bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comparison of two optical coherence tomography–angiography devices in pseudoexfoliation glaucoma versus primary open-angle glaucoma and healthy subjects
Authors: Rebolleda Gema , Pérez-Sarriegui Ane , De Juan Victoria , Ortiz-Toquero Sara , Muñoz-Negrete Francisco J 
Published: October 2018

Purpose: To compare peripapillary vascular parameters derived from two optical coherence tomography angiography devices in pseudoexfoliation glaucoma, primary open-angle glaucoma, and healthy controls and to evaluate their diagnostic accuracy. Methods: Observational, cross-sectional study. In total, 20 eyes with pseudoexfoliation glaucoma, 20 primary open-angle glaucoma eyes matched by peripapillary retinal nerve fiber layer thickness, and 20 control eyes were recruited. Participants underwent standard automated perimetry and peripapillary retinal nerve fiber layer analysis by Optovue and Cirrus optical coherence tomography. Vascular parameters provided by Angiovue and Angioplex optical coherence tomography angiography were compared. Their diagnostic accuracy and correlation with structural and functional parameters were assessed. Results: All peripapillary optical coherence tomography angiography vascular parameters were significantly different among groups (all p < 0.05). The whole image capillary density and peripapillary capillary density by Angiovue were significantly lower in pseudoexfoliation glaucoma compared with primary open-angle glaucoma (p = 0.009 and p = 0.001, respectively). Conversely, vascular parameters by Angioplex were not statistically different between primary open-angle glaucoma and pseudoexfoliation glaucoma. A good correlation was found using Angiovue between whole image capillary density and visual field mean deviation (0.758, p < 0.001), peripapillary capillary density and visual field mean deviation (0.729, p = 0.001), and peripapillary capillary density and peripapillary retinal nerve fiber layer thickness in eyes with pseudoexfoliation glaucoma (0.716, p = 0.001). Angiovue parameters showed higher area under the receiver operating characteristic curves than Angioplex to discriminate among groups. Conclusion: Only Angiovue detected a significantly lower capillary density in pseudoexfoliation glaucoma compared to primary open-angle glaucoma at similar glaucoma damage. Both, Angiovue and Angioplex demonstrated a decreased capillary density in glaucoma eyes compared to healthy eyes. Furthermore, Angiovue-derived vascular parameters showed better correlation with functional and structural parameters and a higher diagnostic capacity to discriminate among groups compared to Angioplex.
Training a Drug to Do New Tricks: Insights on Stability of Meropenem Administered as a Continuous Infusion
Authors: Venugopalan Veena , Manigaba Kayihura , Borgert Samuel J , Cope Jessica , Peloquin Charles A , Klinker Kenneth P 
Published: October 2018

Background: The antibiotic armamentarium used to combat multi-drug resistant organisms (MDROs) include carbapenems. Continuous infusion (CI) dosing is frequently employed to maximize beta-lactam efficacy; however, use of meropenem CI has been limited due to concerns with product instability. Objective: The primary objective of this study was to quantify meropenem serum concentrations to reflect drug stability when administered as CI over 8- or 12-h exchanges. In addition, a stability experiment was performed to further establish meropenem integrity over 12 h. The secondary objectives were to assess the ability of meropenem to achieve target pharmacokinetic/pharmacodynamic (PK/PD) exposures relative to the minimum inhibitory concentration (MIC) of the pathogen, and to determine clinical cure. Methods: This was a retrospective, observational study on use of CI meropenem (infused either over 8- or 12- h) at a 1% concentration. The stability experiment was conducted on 1% meropenem at room temperature. Results: In 22 patients, a median meropenem daily dose of 6 g/day (range 2-6 g/day) resulted in a median serum concentration of 17.8 mg/L (interquartile range, 9.3-27.8 mg/L). In 95% of cases, meropenem delivered as CI resulted in free drug concentrations at or above the MIC of the pathogen for the entire dosing interval. Clinical cure was achieved in 80% of patients included in this review. The stability experiment revealed negligible drug degradation at the end of the 12-h dosing interval. Conclusions: The data from this study provides compelling evidence for the use of meropenem as CI utilizing either a 12- or 8-h exchange process.
Prevalence and correlates of stimulant and depressant pharmacological cognitive enhancement among Norwegian students
Authors: Myrseth Helga , Pallesen Ståle , Torsheim Torbjørn , Erevik Eilin Kristine 
Published: October 2018

Aims: To assess the prevalence and factors associated with stimulant and depressant pharmacological cognitive enhancement (PCE) drug use among Norwegian students. Design: In the first wave (T1), 28,553 students were invited to participate, of whom 9370 (32.8%) responded and completed the survey (mean age = 24.9 years, 63.5% female). One year later (T2) those who had responded to some items at T1 were invited to participate in a follow-up survey, where 4783 (47.2%) responded and completed the survey (mean age = 24.8 years, 64.8% female). Results: Lifetime prevalence of stimulant PCE drug use was 2.1% at T1 and 3.6% at T2. The lifetime prevalence of depressant PCE drug use was 1.5% at T1 and 3.3% at T2. Stimulant PCE drug use at T2 was predicted by low scores on agreeableness and anxiety, high scores on intellect/openness, and alcohol use, and stimulant and depressant PCE drug use at T1; while depressant PCE drug use at T2 was predicted by low scores on extroversion, high scores on conscientiousness, intellect/openness, and anxiety, and stimulant and depressant PCE drug use at T1. Conclusions: The rates of stimulant and depressant PCE drug use increased from T1 to T2. Pharmacological cognitive enhancement drug use may be explained by a combination of a motivation for improving academic achievements and a general inclination towards substance use. The current results may suggest that stimulant PCE drug users are more antisocial and indifferent to rules, while depressant PCE drug users are more motivated by coping with stress.
The efficacy and safety of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation and coronary artery disease: A meta-analysis of randomized trials
Authors: Zelniker Thomas A , Ruff Christian T , Antman Elliott M , Giugliano Robert P 
Published: October 2018

Background: Patients with atrial fibrillation and concomitant coronary artery disease (CAD) are at higher risk for myocardial infarction or cardiovascular death, often require antiplatelet therapy and are therefore exposed to an increased risk of bleeding. This meta-analysis aimed to compare the efficacy and safety profile of non-vitamin K antagonist oral anticoagulants (NOACs) with warfarin in patients with atrial fibrillation and concomitant CAD. Materials and methods: We performed a trial-level meta-analysis of CAD subgroups from four trials of NOAC versus warfarin in patients with atrial fibrillation, comparing the primary trial endpoints (efficacy: stroke or systemic embolic event; safety: International Society on Thrombosis and Haemostasis major bleeding) in patients with versus those without CAD, and used interaction testing to assess for treatment effect modification. Results: In total, 58,606 patients with established CAD were included in this meta-analysis. NOACs reduced the risk of stroke/systemic embolic event irrespective of presence of CAD (CAD: 0.76 (0.56–1.04); no CAD: hazard ratio 0.77 (0.56–1.06); p-INT 0.93). Similarly, there was no effect modification by presence of CAD for major bleeding (CAD: hazard ratio 0.92 (0.65–1.32), no CAD: 0.83 (0.61–1.12); p-INT 0.46) or myocardial infarction (CAD: hazard ratio 0.95 (0.62–1.44); no CAD: hazard ratio 0.95 (0.60–1.50); p-INT = 0.98). While NOACs reduced all-cause mortality in patients without CAD compared with warfarin (hazard ratio 0.85 (0.71–1.02)), there was no difference in mortality between NOACs and warfarin in the CAD group (hazard ratio 0.99 (0.82–1.20); p-INT 0.01). Conclusion: The present meta-analysis of four trials supports that NOACs are safe and at least as effective as warfarin in patients with atrial fibrillation and established CAD.
Comparing Five Comorbidity Indices to Predict Mortality in Chronic Kidney Disease: A Retrospective Cohort Study
Authors: McArthur Eric , Bota Sarah E. , Sood Manish M. , Nesrallah Gihad E. , Kim S Joseph , Garg Amit X. , Dixon Stephanie N. 
Published: October 2018

Background: Several different indices summarize patient comorbidity using health care data. An accurate index can be used to describe the risk profile of patients, and as an adjustment factor in analyses. How well these indices perform in persons with chronic kidney disease (CKD) is not well known. Objective: Assess the performance of 5 comorbidity indices at predicting mortality in 3 different patient groups with CKD: incident kidney transplant recipients, maintenance dialysis patients, and individuals with low estimated glomerular filtration rate (eGFR). Design: Population-based retrospective cohort study. Setting: Ontario, Canada, between 2004 and 2014. Patients: Individuals at the time they first received a kidney transplant, received maintenance dialysis, or were confirmed to have an eGFR less than 45 mL/min per 1.73m2. Measurements: Five comorbidity indices: Charlson comorbidity index, end-stage renal disease-modified Charlson comorbidity index, Johns Hopkins’ Aggregated Diagnosis Groups score, Elixhauser score, and Wright-Khan index. Our primary outcome was 1-year all-cause mortality. Methods: Comorbidity indices were estimated using information in the prior 2 years. Each group was randomly divided 100 times into derivation and validation samples. Model discrimination was assessed using median c-statistics from logistic regression models, and calibration was evaluated graphically. Results: We identified 4111 kidney transplant recipients, 23 897 individuals receiving maintenance dialysis, and 181 425 individuals with a low eGFR. Within 1 year, 108 (2.6%), 4179 (17.5%), and 17 898 (9.9%) in each group had died, respectively. In the validation sample, model discrimination was inadequate with median c-statistics less than 0.7 for all 5 comorbidity indices for all 3 groups. Calibration was also poor for all models. Limitations: The study used administrative health care data so there is the potential for misclassification. Indices were modeled as continuous scores as opposed to indicators for individual conditions to limit overfitting. Conclusions: Existing comorbidity indices do not accurately predict 1-year mortality in patients with CKD. Current indices could be modified with additional risk factors to improve their performance in CKD, or a new index could be developed for this population.
Reliability and Validity of the AOSpine Thoracolumbar Injury Classification System: A Systematic Review
Authors: Abedi Aidin , Mokkink Lidwine B. , Zadegan Shayan Abdollah , Paholpak Permsak , Tamai Koji , Wang Jeffrey C. , Buser Zorica 
Published: October 2018

Study Design: Systematic review. Objectives: The AOSpine thoracolumbar injury classification system (ATLICS) is a relatively simple yet comprehensive classification of spine injuries introduced in 2013. This systematic review summarizes the evidence on measurement properties of this new classification, particularly the reliability and validity of the main morphologic injury types with and without inclusion of the subtypes. Methods: A literature search was performed using PubMed and Embase in September 2016. A revised version of the COSMIN checklist was used for evaluation of the quality of studies. Two independent reviewers performed all steps of the review. Results: Nine articles were included in the final review, all of which evaluated the reliability of the ATLICS and had a fair methodological quality. The reliability of the modifiers was unknown. Overall, the quality of evidence for reliability of the morphologic and neurologic classification sections was low. However, there was moderate evidence for poor interobserver reliability of the morphologic classification when all subtypes were included, and moderate evidence for good intraobserver reliability with exclusion of subtypes. The reliability of the morphologic classification was independent of the observer’s experience and cultural background. Conclusions: ATLICS represents the most current system for evaluation of thoracolumbar injuries. Based on this review, further studies with robust methodological quality are needed to evaluate the measurement properties of ATLICS. Shortcomings of the reliability studies are discussed.
Inverted C-arm Orientation During Simulated Hip Arthroscopic Surgery
Authors: Nadig Nischal , Shaw Kenneth Aaron , Mottern Edward , Bojescul John , Mueller Terry 
Published: October 2018

Background: Fluoroscopic guidance is routinely utilized during hip arthroscopic surgery. Previous studies have shown that the C-arm orientation can significantly affect radiation exposure for both the surgeon and the patient during orthopaedic procedures. However, this has not been previously assessed for hip arthroscopic surgery. Hypothesis: Using an inverted C-arm during hip arthroscopic surgery will reduce radiation exposure to the patient and surgeon. Study Design: Descriptive laboratory study. Methods: A simulation study measured scatter radiation during hip arthroscopic surgery performed in the supine position under fluoroscopic guidance with an anthropomorphic pelvic phantom on a radiolucent operating table. Radiation exposure tested 2 different C-arm orientations: standard and inverted. Testing was performed at 6 locations corresponding to the patient, surgeon’s neck, surgeon’s waist, surgical technician, anesthesiologist, and radiology technician. Statistical analysis was performed using univariate and multivariate analyses assessing radiation exposure between the C-arm orientations. A risk calculation for carcinogenesis was performed based on reported radiation dosages. Results: Radiation exposure (in mGy/min) was more than 100-fold higher for the patient compared with the surgeon in both C-arm orientations. The inverted C-arm orientation resulted in a 2.48-fold decrease in patient radiation exposure when compared with the standard orientation (10.8 mGy/min vs 26.8 mGy/min, respectively). There was a small but significant increase in surgeon radiation exposure in the inverted orientation compared with the standard orientation (0.072 vs 0.067 mGy/min, respectively). The patient’s carcinogenesis risk was decreased 2.64-fold with the inverted orientation compared with the standard orientation (1.4 × 10–5 vs 3.7 × 10–5, respectively). Conclusion: The inverted C-arm orientation resulted in a 2.48-fold decrease in patient radiation exposure with a 2.64-fold decrease in the carcinogenesis risk compared with the standard orientation. Inadvertently, the inverted orientation provided a 9-cm increase in the surgeon’s working area. Our data supported the clinical utilization of the inverted C-arm orientation during hip arthroscopic surgery to minimize patient radiation exposure. Although there was a minimal but significant increase in surgeon radiation exposure with the inverted orientation, we believe that this is negligible when incorporated with standard leaded protective equipment as contrasted with the significant dose reduction for the patient as well as the decreased risk of carcinogenesis and hereditary disorders. Clinical Relevance: Patients undergoing hip arthroscopic surgery routinely acquire radiation exposure during the use of the C-arm. Measures to minimize radiation via the inverted C-arm orientation will decrease the unnecessary risk to the patient while continuing to allow for optimal treatment.
Monocyte-derived macrophages expand the murine stress erythropoietic niche during the recovery from anemia
Authors: Liao Chang , Prabhu K. Sandeep , Paulson Robert F. 
Published: October 2018

Abstract
Anemic stress induces a physiological response that includes the rapid production of new erythrocytes. This process is referred to as stress erythropoiesis. It is best understood in the mouse where it is extramedullary and utilizes signals and progenitor cells that are distinct from bone marrow steady-state erythropoiesis. The development of stress erythroid progenitors occurs in close association with the splenic stress erythropoiesis niche. In particular, macrophages in the niche are required for proper stress erythropoiesis. Here we show that the expansion of the niche occurs in concert with the proliferation and differentiation of stress erythroid progenitors. Using lineage tracing analysis in 2 models of anemic stress, we show that the expansion of the splenic niche is due to the recruitment of monocytes into the spleen, which develop into macrophages that form erythroblastic islands. The influx in monocytes into the spleen depends in part on Ccr2-dependent signaling mediated by Ccl2 and other ligands expressed by spleen resident red pulp macrophages. Overall, these data demonstrate the dynamic nature of the spleen niche, which rapidly expands in concert with the stress erythroid progenitors to coordinate the production of new erythrocytes in response to anemic stress.
Targeted inhibition of PI3Kα/δ is synergistic with BCL-2 blockade in genetically defined subtypes of DLBCL
Authors: Bojarczuk Kamil , Wienand Kirsty , Ryan Jeremy A. , Chen Linfeng , Villalobos-Ortiz Mariana , Mandato Elisa , Stachura Joanna , Letai Anthony , Lawton Lee N. , Chapuy Bjoern , Shipp Margaret A. 
Published: October 2018

Abstract
Inhibition of the B-cell receptor (BCR) signaling pathway is a promising treatment strategy in multiple B-cell malignancies. However, the role of BCR blockade in diffuse large B-cell lymphoma (DLBCL) remains undefined. We recently characterized primary DLBCL subsets with distinct genetic bases for perturbed BCR/phosphoinositide 3-kinase (PI3K) signaling and dysregulated B-cell lymphoma 2 (BCL-2) expression. Herein, we explore the activity of PI3K inhibitors and BCL-2 blockade in a panel of functionally and genetically characterized DLBCL cell line models. A PI3K inhibitor with predominant α/δ activity, copanlisib, exhibited the highest cytotoxicity in all BCR-dependent DLBCLs. The proapoptotic effect of copanlisib was associated with DLBCL subtype-specific dysregulated expression of BCL-2 family members including harakiri (HRK) and its antiapoptotic partner BCL extra large (BCL-xL), BCL2 related protein A1, myeloid cell leukemia 1 (MCL-1), and BCL2 interacting mediator of cell death. Using functional BH3 profiling, we found that the cytotoxic activity of copanlisib was primarily mediated through BCL-xL and MCL-1–dependent mechanisms that might complement BCL-2 blockade. For these reasons, we evaluated single-agent activity of venetoclax in the DLBCLs and identified a subset with limited sensitivity to BCL-2 blockade despite having genetic bases of BCL-2 dysregulation. As these were largely BCR-dependent DLBCLs, we hypothesized that combined inhibition of PI3Kα/δ and BCL-2 would perturb BCR-dependent and BCL-2–mediated survival pathways. Indeed, we observed synergistic activity of copanlisib/venetoclax in BCR-dependent DLBCLs with genetic bases for BCL-2 dysregulation in vitro and confirmed these findings in a xenograft model. These results provide preclinical evidence for the rational combination of PI3Kα/δ and BCL-2 blockade in genetically defined DLBCLs.
PANOPLY: Omics-Guided Drug Prioritization Method Tailored to an Individual Patient
Authors: Kalari Krishna R. , Sinnwell Jason P. , Thompson Kevin J. , Tang Xiaojia , Carlson Erin E. , Yu Jia , Vedell Peter T. , Ingle James N. , Weinshilboum Richard M. , Boughey Judy C. , Wang Liewei , Goetz Matthew P. , Suman Vera 
Published: October 2018

Purpose The majority of patients with cancer receive treatments that are minimally informed by omics data. We propose a precision medicine computational framework, PANOPLY (Precision Cancer Genomic Report: Single Sample Inventory), to identify and prioritize drug targets and cancer therapy regimens. Materials and Methods The PANOPLY approach integrates clinical data with germline and somatic features obtained from multiomics platforms and applies machine learning and network analysis approaches in the context of the individual patient and matched controls. The PANOPLY workflow uses the following four steps: selection of matched controls to the patient of interest; identification of patient-specific genomic events; identification of suitable drugs using the driver-gene network and random forest analyses; and provision of an integrated multiomics case report of the patient with prioritization of anticancer drugs. Results The PANOPLY workflow can be executed on a stand-alone virtual machine and is also available for download as an R package. We applied the method to an institutional breast cancer neoadjuvant chemotherapy study that collected clinical and genomic data as well as patient-derived xenografts to investigate the prioritization offered by PANOPLY. In a chemotherapy-resistant patient-derived xenograft model, we found that that the prioritized drug, olaparib, was more effective than placebo in treating the tumor ( P < .05). We also applied PANOPLY to in-house and publicly accessible multiomics tumor data sets with therapeutic response or survival data available. Conclusion PANOPLY shows promise as a means to prioritize drugs on the basis of clinical and multiomics data for an individual patient with cancer. Additional studies are needed to confirm this approach.
Results From a Health Insurer's Clinical Pathway Program in Breast Cancer
Authors: Gautam Santosh , Sylwestrzak Gosia , Barron John , Chen Xiaoxue , Eleff Michael , Debono David , Nguyen Ann , Fisch Michael 
Published: October 2018

Purpose: Pathway regimens are value-driven, evidence-based therapies that aim at high-quality, affordable cancer care. There are few real-world data to support the value of such regimens, especially for patients with breast cancer. Materials and Methods: Using nationally representative claims data from Anthem, together with clinical data from its Cancer Care Quality Program, we identified patients with breast cancer for whom chemotherapy was initiated between January 2015 and October 2016. On the basis of demographic and clinical characteristics, patients receiving a pathway regimen (on-pathway cohort) were matched to those who did not (off-pathway cohort) using 1:1 propensity score matching. We compared post–6-month quality-of-care outcomes including hospitalization, emergency department visits, need for supportive drugs such as granulocyte colony-stimulating factor, and cost outcomes between the cohorts. Results: There were 959 patients in each cohort after matching. Patients in both cohorts had a similar age distribution (median age, 52 years in the off-pathway cohort v 53 years in the on-pathway cohort), and most presented with stage II disease (49.4% in the off-pathway cohort v 49.8% in the on-pathway cohort); nearly two thirds of each cohort had hormone receptor positive cancer (67.3% in the off-pathway cohort v 64.9% in the on-pathway cohort). The two cohorts had similar rates of hospitalization and emergency department visits; however, the rate of granulocyte colony-stimulating factor use was significantly lower in the on-pathway cohort (72.5% in the on-pathway cohort v 82.8% in the off-pathway cohort; odds ratio, 0.55; P ≤ .0001). The average post–6-month cost of care was $16,176 lower (95% CI, −$24,291 to −$8,061; P ≤ .0001) in the on-pathway cohort. Conclusion: Pathway regimens for breast cancer demonstrate an example of high-value care. They are associated with a reduced cost of care without compromising quality of care.