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Background: Vadadustat is an oral hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor, a class of drugs that stabilize HIF and stimulate erythropoietin and red-cell production.Methods: In two phase 3, randomized, open-label, active-controlled, noninferiority trials, we compared vadadustat with the erythropoiesis-stimulating agent (ESA) darbepoetin alfa in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) not previously treated with an ESA who had a hemoglobin concentration of less than 10 g per deciliter and in patients with ESA-treated NDD-CKD and a hemoglobin concentration of 8 to 11 g per deciliter (in the United States) or 9 to 12 g per deciliter (in other countries). The primary safety end point, assessed in a time-to-event analysis, was the first major adverse cardiovascular event (MACE; a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke), pooled across the two trials. Secondary safety end points included expanded MACE (MACE plus hospitalization for either heart failure or a thromboembolic event). The primary and key secondary efficacy end points in each trial were the mean change in hemoglobin concentration from baseline during two evaluation periods: weeks 24 through 36 and weeks 40 through 52.Results: A total of 1751 patients with ESA-untreated NDD-CKD and 1725 with ESA-treated NDD-CKD underwent randomization in the two trials. In the pooled analysis, in which 1739 patients received vadadustat and 1732 received darbepoetin alfa, the hazard ratio for MACE was 1.17 (95% confidence interval [CI], 1.01 to 1.36), which did not meet the prespecified noninferiority margin of 1.25. The mean between-group differences in the change in the hemoglobin concentration at weeks 24 through 36 were 0.05 g per deciliter (95% CI, -0.04 to 0.15) in the trial involving ESA-untreated patients and -0.01 g per deciliter (95% CI, -0.09 to 0.07) in the trial involving ESA-treated patients, which met the prespecified noninferiority margin of -0.75 g per deciliter.Conclusions: Vadadustat, as compared with darbepoetin alfa, met the prespecified noninferiority criterion for hematologic efficacy but not the prespecified noninferiority criterion for cardiovascular safety in patients with NDD-CKD. (Funded by Akebia Therapeutics and Otsuka Pharmaceutical; PRO2TECT ClinicalTrials.gov numbers, NCT02648347 and NCT02680574.). [ABSTRACT FROM AUTHOR]

Background Olaparib is a poly(ADP-ribose) polymerase inhibitor and cediranib is an oral anti-angiogenic. In the primary analysis of this phase II study, combination cediranib/olaparib improved progression-free survival (PFS) compared with olaparib alone in relapsed platinum-sensitive ovarian cancer. This updated analysis was conducted to characterize overall survival (OS) and update PFS outcomes. Patients and methods Ninety patients were enrolled to this randomized, open-label, phase II study between October 2011 and June 2013 across nine United States-based academic centers. Data cut-off was 21 December 2016, with a median follow-up of 46 months. Participants had relapsed platinum-sensitive ovarian cancer of high-grade serous or endometrioid histology or had a deleterious germline BRCA1 / 2 mutation (g BRCA m). Participants were randomized to receive olaparib capsules 400 mg twice daily or cediranib 30 mg daily and olaparib capsules 200 mg twice daily until disease progression. Results In this updated analysis, median PFS remained significantly longer with cediranib/olaparib compared with olaparib alone (16.5 versus 8.2 months, hazard ratio 0.50; P  = 0.007). Subset analyses within stratum defined by BRCA status demonstrated statistically significant improvement in PFS (23.7 versus 5.7 months, P  = 0.002) and OS (37.8 versus 23.0 months, P  = 0.047) in g BRCA wild-type/unknown patients, although OS was not statistically different in the overall study population (44.2 versus 33.3 months, hazard ratio 0.64; P  = 0.11). PFS and OS appeared similar between the two arms in g BRCA m patients. The most common CTCAE grade 3/4 adverse events with cediranib/olaparib remained fatigue, diarrhea, and hypertension. Conclusions Combination cediranib/olaparib significantly extends PFS compared with olaparib alone in relapsed platinum-sensitive ovarian cancer. Subset analyses suggest this margin of benefit is driven by PFS prolongation in patients without g BRCA m. OS was also significantly increased by the cediranib/olaparib combination in this subset of patients. Additional studies of this combination are ongoing and should incorporate analyses based upon BRCA status. Trial Registration Clinicaltrials.gov Identifier NCT0111648 [ABSTRACT FROM AUTHOR]

Objectives: Tested the prospective relationship of a resilient personality prototype determined prior to disability onset to well-being among persons with and without debilitating functional impairments nine to 10 years later. A resilient profile was expected to predict well-being through its beneficial associations with positive affect, perceived control and social support., Design: Longitudinal, prospective observation study., Methods: Data obtained from participants with no functional impairments at the first assessment of the Midlife in the United States (MIDUS) project and who participated in the second survey (1147 men, 985 women at Time 1). Cluster analysis was used to create personality profiles at the first time point. Differences between resilient and non-resilient individuals were examined. A structural equation model (SEM) tested the prospective effects of resilience on positive affect, perceived control and social support to well-being., Results: A resilient personality profile was identified, as expected (n = 877). Individuals with a resilient personality prototype reported higher social support, positive affect, perceived control, life satisfaction and self-rated health at both measurement occasions than the non-resilient group. The SEM revealed that a resilient prototype operated through the three mediating variables to prospectively predict life satisfaction, and through social support and positive affect to predict self-rated health. These effects were independent of gender and disability severity., Conclusions: A resilient personality profile prospectively operates through positive affect, perceived control and social support to predict well-being following the onset of debilitating impairments. The theoretical and clinical implications of these findings are discussed, and limitations are considered., (© 2025 British Psychological Society.)

Background: The prevalence of type 2 diabetes mellitus (T2DM) remains high and biomarkers related to T2DM are needed to be investigated. This study aimed to investigate the association between neutrophil percentage-to-albumin ratio (NPAR) with all-cause mortality and the risk of cardiovascular disease (CVD) mortality in community-dwelling individuals with T2DM., Methods: This prospective cohort study included 3602 adults aged 20 or above who were diagnosed with diabetes by the American Diabetes Association criteria in the US National Health and Nutrition Examination Survey (NHANES) database from 1999 to 2016, and followed up until 2019. Multivariable Cox proportional hazards regression models were utilized to determine the relationship between NPAR with all-cause mortality and cardiovascular disease (CVD) mortality. Restricted cubic spline regression analyses were employed to explore the nonlinear relationship between NPAR and cardiovascular disease (CVD) mortality. The assessment of nonlinearity was conducted using the likelihood ratio test., Results: After adjustment, the risk ratio for all-cause mortality in the highest NPAR group (≥ 15.40) compared to the lowest serum NPAR reference group (< 13.30) was 1.62 (95% CI, 1.36, 1.94) with P values < 0.001. Nevertheless, the risk ratio for cardiovascular disease (CVD) mortality in the highest NPAR group (≥ 15.40) versus the lowest serum NPAR reference group (< 13.30) was 1.41 (95% CI, 0.99, 2.00) with a P value of 0.06. Among patients with T2DM, serum NPAR levels exhibited a nonlinear correlation with both CVD mortality risk and all-cause mortality risk, with P values < 0.001 for both., Conclusions: This study identified a significant association between elevated levels of the neutrophil percentage-to-albumin ratio (NPAR) and an increased risk of all-cause mortality among individuals with type 2 diabetes mellitus (T2DM). Conversely, no correlation was found between NPAR levels and CVD mortality., Competing Interests: Declarations. Ethics approval and consent to participate: The National Center for Health Statistics’ Research Ethics Review Board reviewed and approved all data collection protocols. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

This article profiles 13 newly approved nitrogen-containing heterocyclic drugs by the U.S. Food and Drug Administration (FDA) in 2023. These drugs target a variety of therapeutic areas including proteinuria in patients with IgA nephropathy, migraine in adults, Rett syndrome, PI3Kδ syndrome, vasomotor symptoms, alopecia areata, acute myeloid leukemia, postpartum depression, myelofibrosis, and various cancer and tumor types. The molecular structures of these approved drugs feature common aromatic heterocyclic compounds such as pyrrole, imidazole, pyrazole, isoxazole, pyridine, and pyrimidine, as well as aliphatic heterocyclic compounds like caprolactam, piperazine, and piperidine. Some compounds also contain multiple heteroatoms like 1,2,4-thiadiazole and 1,2,4-triazole. The article provides a comprehensive overview of the bioactivity spectrum, medicinal chemistry discovery, and synthetic methods for each compound., Competing Interests: Declaration of competing interest We have no known competing finan-cial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Purpose: Recruit and sequence breast cancer subjects in Guatemalan and US Hispanic populations. Identify optimum strategies to recruit Latin American and Hispanic women into genetic studies of breast cancer., Methods: We used targeted gene sequencing to identify pathogenic variants in 19 familial breast cancer susceptibility genes in DNA from unselected Hispanic breast cancer cases in the US and Guatemala. Recruitment across the US was achieved through community-based strategies. In addition, we obtained patients receiving cancer treatment at major hospitals in Texas and Guatemala., Results: We recruited 287 Hispanic US women, 38 (13%) from community-based and 249 (87%) from hospital-based strategies. In addition, we ascertained 801 Guatemalan women using hospital-based recruitment. In our experience, a hospital-based approach was more efficient than community-based recruitment. In this study, we sequenced 103 US and 137 Guatemalan women and found 11 and 10 pathogenic variants, respectively. The most frequently mutated genes were BRCA1, BRCA2, CHEK2, and ATM. In addition, an analysis of 287 US Hispanic patients with pathology reports showed a significantly higher percentage of triple-negative disease in patients with pathogenic variants (41% vs. 15%). Finally, an analysis of mammography usage in 801 Guatemalan patients found reduced screening in women with a lower socioeconomic status (p < 0.001)., Conclusion: Guatemalan and US Hispanic women have rates of hereditary breast cancer pathogenic variants similar to other populations and are more likely to have early age at diagnosis, a family history, and a more aggressive disease. Patient recruitment was higher using hospital-based versus community enrollment. This data supports genetic testing in breast cancer patients to reduce breast cancer mortality in Hispanic women., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objective: To investigate the association between blood urea nitrogen (BUN) levels and diabetic retinopathy (DR) in adults with diabetes mellitus (DM)., Methods: Seven cycles of cross-sectional population information acquired from NHANES(national health and nutrition examination surveys) 2005-2018 were collected, from which a sample of diabetic adults was screened and separated into two groups based on whether or not they had DR, followed by weighted multivariate regression analysis. This study collected a complete set of demographic, biological, and sociological risk factor indicators for DR. Demographic risk factors comprised age, gender, and ethnicity, while biological risk factors included blood count, blood pressure, BMI, waist circumference, and glycated hemoglobin. Sociological risk factors included education level, deprivation index, smoking status, and alcohol consumption., Results: The multiple regression model revealed a significant connection between BUN levels and DR [odds ratio =1.04, 95% confidence interval (1.03-1.05), p -value <0.0001],accounting for numerous variables. After equating BUN levels into four groups, multiple regression modeling showed the highest quartile (BUN>20 mg/dl) was 2.22 times more likely to develop DR than the lowest quartile [odds ratio =2.22, 95% confidence interval (1.69-2.93), p - value <0.0001]. Subgroup analyses revealed that gender, race, diabetes subtype, and duration of diabetes had a regulating effect on the relationship between BUN and DR., Conclusion: BUN levels were related with an increased prevalence of DR, particularly in individuals with BUN >20 mg/dl. These findings highlight the significance of BUN level in assessing the risk of DR., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Du and Luo.)

Objective: The aim of the work described here was to develop and validate a predictive nomogram based on combined image features of gray-scale ultrasonography (US), elastosonography (ES) and contrast-enhanced US (CEUS) to differentiate malignant from benign American College of Radiology Thyroid Imaging, Reporting and Data System (ACR TI-RADS) 3-5 thyroid nodules., Methods: Among 2767 thyroid nodules scanned by CEUS in Xijing Hospital between April 2014 and November 2018, 669 nodules classified as ACR TI-RADS 3-5 were included, with confirmed diagnosis and ES examination. Four hundred fifty-five nodules were set as a training cohort and 214 as a validation cohort. Images were categorized as gray-scale US ACR TI-RADS 3, TI-RADS 4 and TI-RADS 5; ES patterns of ES-1 and ES-2; and CEUS patterns of either heterogeneous hypo-enhancement, concentric hypo-enhancement, homogeneous hyper-/iso-enhancement, no perfusion, hypo-enhancement with sharp margin, island-like enhancement or ring-like enhancement. On the basis of multivariate logistic regression analysis, a predictive nomogram model was developed and validated by receiver operating characteristic curve analysis., Results: In the training cohort, ACR TI-RADS 4 and 5, ES-2, heterogeneous hypo-enhancement, concentric hypo-enhancement and homogeneous hyper-/iso-enhancement were selected as predictors of malignancy by univariate logistic regression analysis. A predictive nomogram (combining indices of ACR TI-RADS, ES and CEUS) indicated excellent predictive ability for differentiating malignant from benign lesions in the training cohort: area under the receiver operating characteristic curve (AUC) = 0.93, 95% confidence interval (CI): 0.90-0.95. The prediction nomogram model was determined to have a sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 0.84, 0.88, 0.91 and 0.81. In the validation cohort, the AUC of the prediction nomogram model was significantly higher than those of the single modalities (p < 0.005) . The AUCs of the validation cohort were 0.93 (95% CI: 0.89-0.96) and 0.93 (95% CI: 0.89-0.97), respectively, for senior and junior radiologists. The prediction nomogram model has a sensitivity, specificity, PPV and NPV of 0.86, 0.87, 0.87 and 0.86., Conclusion: A predictive nomogram model combining ACR TI-RADS, ES and CEUS exhibited potential clinical utility in differentiating malignant from benign ACR TI-RADS 3-5 thyroid nodules., Competing Interests: Conflict of interest The authors declare no conflicts of interest., (Copyright © 2023 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Objectives: Healthcare-associated infections (HAIs) represent a major threat to patient safety and are associated with significant economic burden. Calculating the costs attributable to HAIs is challenging given the various sources of bias. Although HAIs as a reasonably preventable medical harm should have been closely linked to medical insurance incentives, there was little linkage between HAIs and medicare in western China owing to the lack of economic evaluation data. The present study aimed to generate estimates of the attributable costs associated with HAIs and the magnitude of costs growth., Methods: In this cohort study designed horizontally and vertically from 2016 to 2022, we compared outcomes of randomly sampling patients with HAIs and individually matched patients without HAIs in two cohorts at a 6-year interval at 34 hospitals in western China. The primary outcome was the direct medical cost for the entire hospital stay, converted to US dollars ($ for the benchmark year), discounted at 3% annually, and estimated separately in the full analysis set (FAS) and the per protocol set (PPS). We used multiple linear regression to adjust the discounted costs and to assess subgroups effects within each cohort. We nested a dynamic vertical comparison of costs attributable to HAIs between the front and rear cohorts., Results: A total of 230 patients with HAIs in 2016 and 204 patients with HAIs in 2022 were enrolled. After a 1:1 match, all 431 pairs were recruited as FAS, of which 332 pairs as PPS met all matching restrictions. Compared to the 2016 cohort in FAS, the patients with HAIs in 2022 had a significantly older age (64.40 ± 16.45 years), higher repeat hospitalization rate (65 [32.02%] of 203), and lower immune function (69 [33.99%] of 203). The discounted costs and adjusted-discounted costs for patients with HAIs in the 2022 cohort were found to be significantly higher than those of patients without HAIs (discounted costs: $5484.60 [IQR 8426.03] vs $2554.04(4530.82), P < 0.001; adjusted-discounted costs: $5235.90 [3772.12] vs $3040.21(1823.36), P < 0.001, respectively), and also higher than those of patients with HAIs in the 2016 cohort (discounted costs: $5484.60 [8426.03] vs $3553.00 [6127.79], P < 0.001; adjusted-discounted costs: $5235.90 [3772.12] vs $3703.82 [3159.14], P < 0.001, respectively). In vertical comparison of PPS, the incremental costs of the 2022 cohort are 1.48 times higher than those of the 2016 cohort ($964.63(4076.15) vs $652.43 [2533.44], P = 0.084)., Conclusions: This meticulously designed study in western China has successfully and accurately examined the economic burden attributable to HAIs. Their rapidly increasing tendency poses a serious challenge to patients, hospitals, and the medical insurance. A closer linkage between HAIs and ongoing motivating system changes is urgently needed in western China., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The US confronted a "triple-demic" of influenza, respiratory syncytial virus (RSV), and COVID-19 in the winter of 2022, leading to increased respiratory infections and a higher demand for medical supplies. It is urgent to analyze these epidemics and their spatial-temporal co-occurrence, identifying hotspots and informing public health strategies., Methods: We employed retrospective and prospective space-time scan statistics to assess the situations of COVID-19, influenza, and RSV in 51 US states from October 2021 to February 2022, and from October 2022 to February 2023, respectively. This enabled monitoring of spatiotemporal variations for each epidemic individually and collectively., Results: Compared to winter 2021, COVID-19 cases decreased while influenza and RSV infections significantly increased in winter 2022. We found a high-risk cluster of influenza and COVID-19 (not all three) in winter 2021. In late November 2022, a large high-risk cluster of triple-demic emerged in the central US. The number of states at high risk for multiple epidemics increased from 15 in October 2022 to 21 in January 2023., Conclusions: Our study offers a novel spatiotemporal approach that combines both univariate and multivariate surveillance, as well as retrospective and prospective analyses. This approach offers a more comprehensive and timely understanding of how the co-occurrence of COVID-19, influenza, and RSV impacts various regions within the United States. Our findings assist in tailor-made strategies to mitigate the effects of these respiratory infections., (© 2023. The Author(s).)

Despite the success of health programs conducted within African American (AA) churches, research has been limited in understanding the facilitators and barriers of conducting adult health programs in churches led by female AA pastors/leaders. In addition, research has yet to analyze the effect of policy on these church-based health programs. Thus, this pilot study's objective is to use the socio-ecological model (SEM) as a framework to explore female AA pastors' and church leaders' perspectives, in the U.S., on facilitators and barriers that exist when conducting adult health programs within their congregations. Using snowball sampling to recruit AA female church leaders and pastors (n = 6), semi-structured interviews were conducted with study participants. Data were then transcribed and analyzed using First and Second Cycle coding to identify themes. Nine themes emerged from the data, and after stratifying the themes according to the SEM, this study found that facilitators and barriers exist at the intrapersonal, organizational, community, and policy levels of the SEM. It is important for these factors to be considered to ensure that health programs led by AA women pastors/leaders are successful within AA churches. Study limitations and the need for further research are also noted., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This data article presents data from the China Migrants Dynamic Survey (CMDS), a multi-wave, large-scale national cross-sectional survey of China's internal migrants from 2009 to 2018. The CMDS is an annual questionnaire survey conducted by the former National Health and Family Planning Commission (NHFPC) of the People's Republic of China. The respondents included in this survey are internal migrants over 15 years old. The sample was drawn from the China Migrant Population Information System, using multi-stage stratified sampling method and the probability proportional-to-size (PPS) cluster sampling strategy. Between 2009 and 2018, there were 1,527,650 internal migrants from 23 provinces, 5 autonomous regions and 4 municipalities participated in the surveys. The survey tools were a series of self-designed questionnaires with high inheritance and consistency designed and implemented by the NHFPC. The questionnaires mainly contain basic information of the respondents and their family members, migration status, healthcare or health behaviors, public health service utilization, social insurance, social integration, and family planning. The dataset is currently the most widely used survey data on China's internal migrants, offering information on migration patterns, healthcare and health behaviors, use of public health services, access to social security, social integration, and family planning, which are valuable for health planning, health decision-making, and health equity research.

Asian Indians were the first South Asians to immigrate to the United States in the late 1800s and are currently the largest ethnic group of South Asians living in the United States. Despite this the literature on perceived ethnic and racial discrimination experiences among this group is relatively understudied. The documented experiences of Asian Indians who either recently immigrated from India or were born and raised in America pose an important question: what are the experiences of perceived discrimination among Asian Indians living in America, particularly among younger populations who are continuing to develop their racial and ethnic identities? The current study utilized phenomenological methodology to explore the experiences of nine Asian Indian American adolescents' (ages 12-17 years). Data were collected via semi-structured interviews to assess participants' experiences of ethnic and racial discrimination and identity development. Thematic analysis was used to identify themes and subthemes among the participants' responses. Asian Indian adolescents living in the United States report experiencing discrimination at a young age. It is also evident that Asian Indian youth experience significant challenges when developing their sense of ethnic and racial identity while living within the United States. Findings document the racial and ethnic discrimination that Asian Indian adolescents living in the United States may experience from a young age. Importantly, these discrimination experiences are occurring as Asian Indian adolescents are developing their racial and ethnic identities. This study provides insight for future research, which is necessary to fully understand the experiences of Asian Indian adolescents., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Unni, Blake, Salter, Luo and Liew.)

Chimeric antigen receptor T (CAR-T) cells targeting CD19 have achieved great clinical responses in patients with relapsed or refractory (R/R) acute B lymphoblastic leukemia. However, severe adverse events such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome restrict it to further application. Tocilizumab is the corner stone for the treatment of severe CRS. It has been used to treat mild CRS in recent years, whereas some statistical supports clarifying the suitable timing of its administration are lacking. Sixty-seven patients with B-cell acute lymphoblastic leukemia (B-ALL) were treated with CD19-CART and enrolled in the study, of which 33 patients received Tocilizumab. Application of Tocilizumab in patients with grade 2 CRS in American Society for Transplantation and Cellular Therapy (ASTCT) criteria can significantly shorten the duration of CRS without affecting side effects and long-term efficacy. However, a number of patients still developed severe CRS with early use of Tocilizumab, indicating the significance of the introduction of clinical laboratories to assist medications. Statistically, patients with less than fourfold increase in IL-6 levels had a higher incidence of severe CRS after receiving Tocilizumab (37.5% versus. 0%, p=0.0125), which provided a basis for refining CRS intervention strategies under the guidance of IL-6., Clinical Trial Registration: www.clinicaltrials.gov, NCT02965092 and NCT04008251., 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. The reviewer CL declared a shared parent affiliation with the authors to the handling editor at the time of review., (Copyright © 2022 Zhang, Zhou, Wu, Li, Li, Du, Luo, Kou, Lu and Mei.)

During the outbreak of the COVID-19 pandemic, Non-Pharmaceutical and Pharmaceutical treatments were alternative strategies for governments to intervene. Though many of these intervention methods proved to be effective to stop the spread of COVID-19, i.e., lockdown and curfew, they also posed risk to the economy; in such a scenario, an analysis on how to strike a balance becomes urgent. Our research leverages the mobility big data from the University of Maryland COVID-19 Impact Analysis Platform and employs the Generalized Additive Model (GAM), to understand how the social demographic variables, NPTs (Non-Pharmaceutical Treatments) and PTs (Pharmaceutical Treatments) affect the New Death Rate (NDR) at county-level. We also portray the mutual and interactive effects of NPTs and PTs on NDR. Our results show that there exists a specific usage rate of PTs where its marginal effect starts to suppress the NDR growth, and this specific rate can be reduced through implementing the NPTs., Competing Interests: The authors have declared that no competing interests exist.

Background: The COVID-19 pandemic has imposed a large, initially uncontrollable, public health crisis both in the United States and across the world, with experts looking to vaccines as the ultimate mechanism of defense. The development and deployment of COVID-19 vaccines have been rapidly advancing via global efforts. Hence, it is crucial for governments, public health officials, and policy makers to understand public attitudes and opinions towards vaccines, such that effective interventions and educational campaigns can be designed to promote vaccine acceptance., Objective: The aim of this study was to investigate public opinion and perception on COVID-19 vaccines in the United States. We investigated the spatiotemporal trends of public sentiment and emotion towards COVID-19 vaccines and analyzed how such trends relate to popular topics found on Twitter., Methods: We collected over 300,000 geotagged tweets in the United States from March 1, 2020 to February 28, 2021. We examined the spatiotemporal patterns of public sentiment and emotion over time at both national and state scales and identified 3 phases along the pandemic timeline with sharp changes in public sentiment and emotion. Using sentiment analysis, emotion analysis (with cloud mapping of keywords), and topic modeling, we further identified 11 key events and major topics as the potential drivers to such changes., Results: An increasing trend in positive sentiment in conjunction with a decrease in negative sentiment were generally observed in most states, reflecting the rising confidence and anticipation of the public towards vaccines. The overall tendency of the 8 types of emotion implies that the public trusts and anticipates the vaccine. This is accompanied by a mixture of fear, sadness, and anger. Critical social or international events or announcements by political leaders and authorities may have potential impacts on public opinion towards vaccines. These factors help identify underlying themes and validate insights from the analysis., Conclusions: The analyses of near real-time social media big data benefit public health authorities by enabling them to monitor public attitudes and opinions towards vaccine-related information in a geo-aware manner, address the concerns of vaccine skeptics, and promote the confidence that individuals within a certain region or community have towards vaccines., (©Tao Hu, Siqin Wang, Wei Luo, Mengxi Zhang, Xiao Huang, Yingwei Yan, Regina Liu, Kelly Ly, Viraj Kacker, Bing She, Zhenlong Li. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 10.09.2021.)

Background: In the US, one in six men who have sex with men (MSM) with HIV are unaware of their HIV infection. In certain circumstances, access to HIV testing and viral load (VL) monitoring is challenging. The objective of this study was to evaluate the feasibility of conducting laboratory-based HIV and antiretroviral (ARV) drug testing, and VL monitoring as part of two studies on self-collected dried blood spots (DBS)., Methods: Participants were instructed to collect DBS by self-fingerstick in studies that enrolled MSM online. DBS from the first study (N = 1444) were tested with HIV serological assays approved by the Food and Drug Administration (FDA). A subset was further tested with laboratory-modified serological and VL assays, and ARV levels were measured by mass spectrometry. DBS from the second study (N = 74) were only tested to assess VL monitoring., Results: In the first study, the mail back rate of self-collected DBS cards was 62.9%. Ninety percent of DBS cards were received at the laboratory within 2 weeks from the day of collection, and 98% of the cards had sufficient spots for one assay. Concordance between FDA-approved and laboratory-modified protocols was high. The samples with undetectable ARV had higher VL than samples with at least one ARV drug. In the second study, 70.3% participants returned self-collected DBS cards, and all had sufficient spots for VL assay. High VL was observed in samples from participants who reported low ARV adherence., Conclusions: In these studies, MSM were able to collect and provide adequate DBS for HIV testing. The FDA-approved and laboratory-modified testing algorithms performed similarly. DBS collected at home may be feasible for HIV testing, ARV measurement, and monitoring viral suppression.

One approach to delaying the spread of the novel coronavirus (COVID-19) is to reduce human travel by imposing travel restriction policies. Understanding the actual human mobility response to such policies remains a challenge owing to the lack of an observed and large-scale dataset describing human mobility during the pandemic. This study uses an integrated dataset, consisting of anonymized and privacy-protected location data from over 150 million monthly active samples in the USA, COVID-19 case data and census population information, to uncover mobility changes during COVID-19 and under the stay-at-home state orders in the USA. The study successfully quantifies human mobility responses with three important metrics: daily average number of trips per person; daily average person-miles travelled; and daily percentage of residents staying at home. The data analytics reveal a spontaneous mobility reduction that occurred regardless of government actions and a 'floor' phenomenon, where human mobility reached a lower bound and stopped decreasing soon after each state announced the stay-at-home order. A set of longitudinal models is then developed and confirms that the states' stay-at-home policies have only led to about a 5% reduction in average daily human mobility. Lessons learned from the data analytics and longitudinal models offer valuable insights for government actions in preparation for another COVID-19 surge or another virus outbreak in the future.

Since the first case of the novel coronavirus disease (COVID-19) was confirmed in Wuhan, China, social distancing has been promoted worldwide, including in the United States, as a major community mitigation strategy. However, our understanding remains limited in how people would react to such control measures, as well as how people would resume their normal behaviours when those orders were relaxed. We utilize an integrated dataset of real-time mobile device location data involving 100 million devices in the contiguous United States (plus Alaska and Hawaii) from February 2, 2020 to May 30, 2020. Built upon the common human mobility metrics, we construct a Social Distancing Index (SDI) to evaluate people's mobility pattern changes along with the spread of COVID-19 at different geographic levels. We find that both government orders and local outbreak severity significantly contribute to the strength of social distancing. As people tend to practice less social distancing immediately after they observe a sign of local mitigation, we identify several states and counties with higher risks of continuous community transmission and a second outbreak. Our proposed index could help policymakers and researchers monitor people's real-time mobility behaviours, understand the influence of government orders, and evaluate the risk of local outbreaks.

Accurately estimating human mobility and gauging its relationship with virus transmission is critical for the control of COVID-19 spreading. Using mobile device location data of over 100 million monthly active samples, we compute origin-destination travel demand and aggregate mobility inflow at each US county from March 1 to June 9, 2020. Then, we quantify the change of mobility inflow across the nation and statistically model the time-varying relationship between inflow and the infections. We find that external travel to other counties decreased by 35% soon after the nation entered the emergency situation, but recovered rapidly during the partial reopening phase. Moreover, our simultaneous equations analysis highlights the dynamics in a positive relationship between mobility inflow and the number of infections during the COVID-19 onset. This relationship is found to be increasingly stronger in partially reopened regions. Our study provides a quick reference and timely data availability for researchers and decision makers to understand the national mobility trends before and during the pandemic. The modeling results can be used to predict mobility and transmissions risks and integrated with epidemics models to further assess the public health outcomes., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)

Background: Since 2014, the recommended algorithm for laboratory diagnosis of HIV infection in the United States has consisted of an HIV-1/2 antigen/antibody (Ag/Ab) test followed by an HIV-1/2 antibody (Ab) differentiation test and, if necessary, a diagnostic HIV-1 nucleic acid test to resolve discordant or indeterminate results., Methods: Using stored specimens from persons seeking HIV testing who had not received a previous diagnosis or treatment, we compared the performance of a 3-step alternative algorithm consisting of an Ag/Ab test followed by a quantitative HIV-1 RNA viral load assay and, if viral load is not detected, an Ab differentiation test, to that of the recommended algorithm. We calculated the sensitivity and specificity of 5 Ag/Ab tests and the proportion of specimens correctly classified by the alternative algorithm compared with the recommended algorithm. Results were examined separately for specimens classified as early infection, established infection, and false-reactive screening., Results: Sensitivity and specificity were similar among all Ag/Ab tests. Viral load quantification correctly classified all specimens from early infection, all false-reactive screening specimens, and the majority of specimens from established infection., Conclusions: Although cost, regulatory barriers, test availability, and the ability to differentiate early from established infection must be considered, this alternative algorithm can potentially decrease the total number of tests performed and reduce turnaround time, thereby streamlining HIV diagnosis and initiation of treatment.

Importance: Previous studies have suggested that patients with cancer may be at an increased risk of death from unintentional injury, but to our knowledge, no large studies have examined the rates of death from unintentional injury among patients with cancer., Objective: To characterize the incidence of death from unintentional injury among patients with cancer in the United States., Design, Setting, and Participants: This retrospective cohort study included patients diagnosed with a first primary cancer between January 1, 1973, and December 31, 2015, identified from the Surveillance, Epidemiology, and End Results (SEER) program data. Comparisons with the general US population were based on mortality data collected by the National Center for Health Statistics. Analyses were performed from February 1, 2019, to August 15, 2019., Main Outcomes and Measures: Rates and standardized mortality ratios (SMRs) of death from unintentional injury among patients with cancer., Results: A total of 8 271 020 patients with cancer were included in this study (50.2% female; mean [SD] age, 63.0 [15.7] years). Among them, 40 599 deaths from unintentional injury were identified. The rates of death from unintentional injury were 81.90 per 100 000 person-years among patients with cancer and 51.21 per 100 000 person-years in the corresponding US general population. The SMR of death from unintentional injury was 1.60 (95% CI, 1.58-1.61). Higher rates of death from unintentional injury were associated with increasing age at diagnosis (≥80 years; rate ratio [RR], 2.91; 95% CI, 2.84-2.98; P < .001), male sex (RR, 1.69; 95% CI, 1.66-1.73; P < .001), American Indian or Alaskan Native population (RR, 1.48; 95% CI, 1.30-1.68; P < .001), and being unmarried (RR, 1.23; 95% CI, 1.18-1.28; P < .001). Rates of death from unintentional injury were the highest in patients with cancers of the liver (200.37 per 100 000 person-years), brain (175.04 per 100 000 person-years), larynx (148.78 per 100 000 person-years), and esophagus (144.98 per 100 000 person-years). The SMRs were the highest in the first month after cancer diagnosis., Conclusions and Relevance: This study found that the incidence of death from unintentional injury among patients with cancer was significantly higher than that in the general population in the United States. The rates of death from unintentional injury varied by age, sex, race/ethnicity, marital status, cancer site, disease stage, and time since diagnosis. The findings suggest that death from unintentional injury among patients with cancer requires further attention and that initiatives to identify patients at risk and to develop targeted prevention strategies should be prioritized.

Importance: To date, single-agent programmed cell death 1 protein 1 (PD-1)/programmed death ligand 1 (PD-L1) immune checkpoint blockade has shown limited activity in recurrent epithelial ovarian cancer. Combination strategies of PD-1/PD-L1 inhibition with antiangiogenic therapy have the potential for synergistic activity through modulation of the microenvironment and represent a potential therapeutic opportunity in this disease., Objective: To evaluate the activity of combined nivolumab and bevacizumab in women with relapsed ovarian cancer., Design, Setting, and Participants: A single-arm, phase 2 study enrolled patients between February 8, 2017, and December 29, 2017, at 2 sites in the United States; the primary data analysis was completed July 27, 2018. Thirty-eight women with relapsed epithelial ovarian cancer were enrolled in this study. Participants had disease recurrence within 12 months of their last platinum-based therapy and had received between 1 and 3 lines of prior therapy., Interventions: Participants received intravenous nivolumab and intravenous bevacizumab once every 2 weeks., Main Outcome and Measures: The primary end point was objective response rate (ORR) as measured by Response Evaluation Criteria in Solid Tumors 1.1. Secondary end points included evaluation of the ORR by platinum sensitivity, assessment of progression-free survival, assessment of safety data, and investigation of the association of tumor PD-L1 with response to therapy., Results: Of the 38 women enrolled, 18 had platinum-resistant and 20 had platinum-sensitive disease; mean (SD) age was 63.0 (9.1) years. Eleven patients experienced a confirmed response to nivolumab with bevacizumab (ORR, 28.9%; 95% exact binomial CI, 15.4%-45.9%), with 1 additional unconfirmed response. The ORR was 40.0% (19.1%-64.0%) in platinum-sensitive and 16.7% (95% CI 3.6%-41.4%) in platinum-resistant participants. Thirty-four participants (89.5%) experienced at least 1 treatment-related adverse event; 9 participants (23.7%) experienced a grade 3 or higher treatment-related adverse event. Median progression-free survival was 8.1 months (95% CI, 6.3-14.7 months). In 36 histologic samples for which PD-L1 testing could be performed, 22 samples (61.1%) had a PD-L1 tumoral percentage less than 1, and 14 samples (38.9%) had a PD-L1 tumoral percentage of 1 or greater. Ten responses occurred in patients with PD-L1 tumor percentage less than 1, and 2 in patients with PD-L1 tumor percentages of 1 or greater., Conclusions and Relevance: The nivolumab with bevacizumab combination appeared to show activity in patients with relapsed ovarian cancer, with greater activity in the platinum-sensitive setting. Alternative combinational strategies may be necessary in the platinum-resistant setting.

Chlorophyll-a (CHLA) is a key indicator to represent eutrophication status in lakes. In this study, CHLA, total phosphorus (TP), total nitrogen (TN), turbidity (TB), and Secchi depth (SD) collected by the United States Environmental Protection Agency for the National Lakes Assessment in the continental USA were analyzed. Statistical analysis showed that water quality variables in natural lakes have strong patterns of autocorrelations than man-made lakes, indicating the perturbation of anthropogenic stresses on man-made lake ecosystems. Meanwhile, adaptive neuro-fuzzy inference systems (ANFIS) with fuzzy c-mean-clustering algorithm (ANFIS&#95;FC), ANFIS with grid partition method (ANFIS&#95;GP), and ANFIS with subtractive clustering method (ANFIS&#95;SC) were implemented to model CHLA in lakes, and modeling results were compared with the multilayer perceptron neural network models (MLPNN). Results showed that ANFIS&#95;FC models outperformed other models for natural lakes, while for man-made lakes, MLPNN models performed the best. ANFIS&#95;GP models have the lowest accuracies in general. The results indicated that ANFIS models can be screening tools for an overall estimation of CHLA levels of lakes in large scales, especially for natural lakes.

Background: The Determine™ HIV-1/2 Ag/Ab Combo (DC) rapid test can identify HIV-1 infection earlier than rapid antibody-only tests in plasma specimens., Objectives: We compared the performance of DC with a laboratory-based antigen/antibody (Ag/Ab) combo assay in plasma and evaluated antigen reactivity in whole blood specimens., Study Design: We tested by DC 508 plasma specimens collected in a prospective study and 107 sequential plasma and simulated whole blood specimens from 20 seroconversion panels. Previous results using the ARCHITECT (ARC) Ag/Ab combo assay were compared to DC results. In seroconversion panels, the days from the first HIV1 RNA-positive test to first DC-reactive in plasma and whole blood was compared. McNemar's and Wilcoxon signed rank tests were used for statistical analysis., Results: Of 415 HIV-positive samples, ARC detected 396 (95.4%) and DC 337 (81.2%) (p<0.0001). DC was reactive in 50.0% of ARC-reactive/MS-negative, 78.6% of ARC-reactive/MS-indeterminate, and 99.6% of ARC-reactive/MS-HIV-1-positive or -undifferentiated specimens. DC antigen reactivity was higher among ARC-reactive/MS-negative than MS-indeterminate samples. In 20 HIV-1 seroconversion panels, there was a significant difference between DC reactivity in plasma (91.1%) and whole blood (56.4%) (p<0.0001). DC with whole blood showed a significant delay in reactivity compared to plasma (p=0.008)., Conclusions: In plasma, DC was significantly less sensitive than an instrumented laboratory-based Ag/Ab combo assay. DC in plasma was significantly more sensitive compared to whole blood in early HIV-1 infections. With the U.S. laboratory-based diagnostic algorithm, DC as the first step would likely miss a high proportion of HIV-1 infections in early stages of seroconversion., (Published by Elsevier B.V.)

For years, we have relied on population surveys to keep track of regional public health statistics, including the prevalence of non-communicable diseases. Because of the cost and limitations of such surveys, we often do not have the up-to-date data on health outcomes of a region. In this paper, we examined the feasibility of inferring regional health outcomes from socio-demographic data that are widely available and timely updated through national censuses and community surveys. Using data for 50 American states (excluding Washington DC) from 2007 to 2012, we constructed a machine-learning model to predict the prevalence of six non-communicable disease (NCD) outcomes (four NCDs and two major clinical risk factors), based on population socio-demographic characteristics from the American Community Survey. We found that regional prevalence estimates for non-communicable diseases can be reasonably predicted. The predictions were highly correlated with the observed data, in both the states included in the derivation model (median correlation 0.88) and those excluded from the development for use as a completely separated validation sample (median correlation 0.85), demonstrating that the model had sufficient external validity to make good predictions, based on demographics alone, for areas not included in the model development. This highlights both the utility of this sophisticated approach to model development, and the vital importance of simple socio-demographic characteristics as both indicators and determinants of chronic disease.

Food allergy (FA) affects 2%-10% of US children and is a growing clinical and public health problem. Here we conduct the first genome-wide association study of well-defined FA, including specific subtypes (peanut, milk and egg) in 2,759 US participants (1,315 children and 1,444 parents) from the Chicago Food Allergy Study, and identify peanut allergy (PA)-specific loci in the HLA-DR and -DQ gene region at 6p21.32, tagged by rs7192 (P=5.5 × 10(-8)) and rs9275596 (P=6.8 × 10(-10)), in 2,197 participants of European ancestry. We replicate these associations in an independent sample of European ancestry. These associations are further supported by meta-analyses across the discovery and replication samples. Both single-nucleotide polymorphisms (SNPs) are associated with differential DNA methylation levels at multiple CpG sites (P<5 × 10(-8)), and differential DNA methylation of the HLA-DQB1 and HLA-DRB1 genes partially mediate the identified SNP-PA associations. This study suggests that the HLA-DR and -DQ gene region probably poses significant genetic risk for PA.

Background: FDA-approved HIV Antigen/Antibody combo (4th generation) immunoassays (IAs) can identify HIV-1 infections before the Western blot (WB) becomes positive. In the US, increased detection of acute HIV infections has been facilitated by using 4th generation IAs, but there is no FDA-approved 4th generation rapid test (RT). The Alere Determine™ HIV-1/2 Ag/Ab Combo (Determine Combo) RT detects and distinguishes HIV p24 Antigen (Ag) from Antibody (Ab) to HIV-1+HIV-2 and thus has the potential to improve diagnosis of acute HIV infection., Objective: To evaluate the ability of Determine Combo RT to detect acute/early HIV-1 infections and HIV-2 antibody in well-characterized plasma specimens., Study Design: In HIV-1 seroconverters from the US, Determine Combo reactivity was evaluated by performing the 50% cumulative frequency analysis and by comparing with 3rd and 4th generation IAs' reactivity. HIV-2 plasma specimens from Ivory Coast were tested with Determine Combo., Results: The 50% cumulative frequency analysis in 17 seroconverters placed Determine Combo (Ag+/Ab-, Ag+Ab+, Ag-/Ab+) and Ab-component reactivity at 15.5 and 7 days before WB positivity, respectively. In 26 seroconverters, Determine Combo was reactive in 99.0% and 92.5% of 3rd and 4th generation IAs-reactive specimens, respectively. All HIV-2 plasma specimens were Ab-reactive/Ag-non-reactive by Determine Combo., Conclusions: Based on previous results with the same seroconversion panels, combined Ag/Ab reactivity of the Determine Combo appears between FDA-approved 4th and 3rd generation laboratory IAs. These data indicate that this RT could detect HIV-1 infection earlier than other RTs and it performs well in HIV-2 specimens., (Published by Elsevier B.V.)

Background: Elevated macrophage inhibitory cytokine-1 (MIC-1/GDF15) levels in serum mediate anorexia and weight loss in some cancer patients and similarly elevated levels occur in chronic kidney disease (CKD). Serum MIC-1/GDF15 is also elevated in chronic inflammatory diseases and predicts atherosclerotic events independently of traditional risk factors. The relationship between chronic inflammation, decreasing body mass index (BMI) and increased mortality in CKD is not well understood and is being actively investigated. MIC-1/GDF15 may link these features of CKD., Methods: Cohorts of incident dialysis patients from Sweden (n = 98) and prevalent hemodialysis patients from the USA (n = 381) had serum MIC-1/GDF15, C-reactive protein (CRP) levels and BMI measured at study entry. Additional surrogate markers of nutritional adequacy, body composition and inflammation were assessed in Swedish patients. Patients were followed for all-cause mortality., Results: In the Swedish cohort, serum MIC-1/GDF15 was associated with decreasing BMI, measures of nutrition and markers of oxidative stress and inflammation. Additionally, high serum MIC-1/GDF15 levels identified patients with evidence of protein-energy wasting who died in the first 3 years of dialysis. The ability of serum MIC-1/GDF15 to predict mortality in the first 3 years of dialysis was confirmed in the USA cohort. In both cohorts, serum MIC-1/GDF15 level was an independent marker of mortality when adjusted for age, CRP, BMI, history of diabetes mellitus and/or cardiovascular disease and glomerular filtration rate or length of time on dialysis at study entry., Conclusions: MIC-1/GDF15 is a novel independent serum marker of mortality in CKD capable of significantly improving the mortality prediction of other established markers. MIC-1/GDF15 may mediate protein-energy wasting in CKD and represent a novel therapeutic target for this fatal complication.

Introduction: Menthol has long been an important flavorant in tobacco products, and both its historical and present uses are topics of increasing debate. Menthol can exist in eight different stereoisomeric forms (as four enantiomeric pairs) that possess different sensory properties. As regards use in tobacco products, the open scientific literature and available industry documents focus on the D-menthol and l-menthol enantiomeric pair, and in particular on l-menthol, but are ambiguous about the actual importance of D-menthol in tobacco products. This study provides the first openly available measurements regarding the stereoisomeric forms of menthol as found in selected United States sub-brands of smokeless tobacco (SLT), cigarettes, and cigarette smoke., Methods: Gas chromatography/mass spectrometry (GC/MS) was applied using a "chiral" GC column to separate and determine the forms of menthol present in headspace air above various samples of United States sub-brands of SLT, cigarette filler material, and cigarette smoke particulate matter. Additional GC × GC/Time-of-flight mass spectrometry measurements were also made., Results: The dominant form of menthol by far in any of the samples was l-menthol., Conclusions: For the selected cigarettes and SLT products tested from the U.S. market, the only form of menthol found was l-menthol. Other forms may be present in products that were not tested. No evidence was found of thermal racemization upon smoking of l-menthol to a d+l mixture.

In Canada, 74,255 deaths (33% of all deaths) in 2003 were due to cardio-vascular disease (CVD). As one of the most costly diseases, CVD represents a major economic burden on health care systems. The purpose of the present study was to review the literature on the economic costs of CVD in Canada and other developed countries (United States, Europe and Australia) published from 1998 to 2006, with a focus on Canada. Of 1656 screened titles and abstracts, 34 articles were reviewed including six Canadian studies and 17 American studies. While considerable variation was observed among studies, all studies indicated that the costs of treating CVD-related conditions are significant, outlining a convincing case for CVD prevention programs.

Background: Chemotherapy-induced anemia (CIA) commonly occurs in cancer patients receiving conventional myelosuppressive chemotherapy. Two national guidelines regarding the use of erythropoiesis-stimulating agents (ESAs) in CIA were released in 2002. Because of poorer disease outcomes and increased risk of adverse events associated with ESAs in recent studies, the use of ESAs has been increasingly restricted in practice guidelines in the years 2007 and 2008., Objective: The aim of this study was to provide a baseline for adherence to national guidelines in the use of ESAs for CIA between 2002 and 2006., Methods: This retrospective study used the Varian Medical Oncology database (Varian Medical Systems, Inc., Palo Alto, California) of electronic medical records, representing 17 outpatient oncology organizations at 71 clinic locations in the United States. Adults diagnosed with any malignant neoplasm who started conventional cytotoxic chemotherapy between January 1, 2002, and September 30, 2006, were included. The proportion of patients receiving an ESA was calculated by hemoglobin (Hb) level during each chemotherapy cycle, stratified by line of chemotherapy and year. Logistic regression modeling identified predictors of ESA use in anemic patients during the first chemotherapy cycle., Results: The records of 17,731 cancer patients were evaluated. Median (SD) age was 61 (13) years, and 58.9% were female. Most patients (84.1%) had a solid tumor. Many patients (41.3%) received platinum containing chemotherapy and 74.4% received combination chemotherapy. During the first 5 cycles of first-line chemotherapy among patients with CIA (Hb <11 g/dL), ESAs were used by 55.8% of patients at cycle 1 and 68.9% at cycle 5. ESA use in CIA patients increased across lines of chemotherapy and time. Few patients (2.8%) received an ESA at Hb >13 g/dL. The statistically significant predictors of ESA use included age >65 years, eastern US residence, private health insurance, community-based care, and solid tumors, especially lung cancer., Conclusion: The patterns we observed were generally consistent with prevailing ESA labels and national guidelines during 2002 through 2006. Although ESA use in patients with CIA increased over chemotherapy cycles, lines of chemotherapy, and time, <70% of CIA episodes were treated with ESAs during the initial 5 chemotherapy cycles.

Background: Prior to 2007, the erythropoiesis-stimulating agents (ESAs) epoetin alfa and darbepoetin alfa were indicated for use in chemotherapyinduced anemia to achieve target hemoglobin (Hb) levels of approximately 12 grams per deciliter (gm per dL), and treatment was to be withheld if Hb exceeded 13 gm per dL. In March 2007, the FDA changed the labeling of the ESAs to add boxed warnings, updated in November 2007, to include the following key points: (a) ESAs should be used only to treat anemia that occurs in patients with cancer while they are undergoing chemotherapy; (b) treatment with ESAs should be stopped when chemotherapy ends; and (c) dosing ESAs to an Hb target of 12 gm per dL or greater has resulted in more rapid cancer progression or shortened overall survival in patients with breast, head and neck, lymphoid, cervical, and non-small cell lung malignancies. In January 2008, the FDA specified that the increased risk of more rapid tumor growth or shortened survival was associated with ESAs when "administered in an attempt to achieve a Hb level of 12 gm per dL or greater, although many patients did not reach that level." A new black-box warning regarding this association was added to the labels of the ESAs in March 2008, and the FDA mandated further label changes on July 30, 2008, that ESA therapy should not be initiated in patients receiving chemotherapy at Hb levels of 10 gm per dL or higher., Objective: To (a) assess the prevalence and predictors of ESA administrations at Hb levels above 12 gm per dL among patients with a diagnosis of solid or hematologic cancer or myelodysplastic syndrome who began their first regimen of conventional myelosuppressive chemotherapy between 2002 and 2006, and (b) describe patterns of ESA treatment subsequent to the first ESA administration at Hb above 12 gm per dL., Methods: Using the Health Insurance Portability and Accountability Act (HIPAA)-compliant Varian Medical Oncology database of de-identified electronic medical records from 17 U.S. outpatient oncology practices, adults (aged 18 years or older) with any cancer diagnosis who began chemotherapy between January 1, 2002, and September 30, 2006, were identified. The Hb value associated with each ESA administration was defined as the closest Hb measurement within 7 days prior to the ESA administration. A first ESAHb > 12 was defined as the first time an ESA, either epoetin or darbepoetin, was given with an associated Hb greater than 12 gm per dL during the first chemotherapy regimen recorded in the database for each patient. Hb levels and ESA administrations after the first ESAHb > 12 were determined. Logistic regression models identified predictors of initial receipt of an ESAHb > 12, and of receiving further ESA treatment following the first such administration., Results: Between January 1, 2002, and September 30, 2006, there were 17,731 patients on chemotherapy, the mean (SD) age was 60 (13.2) years; 58.9% were female; 24.6% had breast cancer, 22.2% had lung cancer, 15.8% had colorectal cancer, 11.8% had hematologic cancer, and 25.6% had other or multiple cancers. Of these, 8,086 (45.6%) received an ESA at any time during the regimen, and 7,606 (42.9%) received an ESA at a known Hb level (i.e., Hb measurement within 7 days prior to ESA administration). During the first recorded chemotherapy regimen, 1,844 patients (10.4% of the chemotherapy cohort, 24.2% of ESA users with a known Hb; n = 1,226 epoetin, n = 618 darbepoetin) received an ESAHb > 12. Among patients receiving ESA treatment at a known Hb level, significant predictors of receiving an ESAHb > 12 included treatment in a community-based clinic rather than a hospital-affiliated clinic (odds ratio [OR] = 2.96, 95% confidence interval [CI] = 2.40-3.65), location of practice in the eastern United States (OR for Midwest = 0.67, 95% CI = 0.57- 0.78; OR for West = 0.27, 95% CI = 0.22-0.34), hematologic cancer rather than solid tumor (OR = 1.44, 95% CI = 1.21-1.71), private health insurance (OR for public health insurance = 0.80, 95% CI = 0.70-0.93; OR for other/ unknown insurance = 0.54, 95% CI = 0.47-0.62), and year of regimen 2002- 2003 (ORs = 0.75, 0.74, and 0.71 for 2004, 2005, and 2006, respectively). Following the first ESAHb > 12, 276 (22.5%) of the patients on epoetin and 276 (44.7%) on darbepoetin received no further ESA treatment during the next 6 weeks (Pearson chi-square = 96.1, P < 0.001)., Conclusions: This analysis of outpatient oncology practices between 2002 and 2006 revealed that 24% of ESA users with a known Hb level received ESAHb > 12. Dose withholding subsequently occurred in 23%- 45% of those patients. A higher proportion of patients on epoetin than darbepoetin continued ESA treatment after the first administration of ESAHb > 12.

Serodiagnosis of human immunodeficiency virus (HIV) infection in the United States has traditionally relied on a sequential two-test algorithm: an initial screen with an enzyme immunoassay (EIA) and reflex testing of EIA-reactive specimens with a more specific supplemental test such as Western blotting or immunofluorescence. The supplemental tests are tedious, subjective, and expensive. In addition, there have been major improvements in the performance and accuracy of the EIA tests as well as the introduction of rapid serologic tests (RT) and HIV nucleic acid amplification tests (NAAT). Related to these improvements is the possibility that alternative algorithms using combinations of currently approved HIV tests may function as well as if not better than the current algorithm, with more flexibility, improved accuracy, and lower cost. To this end, we evaluated the performance of 12 currently licensed tests and 1 in-house HIV test (6 EIA, 4 RT, and 3 NAAT) on panels of plasma samples from HIV-infected (n = 621 HIV type 1 [HIV-1] and 34 HIV-2) and uninfected (n = 513) people and of sequential specimens from people early in seroconversion (183 specimens from 15 patients). Test combinations were analyzed in two dual-test (sensitivity-optimized and specificity-optimized) algorithms and in a three-test (tie-breaking) algorithm, and performance was compared to the conventional algorithm. The results indicate that alternative algorithm strategies with currently licensed tests compare favorably with the conventional algorithm in detecting and confirming established HIV infection. Furthermore, there was a lower frequency of discordant or indeterminate results that require follow-up testing, and there was improved detection of early infection.

A bridging study was conducted to establish the correlation between a liquid chromatographic (LC) method and a microbial inhibition (MI) method for analysis of amoxicillin residues in catfish muscle. The LC procedure involved precolumn derivatization with formaldehyde followed by LC separation with fluorescence detection. The MI procedure used Bacillus stearothermophilus as the test organism and was validated in this study before the bridging investigation. The 2 methods were compared for determination of both fortified and incurred samples. No significant differences were found between the methods when all data were included in statistical computations. The linear correlation of LC means versus MI means had a slope of 0.972 and a negligible intercept (1.0 ng/g), with a correlation coefficient of 0.9962. LC was more specific and showed better sensitivity than MI for amoxicillin residues at < or = 10 ng/g. For practical purposes, values obtained by the 2 methods can be considered equivalent.