of Arteriopathy (GENOA). We then assessed the association between epigenetic age acceleration and time to self-reported incident CVD using frailty hazard models and investigated CVD risk prediction improvement compared to models with clinical risk scores (Framingham risk score (FRS) and the atherosclerotic cardiovascular disease (ASCVD) risk equation). After adjusting for sex and chronological age, increased epigenetic age acceleration was associated with higher systolic blood pressure (IEAA), higher pulse pressure (EEAA and GrimAA), higher fasting glucose (PhenoAA and GrimAA), higher fasting insulin (EEAA), lower low density cholesterol (GrimAA), and higher triglycerides (GrimAA). A five-year increase in GrimAA was associated with CVD incidence with a hazard ratio of 1.54 (95% CI 1.22-2.01) and remained significant after adjusting for CVD risk factors. The addition of GrimAA to risk score models improved model fit using likelihood ratio tests (P = 0.013 for FRS and P = 0.008 for ASCVD), but did not improve C statistics (P > 0.05). Net reclassification index (NRI) showed small but significant improvement in reassignment of risk categories with the addition of GrimAA to FRS (NRI: 0.055, 95% CI 0.040-0.071) and the ASCVD equation (NRI: 0.029, 95% CI 0.006-0.064)., Conclusions: Epigenetic age acceleration measures are associated with traditional CVD risk factors in an African-American cohort with a high prevalence of hypertension. GrimAA was associated with CVD incidence and slightly improved prediction of CVD events over clinical risk scores.

Considerable progress has been made in the development of anticancer agents over the past few decades, and a lot of new anticancer agents from natural and synthetic sources have been produced. Among heterocyclic compounds, pyrimidine-fused bicyclic heterocycles possess a variety of biological activities such as anticancer, antiviral, etc. To date, 147 pyrimidine-fused bicyclic heterocycles have been approved for clinical assessment or are currently being used in clinic, 57 of which have been approved by FDA for clinical treatment of various diseases, and 22 of them are being used in the clinic for the treatment of different cancers. As the potentially privileged scaffolds, pyrimidine-fused bicyclic heterocycles may be used to discover new drugs with similar biological targets and improved therapeutic efficacy. This review aims to provide an overview of the anticancer applications and synthetic routes of 22 approved pyrimidine-fused bicyclic heterocyclic drugs in clinic., 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 © 2021 Elsevier Masson SAS. All rights reserved.)

Importance: In response to the increase in opioid overdose deaths in the United States, many states recently have implemented supply-controlling and harm-reduction policy measures. To date, an updated policy evaluation that considers the full policy landscape has not been conducted., Objective: To evaluate 6 US state-level drug policies to ascertain whether they are associated with a reduction in indicators of prescription opioid abuse, the prevalence of opioid use disorder and overdose, the prescription of medication-assisted treatment (MAT), and drug overdose deaths., Design, Setting, and Participants: This cross-sectional study used drug overdose mortality data from 50 states obtained from the National Vital Statistics System and claims data from 23 million commercially insured patients in the US between 2007 and 2018. Difference-in-differences analysis using panel matching was conducted to evaluate the prevalence of indicators of prescription opioid abuse, opioid use disorder and overdose diagnosis, the prescription of MAT, and drug overdose deaths before and after implementation of 6 state-level policies targeting the opioid epidemic. A random-effects meta-analysis model was used to summarize associations over time for each policy and outcome pair. The data analysis was conducted July 12, 2020., Exposures: State-level drug policy changes to address the increase of opioid-related overdose deaths included prescription drug monitoring program (PDMP) access, mandatory PDMPs, pain clinic laws, prescription limit laws, naloxone access laws, and Good Samaritan laws., Main Outcomes and Measures: The outcomes of interests were quarterly state-level mortality from drug overdoses, known indicators for prescription opioid abuse and doctor shopping, MAT, and prevalence of drug overdose and opioid use disorder., Results: This cross-sectional study of drug overdose mortality data and insurance claims data from 23 million commercially insured patients (12 582 378 female patients [55.1%]; mean [SD] age, 45.9 [19.9] years) in the US between 2007 and 2018 found that mandatory PDMPs were associated with decreases in the proportion of patients taking opioids (-0.729%; 95% CI, -1.011% to -0.447%), with overlapping opioid claims (-0.027%; 95% CI, -0.038% to -0.017%), with daily morphine milligram equivalent greater than 90 (-0.095%; 95% CI, -0.150% to -0.041%), and who engaged in drug seeking (-0.002%; 95% CI, -0.003% to -0.001%). The proportion of patients receiving MAT increased after the enactment of mandatory PDMPs (0.015%; 95% CI, 0.002% to 0.028%), pain clinic laws (0.013%, 95% CI, 0.005%-0.021%), and prescription limit laws (0.034%, 95% CI, 0.020% to 0.049%). Mandatory PDMPs were associated with a decrease in the number of overdose deaths due to natural opioids (-518.5 [95% CI, -728.5 to -308.5] per 300 million people) and methadone (-122.7 [95% CI, -207.5 to -37.8] per 300 million people). Prescription drug monitoring program access policies showed similar results, although these policies were also associated with increases in overdose deaths due to synthetic opioids (380.3 [95% CI, 149.6-610.8] per 300 million people) and cocaine (103.7 [95% CI, 28.0-179.5] per 300 million people). Except for the negative association between prescription limit laws and synthetic opioid deaths (-723.9 [95% CI, -1419.7 to -28.1] per 300 million people), other policies were associated with increasing overdose deaths, especially those attributed to non-prescription opioids such as synthetic opioids and heroin. This includes a positive association between naloxone access laws and the number of deaths attributed to synthetic opioids (1338.2 [95% CI, 662.5 to 2014.0] per 300 million people)., Conclusions and Relevance: Although this study found that existing state policies were associated with reduced misuse of prescription opioids, they may have the unintended consequence of motivating those with opioid use disorders to access the illicit drug market, potentially increasing overdose mortality. This finding suggests that there is no easy policy solution to reverse the epidemic of opioid dependence and mortality in the US.

Objective: Globally, developed countries such as the United States, Canada, Germany, Korea, have carried out long-term and systematic biomonitoring programs for environmental chemicals in their populations. The China National Human Biomonitoring (CNHBM) was to document the extent of human exposure to a wide array of environmental chemicals, to understand exposure profiles, magnitude and ongoing trends in exposure in the general Chinese population, and to establish a national biorepository., Methods: CNHBM adopted three-stage sampling method to obtain a nationally representative sample of the population. A total of 21,888 participants who were permanent residents in 31 provinces were designed to interviewed in this national biomonitoring (152 monitoring sites × 3 survey units × 2 sexes × 6 age groups × 4 persons = 21,888 persons) in 2017-2018. Unlike the US National Health and Nutrition Examination Survey, the CNHBM will follow the same participants in subsequent cycles allowing for dynamic, longitudinal data sets for epidemiologic follow-up. Each survey cycle of CNHBM will last 2 years and each subsequent cycle will occur 3 years after the prior cycle's completion., Results: In 2017-2018, the CNHBM created a large cohort of Chinese citizens that included districts/counties questionnaire, community questionnaire collecting information on villages/communities, individual questionnaire, household questionnaire, comprehensive medical examination, and collection of blood and urine samples for measurement of clinical and exposure biomarkers. A total of 21,746 participants were finally included in CNHBM, accounting for 99.4% of the designed sample size; and 152 PSUs questionnaires, 454 community questionnaires, 21,619 family questionnaires, 21,712 cases of medical examinations, 21,700 individual questionnaires, 21,701 blood samples and 21,704 urine samples were collected, respectively. Planned analyses of blood and urine samples were to measure both inorganic and organic chemicals, including 13 heavy metals and metalloids, 18 poly- and per-fluorinated alkyl substances, 12 phthalate metabolites, 9 polycyclic aromatic hydrocarbons metabolites, 4 environmental alkylated phenols, and 2 benzene metabolites., Conclusions: CNHBM established the first nationally representative, prospective cohort in the Chinese population to understand the baseline and trend of internal exposure of environmental chemicals in general population, and to understand environmental toxicity., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Genetic factors that influence kidney traits have been understudied for low frequency and ancestry-specific variants., Methods: We combined whole genome sequencing (WGS) data from 23,732 participants from 10 NHLBI Trans-Omics for Precision Medicine (TOPMed) Program multi-ethnic studies to identify novel loci for estimated glomerular filtration rate (eGFR). Participants included European, African, East Asian, and Hispanic ancestries. We applied linear mixed models using a genetic relationship matrix estimated from the WGS data and adjusted for age, sex, study, and ethnicity., Findings: When testing single variants, we identified three novel loci driven by low frequency variants more commonly observed in non-European ancestry (PRKAA2, rs180996919, minor allele frequency [MAF] 0.04%, P = 6.1 × 10 -11 ; METTL8, rs116951054, MAF 0.09%, P = 4.5 × 10 -9 ; and MATK, rs539182790, MAF 0.05%, P = 3.4 × 10 -9 ). We also replicated two known loci for common variants (rs2461702, MAF=0.49, P = 1.2 × 10 -9 , nearest gene GATM, and rs71147340, MAF=0.34, P = 3.3 × 10 -9 , CDK12). Testing aggregated variants within a gene identified the MAF gene. A statistical approach based on local ancestry helped to identify replication samples for ancestry-specific variants., Interpretation: This study highlights challenges in studying variants influencing kidney traits that are low frequency in populations and more common in non-European ancestry., Competing Interests: Declaration of Competing Interest GRA is employed by Regeneron Pharmaceuticals and he owns stock and stock options for Regeneron Pharmaceuticals. BMP serves on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. BMP reports serving on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. Y-DIC, LRY, JCM, BDM, JIR, KDT, JPL, EB, JAS, GRA report grants from NIH during the conduct of the study. Remaining authors have nothing to disclose., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: This study aimed to investigate the associations between previous TORCH infection (cytomegalovirus, toxoplasmosis, herpes simplex virus, and rubella) with pregnancy and neonatal outcomes in couples undergoing IVF/ICSI-ET. Materials and Methods: A total of 18,074 couples underwent fresh IVF/ICSI-ET ( in vitro fertilization/intracytoplasmic sperm injection-embryo transfer) cycles were included in our analyses. TORCH infection status was determined by serological confirmation of cytomegalovirus, toxoplasmosis, herpes simplex virus, and rubella IgG in the absence of IgM antibodies. Clinical pregnancy, ectopic pregnancy, miscarriage, live birth, preterm birth, congenital malformation, and perinatal death were evaluated in both infection and non-infection group. Multivariate logistic regression was applied to calculate odds ratio. Results: Previous toxoplasmosis infection is associated with a significantly decreased preterm birth rate [ P = 0.045, OR = 0.755 (95% CI, 0.571-0.997), Adjusted OR = 0.749 (95%CI, 0.566-0.991)]. No differences in clinical pregnancy, ectopic pregnancy, miscarriage, and perinatal death were observed between the corresponding TORCH infection group [IgM (-) IgG(+)] and the non-infection group [IgM (-) IgG (-)]. Conclusions: Previous TORCH infections were not associated with adverse pregnancy and neonatal outcomes in IVF/ICSI-ET overall, and toxoplasmosis infection might be associated with a lower preterm birth rate in patients underwent IVF/ICSI-ET. The necessity of TORCH IgG screening in IVF procedure might need re-evaluation, and further cost-effective analysis might be helpful for the clinical management strategy., (Copyright © 2020 Liu, Wu, Wang, Wang, Zhao, Chen, Tu, Qian, Liao, Huang, Zhang, Xu and Zhang.)

Objectives: Health insurance availability and affordability are vital elements in diagnosis and treatment of patients with cancer and thus constitute clinical significance as well. Although past studies have explored the disparity in mortality figures for patients with different insurance statuses, this population-based study is pioneering in analyzing the changes in cancer mortality risks over time amid macroeconomic shifts., Study Design: The study uses Surveillance Epidemiology and End Results (SEER) data of 424,889 non-elderly patients with breast, cervical, ovarian, and uterine cancer diagnosed during 2007-2010 and 2011-2015., Methods: In addition to discussing incidence figures and insurance patterns, the study uses Kaplan-Meier and Cox's proportional hazard models to examine the changes in survival probability and mortality risks for insurance-stratified patients with female-specific cancer across the two time periods., Results: Patients without insurance have an increased risk of mortality over time relative to insured patients. Moreover, uninsured patients face this heightened risk more than Medicaid patients., Discussion: Despite public policy measures as well as advancements in diagnostic facilities and treatment technology, the increased relative mortality of patients without insurance limits the long-term affordability of cancer treatment for economically vulnerable patients in comparison with insured patients., (Copyright © 2020 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by cytopenia and extramedullary hematopoiesis, resulting in splenomegaly. Multiple pathological mechanisms (e.g., circulating cytokines and genetic alterations, such as JAKV617F mutation) have been implicated in the etiology of MF, but the molecular mechanism causing resistance to JAK2V617F inhibitor therapy remains unknown. Among MF patients who were treated with the JAK inhibitor ruxolitinib, we compared noncoding RNA profiles of ruxolitinib therapy responders versus nonresponders and found miR-543 was significantly upregulated in nonresponders. We validated these findings by reverse transcription-quantitative PCR. in this same cohort, in 2 additional independent MF patient cohorts from the United States and Romania, and in a JAK2V617F mouse model of MF. Both in vitro and in vivo models were used to determine the underlying molecular mechanism of miR-543 in MF. Here, we demonstrate that miR-543 targets the dioxygenases ten-eleven translocation 1 (TET1) and 2 (TET2) in patients and in vitro, causing increased levels of global 5-methylcytosine, while decreasing the acetylation of histone 3, STAT3, and tumor protein p53. Mechanistically, we found that activation of STAT3 by JAKs epigenetically controls miR-543 expression via binding the promoter region of miR-543. Furthermore, miR-543 upregulation promotes the expression of genes related to drug metabolism, including CYP3A4, which is involved in ruxolitinib metabolism. Our findings suggest miR-543 as a potentially novel biomarker for the prognosis of MF patients with a high risk of treatment resistance and as a potentially new target for the development of new treatment options.

Background: Limited study has detailed the late-term safety and efficacy of chronic total coronary occlusion (CTO) revascularization among multiple centers applying modern techniques and with newer-generation drug-eluting stents., Methods: Among 20 centers, 222 patients enrolled in the XIENCE coronary stent, performance, and technique (EXPERT) CTO trial underwent CTO percutaneous coronary intervention (PCI) with everolimus-eluting stents (EES). Through planned 4-year follow-up, the primary composite endpoint of major adverse cardiac events (MACE; death, myocardial infarction [MI] and target lesion revascularization) and rates of individual component endpoints and stent thrombosis were determined., Results: Demographic, lesion, and procedural characteristics included prior bypass surgery, 9.9%; diabetes, 40.1%; lesion length, 36.1 ± 18.5 mm; and stent length, 51.7 ± 27.2 mm. By 4 years, MACE rates were 31.6 and 22.4% by the pre-specified ARC and per-protocol definitions, respectively. Clinically-indicated target lesion revascularization at 4 years was 11.3%. In landmark analyses of events beyond the first year of revascularization, the annualized rates of target vessel-related MI and clinically-indicated target lesion revascularization were 0.53 and 1.3%, respectively. Through 4 years, the cumulative definite/probable stent thrombosis rate was 1.7% with no events occurring beyond the initial year of index revascularization., Conclusions: In a multicenter registration trial representing contemporary technique and EES, these results demonstrate sustained long-term safety and effectiveness of EES in CTO percutaneous revascularization and can be used to inform shared decision making with patients being considered for CTO PCI relative to late safety and vessel patency., (© 2019 Wiley Periodicals, Inc.)

Background and Purpose: We explored the new BP thresholds and their impact on first-ever stroke risk determinations., Results: During a mean following-up period of 21.85 years, 638 first-ever strokes occurred among 3906 participants. After adjusting for covariates, the hazard ratios for ischemic stroke (IS) in men aged <60 years were significant higher in participants with elevated BP, stage 1 hypertension, and stage 2 hypertension than normal BP (all P<0.05); an increased risk of intracerebral hemorrhage (ICH) was also observed for those with stage 2 hypertension. Similarly, in women aged, the risk of stroke increased for those with stage 2 hypertension both in <60 years and in ≥60 years. Moreover, more than 60% of incident strokes were attributed to systolic BP (SBP) ≥120mmHg and diastolic BP (DBP) <80mmHg in men aged <60 years., Conclusions: Elevated BP increases the risk of developing stroke, particularly in the absence of routine BP measurements and hypertension treatment. A strict BP management target (SBP, <120 mmHg; DBP, <80 mmHg) should be adopted for young and middle-aged men., Methods: This population-based cohort study was conducted between October 1991 and January 2018. The association of BP categories, defined by the 2017 ACC/AHA BP guideline, with first-ever stroke risk was assessed using Cox regression models.

Aim: We investigated sex-based and regional outcomes after contemporary percutaneous coronary intervention (PCI) with the Xience V stent in patients with acute myocardial infarction (AMI)., Methods and Results: This patient level pooled analysis includes three multi-center, prospective post-market registries performed in the US, Japan, and China. A total of 1,938 patients treated with Xience V stents in the setting of AMI were enrolled. Compared to men, women had higher major adverse cardiac events (MACE) (14.1% vs. 9.8% P < 0.01, RR 1.4, 95% CI 1.1-1.4) and all-cause mortality (10% vs. 6.2% P < 0.01, RR 1.61, 95% CI 1.14-2.27) at one year, without any significant difference in device specific outcomes of target vessel failure (TVF). US patients compared to the patients from China and Japan had increased MACE (female: 18% vs. 7.1%, P = 0.0012, male: 15.7% vs. 4.1%, P < 0.0001). Multivariable analysis demonstrated that major bleeding was the strongest predictor of MACE (OR 10.51, 95%CI 4.01-27.50, P < 0.0001), MI (OR 4.26, 95%CI 1.37-13.29, P = 0.012), and all-cause death (OR 5.3, 95%CI 2.32-12.13, P < 0.0001)., Conclusion: Women with AMI who underwent PCI with XIENCE DES have higher all-cause mortality at one year in compared to men. Region based outcomes demonstrated increased MACE among US patients compared to the patients from China and Japan. After adjusting for differences in demographics, major bleeding, rather than female sex, predicted the higher observed all-cause mortality., (© 2018 Wiley Periodicals, Inc.)

Urbanization and industrialization have spurred air pollution, making it a global problem. An understanding of the spatiotemporal characteristics of PM 2.5 and PM 10 concentrations (particulate matter with an aerodynamic diameter of less than 2.5 μm and 10 μm, respectively) is necessary to mitigate air pollution. We compared the characteristics of PM 2.5 and PM 10 concentrations and their trends of China, India, and the U.S. from 2014 to 2017. Particulate matter levels were lowest in the U.S., while China showed higher concentrations, and India showed the highest. Interestingly, significant declines in PM 2.5 and PM 10 concentrations were found in some of the most polluted regions in China as well as the U.S. No comparable decline was observed in India. A strong seasonal trend was observed in China and India, with the highest values occurring in winter and the lowest in summer. The opposite trend was noted for the U.S. PM 2.5 was highly correlated with PM 10 for both China and India, but the correlation was poor for the U.S. With regard to reducing particulate matter pollutant concentrations, developing countries can learn from the experiences of developed nations and benefit by establishing and implementing joint regional air pollution control programs.

Inter-individual variability in blood pressure (BP) is influenced by both genetic and non-genetic factors including socioeconomic and psychosocial stressors. A deeper understanding of the gene-by-socioeconomic/psychosocial factor interactions on BP may help to identify individuals that are genetically susceptible to high BP in specific social contexts. In this study, we used a genomic region-based method for longitudinal analysis, Longitudinal Gene-Environment-Wide Interaction Studies (LGEWIS), to evaluate the effects of interactions between known socioeconomic/psychosocial and genetic risk factors on systolic and diastolic BP in four large epidemiologic cohorts of European and/or African ancestry. After correction for multiple testing, two interactions were significantly associated with diastolic BP. In European ancestry participants, outward/trait anger score had a significant interaction with the C10orf107 genomic region ( p = 0.0019). In African ancestry participants, depressive symptom score had a significant interaction with the HFE genomic region ( p = 0.0048). This study provides a foundation for using genomic region-based longitudinal analysis to identify subgroups of the population that may be at greater risk of elevated BP due to the combined influence of genetic and socioeconomic/psychosocial risk factors., Competing Interests: The authors declare no conflict of interest. The founding sponsors had no role in the design of the study, in the collection, analyses, or interpretation of data, in the writing of the manuscript and in the decision to publish the results. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of NIH, NHLBI, NIA, NIMHD, or NHGRI. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung and Blood Institute, the National Institutes of Health, or the U.S. Department of Health and Human Services.

Objective: The aim of this study was to compare the 2008 Chinese and the 7th edition of the American Joint Committee on Cancer (AJCC) staging systems for nasopharyngeal carcinoma and to provide proposals for updating T and N staging systems of the present staging system., Methods: Between January 2007 and December 2012, a cohort of 752 patients with biopsy-proven, newly diagnosed, non-metastatic nasopharyngeal carcinoma who were treated with intensity-modulated radiotherapy were retrospectively analysed. Prognoses were compared by T stage, N stage, and clinical stage according to the two staging systems for overall survival (OS), local relapse-free survival (LRFS), and distant metastasis-free survival (DMFS)., Results: In terms of both the T and N staging systems, the two current staging systems were comparable in predicting OS. The T classification of the 2008 Chinese staging system was better in predicting LRFS, while the N classification of the 7th edition AJCC staging system was superior in predicting DMFS. In the modern era of intensity-modulated radiotherapy, the staging system should be updated by down-staging the current stage T2 to T1, and it might be rational to merge subcategories N1 and N2., Conclusions: The two current staging systems each had advantages in predicting prognosis. It seems reasonable to downstage T2 to T1 and to merge N1 and N2., Competing Interests: The authors have declared that no competing interests exist.

Purpose: The purpose of this study is to examine the relationship between depressive symptoms and diabetes self-care in African American and Hispanic/Latino patients with type 2 diabetes and whether the association, if any, is mediated by diabetes-related self-efficacy., Methods: The sample included self-report baseline data of African American and Hispanic/Latino patients with type 2 diabetes who were aged ≥18 years and enrolled in a diabetes self-management intervention study. Depressive symptoms were assessed with the 9-item Patient Health Questionnaire. The Summary of Diabetes Self-care Activities measured engagement in healthy eating, physical activity, blood glucose checking, foot care, and smoking. The Diabetes Empowerment Scale-Short Form assessed diabetes-related psychosocial self-efficacy. Indirect effects were examined with the Baron and Kenny regression technique and Sobel testing., Results: Sample characteristics (n = 250) were as follows: mean age of 53 years, 68% women, 54% African American, and 74% with income <$20 000. Depressive symptoms showed a significant inverse association with the self-care domains of general diet, specific diet, physical activity, and glucose monitoring in the African American group. In Hispanics/Latinos, depression was inversely associated with specific diet. Self-efficacy served a significant mediational role in the relation between depression and foot care among African Americans., Conclusions: Self-efficacy mediated the relationship between depression and foot care in the African American group but was not found to be a mediator of any self-care areas within the Hispanic/Latino group. In clinical practice, alleviation of depressive symptoms may improve self-care behavior adherence. Diabetes education may consider inclusion of components to build self-efficacy related to diabetes self-care, especially among African American patients., (© 2016 The Author(s).)

Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and minorities have the worst survival. However, the molecular mechanisms underlying survival disparities have not been elucidated., Methods: In a retrospective study, we assessed association between HNSCC early death (<2 years) and 208 somatic mutations of 10 cancer-related genes in 214 patients: 98 non-Hispanic whites (46%), 72 Hispanic whites (34%), and 44 African Americans (20%)., Results: Hispanic whites and African Americans had significantly higher mutation rates for EGFR, HRAS, KRAS, and TP53. HNSCC early death was significantly associated with 3+ mutations (odds ratio [OR] = 2.78, 95% confidence interval [CI] = 1.16, 6.69), NOTCH1 mutations in non-Hispanic whites (OR = 5.51; 95% CI = 1.22-24.83) and TP53 mutations in Hispanic whites (OR = 3.84; 95% CI = 1.08-13.68) in multivariable analysis adjusted for age, sex, tumor site, and tumor stage., Conclusion: We have provided the proof-of-principal data to link racial/ethnic-specific somatic mutations and HNSCC prognosis and pave the way for precision medicine to overcome HNSCC survival disparities. © 2016 Wiley Periodicals, Inc. Head Neck 38:1234-1241, 2016., (© 2016 Wiley Periodicals, Inc.)

Purpose: Technologic advances have enabled the comprehensive analysis of genetic perturbations in non-small-cell lung cancer (NSCLC); however, African Americans have often been underrepresented in these studies. This ethnic group has higher lung cancer incidence and mortality rates, and some studies have suggested a lower incidence of epidermal growth factor receptor mutations. Herein, we report the most in-depth molecular profile of NSCLC in African Americans to date., Methods: A custom panel was designed to cover the coding regions of 81 NSCLC-related genes and 40 ancestry-informative markers. Clinical samples were sequenced on a massively parallel sequencing instrument, and anaplastic lymphoma kinase translocation was evaluated by fluorescent in situ hybridization., Results: The study cohort included 99 patients (61% males, 94% smokers) comprising 31 squamous and 68 nonsquamous cell carcinomas. We detected 227 nonsilent variants in the coding sequence, including 24 samples with nonoverlapping, classic driver alterations. The frequency of driver mutations was not significantly different from that of whites, and no association was found between genetic ancestry and the presence of somatic mutations. Copy number alteration analysis disclosed distinguishable amplifications in the 3q chromosome arm in squamous cell carcinomas and pointed toward a handful of targetable alterations. We also found frequent SMARCA4 mutations and protein loss, mostly in driver-negative tumors., Conclusion: Our data suggest that African American ancestry may not be significantly different from European/white background for the presence of somatic driver mutations in NSCLC. Furthermore, we demonstrated that using a comprehensive genotyping approach could identify numerous targetable alterations, with potential impact on therapeutic decisions., (© 2015 by American Society of Clinical Oncology.)

Background: Although previous studies have illustrated improvements in surgical cohorts for patients with intervertebral disc herniation, there are limited data on predictors of long-term outcomes comparing surgical and nonsurgical outcomes., Questions/purposes: We assessed outcomes of operative and nonoperative treatment for patients with intervertebral disc herniation and symptomatic radiculopathy at 8 years from the Spine Patient Outcomes Research Trial. We specifically examined subgroups to determine whether certain populations had a better long-term outcome with surgery or nonoperative treatment., Methods: Patients with symptomatic lumbar radiculopathy for at least 6 weeks associated with nerve root irritation or neurologic deficit on examination and a confirmed disc herniation on cross-sectional imaging were enrolled at 13 different clinical sites. Patients consenting to participate in the randomized cohort were assigned to surgical or nonoperative treatment using variable permuted block randomization stratified by site. Those who declined randomization entered the observational cohort group based on treatment preference but were otherwise treated and followed identically to the randomized cohort. Of those in the randomized cohort, 309 of 501 (62%) provided 8-year data and in the observational group 469 of 743 (63%). Patients were treated with either surgical discectomy or usual nonoperative care. By 8 years, only 148 of 245 (60%) of those randomized to surgery had undergone surgery, whereas 122 of 256 (48%) of those randomized to nonoperative treatment had undergone surgery. The primary outcome measures were SF-36 bodily pain, SF-36 physical function, and Oswestry Disability Index collected at 6 weeks, 3 months, 6 months, 12 months, and then annually. Further analysis studied the following factors to determine if any were predictive of long-term outcomes: sex, herniation location, depression, smoking, work status, other joint problems, herniation level, herniation type, and duration of symptoms., Results: The intent-to-treat analysis of the randomized cohort at 8 years showed no difference between surgical and nonoperative treatment for the primary outcome measures. Secondary outcome measures of sciatica bothersomeness, leg pain, satisfaction with symptoms, and self-rated improvement showed greater improvement in the group randomized to surgery despite high levels of crossover. The as-treated analysis of the combined randomized and observational cohorts, adjusted for potential confounders, showed advantages for surgery for all primary outcome measures; however, this has the potential for confounding from other unrecognized variables. Smokers and patients with depression or comorbid joint problems had worse functional outcomes overall (with surgery and nonoperative care) but similar surgical treatment effects. Patients with sequestered fragments, symptom duration greater than 6 months, those with higher levels of low back pain, or who were neither working nor disabled at baseline showed greater surgical treatment effects., Conclusions: The intent-to-treat analysis, which is complicated by high rates of crossover, showed no difference over 8 years for primary outcomes of overall pain, physical function, and back-related disability but did show small advantages for secondary outcomes of sciatica bothersomeness, satisfaction with symptoms, and self-rated improvement. Subgroup analyses identified those groups with sequestered fragments on MRI, higher levels of baseline back pain accompanying radiculopathy, a longer duration of symptoms, and those who were neither working nor disabled at baseline with a greater relative advantage from surgery at 8 years., Level of Evidence: Level II, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.

Age at menopause marks the end of a woman's reproductive life and its timing associates with risks for cancer, cardiovascular and bone disorders. GWAS and candidate gene studies conducted in women of European ancestry have identified 27 loci associated with age at menopause. The relevance of these loci to women of African ancestry has not been previously studied. We therefore sought to uncover additional menopause loci and investigate the relevance of European menopause loci by performing a GWAS meta-analysis in 6510 women with African ancestry derived from 11 studies across the USA. We did not identify any additional loci significantly associated with age at menopause in African Americans. We replicated the associations between six loci and age at menopause (P-value < 0.05): AMHR2, RHBLD2, PRIM1, HK3/UMC1, BRSK1/TMEM150B and MCM8. In addition, associations of 14 loci are directionally consistent with previous reports. We provide evidence that genetic variants influencing reproductive traits identified in European populations are also important in women of African ancestry residing in USA., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

We evaluated associations of race, primary payer at diagnosis, and survival among patients diagnosed in Florida with lung cancer (n = 148,140) and breast cancer (n = 111,795), from 1996 through 2007. In multivariate models adjusted for comorbidities, tumor characteristics, and treatment factors, breast cancer survival was worse for Native American women than for white women (hazard ratio [HR], 1.52; 95% confidence interval [CI], 1.05-2.20) and for women using the Indian Health Service than for women using private insurance (HR, 1.71; 95% CI, 1.33-2.19). No survival association was found for Native American compared with white lung cancer patients or those using the Indian Health Service versus private insurance in fully adjusted models. Additional resources are needed to improve surveillance strategies and to reduce cancer burden in these populations.

Objective: The purpose of this study was to evaluate the quality of compounded 17-hydroxyprogesterone caproate (17-OHPC)., Study Design: Compounded 17-OHPC that was obtained from 15 compounding pharmacies throughout the United States was analyzed for potency, impurities, sterility, and pyrogen status., Results: Eighteen samples were supplied by 15 compounding pharmacies. The concentration of 17-OHPC in all samples was within the specification limits, and all tested samples passed sterility and pyrogen testing. Only 1 of 18 samples was out of specification limits for impurities., Conclusion: Compounded 17-OHPC that was obtained from 15 pharmacies throughout the United States did not raise safety concerns when assessed for potency, sterility, pyrogen status, or impurities., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Objectives: The objective of this analysis was to evaluate the safety and effectiveness of XIENCE V in acute myocardial infarction (AMI)., Background: The XIENCE V(®) Everolimus-eluting coronary stent was superior to the TAXUS(®) paclitaxel-eluting stent in angiographic and clinical outcomes in the SPIRIT II, III, and IV randomized controlled trials, but patients with AMI were excluded., Methods: XIENCE V USA is a large, prospective, multicenter, real-world single-arm postmarket surveillance trial. Consecutive patients undergoing PCI with XIENCE V were enrolled. For this analysis, clinical outcomes in 673 patients presenting with AMI (STEMI, n = 125) were as compared to patients without AMI (n = 3528) at 1 year., Results: At 1 year, ARC-defined stent thrombosis (ST) rates were 1.08% in AMI vs. 0.85% in the non-AMI group (P = 0.4987). The late ST (30 days-1 year) rates were 0.31% vs. 0.47% (AMI vs. non-AMI, P = 0.7551). Rates of target lesion revascularization (TLR) were 4.1% vs. 4.6% (P = 0.6104), and rates of target lesion failure (TLF) were 9.1% vs. 8.5%, (P = 0.5964). With the historical WHO definition of MI, 1 year TLF rates were 7.0% vs. 6.7% (P = 0.8001). Improvements in quality of life, angina frequency, angina stability, and physical limitations occurred at 6 months (each P < 0.0001) and were sustained at 1 year in both groups. There were no significant differences in clinical outcomes between STEMI and non-STEMI patients., Conclusions: At 1 year, AMI patients treated with XIENCE V had low rates of ST, TLR, and TLF, similar to non-AMI patients. Marked improvements in patients' health status in this subgroup were also demonstrated., (Copyright © 2012 Wiley Periodicals, Inc.)

Study Design: Subgroup analysis of prospective, randomized database from the Spine Patient Outcomes Research Trial (SPORT)., Objective: The hypothesis of this study was that patients who received ESI during initial treatment as part of SPORT (The Spine Patient Outcomes Research Trial) would have improved clinical outcome and a lower rate of crossover to surgery than patients who did not receive ESI., Summary of Background Data: The use of epidural steroid injection (ESI) in patients with lumbar spinal stenosis is common, although there is little evidence in the literature to demonstrate its long-term benefit in the treatment of lumbar stenosis., Methods: Patients with lumbar spinal stenosis who received ESI within the first 3 months of enrollment in SPORT (ESI) were compared with patients who did not receive epidural injections during the first 3 months of the study (no-ESI)., Results: There were 69 ESI patients and 207 no-ESI patients. There were no significant differences in demographic factors, baseline clinical outcome scores, or operative details between the groups, although there was a significant increase in baseline preference for nonsurgical treatment among ESI patients (ESI 62% vs. no-ESI 33%, P < 0.001). There was an average 26-minute increase in operative time and an increased length of stay by 0.9 days among the ESI patients who ultimately underwent surgical treatment. Averaged over 4 years, there was significantly less improvement in 36-Item Short Form Health Survey (SF-36) Physical Function among surgically treated ESI patients (ESI 14.8 vs. no-ESI 22.5, P = 0.025). In addition, there was significantly less improvement among the nonsurgically treated patients in SF-36 Body Pain (ESI 7.3 vs. no-ESI 16.7, P = 0.007) and SF-36 Physical Function (ESI 5.5 vs. no-ESI 15.2, P = 0.009). Of the patients assigned to the surgical treatment group, there was a significantly increased crossover to nonsurgical treatment among patients who received an ESI (ESI 33% vs. no-ESI 11%, P = 0.012). Of the patients assigned to the nonoperative treatment group, there was a significantly increased crossover to surgical treatment in the ESI patients (ESI 58% vs. no-ESI 32%, P = 0.003)., Conclusion: Despite equivalent baseline status, ESIs were associated with significantly less improvement at 4 years among all patients with spinal stenosis in SPORT. Furthermore, ESIs were associated with longer duration of surgery and longer hospital stay. There was no improvement in outcome with ESI whether patients were treated surgically or nonsurgically.

Object: Stroke is a leading cause of death and disability. Given that neurologists and neurosurgeons have special expertise in this area, the authors hypothesized that the density of neuroscience providers is associated with reduced mortality rates from stroke across US counties., Methods: This is a retrospective review of the Area Resource File 2009-2010, a national county-level health information database maintained by the US Department of Health and Human Services. The primary outcome variable was the 3-year (2004-2006) average in cerebrovascular disease deaths per million population for each county. The primary independent variable was the combined density of neurosurgeons and neurologists per million population in the year 2006. Multiple regression analysis was performed, adjusting for density of general practitioners (GPs), urbanicity of the county, and socioeconomic status of the residents of the county., Results: In the 3141 counties analyzed, the median number of annual stroke deaths was 586 (interquartile range [IQR] 449-754), the median number of neuroscience providers was 0 (IQR 0-26), and the median number of GPs was 274 (IQR 175-410) per million population. On multivariate adjusted analysis, each increase of 1 neuroscience provider was associated with 0.38 fewer deaths from stroke per year (p < 0.001) per million population. Rural location (p < 0.001) and increased density of GPs (p < 0.001) were associated with increases in stroke-related mortality., Conclusions: Higher density of specialist neuroscience providers is associated with fewer deaths from stroke. This suggests that the availability of specialists is an important factor in survival after stroke, and underlines the importance of promoting specialist education and practice throughout the country.

This study uses national data to describe the patterns and aetiologies for childhood falls in a high-income country, the United States. We conducted a retrospective analysis of data for children aged 0-17 years from the 2007 Nationwide Emergency Department Sample (NEDS). Sample weights provided by NEDS were used to make national estimates. We estimated that in 2007 there were more than 2.3 million paediatric fall-related emergency department (ED) visits at a rate of 3217 visits per 100,000 children. Over 95% of those seen for fall injuries were treated and released. In addition, government sources made payments for just under one-third of these visits. Of those ED visits that result in hospitalisation, we found marked age patterns in bodily location of injury. The impact of fall-related injuries on EDs in the US is substantial within the paediatric population. The use of national level ED data shows age and gender patterns in paediatric fall injury not readily apparent in previous studies. There are patterns in external cause of injury and bodily location of injury that can be used to guide age specific prevention interventions.