tbuckley/cabot-search huggingface dataset:
Real-world antiemetic utilization in patients undergoing carboplatin chemotherapy.
Authors: Michael Polson, Brooke Harrow
Journal: Journal of Clinical Oncology (2018)

10 Background: More than 70% of patients receiving chemotherapy will experience chemotherapy-induced nausea and vomiting (CINV). Chemotherapeutic regimens (regimens) are classified as highly emetogenic, moderately emetogenic, low potential, or minimal risk for emesis. The NCCN has recently reclassified carboplatin emetogenicity according to the AUC (target area under the concentration versus time curve) with a carboplatin AUC ≥4 classified as highly emetogenic and carboplatin AUC &lt; 4 as moderately emetogenic - but highly emetogenic in certain patients. This study assessed use of anti-emetic agents in carboplatin based regimens. Methods: This study consisted of a retrospective analysis of administrative claims data from multiple commercial health plans. Claims from 1/1/2010-10/31/2017 were analyzed. Index date for each patient was the first medical claim of the regimen of interest. Included patients had ≥1 medical claim for the selected regimen and were eligible for both medical and pharmacy benefits for ≥6 months prior to, and 12 months post index date. CINV-related hospitalizations and ER cost and utilization were assessed for patients treated with carboplatin based regimens. Results: In total, 4,430 mostly female (74%) patients met criteria for treatment with a carboplatin-based index regimen. Between 2010 and 2017, the following trends were noted in the study population: Adherence to NCCN recommended 3 drug CINV prophylaxis (triplet therapy) ranged from about 23% to 35%. The rate of CINV related emergency department (ED) visits was 5.3% and the overall rate of CINV related inpatient visits was 0.11%. The average cost for CINV related hospitalization for a carboplatin patient was $8,562 (SD 6,207) with an average LOS of 3.1 days. ED visits that were CINV related cost $2,463 on average (SD 3,054). Conclusions: Guidelines recommend use of up to three agents in the prevention of chemotherapy induced nausea and vomiting. Use of a triplet therapy for CINV prophylaxis in carboplatin based highly emetogenic regimens has increased over time in the plans analyzed and may offer an opportunity to reduce rate of CINV related hospitalizations and ED visits, as well as associated costs.
Fracture Prevention with Zoledronate in Older Women with Osteopenia
Authors: Ian R. Reid, Anne M. Horne, Borislav Mihov, Angela Stewart, Elizabeth Garratt, Sumwai Wong, Katy R. Wiessing, Mark J. Bolland, Sonja Bastin, Gregory D. Gamble
Journal: New England Journal of Medicine (2018)

Bisphosphonates prevent fractures in patients with osteoporosis, but their efficacy in women with osteopenia is unknown. Most fractures in postmenopausal women occur in those with osteopenia, so therapies that are effective in women with osteopenia are needed.We conducted a 6-year, double-blind trial involving 2000 women with osteopenia (defined by a T score of -1.0 to -2.5 at either the total hip or the femoral neck on either side) who were 65 years of age or older. Participants were randomly assigned to receive four infusions of either zoledronate at a dose of 5 mg (zoledronate group) or normal saline (placebo group) at 18-month intervals. A dietary calcium intake of 1 g per day was advised, but calcium supplements were not provided. Participants who were not already taking vitamin D supplements received cholecalciferol before the trial began (a single dose of 2.5 mg) and during the trial (1.25 mg per month). The primary end point was the time to first occurrence of a nonvertebral or vertebral fragility fracture.At baseline, the mean (±SD) age was 71±5 years, the T score at the femoral neck was -1.6±0.5, and the median 10-year risk of hip fracture was 2.3%. A fragility fracture occurred in 190 women in the placebo group and in 122 women in the zoledronate group (hazard ratio with zoledronate, 0.63; 95% confidence interval, 0.50 to 0.79; P<0.001). The number of women that would need to be treated to prevent the occurrence of a fracture in 1 woman was 15. As compared with the placebo group, women who received zoledronate had a lower risk of nonvertebral fragility fractures (hazard ratio, 0.66; P=0.001), symptomatic fractures (hazard ratio, 0.73; P=0.003), vertebral fractures (odds ratio, 0.45; P=0.002), and height loss (P<0.001).The risk of nonvertebral or vertebral fragility fractures was significantly lower in women with osteopenia who received zoledronate than in women who received placebo. (Funded by the Health Research Council of New Zealand; Australian New Zealand Clinical Trials Registry number, ACTRN12609000593235 .).
PlaD: A Transcriptomics Database for Plant Defense Responses to Pathogens, Providing New Insights into Plant Immune System
Authors: Huan Qi, Zhenhong Jiang, Kang Zhang, Shiping Yang, Fei He, Ziding Zhang
Journal: Genomics Proteomics & Bioinformatics (2018)

Abstract High-throughput transcriptomics technologies have been widely used to study plant transcriptional reprogramming during the process of plant defense responses, and a large quantity of gene expression data have been accumulated in public repositories. However, utilization of these data is often hampered by the lack of standard metadata annotation. In this study, we curated 2444 public pathogenesis-related gene expression samples from the model plant Arabidopsis and three major crops (maize, rice, and wheat). We organized the data into a user-friendly database termed as PlaD. Currently, PlaD contains three key features. First, it provides large-scale curated data related to plant defense responses, including gene expression and gene functional annotation data. Second, it provides the visualization of condition-specific expression profiles. Third, it allows users to search co-regulated genes under the infections of various pathogens. Using PlaD, we conducted a large-scale transcriptome analysis to explore the global landscape of gene expression in the curated data. We found that only a small fraction of genes were differentially expressed under multiple conditions, which might be explained by their tendency of having more network connections and shorter network distances in gene networks. Collectively, we hope that PlaD can serve as an important and comprehensive knowledgebase to the community of plant sciences, providing insightful clues to better understand the molecular mechanisms underlying plant immune responses. PlaD is freely available at http://systbio.cau.edu.cn/plad/index.php or http://zzdlab.com/plad/index.php.
Abstract P348: Incidence of Chronic Kidney Disease (CKD) and Association of Major Cardiovascular Risk Factors With CKD in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)
Authors: Ana C Ricardo, Matthew Loop, Esteban Cedillo-Couvert, Jinsong Chen, Michael Flessner, Nora Franceschini, Franklyn Gonzalez, Holly J Mattix-Kramer, Ashley E Moncrieft, Gregory A Talavera, Martha L Daviglus, James P Lash
Journal: Circulation (2017)

Background: The prevalence of major cardiovascular risk factors and chronic kidney disease (CKD) is high in U.S. Hispanics/Latinos. Hypotheses: We assessed the hypotheses that the incidence of CKD will vary by Hispanic/Latino heritage, and that cardiovascular risk factors will be associated with incident CKD among Hispanic/Latino adults. Methods: We used data from HCHS/SOL, the largest community-based cohort of 16,415 self-identified Hispanic/Latino adults from diverse backgrounds in the U.S., aged 18-74 years at visit 1 (baseline, 2008-2011), and ongoing second clinic examination (2014-2017). This preliminary analysis describes results from 7,144 adults who attended visit 1 and 2 by September 2016, and did not have CKD at baseline. Incident CKD was defined as estimated glomerular filtration rate (eGFR) &lt;60 ml/min/1.73m 2 and eGFR decline ≥1 ml/min/year, or urine albumin-to-creatinine ratio (UACR) ≥30 mg/g. Incidence rates for CKD and incidence rate ratios (RR) for the association between cardiovascular risk factors at baseline and incident CKD were estimated using Poisson regression with robust variance while accounting for the complex sampling design of HCHS/SOL. Results: In 5.7 years mean follow-up, 430 individuals developed CKD (61.2% women). The age- and gender-adjusted incidence rate of CKD ranged from 6.0% (South Americans) to 14.9% (Puerto Ricans) per 1000 person-years (Table). Higher systolic blood pressure (RR, 95% CI, 1.02, 1.01-1.02, per one mm Hg increment), glycated hemoglobin (1.17, 1.07-1.27, per one percentage point increment), and log-UACR (3.29, 2.60-4.16, per one unit increment) were significantly associated with incident CKD. LDL and HDL cholesterol were not significantly associated with incident CKD. Conclusions: The incidence of CKD varies markedly by Hispanic/Latino heritage. Systolic blood pressure, glycated hemoglobin and albuminuria are important in the development of CKD in this population. Future work will focus on further evaluation of these differences/associations.
Infographics and digital resources: an international consensus on golf and health
Authors: Andrew D Murray, Christian J Barton, Daryll Archibald, Danny Glover, Iain Robert Murray, Kevin Barker, Roger A Hawkes
Journal: British Journal of Sports Medicine (2018)

New knowledge from research findings rarely produces rapid efficient changes in practice.1 Barton and Merolli2 proposed a model which may help improve knowledge translation via the addition of two novel contemporary steps: multimedia creation and subsequent dissemination (see figure 1).



Figure 1 
Visual representation of a process to improve knowledge translation based on Barton and Merolli’s model.2 



Following this model, we recently produced digital/multimedia resources to help communicate and disseminate the International Consensus on Golf and Health.3 

A systematic literature review and modified Delphi process underpinned the International Consensus on Golf and Health and this was published in the British Journal of Sports Medicine in 2018.3 The Consensus is intended to support (1) golfers and potential golfers; (2) golf facilities and the golf industry; and (3) policy makers to make evidence-informed decisions that can maximise the health benefits of golf and minimise the health risks associated with this sport.

Articles containing visual information are …
Abstract 18245: Palmitic Acid-induced Endothelial Dysfunction in Human Leptomeningeal and Adipose Arterioles
Authors: Seth Truran, Nina Karamanova, Geidy Serrano, Daniel Franco, Camelia Burciu, Thomas Beach, Alex Roher, Raymond Q Migrino
Journal: Circulation (2015)

Introduction: Epidemiologic data show strong link between cardiovascular risk factors and dementia-related illnesses (DRI) such as Alzheimer’s disease (AD) with evidence that the earliest changes in AD involve vascular dysfunction. The mechanisms behind vascular impairment in DRI remain poorly understood, and lack of a human model to study them impedes progress towards a cure. Aim: The aim of the study is to determine the effects of acute exposure to palmitic acid (PA), a saturated fatty acid implicated in atherosclerosis, on endothelium-dependent and smooth muscle dependent function in human leptomeningeal arterioles (LMA) and peripheral adipose tissue arterioles (AA). Methods: LMA from cadavers of brain donors (post-mortem interval 3.3±0.4 hours; 2 with mild cognitive impairment, 1 Parkinson's disease, 1 Lewy body dementia) and abdominal subcutaneous AA from living subjects with no vascular disease undergoing routine surgery were isolated, cannulated and pressurized. Following preconstriction with endothelin-1, baseline (control) dilation response to acetylcholine and papaverine was measured. Arterioles were then exposed to 1 hour of PA (150 μM) and a second dilation response was measured. Results: (see Figure) PA decreased dilator response to acetylcholine in both LMA and AA (PA-induced change in dilator response to acetylcholine 10-4M: -28.1±6.8 % for LMA and -33.8±7.4% for AA, both p&lt;0.05 versus baseline control). There was no significant reduction in dilator response to papaverine. The changes in dilator response with PA versus control were not different between LMA and AA. Conclusions: Acute exposure to PA induced endothelial dysfunction in human leptomeningeal arterioles suggesting a potential mechanism for vascular dysfunction that could contribute to AD. Similarity in response to saturated fatty acid between LMA and AA suggests that AA, which is easier to obtain, may be a novel surrogate human model to study brain microvascular function.
From second to hundredth opinion in medicine: A global consultation platform for physicians
Authors: Evan D. Muse, Job G. Godino, Jessa F. Netting, James F. Alexander, Helen J. Moran, Eric J. Topol
Journal: npj Digital Medicine (2018)

Serious medical diagnostic errors lead to adverse patient outcomes and increased healthcare costs. The use of virtual online consultation platforms may lead to better-informed physicians and reduce the incidence of diagnostic errors. Our aim was to assess the usage characteristics of an online, physician-to-physician, no-cost, medical consultation platform, Medscape Consult, from November 2015 through October 2017. Physicians creating original content were noted as "presenters" and those following up as "responders". During the study period, 37,706 physician users generated a combined 117,346 presentations and responses. The physicians had an average age of 56 years and were from 171 countries on every continent. Over 90% of all presentations received responses with the median time to first response of 1.5 h. Overall, computer- and device-based medical consultation has the capacity to rapidly reach a global medical community and may play a role in the reduction of diagnostic errors.
Chronic Kidney Disease Induces Inflammatory CD40 <sup>+</sup> Monocyte Differentiation via Homocysteine Elevation and DNA Hypomethylation
Authors: Jiyeon Yang, Pu Fang, Daohai Yu, Lixiao Zhang, Daqing Zhang, Xiaohua Jiang, William Y. Yang, Teodoro Bottiglieri, Satya P. Kunapuli, Jun Yu, Eric T. Choi, Yong Ji, Xiaofeng Yang, Hong Wang
Journal: Circulation Research (2016)

Rationale: Patients with chronic kidney disease (CKD) develop hyperhomocysteinemia and have a higher cardiovascular mortality than those without hyperhomocysteinemia by 10-fold. Objective: We investigated monocyte differentiation in human CKD and cardiovascular disease (CVD). Methods and Results: We identified CD40 as a CKD-related monocyte activation gene using CKD-monocyte -mRNA array analysis and classified CD40 monocyte (CD40 + CD14 + ) as a stronger inflammatory subset than the intermediate monocyte (CD14 ++ CD16 + ) subset. We recruited 27 patients with CVD/CKD and 14 healthy subjects and found that CD40/CD40 classical/CD40 intermediate monocyte (CD40 + CD14 + /CD40 + CD14 ++ CD16 – /CD40 + CD14 ++ CD16 + ), plasma homocysteine, S-adenosylhomocysteine, and S-adenosylmethionine levels were higher in CVD and further elevated in CVD+CKD. CD40 and CD40 intermediate subsets were positively correlated with plasma/cellular homocysteine levels, S-adenosylhomocysteine and S-adenosylmethionine but negatively correlated with estimated glomerular filtration rate. Hyperhomocysteinemia was established as a likely mediator for CKD-induced CD40 intermediate monocyte, and reduced S-adenosylhomocysteine/S-adenosylmethionine was established for CKD-induced CD40/CD40 intermediate monocyte. Soluble CD40 ligand, tumor necrosis factor (TNF)-α/interleukin (IL)-6/interferon (IFN)-γ levels were elevated in CVD/CKD. CKD serum/homocysteine/CD40L/increased TNF-α/IL-6/IFN-γ–induced CD40/CD40 intermediate monocyte in peripheral blood monocyte. Homocysteine and CKD serum-induced CD40 monocyte were prevented by neutralizing antibodies against CD40L/TNF-α/IL-6. DNA hypomethylation was found on nuclear factor-κB consensus element in CD40 promoter in white blood cells from patients with CKD with lower S-adenosylmethionine / S-adenosylhomocysteine ratios. Finally, homocysteine inhibited DNA methyltransferase-1 activity and promoted CD40 intermediate monocyte differentiation, which was reversed by folic acid in peripheral blood monocyte. Conclusions: CD40 monocyte is a novel inflammatory monocyte subset that appears to be a biomarker for CKD severity. Hyperhomocysteinemia mediates CD40 monocyte differentiation via soluble CD40 ligand induction and CD40 DNA hypomethylation in CKD.
Valued outcomes in the cancer experience: Patient priorities and control.
Authors: Alexandra Katherine Zaleta, Shauna McManus, Melissa F Miller, Eva Yuen, Kevin Stein, Karen Hurley, Lillie D. Shockney, Sara Goldberger, Mitch Golant, Joanne S. Buzaglo
Journal: Journal of Clinical Oncology (2018)

84 Background: In the era of value-based cancer care, identifying what is important to cancer survivors, and their perceived control over these experiences, can inform shared decision-making and support quality care. We examined cancer patient priorities and control to guide the development of a new measure of patient value, Valued Outcomes in the Cancer Experience (VOICE). Methods: 459 cancer patients completed an online survey and rated level of importance and control over 54 value items (0 = not at all; 4 = very much). Items of most and least importance, items with most and least control, and rating discrepancies (importance-control) were identified. Bivariate associations with socio-demographics were examined. Results: Participants were 86% non-Hispanic White; mean age = 60 years, SD= 10; 38% breast cancer, 18% blood, 9% lung, 9% prostate; mean time since diagnosis = 6.5 years, SD= 6; 22% metastatic. Items of highest importance (quite a bit to very much) included, “Having your health care team (HCT) talk to you in a way that makes sense to you” (99% of participants); “Making decisions for yourself” (99%); “Talking honestly with your HCT about your illness” (99%). Participants reported the most control over, “Talking honestly with your HCT about your illness” (89%); “Making decisions for yourself” (88%), “Understanding your illness” (84%). Greatest discrepancies were, “Having your illness not get worse or come back” (96% Important; 27% Control); “Having energy to do things that are important to you (98% Important; 41% Control); “Being able to afford medical expenses” (96% Important; 49% Control); “Having a death free from suffering” (91% Important; 40% Control); “Having your medical providers communicate with each other about your care” (94% Important; 44% Control). Greater importance/control discrepancies were associated with lower income, unemployment due to disability, and poorer health ( ps &lt; .05). Conclusions: Cancer patients experience notable discrepancies between personal priorities and their ability to control these experiences, suggesting key areas for intervention and support. Next steps include psychometric assessment to refine the VOICE scale to guide clinical and research efforts to improve patient care outcomes.
Inotuzumab ozogamicin in pediatric patients with relapsed/refractory acute lymphoblastic leukemia
Authors: Deepa Bhojwani, Richard Sposto, Nirali N. Shah, Vilmarie Rodriguez, Constance Yuan, Maryalice Stetler-Stevenson, Maureen M. O’Brien, Jennifer L. McNeer, Amrana Quereshi, Aurelie Cabannes, Paul Schlegel, Claudia Rossig, Luciano Dalla-Pozza, Keith August, Sarah Alexander, Jean-Pierre Bourquin, Michel Zwaan, Elizabeth A. Raetz, Mignon L. Loh, Susan R. Rheingold
Journal: Leukemia (2018)

Although inotuzumab ozogamicin (InO) is recognized as an effective agent in relapsed acute lymphoblastic leukemia (ALL) in adults, data on safety and efficacy in pediatric patients are scarce. We report the use of InO in 51 children with relapsed/refractory ALL treated in the compassionate use program. In this heavily pretreated cohort, complete remission was achieved in 67% of patients with overt marrow disease. The majority (71%) of responders were negative for minimal residual disease. Responses were observed irrespective of cytogenetic subtype or number or type of prior treatment regimens. InO was well-tolerated; grade 3 hepatic transaminitis or hyperbilirubinemia were noted in 6 (12%) and grade 3/4 infections in 11 (22%) patients. No patient developed sinusoidal obstruction syndrome (SOS) during InO therapy; however, 11 of 21 (52%) patients who underwent hematopoietic stem cell transplantation (HSCT) following InO developed SOS. Downregulation of surface CD22 was detected as a possible escape mechanism in three patients who developed a subsequent relapse after InO. We conclude that InO is a well-tolerated, effective therapy for children with relapsed ALL and prospective studies are warranted. Identification of risk factors for developing post-HSCT SOS and strategies to mitigate this risk are ongoing.
Creative strategies to address challenges in access.
Authors: Carlos Ruiz, Susan Franco
Journal: Journal of Clinical Oncology (2018)

215 Background: The Cancer Center is structured across multiple campuses with clinics at three different locations. Patients, providers and referring offices encountered difficulty accessing services and encountered a fragmented structure and a non-standardized process. Patient and provider calls often resulted in multiple transfers. Referring providers and patients frequently left a voicemail for new patient appointments. There was no standardized process for addressing urgent clinical calls from patients. This led to delays in access for new patient appointments, delays in patient care and poor patient experience scores. Overall telephone statistics went untracked. Methods: A multidisciplinary team was organized and tasked with the creation of a centralized Cancer Contact Center (CCC). In August 2015 the CCC became a reality with the vision of “One Call Resolution” for anybody needing access to the services of the Cancer Center. Single telephone and fax numbers were created and all staff were placed together in one location. Three distinct job roles made up the CCC: Telephone Operators, as the main point of initial contact; New Patient Coordinators, to facilitate new patient referrals, record collection and scheduling; and Lead Nurses to provide clinical oversight and guidance. Processes were put in place to ensure standardization and consistent outcomes. Operator guidelines were conceived and an articulated approach to managing patient clinical concerns was planned. Clinical triage of these concerns initially involved the Telephone Operators, RN Case Managers and Lead Nurses. Later, clinical triage evolved into the creation of a specific triage line and Triage Nurses for clinical questions and to further ensure patient safety. Results: Patient experience scores relating to telephone accessibility for patients have increased from a 56.9 Top Box score to a 67.5 score. Telephone answer rates have been sustained above 95%. Conclusions: The creation of a centralized Cancer Contact Center has enabled all calls, referrals and clinical triage to be initially managed in one location under a standardized process with sustainable results.