bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tall Man lettering and potential prescription errors: a time series analysis of 42 children's hospitals in the USA over 9 years
Authors: Zhong Wenjun , Feinstein James A , Patel Neil S , Dai Dingwei , Feudtner Chirs 
Published: November 2015

BackgroundDespite the widespread implementation of Tall Man lettering, little evidence exists regarding whether this technique has reduced drug errors due to look-alike sound-alike (LA-SA) drug names. This study evaluated rates of potential LA-SA drug errors in the drug management process through to the point of dispensing before and after implementation of Tall Man lettering in 2007.MethodsWe used detailed pharmacy data for paediatric inpatients (<21 years old) from 42 children's hospitals in 2004–2012. After prespecifying a set of 8 potential LA-SA drug error patterns we searched within each hospitalisation for the occurrence of one of these patterns for a total of 12 LA-SA drug pairs deemed highly relevant to paediatric inpatients. To assess for potential change of error rates before and after Tall Man lettering implementation, we performed segmented regression analyses for each of 11 LA-SA drug pairs (because 1 pair had no detected potential errors) and for the overall total errors of all 11 LA-SA drug pairs.ResultsAmong 1 676 700 hospitalisations, no statistically significant change was detected for either the intercept or the slope of LA-SA error rate for each of the 11 drug pairs or for the combined error rate. In a sensitivity analysis of the moving average of the potential error rate over the entire study period, no downward trend in potential LA-SA drug error rates was evident over any time period 2004 onwards.ConclusionsImplementation of Tall Man lettering in 2007 was not associated with a reduction in the potential LA-SA error rate. Whether Tall Man lettering is effective in clinical practice warrants further study.
Using voluntary reports from physicians to learn from diagnostic errors in emergency medicine
Authors: Okafor Nnaemeka , Payne Velma L , Chathampally Yashwant , Miller Sara , Doshi Pratik , Singh Hardeep 
Published: November 2015

ObjectivesDiagnostic errors are common in the emergency department (ED), but few studies have comprehensively evaluated their types and origins. We analysed incidents reported by ED physicians to determine disease conditions, contributory factors and patient harm associated with ED-related diagnostic errors.MethodsBetween 1 March 2009 and 31 December 2013, ED physicians reported 509 incidents using a department-specific voluntary incident-reporting system that we implemented at two large academic hospital-affiliated EDs. For this study, we analysed 209 incidents related to diagnosis. A quality assurance team led by an ED physician champion reviewed each incident and interviewed physicians when necessary to confirm the presence/absence of diagnostic error and to determine the contributory factors. We generated descriptive statistics quantifying disease conditions involved, contributory factors and patient harm from errors.ResultsAmong the 209 incidents, we identified 214 diagnostic errors associated with 65 unique diseases/conditions, including sepsis (9.6%), acute coronary syndrome (9.1%), fractures (8.6%) and vascular injuries (8.6%). Contributory factors included cognitive (n=317), system related (n=192) and non-remedial (n=106). Cognitive factors included faulty information verification (41.3%) and faulty information processing (30.6%) whereas system factors included high workload (34.4%) and inefficient ED processes (40.1%). Non-remediable factors included atypical presentation (31.3%) and the patients’ inability to provide a history (31.3%). Most errors (75%) involved multiple factors. Major harm was associated with 34/209 (16.3%) of reported incidents.ConclusionsMost diagnostic errors in ED appeared to relate to common disease conditions. While sustaining diagnostic error reporting programmes might be challenging, our analysis reveals the potential value of such systems in identifying targets for improving patient safety in the ED.
Diagnosis of acute ischemia using dual energy CT after mechanical thrombectomy
Authors: Gariani Joanna , Cuvinciuc Victor , Courvoisier Delphine , Krauss Bernhard , Mendes Pereira Vitor , Sztajzel Roman , Lovblad Karl-Olof , Vargas Maria Isabel 
Published: November 2015

Background and purposeTo assess the performance of dual energy unenhanced CT in the detection of acute ischemia after mechanical thrombectomy.MethodsRetrospective study, approved by the local institutional review board, including all patients that underwent intra-arterial thrombectomy in our institution over a period of 2 years. The presence of acute ischemia and hemorrhage was evaluated by three readers. Sensitivity and specificity of the non-contrast CT weighted sum image (NCCT) and the virtual non-contrast reconstructed image (VNC) were estimated and compared using generalized estimating equations to account for the non-independence of regions in each patient.Results58 patients (27 women and 31 men; mean age 70.4 years) were included in the study, yielding 580 regions of interest. Sensitivity and specificity in detecting acute ischemia were higher for all readers when using VNC, with a significant increase in sensitivity for two readers (p<0.001 and 0.01) and a significant increase in specificity in one reader (p<0.001). Specificity in detecting hemorrhage was excellent for all readers.ConclusionsDual energy unenhanced CT VNC images were superior in the identification of acute ischemia in comparison with NCCT.
Copeptin in patients with heart failure and preserved ejection fraction: a report from the prospective KaRen-study
Authors: Hage Camilla , Lund Lars H , Donal Erwan , Daubert Jean-Claude , Linde Cecilia , Mellbin Linda 
Published: November 2015

IntroductionUnderlying mechanisms of heart failure (HF) with preserved ejection fraction (HFPEF) remain unknown. We explored copeptin, a biomarker of the arginine vasopressin system, hypothesising that copeptin in HFPEF is elevated, associated with diastolic dysfunction and N-terminal pro-brain natriuretic peptide (NT-proBNP) and predictive of HF hospitalisation and mortality.Methods and analysisIn a prospective observational substudy of the The Karolinska Rennes (KaRen) 86 patients with symptoms of acute HF and ejection fraction (EF) ≥45% were enrolled. After 4–8 weeks, blood sampling and echocardiography was performed. Plasma-copeptin was analysed in 86 patients and 62 healthy controls. Patients were followed in median 579 days (quartile 1; quartile 3 (Q1;Q3) 276;1178) regarding the composite end point all-cause mortality or HF hospitalisation.Ethics and disseminationThe patients with HFPEF had higher copeptin levels, median 13.56 pmol/L (Q1;Q3 8.56;20.55) than controls 5.98 pmol/L (4.15;9.42; p<0.001). Diastolic dysfunction, assessable in 75/86 patients, was present in 45 and absent in 30 patients. Copeptin did not differ regarding diastolic dysfunction and did not correlate with cardiac function but with NT-proBNP (r=0.223; p value=0.040). In univariate Cox regression analysis log copeptin predicted the composite end point (HR 1.56 (95% CI 1.03 to 2.38; p value=0.037)) but not after adjusting for NT-proBNP (HR 1.39 (95% CI 0.91 to 2.12; p value=0.125)).ConclusionsIn the present patients with HFPEF, copeptin is elevated, correlates with NT-proBNP but not markers of diastolic dysfunction, and has prognostic implications, however blunted after adjustment for NT-proBNP. The HFPEF pathophysiology may be better reflected by markers of neurohormonal activation than by diastolic dysfunction.Trial registration numberClinicalTrials.govNCT00774709.
Preliminary application of a single‐port access technique for laparoscopic ovariohysterectomy in dogs
Authors: Sánchez‐Margallo F. M. , Tapia‐Araya A. , Díaz‐Güemes I. 
Published: November 2015

Laparoscopic ovariohysterectomy using single‐portal access was performed in nine selected owned dogs admitted for elective ovariohysterectomy and the surgical technique and outcomes were detailed. A multiport device (SILS Port, Covidien, USA) was placed at the umbilical area through a single 3 cm incision. Three cannulae were introduced in the multiport device through the access channels and laparoscopic ovariohysterectomy was performed using a 5‐mm sealing device, a 5‐mm articulating grasper and a 5‐mm 30° laparoscope. The mean total operative time was 52.66±15.20 minutes and the mean skin incision during surgery was 3.09±0.20 cm. Of the nine cases examined, in the one with an ovarian tumour, the technique was converted to multiport laparoscopy introducing an additional 5‐mm trocar. No surgical complications were encountered and intraoperative blood loss was minimum in all animals. Clashing of the instruments and reduced triangulation were the main limitations of this technique. The combination of articulated and straight instruments facilitated triangulation towards the surgical field and dissection capability. One month after surgery a complete wound healing was observed in all animals. The present data showed that ovariohysterectomy performed with a single‐port access is technically feasible in dogs. The unique abdominal incision minimises the abdominal trauma with good cosmetic results.
Nrf2 Activation Promotes Keratinocyte Survival during Early Skin Carcinogenesis via Metabolic Alterations
Authors: Rolfs Frank , Huber Marcel , Kuehne Andreas , Kramer Stefan , Haertel Eric , Muzumdar Sukalp , Wagner Johanna , Tanner Yasmine , Böhm Friederike , Smola Sigrun , Zamboni Nicola , Levesque Mitchell P. , Dummer Reinhard , Beer Hans-Dietmar , Hohl Daniel , Werner Sabine , Schäfer Matthias 
Published: November 2015

Abstract
Pharmacologic activation of the transcription factor NRF2 has been suggested to offer a strategy for cancer prevention. In this study, we present evidence from murine tumorigenesis experiments suggesting there may be limitations to this possibility, based on tumorigenic effects of Nrf2 in murine keratinocytes that have not been described previously. In this setting, Nrf2 expression conferred metabolic alterations in keratinocytes that were protumorigenic in nature, affecting enzymes involved in glutathione biosynthesis or in the oxidative pentose phosphate pathway and other NADPH-producing enzymes. Under stress conditions, coordinate increases in NADPH, purine, and glutathione levels promoted the survival of keratinocytes harboring oncogenic mutations, thereby promoting tumor development. The protumorigenic activity of Nrf2 in keratinocytes was particularly significant in a mouse model of skin tumorigenesis that did not rely upon chemical carcinogenesis. In exploring the clinical relevance of our findings, we confirm that NRF2 and protumorigenic NRF2 target genes were activated in some actinic keratoses, the major precancerous lesion in human skin. Overall, our results reveal an unexpected tumor-promoting activity of activated NRF2 during early phases of skin tumorigenesis. Cancer Res; 75(22); 4817–29. ©2015 AACR.
Phase I Clinical Trial of Ipilimumab in Pediatric Patients with Advanced Solid Tumors
Authors: Merchant Melinda S. , Wright Matthew , Baird Kristin , Wexler Leonard H. , Rodriguez-Galindo Carlos , Bernstein Donna , Delbrook Cindy , Lodish Maya , Bishop Rachel , Wolchok Jedd D. , Streicher Howard , Mackall Crystal L. 
Published: November 2015

Abstract
Purpose: Ipilimumab is a first-in-class immune checkpoint inhibitor approved for treatment of metastatic melanoma but not studied in children until this phase I protocol.
Experimental Design: This study examined safety, pharmacokinetics, and immunogenicity, and immune correlates of ipilimumab administered to subjects ≤21 years old with recurrent or progressive solid tumors. Dose escalation cohorts received 1, 3, 5, or 10 mg/m2 intravenously every 3 weeks in a 3 + 3 design. Response was assessed after 6 weeks and 12 weeks, and then every 3 months. Treatment was continued until disease progression or unacceptable toxicity.
Results: Thirty-three patients received 72 doses of ipilimumab. Patients enrolled had melanoma (n = 12), sarcoma (n = 17), or other refractory solid tumors (n = 4). Immune-related adverse events included pancreatitis, pneumonitis, colitis, endocrinopathies, and transaminitis with dose-limiting toxicities observed at 5 and 10 mg/kg dose levels. Pharmacokinetics revealed a half-life of 8 to 15 days. At day 21, subjects had increased levels of cycling T cells, but no change in regulatory T-cell populations. Six subjects had confirmed stable disease for 4 to 10 cycles (melanoma, osteosarcoma, clear cell sarcoma, and synovial sarcoma).
Conclusions: Ipilimumab was safely administered to pediatric patients using management algorithms for immune-related toxicities. The spectrum of immune-related adverse events is similar to those described in adults; however, many of the pediatric toxicities were evident after a single dose. Although no objective tumor regressions were observed with ipilimumab as a single agent, subjects with immune-related toxicities had an increased overall survival compared with those who showed no evidence of breaking tolerance. Clin Cancer Res; 22(6); 1364–70. ©2015 AACR.
Treatment Response Assessment in IDH-Mutant Glioma Patients by Noninvasive 3D Functional Spectroscopic Mapping of 2-Hydroxyglutarate
Authors: Andronesi Ovidiu C. , Loebel Franziska , Bogner Wolfgang , Marjańska Małgorzata , Vander Heiden Matthew G. , Iafrate A. John , Dietrich Jorg , Batchelor Tracy T. , Gerstner Elizabeth R. , Kaelin William G. , Chi Andrew S. , Rosen Bruce R. , Cahill Daniel P. 
Published: November 2015

AbstractPurpose: Measurements of objective response rates are critical to evaluate new glioma therapies. The hallmark metabolic alteration in gliomas with mutant isocitrate dehydrogenase (IDH) is the overproduction of oncometabolite 2-hydroxyglutarate (2HG), which plays a key role in malignant transformation. 2HG represents an ideal biomarker to probe treatment response in IDH-mutant glioma patients, and we hypothesized a decrease in 2HG levels would be measureable by in vivo magnetic resonance spectroscopy (MRS) as a result of antitumor therapy.Experimental Design: We report a prospective longitudinal imaging study performed in 25 IDH-mutant glioma patients receiving adjuvant radiation and chemotherapy. A newly developed 3D MRS imaging was used to noninvasively image 2HG. Paired Student t test was used to compare pre- and posttreatment tumor 2HG values. Test–retest measurements were performed to determine the threshold for 2HG functional spectroscopic maps (fSM). Univariate and multivariate regression were performed to correlate 2HG changes with Karnofsky performance score (KPS).Results: We found that mean 2HG (2HG/Cre) levels decreased significantly (median = 48.1%; 95% confidence interval = 27.3%–56.5%; P = 0.007) in the posttreatment scan. The volume of decreased 2HG correlates (R2 = 0.88, P = 0.002) with clinical status evaluated by KPS.Conclusions: We demonstrate that dynamic measurements of 2HG are feasible by 3D fSM, and the decrease of 2HG levels can monitor treatment response in patients with IDH-mutant gliomas. Our results indicate that quantitative in vivo 2HG imaging may be used for precision medicine and early response assessment in clinical trials of therapies targeting IDH-mutant gliomas. Clin Cancer Res; 22(7); 1632–41. ©2015 AACR.
Decade‐Long Trends in 30‐Day Rehospitalization Rates After Acute Myocardial Infarction
Authors: Chen Han‐Yang , Tisminetzky Mayra , Lapane Kate L. , Yarzebski Jorge , Person Sharina D. , Kiefe Catarina I. , Gore Joel M. , Goldberg Robert J. 
Published: November 2015

Background

There are limited data available describing relatively contemporary trends in 30‐day rehospitalizations among patients who survive hospitalization after an acute myocardial infarction (AMI) in the community setting. We examined decade‐long (2001–2011) trends in, and factors associated with, 30‐day rehospitalizations in patients discharged from 3 central Massachusetts hospitals after
AMI
.

Methods and Results

Residents of the Worcester,
MA
, metropolitan area discharged after AMI from 3 central Massachusetts hospitals on a biennial basis between 2001 and 2011 comprised the study population (N=4810). Logistic regression analyses were used to examine the association between selected factors and 30‐day rehospitalizations. The average age of this population was 69 years, 42% were women, and 92% were white. During the years under study, 18.5% of patients were rehospitalized within 30 days after hospital discharge. Crude 30‐day rehospitalization rates decreased from 20.5% in 2001–2003 to 15.8% in 2009–2011. After adjusting for several patient characteristics, there was a reduced odds of being rehospitalized in 2009–2011 (odds ratio 0.74, 95%
CI
0.61–0.91) compared with 2001–2003; this trend was slightly attenuated after further adjustment for hospital treatment practices. Female sex, having previously diagnosed heart failure and chronic kidney disease, and the development of in‐hospital cardiogenic shock and heart failure were associated with an increased odds of being rehospitalized.

Conclusions
While the likelihood of subsequent short‐term rehospitalizations remained frequent, we observed an encouraging decline during the most recent years under study. Several high‐risk groups were identified for purposes of heightened surveillance and intervention efforts to reduce the likelihood of being readmitted.
Increasing the Diversity of Your Graduate Program: Translating Best Practices into Success
Authors: Burt Melissa A. , Haacker Rebecca , Batchelor Rebecca L. , Denning A. Scott 
Published: November 2015

Abstract
Despite awareness in the geosciences that our field has a substantial lack of diversity in our workforce and student body, and countless efforts to broaden participation, graduate enrollment in the atmospheric sciences by students who are from traditionally underrepresented groups (i.e., African American, Hispanic, and American Indian students) is only slowly increasing, from 6% in 2005 to about 8.5% currently. In 2005, the Department of Atmospheric Science at Colorado State University (CSU) had a minority enrollment of 3.5%, which was lower than the national enrollment statistics of 6.0%. Through a concerted effort to better reflect the demographic makeup of the United States, the department now boasts a figure closer to 16%. Our students do cutting-edge research, participate in field campaigns, and are actively involved in professional societies, such as the American Meteorological Society (AMS). We expect that many of our students will become faculty or researchers and hopefully will mentor students themselves one day. Our article highlights the strategic initiative we have used to increase the diversity in atmospheric science, in hopes that our findings can present a model that can be replicated in other geoscience departments across the nation.
Climate Change Implications for Tropical Islands: Interpolating and Interpreting Statistically Downscaled GCM Projections for Management and Planning
Authors: Khalyani Azad Henareh , Gould William A. , Harmsen Eric , Terando Adam , Quinones Maya , Collazo Jaime A. 
Published: November 2015

AbstractThe potential ecological and economic effects of climate change for tropical islands were studied using output from 12 statistically downscaled general circulation models (GCMs) taking Puerto Rico as a test case. Two model selection/model averaging strategies were used: the average of all available GCMs and the average of the models that are able to reproduce the observed large-scale dynamics that control precipitation over the Caribbean. Five island-wide and multidecadal averages of daily precipitation and temperature were estimated by way of a climatology-informed interpolation of the site-specific downscaled climate model output. Annual cooling degree-days (CDD) were calculated as a proxy index for air-conditioning energy demand, and two measures of annual no-rainfall days were used as drought indices. Holdridge life zone classification was used to map the possible ecological effects of climate change. Precipitation is predicted to decline in both model ensembles, but the decrease was more severe in the “regionally consistent” models. The precipitation declines cause gradual and linear increases in drought intensity and extremes. The warming from the 1960–90 period to the 2071–99 period was 4.6°–9°C depending on the global emission scenarios and location. This warming may cause increases in CDD, and consequently increasing energy demands. Life zones may shift from wetter to drier zones with the possibility of losing most, if not all, of the subtropical rain forests and extinction risks to rain forest specialists or obligates.
Atmospheric Responses to North Atlantic SST Anomalies in Idealized Experiments. Part II: North American Precipitation
Authors: Hu Qi , Veres Michael C. 
Published: November 2015

Abstract
This is the second part of a two-part paper that addresses deterministic roles of the sea surface temperature (SST) anomalies associated with the Atlantic multidecadal oscillation (AMO) in variations of atmospheric circulation and precipitation in the Northern Hemisphere, using a sequence of idealized model runs at the spring equinox conditions. This part focuses on the effect of the SST anomalies on North American precipitation. Major results show that, in the model setting closest to the real-world situation, a warm SST anomaly in the North Atlantic Ocean causes suppressed precipitation in central, western, and northern North America but more precipitation in the southeast. A nearly reversed pattern of precipitation anomalies develops in response to the cold SST anomaly. Further examinations of these solutions reveal that the response to the cold SST anomaly is less stable than that to the warm SST anomaly. The former is “dynamically charged” in the sense that positive eddy kinetic energy (EKE) exists over the continent. The lack of precipitation in its southeast is because of an insufficient moisture supply. In addition, the results show that the EKE of the short- (2–6 day) and medium-range (7–10 day) weather-producing processes in North America have nearly opposite signs in response to the same cold SST anomaly. These competing effects of eddies in the dynamically charged environment (elevated sensitivity to moisture) complicate the circulation and precipitation responses to the cold SST anomaly in the North Atlantic and may explain why the model results show more varying precipitation anomalies (also confirmed by statistical test results) during the cold than the warm SST anomaly, as also shown in simulations with more realistic models. Results of this study indicate a need to include the AMO in the right context with other forcings in an effort to improve understanding of interannual-to-multidecadal variations in warm season precipitation in North America.