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PURPOSE Fertility discussions are an integral part of comprehensive care for pediatric, adolescent, and young adult patients newly diagnosed with cancer and are supported by national guidelines. Current institutional practices are poorly understood. METHODS A cross-sectional survey was distributed to 220 Children's Oncology Group member institutions regarding fertility discussion practices. Descriptive statistics were calculated for all variables. The association between specific practices and selected outcomes on the basis of sex was examined via multivariable logistic regression. RESULTS One hundred forty-four programs (65.5%) returned surveys. Of these, 65 (45.1%) reported routine discussions of fertility with all female patients and 55 (38.5%) all male patients (P 5 .25). Ninety-two (63.8%) reported no specific criteria for offering females fertility preservation (FP), compared with 40 (27.7%) for males (P, .001). Program characteristics associated with fertility discussions included reproductive endocrinology and infertility on site (females odds ratio [OR], 2.1; 95% CI, 1.0 to 4.3), discussion documentation mandate (females OR, 2.3; 95% CI, 1.0 to 5.5; males OR, 3.5; 95% CI, 1.4 to 8.7), and cumulative institution-based FP infrastructure (which included [1] routine practice of documentation, [2] template for documentation, [3] mandate for documentation, and [4] availability of FP navigation; females OR, 1.6; 95%CI, 1.1 to 2.3; males OR, 2.3; 95%CI, 1.6 to 3.4). Utilization of practices unsupported by guidelines included offering sperm banking after treatment initiation (39/135 programs; 28.9%), gonadotropin-releasing hormone analogs for ovarian suppression/FP (75/144 programs; 52.1%), ovarian tissue cryopreservation at diagnosis for patients with leukemia (19/64 programs; 29.7%), and testicular tissue cryopreservation (23/138 programs; 16.7%) not part of a clinical trial. CONCLUSION Despite recommended guidelines, fertility discussions with patients/families before treatment initiation are not routine at Children's Oncology Group institutions. Standard criteria to determine which options should be offered to patients are more common for males than females. [ABSTRACT FROM AUTHOR]

Once unimaginable, fertility management is now a nationally established part of cancer care in institutions, from academic centers to community hospitals to private practices. Over the last two decades, advances in medicine and reproductive science have made it possible for men, women and children to be connected with an oncofertility specialist or offered fertility preservation soon after a cancer diagnosis. The Oncofertility Consortium's National Physicians Cooperative is a large-scale effort to engage physicians across disciplines - oncology, urology, obstetrics and gynecology, reproductive endocrinology, and behavioral health - in clinical and research activities to enable significant progress in providing fertility preservation options to children and adults. Here, we review the structure and function of the National Physicians Cooperative and identify next steps. [ABSTRACT FROM AUTHOR]

This paper proposes a new probabilistic approach for describing uncertainty in the ensembles of latent heat flux proxies. The proxies are obtained from hourly Bowen ratio and satellite-derived measurements, respectively, at several locations in the southern Great Plains region in the United States. The novelty of the presented approach is that the proxies are not considered separately, but as bivariate samples from an underlying probability density function. To describe the latter, the use of Gaussian mixture density models—a class of nonparametric, data-adaptive probability density functions—is proposed. In this way any subjective assumptions (e.g., Gaussianity) on the form of bivariate latent heat flux ensembles are avoided. This makes the estimated mixtures potentially useful in nonlinear interpolation and nonlinear probabilistic data assimilation of noisy latent heat flux measurements. The results in this study show that both of these applications are feasible through regionalization of estimated mixture densities. The regionalization scheme investigated here utilizes land cover and vegetation fraction as discriminatory variables. [ABSTRACT FROM AUTHOR]

It is well documented that in the United States, real estate investment trust (REIT) initial public offerings (IPOs) have an abnormally low initial-day return when compared to that of industrial firm IPOs. Researchers suspect that the abnormal return pattern of REIT IPOs is caused by their unique real estate holdings. Examination of 399 IPOs issued in Hong Kong during the 1986-1997 period reveals strong evidence that suggests that underlying real estate holdings cannot be the sole reason for the observed low initial-day return of REIT IPOs. This investigation indicates that there is a need to re-think the current explanations for the abnormal performance of REIT IPOs. [ABSTRACT FROM AUTHOR]

Focuses on the relationships between land use and groundwater for Finney County, Kansas. Role of groundwater in land use practices; Importance of proper management of land and water resources; Application of the geographic information system.

Objective: To compare antimüllerian hormone (AMH) patterns by cancer status and treatment exposures across 6 years after incident breast cancer using administrative data.Design: In a cross-sectional design, AMH levels in patients who developed incident breast cancer between ages 15-39 years during 2005-2019 were matched 1:10 to levels in females without cancer in the OptumLabs Data Warehouse. Modeled AMH patterns were compared among cyclophosphamide-based chemotherapy, non-cyclophosphamide-based chemotherapy, no chemotherapy, and no breast cancer groups.Setting: Commercially insured females in the United States.Patient(s): Females with and without breast cancer.Exposure(s): Breast cancer, cyclophosphamide- and non-cyclophosphamide-based chemotherapy.Main Outcome Measure(s): AMH levels.Result(s): A total of 233 patients with breast cancer (mean age, 34 years; standard deviation, 3.7 years) contributed 278 AMH levels over a median of 2 years (range, 0-6.7 years) after diagnosis; 52% received cyclophosphamide-based chemotherapy, 17% received non-cyclophosphamide-based chemotherapy (80% platinum-based), and 31% received no chemotherapy. A total of 2,777 matched females without cancer contributed 2,780 AMH levels. The pattern of AMH levels differed among the 4 groups. Among females without cancer and breast cancer survivors who did not undergo chemotherapy, AMH declined linearly over time. In contrast, among those who received cyclophosphamide-based and noncyclophosphamide-based chemotherapy, a nonlinear pattern of AMH level of initial fall during chemotherapy, followed by an increase over 2-4 years, and then by a plateau over 1-2 years before a decline was observed.Conclusion(s): In breast cancer survivors, AMH levels from administrative data supported ovarian toxicity of non-cyclophosphamide-based chemotherapy in breast cancer and efficiently depicted the timing and duration of changes in ovarian reserve to reflect the residual reproductive lifespan. [ABSTRACT FROM AUTHOR]

Objective: To estimate the association between perceived fertility potential and contraception use and to characterize factors important in contraceptive decision making in reproductive-age, female cancer survivors.Design: Cross-sectional study.Setting: Participants were from two state cancer registries, physician referrals, and cancer survivor advocacy groups in the United States.Patient(s): A total of 483 female survivors aged 18-40 years.Intervention(s): Online questionnaire.Main Outcome Measure(s): Contraception use.Result(s): Eighty-four percent of participants used contraception; 49.7% used highly effective, World Health Organization tiers I and II methods (surgical sterilization, intrauterine devices, contraceptive implant, combined hormonal contraceptives, medroxyprogesterone acetate, progestin-only pills, contraceptive diaphragm). Contraception non-use was more common among survivors who perceived themselves to be infertile, compared with survivors who perceived themselves to be as or more fertile than similarly aged peers (prevalence ratio 4.0, 95% confidence interval 2.5-7.4). In mediation analysis that adjusted for clinical infertility, 59% of the association between prior chemotherapy and contraception non-use was explained by perceived infertility. Contraception efficacy (n = 62, 25.8%) and ease of use (n = 50, 20.8%) were the most cited reasons for using tier I/II methods; compared with lack of hormones (n = 81, 49.7%) as the predominant reason for using less-effective, tier III/IV methods.Conclusion(s): Although female, reproductive-age cancer survivors had high uptake of contraception, those who perceived themselves to be infertile were less likely to use contraception. Throughout survivorship, clinicians should counsel survivors on fertility potential in the context of their prior cancer treatments and on factors, including contraceptive efficacy and hormone-free contraception, that inform reproductive decision making in this population. [ABSTRACT FROM AUTHOR]

Objective: To test whether emergency contraception use in reproductive-aged cancer survivors is higher than in the general U.S. population and evaluate factors associated with use among survivors.Design: A retrospective cohort study compared emergency contraception use between cancer survivors in the Reproductive Window Study on ovarian function after cancer and in the general population in the 2006-2010 National Survey for Family Growth. In a cross-sectional analysis of survivors, multivariable models were used to test associations between participant characteristics and emergency contraception use.Setting: Not applicable.Patient(s): A total of 616 female cancer survivors aged 18-40.Intervention(s): None.Main Outcome Measure(s): Self-reported emergency contraception use.Result(s): The mean age of survivors was 33.4 ± 4.7, at a mean 7.5 years since diagnosis. Breast cancer (22%), Hodgkin lymphoma (18%), and leukemia (8%) were the most common cancers. Since diagnosis, 156 (25.3%) used emergency contraception, 60% because of not otherwise using contraception. Age-adjusted prevalence of use was higher in survivors than in the general population (28.3% [95% confidence interval (CI) 24.7-31.9] vs. 12.0% [95% CI 11.1-12.9]). In multivariable analysis among survivors, nonwhite race (prevalence ratio [PR] 1.3, 95% CI 1.0-1.8), breast cancer (PR 0.6, 95% CI 0.4-1.0), partnered relationship (PR 0.6, 95% CI 0.5-0.9), and older age (age 36-40 vs. 31-35; PR 0.7, 95% CI 0.5-1.0) were associated with emergency contraception.Conclusion(s): Female young adult cancer survivors were significantly more likely to use emergency contraception compared with the general population. Populations including nonwhite survivors have a higher risk, suggesting differences in family planning care. Strategies to improve contraception and decrease the need for emergency contraception are needed. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to investigate the association between Serum Albumin Levels (ALB) and erectile dysfunction (ED) within the U.S. general population., Methods: We conducted a cross-sectional analysis using data from the National Health and Nutrition Examination Survey (NHANES) 2001-2004 cycles. Serum albumin was analyzed both as a continuous variable and categorized into quartiles. Erectile dysfunction (ED) was assessed via self-reported questionnaires. The association between serum albumin and erectile dysfunction was evaluated using weighted logistic regression models across four models: (1) Crude model (unadjusted); (2) Model 1: Adjusted for age, race, poverty-to-income ratio (PIR), marital status, education level, and body mass index (BMI); (3) Model 2: Adjusted for factors in Model 1 plus physical activity, smoking status, drinking status, and Healthy Eating Index (HEI-2015); (4) Model 3: Adjusted for factors in Model 2 plus remaining potential covariates. A generalized additive model (GAM) was employed to examine non-linear associations, followed by subgroup analyses and interaction tests., Results: A total of 2925 participants were included in the study, of which 747 were diagnosed with ED. After adjusting for all covariates, a significant negative association was found between ALB and ED (OR: 0.53, 95% CI: 0.29-0.97, P = 0.04). Higher ALB quartiles were significantly correlated with a decreased risk of ED [Q4 vs. Q1: OR: 0.56 (0.35-0.90), P =  0.02; P for trend =  0.03]. The GAM and smoothed curve fit indicated a linear relationship between ALB and the risk of ED. Stratified and interaction tests further substantiated the inverse relationship between ALB and ED prevalence., Conclusions: This study revealed an inverse association between ALB and ED. Therefore, it is important for clinicians to recognize the assessment of ALB in patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Wen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The association between depression and serum total prostate-specific antigen (PSA) concentrations remains unclear. To explore whether there is a relationship between depression and PSA in American males without prostate cancer (PCa), according to the National Health and Nutrition Examination Survey (NHANES) database., Methods: Three biennial cycles of survey data from 2005 to 2010 were used in our study. Multivariate adjusted regression analysis, stratified analysis, trend testing, smooth curve fitting and multiple imputation (MI) were our main research methods. Depression was assessed by the Patient Health Questionnaire-9 (PHQ-9)., Results: The study included a total of 4185 participants. After adjusting all covariates, whether depression was used as a continuous [β = -0.038; 95% confidence interval (CI): -0.059, -0.017; P < 0.001] or categorical variable (P for trend = 0.001), especially in the mild [β = -0.239; 95% CI: -0.473, -0.006; P = 0.044)] and moderate [β = -0.499; 95% CI: -0.907, -0.092; P = 0.016)] depression groups, it was associated with a decrease in serum PSA concentrations. Smoothing curve fitting found the presence of a linear relationship, with PSA reduced by 0.038 ng/ml or 0.026 ng/ml (log-2 transformed total PSA) for each additional unit of depression score. Similar results were obtained for complete data after MI or data categorized by depressive symptoms., Conclusions: Depression score is inversely correlated with serum total PSA concentrations among American men, and there is an interaction between depression and myocardial infarction., Clinical Trial Number: Not applicable., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Millions of Americans endure post-COVID conditions (PCC), yet research often lacks pre-illness measurements, relying primarily on follow-up assessments for analysis. The study aims to examine the prevalence of PCC, including cognitive impairment, functional limitation, and depressive symptoms, along with relevant risk factors, while controlling for individuals' pre-illness status measured in 2018. A cross-sectional retrospective study utilized the 2018 and 2020 Health and Retirement Study surveys. Sample included individuals with COVID-19 (n = 409; average age 64) and individuals without COVID-19 (n = 8689; average age 59). COVID-19 positive: Individuals with positive tests, physician diagnoses, emergency room visits, or hospitalizations for COVID-19 between 2019-2020. Cognition was assessed using immediate and delayed word-recall tests, serial seven subtractions, and backward counting. Functional status was measured using limitations in activities of daily living (ADLs) and instrumental ADLs. Depressive symptoms were measured using the modified Center for Epidemiology Studies Depression scale. Participants' perception of experiencing PCC was collected. Logistic regression and propensity score matching were employed for these analyses. Among 409 COVID-19-positive respondents (14% hospitalized), 24% exhibited new impairments after COVID-19 infection. Noteworthy increases in functional limitation (OR [95% CI]: 2.18 [0.95, 0.97], p < 0.001) and a marginal rise in cognitive impairment (1.79 [0.99, 3.32], p = 0.053) following COVID-19 infection were observed in comparison to their pre-COVID-19 baseline. Compared to 8689 non-COVID-19 cases, the 409 COVID-19 positives showed increased functional decline (1.78 [1.26, 2.51], p = 0.001) and depressive symptoms (1.41 [1.04, 1.91], p = 0.03). Factors associated with PCC included pre-existing impairments, lower education, female gender, prior hospitalization, higher comorbidity, lower wealth, and mild COVID-19. A notable number of respondents, especially older individuals with fewer pre-existing health conditions, experienced PCC without awareness. Compared to an individual's pre-illness baseline and uninfected individuals, being positive for COVID-19 raised the risk of functional limitation, depressive symptoms, and cognitive impairment. Additionally, addressing PCC through both subjective and objective approaches is essential to alleviate individual and societal burdens., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Su 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.)

Importance: Limited access to healthy foods, resulting from residence in neighborhoods with low food access, is a public health concern. The contribution of this exposure in early life to child obesity remains uncertain., Objective: To examine associations of neighborhood food access during pregnancy or early childhood with child body mass index (BMI) and obesity risk., Design, Setting, and Participants: Data from cohorts participating in the US nationwide Environmental Influences on Child Health Outcomes consortium between January 1, 1994, and March 31, 2023, were used. Participant inclusion required a geocoded residential address in pregnancy (mean 32.4 gestational weeks) or early childhood (mean 4.3 years) and information on child BMI., Exposures: Residence in low-income, low-food access neighborhoods, defined as low-income neighborhoods where the nearest supermarket is more than 0.5 miles for urban areas or more than 10 miles for rural areas., Main Outcomes and Measures: BMI z score, obesity (age- and sex-specific BMI ≥95th percentile), and severe obesity (age- and sex-specific BMI ≥120% of the 95th percentile) from age 0 to 15 years., Results: Of 28 359 children (55 cohorts; 14 657 [51.7%] male and 13 702 [48.3%] female; 590 [2.2%] American Indian, Alaska Native, Native Hawaiian, or Other Pacific Islander; 1430 [5.4%] Asian; 4034 [15.3%] Black; 17 730 [67.2%] White; and 2592 [9.8%] other [unspecified] or more than 1 race; 5754 [20.9%] Hispanic and 21 838 [79.1%] non-Hispanic) with neighborhood food access data, 23.2% resided in low-income, low-food access neighborhoods in pregnancy and 24.4% in early childhood. After adjusting for individual sociodemographic characteristics, residence in low-income, low-food access (vs non-low-income, low-food access) neighborhoods in pregnancy was associated with higher BMI z scores at ages 5 years (β, 0.07; 95% CI, 0.03-0.11), 10 years (β, 0.11; 95% CI, 0.06-0.17), and 15 years (β, 0.16; 95% CI, 0.07-0.24); higher obesity risk at 5 years (risk ratio [RR], 1.37; 95% CI, 1.21-1.55), 10 years (RR, 1.71; 95% CI, 1.37-2.12), and 15 years (RR, 2.08; 95% CI, 1.53-2.83); and higher severe obesity risk at 5 years (RR, 1.21; 95% CI, 0.95-1.53), 10 years (RR, 1.54; 95% CI, 1.20-1.99), and 15 years (RR, 1.92; 95% CI, 1.32-2.80). Findings were similar for residence in low-income, low-food access neighborhoods in early childhood. These associations were robust to alternative definitions of low income and low food access and additional adjustment for prenatal characteristics associated with child obesity., Conclusions: Residence in low-income, low-food access neighborhoods in early life was associated with higher subsequent child BMI and higher risk of obesity and severe obesity. We encourage future studies to examine whether investments in neighborhood resources to improve food access in early life would prevent child obesity.

Background: Nusinersen is the first drug for precise targeted therapy of spinal muscular atrophy, a rare disease that occurs in one of 10,000 to 20,000 live births. Therefore, thorough and comprehensive reports on the safety of nusinersen in large, real-world populations are necessary. This study aimed to mine the adverse event (AE) signals related to nusinersen through the Food and Drug Administration Adverse Event Reporting System (FAERS) database., Methods: We extracted reports of AEs with nusinersen as the primary suspect from FAERS between December 2016 and March 2023. Reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN) were used for AE signal detection., Results: We extracted a total of 4807 suspected AE cases with nusinersen as the primary suspect from the FAERS database. Among them, 106 positive signals were obtained using the ROR and BCPNN. The highest frequency reported systemic organ class was general disorders and administration site conditions. Common clinical AEs of nusinersen were detected in the FAERS database, such as pneumonia, vomiting, back pain, headache, pyrexia, and post-lumbar puncture syndrome. In addition, we identified potential unexpected serious AEs through disproportionality analysis, including sepsis, seizure, epilepsy, brain injury, cardiorespiratory arrest, and cardiac arrest., Conclusions: Analyzing large amounts of real-world data from the FAERS database, we identified potential new AEs of nusinersen by disproportionate analysis. It is advantageous for health care professionals and pharmacists to concentrate on effectively managing high-risk AEs of nusinersen, improve medication levels in clinical settings, and uphold patient medication safety., Competing Interests: Declaration of competing interest The author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Epilepsy is a major global health challenge, affecting approximately 50 million people across the globe and resulting in significant economic impacts on individuals and society. Oxidative stress is implicated in the pathogenesis of epilepsy, highlighting the potential of antioxidant-rich dietary patterns in offering preventive and protective benefits by mitigating oxidative stress. The Composite Dietary Antioxidant Index (CDAI) provides a measure for assessing dietary antioxidant intake, yet its link to epilepsy remains unexplored., Methods: Our analysis utilized data from the National Health and Nutrition Examination Survey (NHANES) spanning 2013 to 2018, including 20,180 screened participants. Weighted logistic regression models were employed to examine the association between the CDAI and epilepsy prevalence. Non-linear associations were explored through restricted cubic splines (RCS), and the relationships between individual antioxidant components within the CDAI and epilepsy were also assessed., Results: After adjusting for potential confounders, a negative association between the CDAI and epilepsy was suggested (OR = 0.991; p = 0.087, 95% CI [0.819,1.014]). Stratification of CDAI into quartiles revealed a significantly reduced risk of epilepsy in higher CDAI quartiles (Q3 and Q4) compared to the lowest quartile (Q1) (Q3: OR = 0.419; p = 0.030, 95% CI [0.192, 0.914]; Q4: OR = 0.421; p = 0.004, 95% CI [0.239, 0.742]), with a significant trend observed across quartiles (p for trend = 0.013). RCS analysis suggested a nonlinear association between CDAI levels and epilepsy (non-linear p = 0.049), which, however, was not statistically significant after full adjustment (non-linear p = 0.103). Additionally, significant negative correlations with epilepsy were observed for vitamin A and zinc (Vitamin A: OR = 0.999; p = 0.012, 95% CI [0.998, 1.000]; Zinc: OR = 0.931; p = 0.042, 95% CI [0.869, 0.997])., Conclusions: Our research indicates a correlation where higher CDAI levels correspond to a reduced risk of epilepsy. Therefore, embracing a diet rich in antioxidants could be beneficial in preventing epilepsy. This finding holds considerable potential for shaping future strategies in both epilepsy prevention and treatment., (© 2024. The Author(s).)

Financial toxicity is common in individuals with COVID-19 and Long COVID. However, the extent of financial toxicity experienced, in comparison to other common comorbidities, is uncertain. Contributing factors exacerbating financial challenges in Long COVID are also unclear. These knowledge gaps are addressed via a cross-sectional analysis utilizing data from the 2022 National Health Interview Survey (NHIS), a representative sample drawn from the United States. COVID-19 cases were identified through self-reported positive testing or physician diagnoses. Long COVID was defined as experiencing COVID-19-related symptoms for more than three months. Comorbidity was assessed based on self-reported diagnoses of ten doctor-diagnosed conditions (Yes/No). Financial toxicity was defined as having difficulty paying medical bills, cost-related medication nonadherence, delaying healthcare due to cost, and/or not obtained healthcare due to cost. A total of 27,492 NHIS 2022 respondents were included in our analysis, representing 253 million U.S. adults. In multivariable logistic regression models, adults with Long COVID (excluding respondents with COVID-19 but not Long COVID), showed increased financial toxicity compared to those with other comorbidities, such as epilepsy (OR [95% CI]: 1.69 [1.22, 2.33]), dementia (1.51 [1.01, 2.25]), cancer (1.43 [1.19, 1.71]) or respiratory/cardiovascular conditions (1.18 [1.00, 1.40]/1.23 [1.02, 1.47]). Long COVID-related financial toxicity was associated with female sex, age <65 years, lack of medical insurance, current paid employment, residence region, food insecurity, fatigue, mild to severe depression symptoms experienced during the survey completion, visits to hospital emergency rooms, presence of arthritis, cardiovascular or respiratory conditions, and social activity limitations. In conclusion, American adults with Long COVID, but not those who had prior COVID-19 infection without Long COVID, exhibited a higher prevalence of financial toxicity compared to individuals with common comorbidities. Vulnerable populations were at greater risk for financial toxicity. These findings emphasize the importance of evaluating strategies to reduce economic burden and increase awareness of the effect of Long COVID-related financial toxicity on patient's healthcare and health status., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Su 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: To estimate the effect of platinum-based chemotherapy on live birth (LB) and infertility after cancer, in order to address a lack of treatment-specific fertility risks for female survivors of adolescent and young adult cancer, which limits counseling on fertility preservation decisions., Design: Retrospective cohort study., Setting: US administrative database., Patients: We identified incident breast, colorectal, and ovarian cancer cases in females aged 15-39 years who received platinum-based chemotherapy or no chemotherapy and matched them to females without cancer., Intervention: Platinum-based chemotherapy., Main Outcome Measures: We estimated the effect of chemotherapy on the incidence of LB and infertility after cancer, overall, and after accounting for competing events (recurrence, death, and sterilizing surgeries)., Results: There were 1,287 survivors in the chemotherapy group, 3,192 in the no chemotherapy group, and 34,147 women in the no cancer group, with a mean age of 33 years. Accounting for competing events, the overall 5-year LB incidence was lower in the chemotherapy group (3.9%) vs. the no chemotherapy group (6.4%). Adjusted relative risks vs. no chemotherapy and no cancer groups were 0.61 (95% confidence interval [CI] 0.42-0.82) and 0.70 (95% CI 0.51-0.93), respectively. The overall 5-year infertility incidence was similar in the chemotherapy group (21.8%) compared with the no chemotherapy group (20.7%). The adjusted relative risks vs. no chemotherapy and no cancer groups were 1.05 (95% CI 0.97-1.15) and 1.42 (95% CI 1.31-1.53), respectively., Conclusions: Cancer survivors treated with platinum-based chemotherapy experienced modestly increased adverse fertility outcomes. The estimated effects of platinum-based chemotherapy were affected by competing events, suggesting the importance of this analytic approach for interpretations that ultimately inform clinical fertility preservation decisions., (Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: This study investigates how access to assistive technologies affects employment and earnings among people with disabilities., Methods: We first document employment and earnings gaps associated with specific impairments and activity limitations using 2017-2021 American Community Survey and 2014 Survey of Income and Program Participation data. We then use accommodations data from the 2012, 2019, and 2021 Current Population Survey (CPS) Disability Supplements to examine employment and earnings growth for people with disabilities related both to any, and to technology-based, accommodations. We also provide short descriptions of three developing assistive technologies that assist people with upper body impairments, visual impairments, and anxiety conditions., Results: Almost all impairments and activity limitations are linked to lower employment and earnings, with especially low employment among people with mobility impairments and particularly low earnings among those with cognitive impairments. About one-tenth of workers with disabilities received any accommodations, and 3-4% received equipment-based accommodations in the 2012-2021 period; these figures increased slightly over the period. The occupations with the highest disability accommodations rates had greater disability employment growth from 2012 to 2021, but disability pay gaps did not decrease more in these occupations. The three developing assistive technologies we describe illustrate the potential to reduce the estimated employment and earnings deficits., Conclusion: Assistive technology accommodations have potential for improving employment outcomes for people with disabilities., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Serum prostate-specific antigen (PSA) is a primary metric for diagnosis and prognosis of prostate cancer (PCa). Exposure to heavy metals, such as lead, cadmium, mercury, and zinc can impact PSA levels in PCa patients. However, it is unclear whether this effect also occurs in men without PCa, which may lead to the overdiagnosis of PCa., Method: Data on a total of 5089 American men who had never been diagnosed with PCa were obtained from the National Health and Nutrition Examination Survey performed from 2003-2010. The relationship between serum PSA levels (dependent variable) and concentrations of lead (μmol/L), cadmium (nmol/L), and mercury (μmol/L) were investigated with dietary zinc intake being used as a potential modifier or covariate in a weighted linear regression model and a generalized additive model. A series of bootstrapping analyses were performed to evaluate sensitivity and specificity using these models., Results: Regression analyses suggested that, in general, lead, cadmium, or mercury did not show an association with PSA levels, which was consistent with the results of the bootstrapping analyses. However, in a subgroup of participants with a high level of dietary zinc intake (≥14.12 mg/day), a significant positive association between cadmium and serum PSA was identified (1.06, 95% CI, P = 0.0268, P for interaction=0.0249)., Conclusions: With high-level zinc intake, serum PSA levels may rise in PCa-free men as the exposure to cadmium increases, leading to a potential risk of an overdiagnosis of PCa and unnecessary treatment. Therefore, environmental variables should be factored in the current diagnostic model for PCa that is solely based on PSA measurements. Different criteria for PSA screening are necessary based on geographical variables. Further investigations are needed to uncover the biological and biochemical relationship between zinc, cadmium, and serum PSA levels to more precisely diagnose PCa., 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 Inc. All rights reserved.)

Background: Limited capacity in the emergency department (ED) secondary to boarding and crowding has resulted in patients receiving care in hallways to provide access to timely evaluation and treatment. However, there are concerns raised by physicians and patients regarding a decrease in patient centered care and quality resulting from hallway care. We sought to explore social risk factors associated with hallway placement and operational outcomes., Study Design/methods: Observational study between July 2017 and February 2020. Primary outcome was the adjusted odds ratio (aOR) of patient placement in a hallway treatment space adjusting for patient demographics and ED operational factors. Secondary outcomes included left without being seen (LWBS), discharge against medical advice (AMA), elopement, 72-h ED revisit, 10-day ED revisit and escalation of care during boarding., Results: Among 361,377 ED visits, 100,079 (27.7%) visits were assigned to hallway beds. Patient insurance coverage (Medicaid (aOR 1.04, 95% CI 1.01,1.06) and Self-pay/Other (1.08, (1.03, 1.13))) with comparison to private insurance, and patient sex (Male (1.08, (1.06, 1.10))) with comparison to female sex are associated with higher odds of hallway placement but patient age, race, and language were not. These associations are adjusted for ED census, triage assigned severity, ED staffing, boarding level, and time effect, with social factors mutually adjusted. Additionally adjusting for patients' social factors, patients placed in hallways had higher odds of elopement (1.23 (1.07,1.41)), 72-h ED revisit (1.33 (1.08, 1.64)) and 10-day ED revisit (1.23 (1.11, 1.36)) comparing with patients placed in regular ED rooms. We did not find statistically significant associations between hallway placement and LWBS, discharge AMA, or escalation of care., Conclusion: While hallway usage is ad hoc, we find consistent differences in care delivery with those insured by Medicaid and self-pay or male sex being placed in hallway beds. Further work should examine how new front-end processes such as provider in triage or split flow may be associated with inequities in patient access to emergency and hospital care., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Importance: Emergency department (ED) triage models are intended to queue patients for treatment. In the absence of higher acuity, patients of the same acuity should room in order of arrival., Objective: To characterize disparities in ED care access as unexplained queue jumps (UQJ), or instances in which acuity and first come, first served principles are violated., Design, Setting, and Participants: Retrospective, cross-sectional study between July 2017 and February 2020. Participants were all ED patient arrivals at 2 EDs within a large Northeast health system. Data were analyzed from July to September 2022., Exposure: UQJ was defined as a patient being placed in a treatment space ahead of a patient of higher acuity or of a same acuity patient who arrived earlier., Main Outcomes and Measures: Primary outcomes were odds of a UQJ and association with ED outcomes of hallway placement, leaving before treatment complete, escalation to higher level of care while awaiting inpatient bed placement, and 72-hour ED revisitation. Secondary analysis examined UQJs among high acuity ED arrivals. Regression models (zero-inflated Poisson and logistic regression) adjusted for patient demographics and ED operational variables at time of triage., Results: Of 314 763 included study visits, 170 391 (54.1%) were female, the mean (SD) age was 50.46 (20.5) years, 132 813 (42.2%) patients were non-Hispanic White, 106 401 (33.8%) were non-Hispanic Black, and 66 465 (21.1%) were Hispanic or Latino. Overall, 90 698 (28.8%) patients experienced a queue jump, and 78 127 (24.8%) and 44 551 (14.2%) patients were passed over by a patient of the same acuity or lower acuity, respectively. A total of 52 959 (16.8%) and 23 897 (7.6%) patients received care ahead of a patient of the same acuity or higher acuity, respectively. Patient demographics including Medicaid insurance (incident rate ratio [IRR], 1.11; 95% CI, 1.07-1.14), Black non-Hispanic race (IRR, 1.05; 95% CI, 1.03-1.07), Hispanic or Latino ethnicity (IRR, 1.05; 95% CI, 1.02-1.08), and Spanish as primary language (IRR, 1.06; 95% CI, 1.02-1.10) were independent social factors associated with being passed over. The odds of a patient receiving care ahead of others were lower for ED visits by Medicare insured (odds ratio [OR], 0.92; 95% CI, 0.88-0.96), Medicaid insured (OR, 0.81; 95% CI, 0.77-0.85), Black non-Hispanic (OR, 0.94; 95% CI, 0.91-0.97), and Hispanic or Latino ethnicity (OR, 0.87; 95% CI, 0.83-0.91). Patients who were passed over by someone of the same triage severity level had higher odds of hallway bed placement (OR, 1.01; 95% CI, 1.00-1.02) and leaving before disposition (OR, 1.02; 95% CI, 1.01-1.04)., Conclusions and Relevance: In this cross-sectional study of ED patients in triage, there were consistent disparities among marginalized populations being more likely to experience a UQJ, hallway placement, and leaving without receiving treatment despite being assigned the same triage acuity as others. EDs should seek to standardize triage processes to mitigate conscious and unconscious biases that may be associated with timely access to emergency care.

Purpose People with disabilities (PWD) are less likely to be employed than those without disabilities. Reasonable job accommodations are an essential factor for ensuring equal access to jobs for PWD. However, use of job accommodation is less than optimal among PWD with various types of disabilities. Sometimes, PWD have co-occurring impairments, which might affect accommodation use. This research aimed to explore disability phenotypes, frequently used accommodations, and employee- and job-related factors associated with the extent of job accommodation use. Methods A cross-sectional online survey of PWD was conducted in the Midwest region of the United States. Latent class analyses were used to identify disability phenotypes. Descriptive analysis and stepwise Poisson regression were used to identify factors associated with job accommodation use. Results A total of 326 PWD with work experience after acquiring a disability were included in this analysis. We identified three disability phenotypes: (1) Severe disability in cognitive, physical, emotional, communication and visual domains (32%), (2) Moderate cognitive and low physical disability (48%), and (3) High physical disability phenotypes (20%). 80% of PWD received at least one accommodation. Flexible working schedules, telework, and access to a support person in the workplace were the most common accommodations. Employee- (age, disability phenotypes, motor function) and job-related factors (job preparation, self-employment) are associated dependently with accommodation use. Conclusion This analysis identifies three disability phenotypes and highlights both employee- and job-related factors associated with accommodations used. It may be beneficial to consider multiple contextual factors, including co-occurring disability, employee- and job-related factors, when assisting people with job accommodations., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The assessment of collaterals before endovascular thrombectomy (EVT) therapy play a pivotal role in clinical decision-making for acute stroke patients., Objective: To investigate the correlation between hypoperfusion intensity ratio (HIR), collaterals on digital subtraction angiography (DSA), and infarct growth in acute stroke patients who underwent EVT therapy., Methods: Patients with acute ischemic stroke (AIS) who underwent EVT therapy were enrolled retrospectively. HIR was assessed through magnetic resonance imaging (MRI) and was defined as the Tmax > 10 s lesion volume divided by the Tmax > 6 s lesion volume. Collaterals were assessed on DSA using the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) scale. Good collaterals were defined as ASITN/SIR score 3-4 and poor collaterals were defined as ASITN/SIR score 0-2. Spearman's rank correlation analysis was used to evaluate the correlation between HIR, collaterals, infarct growth, and functional outcome., Results: A total of 115 patients were included. Patients with good collateral (n = 59) had smaller HIR (0.29 ± 0.07 vs. 0.52 ± 0.14; t = 10.769, P < 0.001) and infarct growth (8.47 ± 2.40 vs. 14.37 ± 5.28; t = 7.652, P < 0.001) than those with poor collateral (n = 56)., Discussion: The ROC analyses showed that the optimal cut-off value of HIR was 0.40, and the sensitivity and specificity for predicting good collateral were 85.70% and 96.61%, respectively. With the optimal cut-off value, patients with HIR < 0.4 (n = 67) had smaller infarct growth (8.86 ± 2.59 vs. 14.81 ± 5.52; t = 6.944, P < 0.001) than those with HIR ≥ 0.4 (n = 48). Spearman's rank correlation analysis showed that HIR had a correlation with ASITN/SIR score (r = -0.761, P < 0.001), infarct growth (r = 0.567, P < 0.001), and mRS at 3 months (r = -0.627, P < 0.001)., Conclusion: HIR < 0.4 is significantly correlated with good collateral status and small infarct growth. Evaluating HIR before treatment may be useful for guiding EVT and predicting the functional outcome of AIS patients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Identification of novel non-invasive biomarkers is critical for the early diagnosis of lung adenocarcinoma (LUAD), especially for the accurate classification of pulmonary nodule. Here, a multiplexed assay is developed on an optimized nanoparticle-based laser desorption/ionization mass spectrometry platform for the sensitive and selective detection of serum metabolic fingerprints (SMFs). Integrative SMFs based multi-modal platforms are constructed for the early detection of LUAD and the classification of pulmonary nodule. The dual modal model, metabolic fingerprints with protein tumor marker neural network (MP-NN), integrating SMFs with protein tumor marker carcinoembryonic antigen (CEA) via deep learning, shows superior performance compared with the single modal model Met-NN (p < 0.001). Based on MP-NN, the tri modal model MPI-RF integrating SMFs, tumor marker CEA, and image features via random forest demonstrates significantly higher performance than the clinical models (Mayo Clinic and Veterans Affairs) and the image artificial intelligence in pulmonary nodule classification (p < 0.001). The developed platforms would be promising tools for LUAD screening and pulmonary nodule management, paving the conceptual and practical foundation for the clinical application of omics tools., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Background: The newly described ABCD-10 (age, bicarbonate, cancer, dialysis, 10% body surface area [BSA]) is a 5-item mortality prediction model for patients with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). It was developed in the United States, has at present been externally tested only in the United States, Spain, and Singapore, and remains to be validated in resource-restricted settings. We sought to compare the accuracy of ABCD-10 and Score of Toxic Epidermal Necrolysis (SCORTEN) in predicting in-hospital mortality in a cohort from central China. Due to disease progression affecting the accuracy of the prediction model during hospitalization, for example, higher predictive accuracy of SCORTEN based on parameters collected on day 3 of hospitalization, we also assessed the overall predictive value of ABCD-10 on days 1 and 3, respectively., Methods: A retrospective study was performed over a 10-year period (2010-2020) from 3 medical institutions in Wuhan. The performance of predictive models was assessed by both discrimination and calibration. Receiver-operating characteristic (ROC) curves, Hosmer-Lemeshow goodness-of-fit tests and calibration plots were used to evaluate the model discrimination and calibration., Results: Of 84 included patients, 11 (13.1%) did not survive. The discrimination power of ABCD-10 was not significantly different from that of SCORTEN (area under the curve: day 1, p > 0.05; day 3, p > 0.05). Although the calibration of ABCD-10 was good, it was inferior to SCORTEN as it underestimated total mortality (Hosmer-Lemeshow goodness-of-fit test: day 1, p = 0.17 vs. p = 0.63; day 3, p = 0.35 vs. p = 0.93). Besides, the performance of ABCD-10 was slightly better on day 3 relative to day 1. During hospitalization, bacteremia developed in 21 (25.0%) patients, which was associated with a higher risk of death in our cohort (odds ratio, 22.88; 95% CI, 4.38-119.40; p < 0.001)., Conclusion: ABCD-10 showed acceptable overall performance, but revealed mortality underestimation and was inferior to the performance of SCORTEN. In consistence with SCORTEN, ABCD-10 was a better model when using values collected at day 3 of hospitalization relative to day 1., (© 2021 S. Karger AG, Basel.)

Importance: Multiple US states recently passed laws mandating health insurance coverage for fertility preservation (FP) services to improve access to care for patients with cancer, for whom FP service expenses can be prohibitive. Key unanswered questions include how heterogeneous benefit mandate laws and regulations are and how this variation may affect implementation, access, and utilization., Objective: To describe the design of state-level FP health insurance benefit mandate laws and regulations and derive guidance on best practices and implementation needs., Design, Setting, and Population: Legal mapping and implementation science framework-guided analyses were conducted on 11 US state laws that mandate health insurance benefit coverage for FP services for patients at risk of iatrogenic infertility from medical treatments and on related insurer regulations. Design features of laws and regulations and the implementation process were summarized by themes (eg, coverage specification)., Exposures: State jurisdiction., Main Outcomes and Measures: Main outcomes were the scope and specificity of mandated FP insurance coverage and the role of clinical practice guidelines and insurer regulations in implementation., Results: Between June 2017 and March 2021, 11 states passed FP benefit mandate laws. States took a median (range) of 283 (0-640) days to implement mandates, and a majority issued regulatory guidance after the law was in effect. While standard-of-care procedures such as embryo cryopreservation require medical evaluation, medications, ultrasonography and laboratory monitoring, oocyte retrieval, embryo derivation, cryopreservation, and storage, there was variation in which services were specified for inclusion or exclusion in the laws and/or regulator guidance. The majority of state laws and regulator guidance reference medical society clinical practice guidelines and federal policies (Affordable Care Act and Health Insurance Portability and Accountability Act)., Conclusions and Relevance: In this qualitative assessment of 11 state-level FP benefit mandates, variation that may influence patient access was identified in the design and implementation of the mandates. As clinical stakeholders aim to understand and/or shape these laws and their implementation, key considerations included specificity and flexibility of benefit design to be clinically meaningful, expansion of clinical practice guidelines to inform benefit coverage, inclusion of publicly insured and self-insured populations for universal access, and consistency between state and federal policies.

Helicobacter pylori outer membrane inflammatory protein A (OipA) was originally named for its role in inducing inflammation in the host, as evidenced by high mucosal IL-8 levels. Expression of OipA is regulated by phase variation of a CT dinucleotide-repeat located in the 5' region of the gene. However, little is known about OipA geographic diversity across isolates. To address this gap, we conducted a large-scale molecular epidemiologic analysis using H. pylori clinical isolates obtained from two geographically distinct populations: Korea and the United States (US). Most Korean isolates (98.7%) possessed two copies of oipA located at two specific loci (A and B) while all US isolates contained only one copy of oipA at locus A. Furthermore, most Korean oipA (94.8%) possessed three or less CT repeats while most US oipA (96.6%) contained five or more CT repeats. Among the two copies, all Korean H. pylori possessed at least one oipA 'on' phase variant while the single copy of oipA in US isolates showed 56.2% 'on' and 43.8% 'off.' Thus, host differences seem to have driven geographic diversification of H. pylori across these populations such that OipA expression in US isolates is still regulated by phase variation with 5 or more CT repeats, while Korean isolates always express OipA; duplication of the oipA combined with a reduction of CT repeats to three or less ensures continued expression. En masse, these findings suggest that diversity in the oipA gene copy number, CT repeats, and phase variation among H. pylori from different populations may confer a benefit in adaptation to particular host populations., (© 2021. The Microbiological Society of Korea.)

Background: Joblessness is common after ARDS, but related risk factors are not fully understood., Research Question: What is the association between survivors' pre-ARDS workload and post-ARDS functional impairment, pain, and fatigue with their return to work (RTW) status?, Study Design and Methods: The U.S. Occupational Information Network (O∗NET) was used to determine pre-ARDS workload for participants in the ARDS Network Long-Term Outcomes Study (ALTOS). Post-ARDS functional impairment was assessed using the Mini-Mental State Examination and SF-36 Physical Functioning, Social Functioning, and Mental Health sub-scales, and categorized as either no impairments, only psychosocial impairment, physical with low psychosocial impairment, or physical with high psychosocial impairment. Post-ARDS pain and fatigue were assessed using the SF-36 pain item and Functional Assessment of Chronic Illness Therapy-Fatigue Scale fatigue scale, respectively. Generalized linear mixed modeling methods were used to evaluate associations among pre-ARDS workload, post-ARDS functional impairment, and symptoms of pain and fatigue with post-ARDS RTW., Results: Pre-ARDS workload was not associated with post-ARDS RTW. However, as compared with survivors with no functional impairment, those with only psychosocial impairment (OR [CI]: 0.18 [0.06-0.50]), as well as physical impairment plus either low psychosocial impairment (0.08 [0.03-0.22]) or high psychosocial impairment (0.01 [0.003-0.05]) had lower odds of working. Pain (0.06 [0.03-0.14]) and fatigue (0.07 [0.03-0.16]) were also negatively associated with RTW., Interpretation: For previously employed survivors of ARDS, post-ARDS psychosocial and physical impairments, pain, and fatigue were negatively associated with RTW, whereas pre-ARDS workload was not associated. These findings are important for designing and implementing vocational interventions for ARDS survivors., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate elevation of anti-citrullinated protein antibodies (ACPAs) before diagnosis of rheumatoid arthritis (RA) and risks for chronic obstructive pulmonary disease (COPD) or asthma., Methods: We performed a matched cohort study nested within the Nurses' Health Studies among women who donated blood. Women with incident RA after blood draw (self-reported, then confirmed by medical records) were each matched to 3 controls by age, cohort, year, and menopausal factors. Pre-RA ACPA positivity was defined as >99th percentile of control distribution by a research assay or by cyclic citrullinated peptide in a subset. Incident COPD and asthma after index date (date of blood draw) were identified by questionnaires. Cox regression estimated hazard ratios (HRs) for incident COPD or asthma (in separate analyses) associated with pre-RA, pre-RA ACPA+, or pre-RA ACPA- phenotypes each compared to their matched non-RA controls., Results: We analyzed 283 women who were pre-RA and 842 controls; blood was donated a mean ± SD of 9.7 ± 5.8 years before RA diagnosis. Fifty-nine women (20.8%) were pre-RA ACPA+. There were 107 cases of incident COPD and 105 incident asthma cases during 21,489 person-years of follow-up. Pre-RA ACPA+ was associated with increased COPD risk (HR 3.04 [95% confidence interval (95% CI) 1.33-7.00]) after adjusting for covariates including smoking pack-years. Pre-RA ACPA+ had an HR for asthma of 1.74 (multivariable 95% CI 0.72-4.24), similar to the risk of asthma for pre-RA ACPA- (HR 1.65 [95% CI 1.11-2.46])., Conclusion: Women with elevated ACPA before RA diagnosis had increased risk for developing COPD compared to controls. Women who later developed RA were more likely to develop asthma than controls, regardless of pre-RA ACPA status., (© 2020, American College of Rheumatology.)

Objective: To elucidate how postdiagnosis multimorbidity and lifestyle changes contribute to the excess mortality of rheumatoid arthritis (RA)., Methods: We performed a matched cohort study among women in the Nurses' Health Study (1976-2018). We identified women with incident RA and matched each by age and year to 10 non-RA comparators at the RA diagnosis index date. Specific causes of death were ascertained via death certificates and medical record review. Lifestyle and morbidity factors were reported biennially; 61 chronic conditions were combined into the Multimorbidity Weighted Index (MWI). After adjusting for baseline confounders, we used inverse probability weighting analysis to examine the mediating influence of postindex MWI scores and lifestyle factors on total, cardiovascular, and respiratory mortality, comparing women with RA to their matched comparators., Results: We identified 1,007 patients with incident RA and matched them to 10,070 non-RA comparators. After adjusting for preindex confounders, we found that hazard ratios (HRs) and 95% confidence intervals (95% CIs) were higher for total mortality (HR 1.46 [95% CI 1.32, 1.62]), as well as cardiovascular (HR 1.54 [95% CI 1.22, 1.94]) and respiratory (HR 2.75 [95% CI 2.05, 3.71]) mortality in patients with RA compared to non-RA comparators. Adjusting for postindex lifestyle factors (physical activity, body mass index, diet, smoking) attenuated but did not substantially account for this excess RA mortality. After additional adjustment for postindex MWI scores, patients with RA had HRs of 1.18 (95% CI 1.05, 1.32) for total, 1.19 (95% CI 0.94, 1.51) for cardiovascular, and 1.93 (95% CI 1.42, 2.62) for respiratory mortality., Conclusion: We found that MWI scores substantially accounted for the excess total and cardiovascular mortality among women with RA. This finding underscores the importance of monitoring for the total disease burden as a whole in monitoring patients with RA., (© 2019, American College of Rheumatology.)

Objectives: RA develops slowly over years. We tested for metabolic changes prior to RA onset using a large non-targeted metabolomics platform to identify novel pathways and advance understanding of RA development., Methods: Two hundred and fifty-four incident RA cases with plasma samples drawn pre-RA onset in the Nurses' Health Study (NHS) cohorts were matched 1:2 to 501 controls on age, race, menopause/post-menopausal hormone use and blood collection features. Relative abundances of 360 unique, known metabolites were measured. Conditional logistic regression analyses assessed associations between metabolites and incidence of RA, adjusted for age, smoking and BMI, accounting for multiple comparisons. Subgroup analyses investigated seropositive (sero+) RA and RA within 5 years of sample collection. Significant metabolites were then tested in a female military pre-RA case-control study (n = 290)., Results: In the NHS, metabolites associated with RA and sero+RA in multivariable models included 4-acetamidobutanoate (odds ratio (OR) = 0.80/S.d., 95% CI: 0.66, 0.95), N-acetylputrescine (OR = 0.82, 95% CI: 0.69, 0.96), C5 carnitine (OR = 0.84, 95% CI: 0.71, 0.99) and C5:1 carnitine (OR = 0.81, 95% CI: 0.68, 0.95). These were involved primarily in polyamine and leucine, isoleucine and valine metabolism. Several metabolites associated with sero+RA within 5 years of diagnosis were replicated in the independent military cohort: C5 carnitine (OR = 0.55, 95% CI: 0.33, 0.92), C5:1 carnitine (OR = 0.62, 95% CI: 0.39, 0.99) and C3 carnitine (OR = 0.57, 95% CI: 0.36, 0.91)., Conclusion: Several metabolites were inversely associated with incidence of RA among women. Three short-chain acylcarnitines replicated in a smaller dataset and may reflect inflammation in the 5-year period prior to sero+RA diagnosis., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Importance: There is a lack of studies exploring the performance of a deep learning survival neural network in non-small cell lung cancer (NSCLC)., Objectives: To compare the performances of DeepSurv, a deep learning survival neural network with a tumor, node, and metastasis staging system in the prediction of survival and test the reliability of individual treatment recommendations provided by the deep learning survival neural network., Design, Setting, and Participants: In this population-based cohort study, a deep learning-based algorithm was developed and validated using consecutive cases of newly diagnosed stages I to IV NSCLC between January 2010 and December 2015 in a Surveillance, Epidemiology, and End Results database. A total of 127 features, including patient characteristics, tumor stage, and treatment strategies, were assessed for analysis. The algorithm was externally validated on an independent test cohort, comprising 1182 patients with stage I to III NSCLC diagnosed between January 2009 and December 2013 in Shanghai Pulmonary Hospital. Analysis began January 2018 and ended June 2019., Main Outcomes and Measures: The deep learning survival neural network model was compared with the tumor, node, and metastasis staging system for lung cancer-specific survival. The C statistic was used to assess the performance of models. A user-friendly interface was provided to facilitate the survival predictions and treatment recommendations of the deep learning survival neural network model., Results: Of 17 322 patients with NSCLC included in the study, 13 361 (77.1%) were white and the median (interquartile range) age was 68 (61-74) years. The majority of tumors were stage I disease (10 273 [59.3%]) and adenocarcinoma (11 985 [69.2%]). The median (interquartile range) follow-up time was 24 (10-43) months. There were 3119 patients who had lung cancer-related death during the follow-up period. The deep learning survival neural network model showed more promising results in the prediction of lung cancer-specific survival than the tumor, node, and metastasis stage on the test data set (C statistic = 0.739 vs 0.706). The population who received the recommended treatments had superior survival rates than those who received treatments not recommended (hazard ratio, 2.99; 95% CI, 2.49-3.59; P < .001), which was verified by propensity score-matched groups. The deep learning survival neural network model visualization was realized by a user-friendly graphic interface., Conclusions and Relevance: The deep learning survival neural network model shows potential benefits in prognostic evaluation and treatment recommendation with respect to lung cancer-specific survival. This novel analytical approach may provide reliable individual survival information and treatment recommendations.

Limited research has been conducted on the contributions of local and nonlocal emission sources to ambient fine particulate matter (PM 2.5 ) and ozone (O 3 ) and their associated mortality. In this study, we estimated the total mortality resulting from long-term PM 2.5 and O 3 exposures in California in 2012 using multiple concentration response functions (CRFs) and attributed the estimated mortality to different emission groups. The point estimates of PM 2.5 -associated mortality in California ranged from 12,700 to 26,700, of which 53% were attributable to in-state anthropogenic emissions. Based on new epidemiological evidence, we estimated that O 3 could be associated with up to 13,700 deaths from diseases of both the respiratory and cardiovascular systems in California. In addition, 75% of the ambient O 3 in California was due to distant emissions outside the western United States, leading to 92% of the O 3 -associated mortality. Overall, distant emissions lead to greater mortality burdens of air pollution in California than local anthropogenic emissions., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Breast cancer survivorship care plans (SCP) have limited content addressing women's health issues. This trial tested if young breast cancer survivors who receive a web-based, women's health SCP were more likely to improve on at least one of the four targeted issues (hot flashes, fertility-related concerns, contraception, and vaginal symptoms) compared to attention controls., Methods: A randomized controlled trial recruited female survivors ages 18-45 at diagnosis, 18-50 at enrollment, completed primary cancer treatment, and had a significant women's health issue: moderate or higher fertility-related concerns; ≥ 4 hot flashes/day with ≥ 1 of moderate severity; ≥ 1 moderate vaginal atrophy symptoms; or not contracepting/using less effective methods. Survivors underwent stratified, block randomization with equal allocation to intervention and control groups. The intervention group accessed the online SCP; controls accessed curated resource lists. In intention-to-treat analysis, the primary outcome of improvement in at least one issue by 24 weeks was compared by group., Results: 182 participants (86 intervention, 96 control), mean age 40.0 ± 5.9 and 4.4 ± 3.2 years since diagnosis, were randomized. 61 intervention group participants (70.9%) improved, compared to 55 controls (57.3%) (OR 1.82, 95% CI 0.99-3.4, p = 0.057). The following issue-specific improvements were observed in the intervention versus control arms: fertility-related concerns (27.9% vs. 14.6%, OR 2.3, 95% CI 1.1-4.8); hot flashes (58.5% vs. 55.8%, OR 1.1, 95% CI 0.57-2.2); vaginal symptoms (42.5% vs. 40.7%, OR 1.1, 95% CI 0.6-2.0); contraception (50% vs. 42.6%, OR 1.4, 95% CI 0.74-2.5)., Conclusions: In young breast cancer survivors, a novel, web-based SCP did not result in more change in the primary outcome of improvement in at least one of the four targeted women's health issues, than the attention control condition. The intervention was associated with improved infertility concerns, supporting efficacy of disseminating accessible, evidence-based women's health information to this population.

Background: Helicobacter pylori encodes numerous outer membrane proteins (OMPs), but only a few have been characterized in depth. Deletion, duplication, and allelic variation of many of the H. pylori OMPs have been reported, which suggests that these proteins may play key roles in host adaptation. Herein, we characterize the variation observed within the Hom family of OMPs in H. pylori obtained from two geographically distinct populations., Materials and Methods: PCR genotyping of the hom genes was carried out using clinical isolates from South Korea and the United States. A combination of statistical, phylogenetic, and protein modeling analyses was conducted to further characterize the hom variants., Results: Variations in the closely related hom genes, homA and homB, occur in regions that are predicted to encode environmentally exposed loops. A similar phenomenon is true for homC S as compared to homC L . Conversely, little variation was observed in homD. Certain variants of the Hom family of proteins were more prominent in isolates from the Korean population as compared to isolates from the United States., Conclusion: En masse, our data show that the homA, homB, and homC profiles vary based upon the geographic origin of the strain; however, the fourth member of the hom family, homD, is more highly conserved. Additionally, protein topology modeling showed that many of the less well-conserved regions between homA and homB and between homC S and homC L corresponded to predicted environmentally exposed loops, suggesting that the divergence of the Hom family may be due to host adaptation/pressure., (© 2018 John Wiley & Sons Ltd.)

Infection with Helicobacter pylori is a major risk factor for development of gastric disease, including gastric cancer. Patients infected with H. pylori strains that express CagA are at even greater risk of gastric carcinoma. Given the importance of CagA, this report describes a new molecular mechanism by which the cagA copy number dynamically expands and contracts in H. pylori Analysis of strain PMSS1 revealed a heterogeneous population in terms of numbers of cagA copies; strains carried from zero to four copies of cagA that were arranged as direct repeats within the chromosome. Each of the multiple copies of cagA was expressed and encoded functional CagA; strains with more cagA repeats exhibited higher levels of CagA expression and increased levels of delivery and phosphorylation of CagA within host cells. This concomitantly resulted in more virulent phenotypes as measured by cell elongation and interleukin-8 (IL-8) induction. Sequence analysis of the repeat region revealed three cagA homologous areas (CHAs) within the cagA repeats. Of these, CHA-ud flanked each of the cagA copies and is likely important for the dynamic variation of cagA copy numbers. Analysis of a large panel of clinical isolates showed that 7.5% of H. pylori strains isolated in the United States harbored multiple cagA repeats, while none of the tested Korean isolates carried more than one copy of cagA Finally, H. pylori strains carrying multiple cagA copies were differentially associated with gastric disease. Thus, the dynamic expansion and contraction of cagA copy numbers may serve as a novel mechanism by which H. pylori modulates gastric disease development. IMPORTANCE Severity of H. pylori -associated disease is directly associated with carriage of the CagA toxin. Though the sequences of the CagA protein can differ across strains, previous analyses showed that virtually all H. pylori strains carry one or no copies of cagA This study showed that H. pylori can carry multiple tandem copies of cagA that can change dynamically. Isolates harboring more cagA copies produced more CagA, thus enhancing toxicity to host cells. Analysis of 314 H. pylori clinical strains isolated from patients in South Korea and the United States showed that 7.5% of clinical strains in the United States carried multiple cagA copies whereas none of the South Korean strains did. This study demonstrated a novel molecular mechanism by which H. pylori dynamically modulates cagA copy number, which affects CagA expression and activity and may impact downstream development of gastric disease., (Copyright © 2017 Jang et al.)

Background: Among postmenopausal breast cancer survivors, poor physical health has been associated with higher risks of breast cancer events. Obesity and physical inactivity are known risk factors for poor physical health, while circulating estrogen is an additional potential risk factor. We tested the hypothesis that the relationship between poor physical health and worse breast cancer outcomes is mediated by higher estrogen concentrations associated with body size and physical inactivity., Methods: We used data from 1030 postmenopausal breast cancer survivors to examine the association between serum estradiol levels, body mass index (BMI), physical activity, and RAND-36-item Health Survey (SF-36) physical health., Results: In univariate analysis, poor physical health was associated with higher estradiol levels, in addition to obesity and low physical activity. Higher estradiol levels were significantly associated with higher odds of poor physical health (odds ratio, OR, 1.20 [95% confidence interval 1.03-1.39]) in a multivariable model adjusting for age, cancer stage and treatment, alcohol use, and physical activity. However, the relationship between estradiol levels and poor physical health was no longer significant (OR 1.06 [0.91-1.24]) after adding BMI in the model. In multivariate analysis, only poor physical health resulted in higher risks of recurrence (hazard ratio 1.33 [95% CI 1.08-1.64])., Conclusions: These findings indicate that estradiol is related to poor physical health, but is not an independent risk factor from body size or inactivity. While obesity and physical activity in survivorship are potential targets for improving physical health, other biological processes that impact physical health, e.g. inflammation, remain to be identified.

The introduction of new treatments for esophageal cancer including surgery, chemotherapy, radiotherapy, or a combination of these modalities has not only improved patient survival, but may also increase the risk of the second primary cancers. The available evidence is conflicting with most risk estimates based on sparse numbers. Here we estimated standardized incidence ratios (SIRs) of second cancer among 24,557 esophageal cancer survivors (at least 2 months) in the Surveillance, Epidemiology, and End Results (SEER) Program between 1973 and 2007, who had been followed up for median 6.5 years (range 2 months-29.3 years). Second cancer risk was statistically significantly elevated (SIR = 1.34, 95% confidence interval [CI]= 1.25-1.42) among the survivors compared with the general population; the SIRs for cancers of oral and pharynx, stomach, small intestine, larynx, lung and bronchus, thyroid and prostate cancer were 8.64 (95% CI = 7.36-10.07), 2.87 (95% CI = 2.10-3.82), 3.80 (95% CI = 1.82-7.00), 3.19 (95% CI = 2.12-4.61), 1.68 (95% CI = 1.46-1.93), 2.50 (95% CI = 1.25-4.47), and 0.77 (95% CI = 0.65-0.90), respectively. Radiotherapy raised cancer risk of larynx (SIR = 3.98, 95% CI = 2.43-6.14) and thyroid (SIR = 3.57, 95% CI = 1.54-7.03) among all esophageal cancer survivors. For patients who had 5-9 years of follow up after radiotherapy, the SIR for lung cancer was 3.46 (95% CI = 2.41-4.82). Patients with esophageal cancer are at increased risks of second cancers of oral and pharynx, larynx, lung, and thyroid, while at a decreased risk for prostate cancer. These findings indicate that radiotherapy for esophageal cancer patients may increase risk of developing second cancers of larynx, lung, and thyroid. Thus, randomized clinical trials to address the association of radiotherapy and the risk of secondary cancer are warranted., (© 2011 Copyright the Authors. Journal compilation © 2011, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.)

Purpose: Hot flashes (HF) affect a large proportion of breast cancer (BC) survivors and can negatively affect their quality of life. Treatments other than estrogen replacement to alleviate HF are needed. Body weight is related to hot flashes, but little is known about the effect of weight change on HF., Patients and Methods: We used data from 3,088 women previously treated for early-stage BC who were enrolled onto the Women's Healthy Eating and Living study to examine the association between weight change after a breast cancer diagnosis and the odds of reporting HF., Results: Overall, 36.1% of participants reported moderate to severe HF at study entry. At 2 years postdiagnosis, 69.2% of women remained within 10%, 4.8% lost at least 10%, and 26.0% gained at least 10% of their prediagnosis weight. Those who gained at least 10% of their prediagnosis weight had a greater risk of reporting HF than women who remained weight stable in that same period (odds ratio [OR], 1.33; 95% CI, 1.11 to 1.60; P = .003). Weight loss of at least 10% of prediagnosis weight was associated with a nonsignificant reduced risk (OR, 0.72; 95% CI, 0.47 to 1.08; P = .118) of reporting HF. However, the trend of weight change (weight loss and weight gain) on HF was significant both when examined categorically (P = .03) and continuously (P < .001)., Conclusion: Prevention of weight gain after a BC diagnosis-a modifiable behavior-may offer a viable intervention for relief of HF. Effects of intentional weight loss in BC survivors requires further study.

Evidence-based medicine (EBM) is defined as a set of processes that facilitate the conscientious, explicit, and judicious integration of individual clinical expertise with the best available external clinical evidence from systematic research in making decisions about the care of individual patients. EBM focuses not only on grading the strength of the evidence but also on the processes and tools that are necessary for clinicians to continually upgrade their knowledge and skills for those problems encountered in daily practice. This article, authored by members of the Duke Pediatric Psychiatry EBM Seminar Team, (1) describes EBM as applied to the training of child and adolescent psychiatrists in the Division of Child and Adolescent Psychiatry, Department of Psychiatry at Duke University Medical Center; (2) presents a simplified discussion of EBM as a technology for training and patient care; (3) discusses the basic principles and procedures for teaching EBM in the setting of a multidisciplinary training program; and (4) briefly mentions two training and research initiatives that are furthered by incorporating EBM.

Introduction: Computer-based outbreak and disease surveillance requires high-quality software that is well-supported and affordable. Developing software in an open-source framework, which entails free distribution and use of software and continuous, community-based software development, can produce software with such characteristics, and can do so rapidly., Objectives: The objective of the Real-Time Outbreak and Disease Surveillance (RODS) Open Source Project is to accelerate the deployment of computer-based outbreak and disease surveillance systems by writing software and catalyzing the formation of a community of users, developers, consultants, and scientists who support its use., Methods: The University of Pittsburgh seeded the Open Source Project by releasing the RODS software under the GNU General Public License. An infrastructure was created, consisting of a website, mailing lists for developers and users, designated software developers, and shared code-development tools. These resources are intended to encourage growth of the Open Source Project community. Progress is measured by assessing website usage, number of software downloads, number of inquiries, number of system deployments, and number of new features or modules added to the code base., Results: During September--November 2003, users generated 5,370 page views of the project website, 59 software downloads, 20 inquiries, one new deployment, and addition of four features., Conclusions: Thus far, health departments and companies have been more interested in using the software as is than in customizing or developing new features. The RODS laboratory anticipates that after initial installation has been completed, health departments and companies will begin to customize the software and contribute their enhancements to the public code base.