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Background: Associations between constipation and dietary fibre and water intake, as well as various lifestyle factors, have not been fully evaluated. The present study aimed to investigate associations between fibre and water intake and constipation, as well as other possible risk factors for constipation, in a large adult population. Methods: Data obtained from 14 024 adults aged ≥20 years from three cycles of the National Health and Nutrition Examination Survey (NHANES) 2005–2010, who had completed a bowel health questionnaire, were included in this cross‐sectional population‐based study. Variables included demographics, lifestyle and dietary factors, comorbidities and laboratory parameters. Logistic regression analyses were performed to determine associations between potential risk factors and constipation. Results: Among 17 132 participants ≥20 years, 2401 (14%) did not complete bowel health questionnaires and were excluded, along with pregnant women (n = 461) and participants without dietary sample weight on day 1 (n = 246), leaving data from 14 024 participants available for analysis. Multivariate analysis revealed that black race/ethnicity [odds ratio (OR) = 1.380, 95% confidence interval (CI) = 1.054–1.809], a lower than 12th grade education (OR = 1.420, 95% CI = 1.154–1.749) or high school education (OR = 1.339, 95% CI = 1.057–1.697), lower income/poverty ratios (1.3–3.49 versus ≥3.5: OR = 1.261, 95% CI = 1.015–1.567), normal weight (OR = 1.913, 95% CI = 1.534–2.386) or overweight (OR = 1.536, 95% CI = 1.207–1.955), depression (OR = 1.610, 95% CI = 1.119–2.315) and poor teeth (OR = 1.441, 95% CI = 1.100–1.888) were associated with an increased risk for constipation. Lower dietary fibre intake was associated with a greater risk of constipation. Total water consumption was significantly associated an with an increased risk of constipation in univariate analysis, but not in multivariate analysis. Conclusions: Lower dietary fibre intake, but not poor water consumption, was associated with a greater risk of constipation in US adults. [ABSTRACT FROM AUTHOR]

Medicaid is a US government insurance programme designed primarily for poor individuals, with expenditures that rose more than 13% in 2002. Thirty-five states have programmes allowing individuals to incur medical expenses at a rate that would make them poor enough to meet Medicaid eligibility criteria. This paper examines the cost of providing care to those spending-down to Medicaid compared to those eligible without spending-down. This longitudinal cohort study compiled inpatient, outpatient and Medicaid data from three academic Infectious Diseases clinics serving approximately 40% of the reported HIV-positive population in North Carolina. Participants included all HIV-positive patients who received care in one of three clinics and received Medicaid coverage at any time from 1996 to 2000 (1,495 individuals). Overall, those who needed to spend-down to Medicaid incurred higher medical costs, following a distinctive pattern of high costs when initially qualified and when ending coverage, and low costs while on spend-down. US states may wish to consider expanding Medicaid's categorically eligible criteria or significantly reducing the frequency with which persons must spend-down to become eligible for Medicaid. [ABSTRACT FROM AUTHOR]

Characterizes the iron oxide coatings on sand grains from the Atlantic coastal plain in the United States, using transmission electron microscopy. Geologic setting; Color of the coatings; Parallel crystallographic orientations of the nanocrystals; Distribution pattern of aluminum, silicon and iron.

Background: Lung cancer is the most common cancer and a leading cause of cancer-related deaths globally. The aim of this study was to evaluate the incidence and mortality of lung cancer worldwide in 2022 and to project the number of new cases and deaths due to lung cancer in China and the United States in 2050., Methods: In this study, data from the GLOBCAN 2022 database were used to analyze lung cancer incidence and mortality. The current status of lung cancer incidence and deaths was described by country/region, sex, age, and the human development index (HDI), and future lung cancer incidence and deaths in China and the United States were projected for 2050., Results: Globally, an estimated 2,480,675 new lung cancer cases and 1,817,469 lung cancer-related deaths occurred in 2022, with age-standardized incidence rates (ASIRs) and age-standardized mortality rates (ASMRs) of 23.6/100,000 and 16.8/100,000, respectively. In China, the ASIR and ASMR for male lung cancer patients were approximately 1.7 times and 2.7 times greater than those for female lung cancer patients, respectively. The ASIR and ASMR in high-HDI countries were approximately 8.5 times and 6.5 times those in low-HDI countries, respectively. It is estimated that in 2050, there will be approximately 1120 thousand new cases and 960 thousand deaths among Chinese men, 680 thousand new cases and 450 thousand deaths among Chinese women, approximately 170 thousand new cases and 110 thousand deaths among American men, and 160 thousand new cases and 90 thousand deaths among American women., Conclusions: There are significant differences in the incidence and mortality of lung cancer among different regions and sexes. Therefore, sex factors need to be considered in the prevention, screening, and treatment strategies of lung cancer, and the implementation of tertiary prevention measures for lung cancer, especially primary and secondary prevention, needs to be actively promoted., (Copyright © 2024 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Background: Neurofilament light chain (NFL), a biomarker of neuroaxonal damage, has been linked to inflammation and depressive disorders, albeit with inconsistent results. We aimed to evaluate the association between serum NFL concentration and clinically relevant depressive symptoms in the general population and to examine the potential involvement of systemic inflammation in this association., Methods: The data of 1881 adults aged 20-75 years were extracted from the National Health and Nutrition Examination Survey (NHANES) 2013-2014 cycle. Serum NFL levels were quantified using a highly sensitive immunoassay. Further, markers of systemic inflammation, including systemic immune inflammation index (SII), system inflammation response index (SIRI), and white blood cell (WBC) counts were calculated based on whole blood cell counts. Clinically relevant depressive symptoms were evaluated using the 9-item Patient Health Questionnaire (PHQ-9) with a cut-off score of 10., Results: After adjusting for potential confounders, we found that each one-unit increase in ln-transformed serum NFL concentration was significantly associated with a 1.37-fold increase in the risk of clinically relevant depressive symptoms (95 % confidence interval [CI]: 1.06, 1.77; p = 0.017). Serum NFL level was significantly related to increased SII (regression coefficient [β] = 0.04, 95%CI: 0.01, 0.08; p = 0.027), SIRI (β = 0.09, 95%CI: 0.05, 0.14; p < 0.001), and WBC (β = 0.05, 95%CI: 0.03, 0.07; p < 0.001), respectively. These significant associations were observed only in elderly participants., Limitations: The cross-sectional study design is limited in causal inference., Conclusions: Our findings indicate that serum NFL levels are related to an increased risk of clinically relevant depressive symptoms and higher levels of markers of systemic inflammation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Microbial challenge in-use studies are performed to evaluate the potential for microbial proliferation in preservative-free single-dose biological products after first puncture and potential accidental contamination during dose preparation (e.g., reconstitution or dilution) and storage. These studies, in addition to physicochemical in-use stability assessments, are used as part of product registration to define in-use hold times in Prescribing Information and in the pharmacy manual in the case of clinical products. There are no formal guidance documents describing regulator expectations on how to conduct microbial challenge in-use studies and interpret microbial data to assign in-use storage hold times. In lieu of guidance, US Food and Drug Administration (FDA) regulators have authored publications and presentations describing regulator expectations. Insufficient or unavailable microbial challenge data can result in shortened in-use hold times, thus microbial challenge data enables flexibility for health care providers (HCPs) and patients while ensuring patient safety. A cross-industry/FDA in-use microbial working group was formed through the Innovation & Quality (IQ) Consortium to gain alignment among industry practice and regulator expectations. The working group assessed regulatory guidance, current industry practice via a blinded survey of IQ Consortium member companies, and scientific rationale to align on recommendations for experimental design, execution of microbial challenge in-use studies, and a decision tree for microbial data interpretation to assign in-use hold times. Besides the study execution and data interpretation, additional considerations are discussed including the use of platform data for clinical stage products, closed system transfer devices (CSTDs), transport of dose solutions, long infusion times, and the use of USP <797> by HCPs for preparing sterile drugs for administration. The recommendations provided in this article will help streamline biological product development, ensure consistency on assignment of in-use hold times in biological product labels across industry, and provide maximum allowable flexibility to HCPs and patients while ensuring patient safety., (© PDA, Inc. 2024.)

Background: The prognostic value of triglyceride-glucose (TyG) related indices in non-alcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) is still unclear. This study aimed to determine the associations between TyG-related indices and long-term mortality in this population., Methods: The data came from the National Health and Nutrition Examination Survey (NHANES III) and National Death Index (NDI). Baseline TyG, TyG combining with body mass index (TyG-BMI), and TyG combining with waist circumference (TyG-WC) indices were calculated, and mortality status was determined through 31 December 2019. Multivariate Cox and restricted cubic spline (RCS) regression models were performed to evaluate the relationship between TyG-related indices and long-term mortality among participants with NAFLD/MASLD. In addition, we examined the association between TyG-related indices and all-cause mortality within subgroups defined by age, sex, race/ethnicity, and fibrosis-4 index (FIB-4)., Results: There were 10,390 participants with completed ultrasonography and laboratory data included in this study. NAFLD was diagnosed in 3672/10,390 (35.3%) participants, while MASLD in 3556/10,390 (34.2%) amongst the overall population. The multivariate Cox regression analyses showed high levels of TyG-related indices, particularly in TyG-BMI and TyG-WC indices were significantly associated with the all-cause mortality, cardiovascular mortality, and diabetes mortality in either NAFLD or MASLD. The RCS curves showed a nonlinear trend between three TyG-related indices with all-cause mortality in either NAFLD or MASLD. Subgroup analyses showed that TyG-BMI and TyG-WC indices were more suitable for predicting all-cause mortality in patients without advanced fibrosis., Conclusion: Our study highlights the clinical value of TyG-related indices in predicting the survival of the NAFLD/MASLD population. TyG-BMI and TyG-WC indices would be the surrogate biomarkers for the follow-up of the population without advanced fibrosis., (© 2024. The Author(s).)

Background and Aims: Vascular calcification has been linked to bone mineral density (BMD). This study aimed to investigate the association between BMD and abdominal aortic calcification (AAC)., Methods and Results: Data from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) were utilized. Participants lacking BMD and AAC score data were excluded. BMD at the femoral neck was measured using dual-energy X-ray absorptiometry. AAC scores were assessed using the Kauppila scoring system, with AAC defined as a score greater than zero, and severe AAC defined as a score greater than six. Weighted multivariable regression analysis and subgroup analysis were conducted to examine the independent relationship between BMD and AAC score, AAC, and severe AAC. A total of 2965 participants were included. After adjusting for multiple covariates, BMD showed a negative association with higher AAC scores (β = -0.17, 95% CI -0.29, -0.05, p = 0.0066). The odds of having AAC and severe AAC decreased by 9% and 16%, respectively, for every one-unit increase in BMD (AAC: odds ratio [OR] = 0.91, 95% CI 0.82, 1.00, p = 0.0431; severe AAC: OR = 0.84, 95% CI 0.71, 0.99, p = 0.0334)., Conclusion: Low BMD is associated with higher AAC scores and an increased risk of AAC and severe AAC. Considering the detrimental impact of low BMD on cardiovascular health, individuals with AAC should be evaluated for osteopenia and osteoporosis in clinical settings., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Since 2006, the human papillomavirus (HPV) vaccine has been recommended for females aged 9-26 years in the United States. Aiming to evaluate the early effect of the HPV vaccine on cervical cancer, this study assessed the incidence of cervical cancer by age and histology before and after the introduction of HPV vaccination., Methods: Data on cervical cancer incidence from 1975-2019 were extracted from the Surveillance, Epidemiology, and End Results Program. Joinpoint regression was used to determine temporal trends over time. Future cervical cancer incidence (2015-2039) was projected using Bayesian age-period-cohort analysis. Age-period-cohort (APC) models were created to evaluate age, period, and cohort effects., Results: For overall cervical cancer and cervical squamous cell carcinoma (SCC), incidence rate showed decreasing trends (-0.7%, and -1.0% annually, respectively), whereas cervical adenocarcinoma (AC) incidence continuously increased (2.6% annually). The incidence trends for AC were stable in the 20-24 and 25-29-year age groups, whereas there was an increasing trend in older age groups. Similarly, the projected trend for AC in females aged 20-30 years exhibited a decline, whereas an increase was predicted in the 31-40-year age group, especially in the 35-44 year age group. The birth cohort and period effects in SCC and AC were extracted from APC models., Discussion: During the period of 1975-2019, the incidence of cervical AC remained almost unchanged in the age groups receiving HPV vaccines while increased in the age groups not receiving HPV vaccines. The birth cohort effects of SCC and AC of the cervix provided evidence supporting the effectiveness of the HPV vaccine in preventing cervical cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pei, Shu, Wu, Li, Xu, Jiang and Zhu.)

Background: Currently, 19 disease-modifying therapies (DMTs) have been approved for the treatment of patients with relapsing forms of multiple sclerosis (RMS)., Objective: The objective of this study was to conduct a systematic review and network meta-analysis to evaluate the efficacy and safety of DMTs in adults with RMS., Methods: We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, the Food and Drug Administration, and European Medicines Agency websites for randomized controlled trials (RCTs) (from inception to July 2021). Eligible RCTs evaluated approved treatments for RMS as monotherapy and reported at least one of the primary outcome measures of interest. The primary outcome was efficacy (annualized relapse rate and 12-week confirmed disability progression) and safety (serious adverse events [AEs] and discontinuation due to AEs). We assessed the risk of bias (RoB) of included studies using the Cochrane RoB tool version 2.0 (https://www.bmj.com/content/343/bmj.d5928) for RCTs. Surface under the cumulative ranking (SUCRA) was used to rank therapies and to assess quality of general evidence, respectively. The Grading of Recommendations Assessment, Development and Evaluation framework was used to rank therapies and to assess quality of general evidence., Results: A total of 43 records represent 45 RCTs selected for network meta-analysis. In total, 30,720 participants (median of 732; interquartile range: 248-931) were included, of which 67% were female. By SUCRA analysis, alemtuzumab (94.3%) presented the highest probability of being the best alternative for annualized relapse rate, whereas ofatumumab (93.5%) presented the highest probability of being the best alternative for 12-week confirmed disability progression. Interferon beta-1b subcutaneous (87.0%) presented the highest probability of the best safety among all DMTs for serious AEs, whereas alemtuzumab (92.4%) presented the highest probability of the best safety among all DMTs for discontinuation due to AEs., Conclusion: Network meta-analysis shows that alemtuzumab and ofatumumab present the highest efficacy among DMTs. Because there is little difference between these probabilities for many treatments, health professionals should use clinical shared decision making when formulating treatment plans with patients., (Copyright © 2022 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Background: The field of cardiothoracic surgery has been striving to increase its gender and racial diversity. We sought to examine changes in gender and racial diversity in cardiothoracic fellowships and integrated residencies in the past decade., Methods: Accreditation Council for Graduate Medical Education data were obtained from 2011 to 2019. Linear trends were assessed for year-by-year data. Average percentages of women and underrepresented minorities were then calculated in 3-year intervals. Intervals were compared with Student's t test and χ 2 tests., Results: There was no statistically significant increase in percent female trainees in cardiothoracic fellowships (18.5% to 22.1%, P = .10) or integrated residencies (22.8% to 27.8%, P = .17), despite a significant increase in percent female applicants to fellowship (18.2% to 35.3%, P < .01) and integrated residency (8.9% to 33.0%, P < .01). Cardiothoracic fellowships had no increase in underrepresented minority trainees (8.3% to 9.4%, P = .48). Underrepresented minority trainees in integrated residencies increased from 2.7% to 6.9% (P = .03). Although there was no significant increase in underrepresented minority applicants to fellowships (10.2% to 11.3%, P = .66), the percent of underrepresented minority applicants to integrated residencies increased from 13.1% to 19.3% (P < .01)., Conclusions: Cardiothoracic surgery training programs are attracting more female applicants, but that has not yet resulted in a higher percentage of female trainees. Although percentages of underrepresented minorities increased among integrated residency applicants and trainees, they remain low compared with other specialties. These data reflect positive changes but also highlight that much remains to be done to increase diversity in cardiothoracic surgery training., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: Lung cancer incidences tend to be higher among males than females in both China and the United States, yet secular incidence patterns are different due to distinct population and environmental exposures. We examined long-term and future trends of lung cancer incidence, as well as the associations of age, period, and cohort effects with gender disparities., Methods: Using data from the Cancer Incidence in Five Continents from 1978 to 2012, we calculated age-standardized, age-specific incidence, and male-to-female incidence rate ratios (IRR), and conducted an age-period-cohort analysis. The average annual percentage change (AAPC) of the trends was obtained by Joinpoint Regression. Bayesian age-period-cohort analysis was also conducted to project incidences to 2032., Results: In China, age-standardized incidence revealed a decreasing trend among males, but showed increasing trends among the younger age groups (30-54 years) in females. Age-standardized incidence rates of males decreased but remained stable among females from 1972 to 2012 in the United States. Male-to-female incidence rate ratios narrowed in both countries and reversed among younger birth cohorts in the United States. Gender disparities are expected to continue to diminish in both countries, and incidence among females appears to exceed that of males in the United States by around 2023-2027., Conclusion: Gender disparities in lung cancer incidence persist and will continue into the future in both countries, but our findings suggested that smoking may play different roles in gender disparities in lung cancer incidence between the two countries. Further population-based epidemiological studies among females in China are imperative., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction: The 2014 Medicaid expansion was intended to improve access to care. We hypothesized that Medicaid expansion would be associated with improved gastric cancer (GC) outcomes., Methods: We selected patients with a new primary diagnosis of GC from the National Cancer Database. We compared states that expanded Medicaid in 2014 to those that did not. We compared pre-and post-expansion intervals 2012-2013 and 2015-2016., Results: There was an increase in patients diagnosed with stage 0-2 GC from 38% to 41.5% [p < 0.01] in expansion states (ES), but no change at 38.9% in non-expansion states (NES). Uninsured and Medicaid patients diagnosed with stages 0-2 GC increased in ES from 32.4% to 37.8% [p = 0.01] and decreased in NES from 29.7% to 27.3% [p = n.s.]. Uninsured and Medicaid patients receiving treatment rose from 87.0% to 90.3% in ES [p < 0.01] and in NES 83.9%-84.9% [p = n.s.]. Twelve-month survival for ES rose from 68.1% to 70.6% [p = 0.03] and in NES decreased 65.2%-65.1% [p = n.s.]., Conclusion: Increased healthcare access may be related to earlier diagnosis and improved outcomes in GC., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background and Purpose: Intracranial vessel wall MR imaging is an emerging technique for intracranial vasculopathy assessment. Our aim was to investigate intracranial vessel wall MR imaging use by the American Society of Neuroradiology (ASNR) members at their home institutions, including indications and barriers to implementation., Materials and Methods: The ASNR Vessel Wall Imaging Study Group survey on vessel wall MR imaging use, frequency, applications, MR imaging systems and field strength used, protocol development approaches, vendor engagement, reasons for not using vessel wall MR imaging, ordering-provider interest, and impact on clinical care, was distributed to the ASNR membership between April 2 and August 30, 2019., Results: There were 532 responses; 79 were excluded due to nonresponse and 42 due to redundant institutional responses, leaving 411 responses. Fifty-two percent indicated that their institution performs vessel wall MR imaging, with 71.5% performed at least 1-2 times/month, most frequently on 3T MR imaging, and 87.7% using 3D sequences. Protocols most commonly included were T1-weighted pre- and postcontrast and TOF-MRA; 60.6% had limited contributions from vendors or were still in protocol development. Vasculopathy differentiation (94.4%), cryptogenic stroke (41.3%), aneurysm (38.0%), and atherosclerosis (37.6%) evaluation were the most common indications. For those not performing vessel wall MR imaging, interpretation (53.1%) or technical (46.4%) expertise, knowledge of applications (50.5%), or limitations of clinician (56.7%) or radiologist (49.0%) interest were the most common reasons. If technical/expertise obstacles were overcome, 56.4% of those not performing vessel wall MR imaging indicated that they would perform it. Ordering providers most frequently inquiring about vessel wall MR imaging were from stroke neurology (56.5%) and neurosurgery (25.1%), while 34.3% indicated that no providers had inquired., Conclusions: More than 50% of neuroradiology groups use vessel wall MR imaging for intracranial vasculopathy characterization and differentiation, emphasizing the need for additional technical and educational support, especially as clinical vessel wall MR imaging implementation continues to grow., (© 2022 by American Journal of Neuroradiology.)

Context: Health inequity is often associated with race-ethnicity., Objective: To determine the prevalence of insulin pump therapy and continuous glucose monitoring (CGM) among Medicare beneficiaries with type 1 diabetes (T1D) by race-ethnicity, and to compare diabetes-related technology users with nonusers., Design: The prevalence of technology use (pump, CGM) was determined by race-ethnicity for enrollees in coverage years (CY) 2017-2019 in the Medicare fee-for-service database. Using CY2019 data, technology users were compared with nonusers by race-ethnicity, sex, average age, Medicare eligibility criteria, and visit to an endocrinologist., Setting: Community., Patients or Other Participants: Beneficiaries with T1D and at least 1 inpatient or 2 outpatient claims in a CY., Intervention(s): Pump or CGM therapy, visit to an endocrinologist., Main Outcome Measure(s): Diabetes-related technology use by race-ethnicity groups., Results: Between 2017 and 2019, CGM and insulin pump use increased among all groups. Prevalence of insulin pump use was < 5% for Black and Other beneficiaries yet increased from 14% to 18% among White beneficiaries. In CY2019, 57% of White patients used a pump compared with 33.1% of Black and 30.3% of Other patients (P < 0.001). Black patients were more likely than White patients to be eligible because of disability/end-stage renal disease or to be Medicare/Medicaid eligible (both P < 0.001), whether using technology or not. Significant race-ethnicity differences (P < 0.001) existed between technology users and nonusers for all evaluated factors except visiting an endocrinologist., Conclusions: Significant race-ethnicity associated differences existed in T1D management. The gap in diabetic technology adoption between Black and White beneficiaries grew between 2017 and 2019., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Lung cancer is one of the most common malignancies in the United States, and the common metastatic sites in advanced non-small cell lung cancer (NSCLC) are bone, brain, adrenal gland, and liver, respectively, among which patients with liver metastases have the worst prognosis. We retrospectively analyzed 1963 patients diagnosed with NSCLC combined with liver metastases between 2010 and 2015. Independent prognostic factors for patients with liver metastases from NSCLC were identified by univariate and multivariate Cox regression analysis. Based on this, we developed a nomogram model via R software and evaluated the performance and clinical utility of the model by calibration curve, receiver operating characteristic curves, and decision curve analysis (DCA). The independent prognostic factors for NSCLC patients with liver metastases included age, race, gender, grade, T stage, N stage, brain metastases, bone metastases, surgery, chemotherapy, and tumor size. The area under the curve predicting OS at 6, 9, and 12 months was 0.793, 0.787, and 0.784 in the training cohort, and 0.767, 0.771, and 0.773 in the validation cohort, respectively. Calibration curves of the nomogram showed high agreement between the outcomes predicted by the nomogram and the actual observed outcomes, and the DCA further demonstrated the value of the clinical application of the nomogram. By analyzing the Surveillance, Epidemiology, and End Results database, we established and verified a prognostic nomogram for NSCLC patients with liver metastases, to personalize the prognosis of patients. At the same time, the prognostic nomogram has a satisfactory accuracy and the results are a guide for the development of patient treatment plans., (© 2022. The Author(s).)

Background: Little is known about the association between physical activity before cancer diagnosis and survival among lung cancer patients. In this pooled analysis of 11 prospective cohorts, we investigated associations of prediagnosis leisure-time physical activity (LTPA) with all-cause and lung cancer-specific mortality among incident lung cancer patients., Methods: Using self-reported data on regular engagement in exercise and sports activities collected at study enrollment, we assessed metabolic equivalent hours (MET-h) of prediagnosis LTPA per week. According to the Physical Activity Guidelines for Americans, prediagnosis LTPA was classified into inactivity, less than 8.3 and at least 8.3 MET-h per week (the minimum recommended range). Cox regression was used to estimate hazard ratios (HRs) and 95% confidence interval (CIs) for all-cause and lung cancer-specific mortality after adjustment for major prognostic factors and lifetime smoking history., Results: Of 20 494 incident lung cancer patients, 16 864 died, including 13 596 deaths from lung cancer (overall 5-year relative survival rate = 20.9%, 95% CI = 20.3% to 21.5%). Compared with inactivity, prediagnosis LTPA of more than 8.3 MET-h per week was associated with a lower hazard of all-cause mortality (multivariable-adjusted HR = 0.93, 95% CI = 0.88 to 0.99), but not with lung cancer-specific mortality (multivariable-adjusted HR = 0.99, 95% CI = 0.95 to 1.04), among the overall population. Additive interaction was found by tumor stage (Pinteraction = .008 for all-cause mortality and .003 for lung cancer-specific mortality). When restricted to localized cancer, prediagnosis LTPA of at least 8.3 MET-h per week linked to 20% lower mortality: multivariable-adjusted HRs were 0.80 (95% CI = 0.67 to 0.97) for all-cause mortality and 0.80 (95% CI = 0.65 to 0.99) for lung cancer-specific mortality., Conclusions: Regular participation in LTPA that met or exceeded the minimum Physical Activity Guidelines was associated with reduced hazards of mortality among lung cancer patients, especially those with early stage cancer., (© The Author(s) 2022. Published by Oxford University Press.)

Ultra-sensitive detection of 2,4,6-trinitrotoluene (TNT) plays an important role in society security and human health. The Raman probe molecule p-aminothiophenol (PATP) can interact with TNT in three ways to form a TNT-PATP complex. In this paper, a 'sandwich' structure was developed to detect TNT with high sensitivity. Au nano-pillar arrays (AuNPAs) substrates modified by low-concentration PATP through Au-S bonds were acted as capture probe for TNT. Meanwhile, Ag nano-particles (AgNPs) modified by PATP at higher concentration were employed as tags for surface-enhanced Raman scattering (SERS). The formation of the TNT-PATP complex is not only the means by which AuNPAs substrates recognize and capture TNT, but also links the SERS tags to TNT, forming an AuNPAs-TNT-AgNPs 'sandwich' structure. The Raman signal of PATP was greatly enhanced mainly because novel 'hot spots' formed between the AuNPAs and AgNPs of the 'sandwich' structure. The Raman signal of PATP was further amplified by the chemical enhancement effect induced by the TNT-PATP complex formation. Based on this mechanism, the limit of detection (LOD) of TNT was determined from the Raman signal of PATP. The LOD reached 10 -9  mg/mL (4.4 × 10 -12  M), much lower than that suggested by the US Environmental Protection Agency (88 nM). Moreover, TNT was selectively detected over several TNT analogues 2,4-dinitrotoluene (DNT), p-nitrotoluene (NT) and hexogen (RDX). Finally, the 'sandwich' structure was successfully applied to TNT detection in environmental water and sand., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Previous studies have demonstrated an association between nonselective beta-blockers (NSBBs) and lower risk of hepatocellular carcinoma (HCC) in cirrhosis. However, there has been no population-based study investigating the risk of HCC among cirrhotic patients treated using carvedilol., Aims: To determine the risk of HCC among cirrhotic patients with NSBBs including carvedilol., Methods: This retrospective cohort study utilised the Cerner Health Facts database in the United States from 2000 to 2017. Kaplan-Meier estimate, Cox proportional hazards regression, and propensity score matching (PSM) were used to test the HCC risk among the carvedilol, nadolol, and propranolol groups compared with no beta-blocker group., Results: The final cohort comprised 107 428 eligible patients. The 100-month cumulative HCC incidence of NSBBs was significantly lower than the no beta-blocker group (carvedilol (11.24%) vs no beta-blocker (15.69%), nadolol (27.55%) vs no beta-blocker (32.11%), and propranolol (26.17%) vs no beta-blocker (28.84%) (P values < 0.0001). NSBBs were associated with a significantly lower risk of HCC (Hazard ratio: carvedilol 0.61 (95% CI 0.51-0.73), nadolol 0.74 (95% CI 0.63-0.87), propranolol 0.75 (95% CI 0.66-0.84) after PSM in the multivariate cox analysis. In subgroup analysis, NSBBs reduced the risk of HCC in cirrhosis with complications and non-alcoholic cirrhosis., Conclusions: NSBBs, including carvedilol, were associated with a significantly decreased risk of HCC in patients with cirrhosis when compared with no beta-blocker regardless of complications status. Future randomised-controlled studies comparing the incidence of HCC among NSBBs should elucidate which NSBB would be the best option to prevent HCC in cirrhosis., (© 2021 John Wiley & Sons Ltd.)

Introduction: Hospital readmissions constitute an important component of associated costs of a disease and can contribute a significant burden to healthcare. The majority of studies evaluating readmissions following laparoscopic cholecystectomy (LC) comprise of single center studies and thus can underestimate the actual incidence of readmission. We sought to examine the rate and causes of readmissions following LC using a large longitudinal database., Methods: The New York SPARCS database was used to identify all adult patients undergoing laparoscopic cholecystectomy for benign biliary disease between 2000 and 2016. Due to the presence of a unique identifier, patients with readmission to any New York hospital were evaluated. Planned versus unplanned readmission rates were compared. Following univariate analysis, multivariable logistic regression model was used to identify risk factors for unplanned readmissions after accounting for baseline characteristics, comorbidities and complications., Results: There were 591,627 patients who underwent LC during the studied time period. Overall 30-day readmission rate was 4.94% (n = 29,245) and unplanned 30-days readmission rate was 4.58% (n = 27,084). Female patients were less likely to have 30-day unplanned readmissions. Patients with age older than 65 or younger than 29 were more likely to have 30-day unplanned readmissions compared to patients with age 30-44 or 45-64. Insurance status was also significant, as patients with Medicaid/Medicare were more likely to have unplanned readmissions compared to commercial insurance. In addition, variables such as Black race, presence of any comorbidity, postoperative complication, and prolonged initial hospital length of stay were associated with subsequent readmission., Conclusion: This data show that readmissions rates following LC are relatively low; however, majority of readmissions are unplanned. Most common reason for unplanned readmissions was associated with complications of the procedure or medical care. By identifying certain risk groups, unplanned readmissions may be prevented.

Data addressing prognostication in patients with HIV related Burkitt lymphoma (HIV-BL) currently treated remain scarce. We present an international analysis of 249 (United States: 140; United Kingdom: 109) patients with HIV-BL treated from 2008 to 2019 aiming to identify prognostic factors and outcomes. With a median follow up of 4.5 years, the 3-year progression-free survival (PFS) and overall survival (OS) were 61% (95% confidence interval [CI] 55% to 67%) and 66% (95%CI 59% to 71%), respectively, with similar results in both countries. Patients with baseline central nervous system (CNS) involvement had shorter 3-year PFS (36%) compared to patients without CNS involvement (69%; P < .001) independent of frontline treatment. The incidence of CNS recurrence at 3 years across all treatments was 11% with a higher incidence observed after dose-adjusted infusional etoposide, doxorubicin, vincristine, prednisone, cyclophosphamide (DA-EPOCH) (subdistribution hazard ratio: 2.52; P = .03 vs other regimens) without difference by CD4 count 100/mm3. In multivariate models, factors independently associated with inferior PFS were Eastern Cooperative Oncology Group (ECOG) performance status 2-4 (hazard ratio [HR] 1.87; P = .007), baseline CNS involvement (HR 1.70; P = .023), lactate dehydrogenase >5 upper limit of normal (HR 2.09; P < .001); and >1 extranodal sites (HR 1.58; P = .043). The same variables were significant in multivariate models for OS. Adjusting for these prognostic factors, treatment with cyclophosphamide, vincristine, doxorubicin, and high-dose methotrexate, ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC) was associated with longer PFS (adjusted HR [aHR] 0.45; P = .005) and OS (aHR 0.44; P = .007). Remarkably, HIV features no longer influence prognosis in contemporaneously treated HIV-BL., (© 2021 by The American Society of Hematology.)

Introduction: Small Bowel Obstruction (SBO) is a common reason for emergency department (ED) visits in the United States. However, little is known regarding the clinical course of these patients. This study aims to identify all patients presenting to the ED in New York State with SBO and follow their clinical course., Methods: The New York SPARCS administrative database was used to identify all patients who presented to an ED with the diagnosis of SBO from 2012 to 2014. Patients were followed to identify discharges from the ED, admissions, operations, 30-day readmissions, transfers, and in-hospital death., Results: Between 2012 and 2014, 43,567 ED visits (events) from 35,646 patients were identified, with 2824 (6.5%) resulting in direct discharge from the ED. A majority (n = 31,193; 71.6%) of ED visits were admitted to the presenting institution without surgery, while 7673 (17.6%) were admitted and underwent surgery. A minority (n = 1947; 4.5%) were transferred to a tertiary center. The overall 30-day readmission rate was 17.9%. Those who underwent surgery were more likely to experience in-hospital death but less likely to have 30-day readmission., Conclusion: To our knowledge, this is the first study that examines the disposition of all patients presenting to the ED with SBO in a large statewide cohort. The majority of admitted patients underwent non-operative management, with overall low rates of readmission, transfer, and in-hospital death.

Rotavirus C (RVC) is associated with acute diarrhoea in both children and young animals. Because of its frequent occurrence, additional sequences have recently been generated. In this study, we sequenced 21 complete genomes from porcine diarrhoea samples and analysed them together with all available reference sequences collected from the GenBank database [National Center for Biotechnology Information (NCBI)]. Based on phylogenetic analysis and genetic distance calculation, the number of each segment was identified as 31G, 26P, 13I, 5R, 5C, 5M, 12A, 10 N, 9T, 8E and 4 H for genotypes encoding VP7, VP4, VP6, VP1, VP2, VP3 and NSP1, NSP2, NSP3, NSP4 and NSP5, respectively. From the analysis, genotypes G19-G31, P[22]-P[26], R5, A9-A12, N9-N10, T7-T9 and E6-E8 were defined as newly identified genotypes, and genotype C6 was combined with C5, and M6 was combined with M1, due to their closely related nature. Estimated with the identity frequency ratio between the intergenotype and intragenotype, the nucleotide identity cutoff values for different genotypes were determined as 85, 85, 86, 84, 83, 84, 82, 87, 84, 81 and 79 % for VP7, VP4, VP6, VP1, VP2, VP3, NSP1, NSP2, NSP3, NSP4 and NSP5, respectively. Genotyping of the 49 US strains indicated possible segment reassortment in 9 of the 11 segments, with the exceptions being VP1 and NSP5, and the most prevalent genotypes for each segment genes in the USA were G6/G5/G21/G9-P5/P4-I6/I5-R1-C5-M1-A8-N1/N10-T1-E1-H1. Our study updated the genotypes of RVC strains and provided more evidence of RVC strain diversity that may be relevant to better understand genetic diversity, and the distribution and evolution of RVC strains.

Purpose: Burkitt lymphoma (BL) has unique biology and clinical course but lacks a standardized prognostic model. We developed and validated a novel prognostic index specific for BL to aid risk stratification, interpretation of clinical trials, and targeted development of novel treatment approaches., Methods: We derived the BL International Prognostic Index (BL-IPI) from a real-world data set of adult patients with BL treated with immunochemotherapy in the United States between 2009 and 2018, identifying candidate variables that showed the strongest prognostic association with progression-free survival (PFS). The index was validated in an external data set of patients treated in Europe, Canada, and Australia between 2004 and 2019., Results: In the derivation cohort of 633 patients with BL, age ≥ 40 years, performance status ≥ 2, serum lactate dehydrogenase > 3× upper limit of normal, and CNS involvement were selected as equally weighted factors with an independent prognostic value. The resulting BL-IPI identified groups with low (zero risk factors, 18% of patients), intermediate (one factor, 36% of patients), and high risk (≥ 2 factors, 46% of patients) with 3-year PFS estimates of 92%, 72%, and 53%, respectively, and 3-year overall survival estimates of 96%, 76%, and 59%, respectively. The index discriminated outcomes regardless of HIV status, stage, or first-line chemotherapy regimen. Patient characteristics, relative size of the BL-IPI groupings, and outcome discrimination were consistent in the validation cohort of 457 patients, with 3-year PFS estimates of 96%, 82%, and 63% for low-, intermediate-, and high-risk BL-IPI, respectively., Conclusion: The BL-IPI provides robust discrimination of survival in adult BL, suitable for use as prognostication and stratification in trials. The high-risk group has suboptimal outcomes with standard therapy and should be considered for innovative treatment approaches.

Background: The prevalence of obstructive sleep apnoea (OSA) is high in patients with hypertrophic cardiomyopathy. The effect of septal myectomy on OSA is not clear. This study aimed to examine the association between hypertrophic obstructive cardiomyopathy and OSA before and after septal myectomy., Method: We included 85 consecutive patents with a confirmed diagnosis of hypertrophic obstructive cardiomyopathy who underwent septal myectomy. Polysomnography was performed in all patients before and 3 months after the surgery., Results: Of the 85 patients, 49 (58%) were diagnosed with OSA. Patients with OSA were significantly older than those without OSA. The incidence of atrial fibrillation significantly increased during the perioperative period in patients with OSA (p = 0.03). The severity of OSA significantly increased 3 months after surgery, as determined by the apnoea-hypopnoea index (AHI; p < 0.001), obstructive apnoea index (p = 0.024), and hypopnoea index (p = 0.003), whereas central apnoea index was decreased (p = 0.008). In the multivariate linear regression analysis, mean oxygen desaturation and time% with SpO 2 <90% during sleep before surgery were significantly associated with increased AHI, independently of body mass index and sex (p = 0.026 and p = 0.007, respectively; adjusted R 2  = 0.365)., Conclusions: The severity of OSA significantly increased 3 months after septal myectomy as determined by AHI, obstructive apnoea index, and hypopnoea index. Mean oxygen saturation and time% with SpO 2 <90% during sleep before surgery were independently associated with the increase of AHI. However, the specific mechanism of such deterioration of OSA after septal myectomy needs to be determined in detail., (Copyright © 2019 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Objective: To examine crash rates over time among 16-17-year-old drivers compared to older drivers., Methods: Data were from a random sample of 854 of the 3,500 study participants in SHRP 2, a U.S. national, naturalistic driving (instrumented vehicle) study. Crashes/10,000 miles by driver age group, 3-month period, and sex were examined within generalized linear mixed models., Results: Analyses of individual differences between age cohorts indicated higher incidence rates in the 16-17-year old cohort relative to older age groups each of the first four quarters (except the first quarter compared to 18-20 year old drivers) with incident rate ratios (IRR) ranging from 1.98 to 18.90, and for the full study period compared with drivers 18-20 (IRR = 1.69, CI = 1.00, 2.86), 21 to 25 (IRR = 2.27, CI = 1.31, 3.91), and 35 to 55 (IRR = 4.00, CI = 2.28, 7.03). Within the 16-17-year old cohort no differences were found in rates among males and females and the decline in rates over the 24-month study period was not significant., Conclusions: The prolonged period of elevated crash rates suggests the need to enhance novice young driver prevention approaches such as Graduated Driver's Licensing limits, parent restrictions, and post-licensure supervision and monitoring. Practical Applications: Increases are needed in Graduated Driver's Licensing limits, parent restrictions, and postlicensure supervision and monitoring., (Published by Elsevier Ltd.)

Objective: The objective of this study was to examine whether reduced awareness of memory deficits in individuals with dementia is associated with more frequent need for Medicare home health care services., Methods: Cross-sectional analyses were conducted in a multicenter, clinic-based cohort. In total, 192 participants diagnosed with dementia and their informants were independently asked whether or not the participant demonstrated cognitive symptoms of dementia related to memory and word-finding. Participant self-awareness was measured as the discrepancy between participant and caregiver report of these symptoms. Annual Medicare home health benefit use data was obtained from Medicare claims matched by year to the Predictors study visit., Results: Participants that used home health services had lower awareness scores than those who did not. Awareness remained independently associated with home health use in a logistic regression adjusted for age, gender, education, caregiver relationship, global cognition, dementia subtype, and medical comorbidities., Implications: Reduced self-awareness of memory deficits in individuals with dementia is associated with more frequent use of Medicare home health services. The disproportionate use of in-home assistance as a function of awareness level may reflect dangers faced by patients, and challenges faced by caregivers, when patients have limited awareness of their memory deficits. Current results have implications for clinical care, caregiver education, and models of health care utilization.

Background: The benefit of preoperative chemoradiation (CXRT) over preoperative chemotherapy alone ("chemotherapy" hereafter) is unknown. By analyzing the National Cancer Database (NCDB), we investigated whether preoperative CXRT improves the incidence of primary tumor pathologic complete response (ypT0) and overall survival (OS) compared with preoperative chemotherapy in patients with gastric cancer., Methods: Patients with non-metastatic gastric adenocarcinoma who underwent CXRT or chemotherapy followed by gastrectomy were included. Propensity score matching with a ratio of 1:1 was implemented to reduce selection bias. A conditional logistic regression model was used to compare incidences of ypT0 between groups, and Cox proportional hazards model was used to compare OS., Results: We identified 8464 patients. Median patient age was 63 years; 76% were male and 79% were white. ypT0 was observed in 16.1% of patients in the CXRT group and 6.6% in the chemotherapy group (p < 0.001). After propensity score matching, a total of 2408 patients were matched. CXRT was associated with a higher incidence of ypT0 (OR 2.28, 95% CI 1.76-2.95; p < 0.0001) and higher frequency of R0 resection (92 vs. 86%; p < 0.001). However, CXRT was not associated with longer OS (HR 1.03, 95% CI 0.92-1.15; p = 0.63). Safety profiles (30-day mortality, 30-day readmission, and length of hospital stay) were equivalent between groups., Conclusions: In this study of gastric cancer patients from the NCDB, CXRT was associated with a higher incidence of ypT0 and R0 resection compared with chemotherapy, although it was not associated with a longer OS.

We investigated the incidence trends for adenocarcinoma (AC) of the cervix among individuals belonging to the 20-44-year age group in the USA and compared the observed birth cohort incidence patterns with the changing patterns of exposure to potential risk factors associated with AC of the cervix, such as infection with human papillomavirus, use of diethylstilbestrol (DES), obesity, and use of oral contraceptives. Using data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program for 1973-2010, we conducted age-period-cohort modeling to evaluate birth cohort patterns on incidence trends of AC of the cervix over time. The increase in the incidence of AC of the cervix started among those born around the mid 1940s and accelerated up until around the mid 1960s birth cohort in both whites and all races combined, regardless of the assumed period slope. There was a suggestion that the incidence rates of AC of the cervix slowed down after the 1975 birth cohort in both whites and all races combined. DES was used by millions of women in the USA as a synthetic estrogen between the years 1940 and 1971. This time period of DES use among pregnant women parallels the observed birth cohort trends in our study, whereby a notable acceleration in the incidence rates of AC of the cervix was observed among those born in the mid 1940s through the mid 1975s. Thus, our results appear to suggest that in-utero exposure to DES might be at least partly responsible for the observed incidence pattern of AC of the cervix as observed in this study.

Inclusion of biospecimens in population-based studies is an integral part of understanding disease etiology, identifying biomarkers and developing prevention and treatment strategies. The Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial collected, processed and stored biospecimens from participants to create a biorepository of specimens which serves as a useful resource for a broad research community. PLCO collected blood samples from consented screening arm participants at six screening rounds and a buccal sample from consented control arm participants. In addition, formalin-fixed paraffin embedded tumor tissue specimens were collected for participants in both arms for selected cancer sites. Collection of biospecimens at multiple timepoints (i.e. serial samples) and prior to cancer diagnosis, paired with rich epidemiologic and screening data, makes the PLCO collection of biospecimens a uniquely valuable resource. As such, access to the PLCO biorepository is granted to investigators by a rigorous scientific review process and guided by a steering committee which is responsible for developing and implementing the biospecimen use policies. Here, we describe the procedures for biospecimen collection, processing, storage, requisition, and distribution, as well as data management employed in PLCO. We also provide examples of how the biospecimens have been used to advance cancer research and describe relevant lessons learned to help inform cohorts wishing to add or modify biospecimen collection.

Objectives: Hodgkin's lymphoma (HL) is one of the most common cancers among young adults. We investigated the time trends for HL among the 20-44 age group in the USA by gender to identify the potential factors accounting for the incidence trends., Methods: Using data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program for 1973-2010, we conducted age-period-cohort modeling to evaluate birth cohort patterns on incidence trends of HL over time., Results: For all races combined, the age-adjusted incidence patterns were similar to that of whites. The birth cohort patterns for whites and all races were similar, but the patterns differed according to gender. Specifically, except for the 1970-1975 birth cohort, all other birth cohorts showed an increasing birth cohort trend for females. Conversely, there was a decreasing cohort trend in males beginning in the 1960 birth cohort regardless of the assumptions of the period effect., Conclusion: The established risk factors for HL can seemingly not explain the gender disparities of the cohort pattern, which necessitates further analytical epidemiological studies to explore the risk factors for this disease with respect to potential differences by gender and by histological subtype.

Background: The behavioral and psychological symptoms associated with dementia (BPSD) can be burdensome to informal/family caregivers, negatively affecting mental health and expediting the institutionalization of patients. Because the dementia patient-caregiver relationship extends over long periods of time, it is useful to examine how BPSD impact caregiver depressive symptoms at varied stages of illness. The goal of this study was to assess the association of BPSD that occur during early stage dementia with subsequent caregiver depressive symptoms., Methods: Patients were followed from the early stages of dementia every six months for up to 12 years or until death (n = 160). Caregiver symptoms were assessed on average 4.5 years following patient's early dementia behaviors. A generalized estimating equation (GEE) extension of the logistic regression model was used to determine the association between informal caregiver depressive symptoms and BPSD symptoms that occurred at the earliest stages dementia, including those persistent during the first year of dementia diagnosis., Results: BPSD were common in early dementia. None of the individual symptoms observed during the first year of early stage dementia significantly impacted subsequent caregiver depressive symptoms. Only patient agitation/aggression was associated with subsequent caregiver depressive symptoms (OR = 1.76; 95% CI = 1.04-2.97) after controlling for concurrent BPSD, although not in fully adjusted models., Conclusions: Persistent agitation/aggression early in dementia diagnosis may be associated with subsequent depressive symptoms in caregivers. Future longitudinal analyses of the dementia caregiving relationship should continue to examine the negative impact of persistent agitation/aggression in the diagnosis of early stage dementia on caregivers.

Objectives: There is evidence indicating that the trends in colorectal cancer (CRC) incidence rates in the United States differ according to CRC subsites, including for ascending cancer which has shown a different pattern from the overall trends. We investigated the time trends for ascending and descending colon cancer in the United States by race and gender to identify the specific components that may account for the incidence trends., Methods: Using data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program for 1973-2008, we conducted age-period-cohort modeling to evaluate birth cohort patterns and evaluate age-period-cohort effects on incidence trends of colon cancer over time., Results: A clear birth cohort pattern was observed for both ascending and descending colon cancer, and the incidence rates of ascending colon cancer in the more recent birth cohorts were higher compared to earlier cohorts particularly for black males and females. This increase was most obvious in the younger age groups and appeared to accelerate, especially for black females. For descending colon cancer, the study suggested an increase in the birth cohort slope in the later birth cohorts for all gender and race groups, after a period of decline in earlier birth cohorts., Conclusion: The increase in incidence rates of both ascending and descending colon cancer in more recent birth cohorts for blacks suggests the need for targeted public health strategies to increase CRC screening. Further, additional etiological studies are warranted to evaluate factors responsible for the observed trends in more recent birth cohorts, including differences by subsites, race, and/or gender.

Objective: To test the hypothesis that bladder cancer is a heterogeneous disease., Patients and Methods: We examined the temporal trends of bladder cancer by histological subtype and by disease stage and grade using the National Cancer Institute's Surveillance, Epidemiology, and End Results data collected in 1973-2007., Results: The age-adjusted incidence rates of bladder cancer showed a slight decrease from 1973 to 2007 (annual percentage change [APC] = -0.4, P < 0.05). Although the age-adjusted incidence rates of non-papillary transitional cell carcinoma decreased by about 53% from 7.9 per 100,000 in 1973 to 3.7 per 100,000 in 2007 (APC = -2.2, P < 0.05), the age-adjusted incidence rates of papillary transitional cell carcinoma increased by about 56% from 6.8 per 100,000 in 1973 to 10.6 per 100,000 in 2007 (APC = 0.5, P < 0.05). Among other rare histological subtypes, except for small cell carcinoma which showed a slightly rising trend, squamous cell carcinoma, adenocarcinoma and others all presented a decreasing trend. Similar patterns were found for different stages (localized, regional and distant), but a dramatic increasing trend of grade IV was found between 1998 and 2007 when a corresponding decreasing trend was shown for grades I, II and III., Conclusion: The results support the hypothesis that bladder cancer is a heterogeneous disease and taking disease heterogeneity into consideration in future epidemiological studies is essential., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

The need and opportunity to discover therapeutics for rare or orphan diseases are enormous. Due to limited prevalence and/or commercial potential, of the approximately 6000 orphan diseases (defined by the FDA Orphan Drug Act as <200 000 US prevalence), only a small fraction (5%) is of interest to the biopharmaceutical industry. The fact that drug development is complicated, time-consuming and expensive with extremely low success rates only adds to the low rate of therapeutics available for orphan diseases. An alternative and efficient strategy to boost the discovery of orphan disease therapeutics is to find connections between an existing drug product and orphan disease. Drug Repositioning or Drug Repurposing--finding a new indication for a drug--is one way to maximize the potential of a drug. The advantages of this approach are manifold, but rational drug repositioning for orphan diseases is not trivial and poses several formidable challenges--pharmacologically and computationally. Most of the repositioned drugs currently in the market are the result of serendipity. One reason the connection between drug candidates and their potential new applications are not identified in an earlier or more systematic fashion is that the underlying mechanism 'connecting' them is either very intricate and unknown or indirect or dispersed and buried in an ever-increasing sea of information, much of which is emerging only recently and therefore is not well organized. In this study, we will review some of these issues and the current methodologies adopted or proposed to overcome them and translate chemical and biological discoveries into safe and effective orphan disease therapeutics.

Surfactant modified zeolites (SMZs) have the capacity to target various types of water contaminants at relatively low cost and thus are being increasingly considered for use in improving water quality. It is important to know the surfactant loading performance of a zeolite before it is put into application. In this work we compare the loading capacity of a surfactant, hexadecyltrimethylammonium bromide (HDTMA-Br), onto four natural zeolites obtained from specific locations in the USA, Croatia, China, and Australia. The surfactant loading is examined using thermogravimetric analysis (TGA), Fourier transform infrared (FT-IR) spectroscopy, and Raman spectroscopy. We then compare the resulting SMZs performance in removing nitrate from water. Results show that TGA is useful to determine the HDTMA loading capacity on natural zeolites. It is also useful to distinguish between a HDTMA bi-layer and a HDTMA mono-layer on the SMZ surface, which has not been previously reported in the literature. TGA results infer that HDTMA (bi-layer) loading decreases in the order of US zeolite>Croatian zeolite>Chinese zeolite>Australian zeolite. This order of loading explains variation in performance of nitrate removal between the four SMZs. The SMZs remove 8-18 times more nitrate than the raw zeolites. SMZs prepared from the selected US and Croatian zeolites were more efficient in nitrate removal than the two zeolites commercially obtained from Australia and China., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Sweet sorghum has the potential to become a versatile feedstock for large-scale bioenergy production given its sugar from stem juice, cellulose/hemicellulose from stalks, and starch from grain. However, for researchers to maximize its feedstock potential a first step includes additional evaluations of the 2,180 accessions with varied origins in the US historic sweet sorghum collection. To assess genetic diversity of this collection for bioenergy breeding and population structure for association mapping, we selected 96 accessions and genotyped them with 95 simple sequence repeat markers. Subsequent genetic diversity and population structure analysis methods identified four subpopulations in this panel, which correlated well with the geographic locations where these accessions originated or were collected. Model comparisons for three quantitative traits revealed different levels of population structure effects on flowering time, plant height, and brix. Our results suggest that diverse germplasm accessions curated from different geographical regions should be considered for plant breeding programs to develop sweet sorghum cultivars or hybrids, and that this sweet sorghum panel can be further explored for association mapping.

Background: The incidence of papillary thyroid cancer has been reported to be increasing during the past three decades, with a 65-126% increase between 1975 and 2004. The reason for the increase is currently unknown. This study examined the incidence pattern of papillary thyroid cancer in the United States, and evaluated the components of birth cohort (defined based on year of birth), time period, and age as determinants of the observed time trend of the disease., Methods: Using the data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program for 1973-2004, we conducted both univariate analysis and age-period-cohort modeling to evaluate birth cohort patterns and evaluate age, period, and cohort effects on incidence trends over time., Results: The increasing incidence showed a clear birth cohort pattern for both men and women. The results from age-period-cohort modeling showed that, while period effect appeared to have had an impact on the observed incidence trends, birth cohort effect may also explain part of the increasing trend in papillary thyroid carcinoma during the study period, especially among women., Conclusion: While a period effect that is likely due to advancements in diagnostic techniques and increased medical detection of small thyroid nodules may explain some of the observed increase in the incidence, we speculate that birth cohort-related changes in environmental exposures (such as increased exposure to diagnostic X-rays and polybrominated diphenyl ethers) have also contributed to the observed increase in papillary thyroid cancer during the past decades.

Aim: While clinical endpoints provide important information on the efficacy of treatment in controlled conditions, they often are not relevant to decision makers trying to gauge the potential economic impact or value of new treatments. Therefore, it is often necessary to translate changes in cognition, function or behavior into changes in cost or other measures, which can be problematic if not conducted in a transparent manner. The Dependence Scale (DS), which measures the level of assistance a patient requires due to AD-related deficits, may provide a useful measure of the impact of AD progression in a way that is relevant to patients, providers and payers, by linking clinical endpoints to estimates of cost effectiveness or value. The aim of this analysis was to test the association of the DS to clinical endpoints and AD-related costs., Method: The relationship between DS score and other endpoints was explored using the Predictors Study, a large, multi-center cohort of patients with probable AD followed annually for four years. Enrollment required a modified Mini-Mental State Examination (mMMS) score >or= 30, equivalent to a score of approximately >or= 16 on the MMSE. DS summated scores (range: 0- 15) were compared to measures of cognition (MMSE), function (Blessed Dementia Rating Scale, BDRS, 0-17), behavior, extrapyramidal symptoms (EPS), and psychotic symptoms (illusions, delusions or hallucinations). Also, estimates for total cost (sum of direct medical cost, direct non-medical cost, and cost of informal caregivers' time) were compared to DS scores., Results: For the 172 patients in the analysis, mean baseline scores were: DS: 5.2 (SD: 2.0), MMSE: 23.0 (SD: 3.5), BDRS: 2.9 (SD: 1.3), EPS: 10.8%, behavior: 28.9% psychotic symptoms: 21.1%. After 4 years, mean scores were: DS: 8.9 (SD: 2.9), MMSE: 17.2 (SD: 4.7), BDRS: 5.2 (SD: 1.4), EPS: 37.5%, behavior: 60.0%, psychotic symptoms: 46.7%. At baseline, DS scores were significantly correlated with MMSE (r=-0.299, p < 0.01), BDRS (r=0.610, p < 0.01), behavior (r=.2633, p=0.0005), EPS (r=0.1910, p=0.0137) and psychotic symptoms (r=0.253, p < 0.01); and at 4-year follow-up, DS scores were significantly correlated with MMSE (r=-0.3705, p=0.017), BDRS (r=0.6982, p < 0.001). Correlations between DS and behavior (-0.0085, p=0.96), EPS (r=0.3824, p=0.0794), psychotic symptoms (r=0.130, ns) were not statistically significant at follow-up. DS scores were also significantly correlated with total costs at baseline (r=0.2615, p=0.0003) and follow-up (r=0.3359, p=0.0318)., Discussion: AD is associated with deficits in cognition, function and behavior, thus it is imperative that these constructs are assessed in trials of AD treatment. However, assessing multiple endpoints can lead to confusion for decision makers if treatments do not impact all endpoints similarly, especially if the measures are not used typically in practice. One potential method for translating these deficits into a more meaningful outcome would be to identify a separate construct, one that takes a broader view of the overall impact of the disease. Patient dependence, as measured by the DS, would appear to be a reasonable choice - it is associated with the three clinical endpoints, as well as measures of cost (medical and informal), thereby providing a bridge between measures of clinical efficacy and value in a single, transparent measure.

With the incidence and prevalence of lymphoid neoplasms increasing, a comparison of survival patterns by subtype may provide critical clues for improving the disease burden. We conducted a comprehensive survival analysis for 254,702 lymphoid neoplasm cases diagnosed during 1973-2003 at 17 Surveillance, Epidemiology and End Results (SEER) registries according to the World Health Organization (WHO) classification introduced in 2001. The best survival was observed for Hodgkin lymphoma among young patients, and the worst survival was observed among cases with plasma cell neoplasms, particularly plasma cell leukemia, in all racial groups. Being diagnosed at a lower stage without B-symptoms and a non-HIV/AIDS status favored survival for each type of lymphoma. Males typically had lower survival rates than females, but the opposite was observed for Burkitt lymphoma/leukemia among non-whites and multiple myeloma among non-Hispanic whites. Non-Hispanic whites typically had higher survival rates than blacks with the exception of multiple myeloma. Survival rates decline with age at diagnosis among elders, while the patterns were diverse by subtype among younger cases. The differences in lymphoma survival patterns suggest that distinct prognostic risk factors impact survival by subtype and that future research and public health interventions should address racial disparities in lymphoma survivorship.

The monitoring of environmental radiation has been carried out across the United States by the U.S. Environmental Protection Agency's RadNet (formerly the Environmental Radiation Ambient Monitoring System, ERAMS) and the Global Network Program (GNP) of the Environmental Measurements Laboratory (EML), and in the People's Republic of China (PRC) by their National Radioactivity Contamination Monitoring System (NRCMS). It is expected that an awareness of the similarities and differences in the structure and operation of these programs will prove helpful to both countries and perhaps others as they continue to develop their monitoring capabilities.

Objectives: To estimate long-term trajectories of direct cost of caring for patients with Alzheimer disease (AD) and examine the effects of patients' characteristics on cost longitudinally., Methods: The sample is drawn from the Predictors Study, a large, multicenter cohort of patients with probable AD, prospectively followed up annually for up to 7 years in three university-based AD centers in the United States. Random effects models estimated the effects of patients' clinical and sociodemographic characteristics on direct cost of care. Direct cost included cost associated with medical and nonmedical care. Clinical characteristics included cognitive status (measured by Mini-Mental State Examination), functional capacity (measured by Blessed Dementia Rating Scale [BDRS]), psychotic symptoms, behavioral problems, depressive symptoms, extrapyramidal signs, and comorbidities. The model also controlled for patients' sex, age, and living arrangements., Results: Total direct cost increased from approximately 9,239 dollars per patient per year at baseline, when all patients were at the early stages of the disease, to 19,925 dollars by year 4. After controlling for other variables, a one-point increase in the BDRS score increased total direct cost by 7.7%. One more comorbid condition increased total direct cost by 14.3%. Total direct cost was 20.8% lower for patients living at home compared with those living in an institutional setting., Conclusions: Total direct cost of caring for patients with Alzheimer disease increased substantially over time. Much of the cost increases were explained by patients' clinical and demographic variables. Comorbidities and functional capacity were associated with higher direct cost over time.

Background: Few studies on cost of caring for patients with Alzheimer disease (AD) have simultaneously considered multiple dimensions of disease costs and detailed clinical characteristics., Objective: To estimate empirically the incremental effects of patients' clinical characteristics on disease costs., Methods: Data are derived from the baseline visit of 180 patients in the Predictors Study, a large, multicenter cohort of patients with probable AD followed from early stages of the disease. All patients initially lived at home, in retirement homes, or in assisted living facilities. Costs of direct medical care included hospitalizations, outpatient treatment and procedures, assistive devices, and medications. Costs of direct nonmedical care included home health aides, respite care, and adult day care. Indirect costs were measured by caregiving time. Patients' clinical characteristics included cognitive status, functional capacity, psychotic symptoms, behavioral problems, depressive symptoms, extrapyramidal signs, comorbidities, and duration of illness., Results: A 1-point increase in the Blessed Dementia Rating Scale score was associated with a $1,411 increase in direct medical costs and a $2,718 increase in unpaid caregiving costs. Direct medical costs also were $3,777 higher among subjects with depressive symptoms than among those who were not depressed., Conclusions: Medical care costs and unpaid caregiving costs relate differently to patients' clinical characteristics. Poorer functional status is associated with higher medical care costs and unpaid caregiving costs. Interventions may be particularly useful if targeted in the areas of basic and instrumental activities of daily living.

Mineralogical compositions and their spatial distributions are important initial conditions for reactive transport modeling. However, popular Kd-based "reactive" transport models only require contaminant concentrations in the pore fluids as initial conditions, and minerals implicitly represent infinite sources and sinks in these models. That situation results in a general neglect of mineralogical characterization in site investigations. This study uses a coupled multi-component reactive mass transport model to predict the natural attenuation of a ground water plume at a uranium mill tailings site in western USA. Numerous ground water geochemistry data are available at this site, but mineralogical data are sketchy. Even given the well-defined pore fluid chemistry, variations of secondary mineral species and mineral abundances in the aquifer resulted in significantly different modeling outcomes. Results show that the amount of calcite in the aquifer determines the distances of plume migration. The possible presence of jurbanite, an aluminum sulfate phase, can store acidity temporarily but cause more severe contamination on a later date. The surfaces of iron oxyhydroxides can store significant amounts of sulfate and protons and serve as a second source for prolonged contamination. These simulations under field conditions illustrate that mineralogical compositions are an essential requirement for accurate prediction of contaminant fate and transport.

Objectives: The purpose of the study was to examine on a national level the informal costs of caring for elderly community-dwelling male veterans with dementia by female caregivers and the relationships between informal costs and disease severity, and between informal costs and dementia problem behaviors., Methods: Female primary caregivers were drawn from the first wave (N = 2043) of the National Longitudinal Caregiver Study, a survey of informal caregivers of elderly male veterans diagnosed with probable Alzheimer's disease or vascular dementia. Cost measures include the following four items: value of caregiving time, caregiver's lost income, out-of-pocket expenditures for formal caregiving services, and caregiver's excess health costs. Disease severity was indexed by the number of impairments in activities of daily living. Patient's problem behaviors were measured using the Behavior Rating Scale-Dementia., Results: The annual cost of providing informal care to elderly community-dwelling veterans with dementia was estimated to be $18,385 per patient in 1998. The larger components of this cost are caregiving time ($6,295) and caregiver's lost earnings ($10,709). All aspects of costs increase with disease severity and problem behavior. Most of this cost increase derives from the increased caregiving time required for the provision of physical care., Discussion: This study provides a comprehensive estimate of the excess costs that result from providing informal dementia care in the community. Unlike previous studies, our estimates excluded costs that caregivers would have incurred if they had not been caregivers. Therefore, results reported here reflect only costs due to informal dementia care.