bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Impact of Maryland's Global Budget Payment Reform on Emergency Department Admission Rates in a Single Health System
Authors: Galarraga Jessica E. , Frohna William J. , Pines Jesse M. 
Published: June 2018

AbstractBackgroundIn 2014, the state of Maryland (MD) moved away from fee‐for‐service payments and into a global budget revenue (GBR) structure where hospitals have a fixed revenue target, independent of patient volume or services provided. We assess the effects of GBR adoption on emergency department (ED) admission decisions among adult encounters.MethodsWe used hospital medical record and billing data from adult ED encounters from January 1, 2011, through December 31, 2015, with four MD hospitals and two District of Columbia (DC) hospitals within the same health system. We performed difference‐in‐differences analysis and calculated the effects of the GBR model on ED admission rates (inpatient and observation) using hospital fixed‐effect regression adjusted for patient, hospital, and community factors. We also examined changes in the distribution of acuity among ED admissions with GBR adoption.ResultsThe study sample included 1,492,953 ED encounters with a mean ED admission rate of 20.5%. The ED admission rate difference pre‐ and post‐GBR was –1.14% (95% confidence interval [CI] = –0.89 to –1.40) for MD hospitals and –0.04% (95% CI = –0.24 to 0.32) for DC hospitals with a difference‐in‐differences result of –1.10% (95% CI = –1.34 to –0.86). This change was attributable to a –3.3% (95% CI = –3.54 to –3.08) decline in inpatient admissions and 2.7% (95% CI = 2.53 to 2.79) increase in observation admissions. Declines in admissions were observed primarily among mild‐to‐moderate severity of illness encounters with a low risk of mortality.ConclusionsWithin the same health system, implementation of global budgeting in MD hospitals was associated with a decline in ED admissions—particularly lower‐acuity admissions—compared to DC hospitals that remained under fee‐for‐service payments.
Executive stock option vesting conditions, corporate governance and CEO attributes: evidence from Australia
Authors: Qu Xin , Percy Majella , Stewart Jenny , Hu Fang 
Published: June 2018

AbstractWe investigate the association between executive stock option (ESO) vesting conditions, corporate governance and CEO attributes. Using observations from the 250 largest Australian firms, we find that stronger corporate governance is positively associated with the length of the vesting period and the use of performance hurdles. We also find that when CEOs approach retirement, firms are more likely to grant longer time‐vesting options but are less likely to impose performance hurdles. Further, more powerful CEOs appear to influence the granting of ESOs with less restrictive vesting conditions. Our findings suggest that both corporate governance and CEO attributes significantly shape the design of ESOs.
Association between COMT SNP variation and timidity in Golden and Labrador Retrievers
Authors: Luo D. , Ma X. , Bai J. , Zhou Z. , Wang F. , Wang A. , Wang J. 
Published: June 2018

SummaryTimidity in dogs is a trait with high heritability. However, the relevant genetic factors and markers associated with this condition are largely unknown. The function of the catechol‐O‐methyl transferase (COMT) gene has been found to be associated with human fearful or anxious emotions, and the COMT:p.Val158Met polymorphism locus is significantly related to anxious behavior. In the present study, the correlation between timidity and four single nucleotide polymorphism (SNP) variations (C.‐1666C>G c.39A>G, c.216G>A, c.482G>A) of the COMT gene was investigated in dogs. The evaluation was based on the dog courage assessment assay and a genotype and haplotype analysis in Labrador Retrievers (LR) and Golden Retrievers (GR). The principal components analysis factor structure of the courage phenotype was invariant between LR and GR. Sex, breed and age had no statistically significant effect on the timidity of the dogs. All SNP loci detected were in Hardy–Weinberg equilibrium. The c.39A>G locus was removed in the subsequent association analysis due to the significant difference between LR and GR in genotype distributions. Intriguingly, the genotypes and haplotypes of the COMT gene were significantly and highly correlated with the timidity of LR and GR. The A alleles of the COMT:c.216G>A and c.482G>A loci appeared to play a dominant role in the timid behavior of the dogs. This result supports and broadens the warrior/worrier hypothesis and will have important implications for the understanding of the evolution of temperament in dogs. Additionally, the results provide predictive genetic markers for temperament in dogs.
Observation of “complete clinical response” in rectal cancer after neoadjuvant chemoradiation: The Flinders experience
Authors: Sposato Luigi A. , Lam Yick , Karapetis Chris , Vatandoust Sina , Roy Amitesh , Hakendorf Paul , Dwyer Andrew , de Fontgalland Dayan , Hollington Paul , Wattchow David 
Published: June 2018

AbstractAimObservation with close follow‐up (“watch and wait”) is a recognized treatment option in patients who achieve a complete clinical response to long course chemoradiotherapy. This review of a prospective database aims to evaluate the clinical outcomes among patients with a complete clinical response managed with observation.MethodsA prospective study of 32 patients who achieved a complete clinical response was undertaken. The primary outcomes measured were overall and recurrence‐free survival, and rate of organ preservation in patients who deferred immediate surgery.ResultsSeven patients developed local regrowth over a median follow‐up period of 38 months (range, 9–91 months). Median time to detection was 12 months. All seven underwent salvage surgery with complete surgical clearance. One patient developed combined local and systemic recurrence following a low anterior resection. Organ preservation was possible in 25 (78%) patients who sustained a complete clinical response with no evidence of local regrowth or disease recurrence. Among the patients who sustained a complete response, two developed isolated systemic disease. Overall and recurrence‐free survival was 95.7% and 87.0%, respectively.ConclusionThe majority of patients with rectal cancer who achieved a complete clinical response after chemoradiotherapy and managed with a “watch and wait” approach preserved their rectum and did not develop cancer relapse. Salvage surgery was achieved in all patients who developed local regrowth. The study supports a period of observation in rectal cancer patients who achieve a complete clinical response.
The changing paradigm of management in melanoma brain metastases
Authors: Ladwa Rahul , Atkinson Victoria 
Published: June 2018

AbstractAimImproved systemic treatment has improved the prognosis of metastatic melanoma (MM). However, brain metastases (BMs) are a frequent complication. We aimed to explore the outcome of these patients with modern therapeutic options.MethodWe retrospectively analyzed 142 patients diagnosed with BM from MM at two institutions in Brisbane, Queensland, Australia during 2009–2016. Basic clinico‐pathological parameters, treatments used and mortality data were collected.ResultsWith a median follow‐up of 8 months, 115 patients had died, 112 from MM and 99 from neurologic death. Management included ablative therapy (n = 8), ablative therapy with targeted/immunotherapy (n = 54), targeted/immunotherapy (n = 55) and whole‐brain radiotherapy/best supportive care (n = 25). The median overall survival (OS) was 8 (6.9–9.1) months. Statistically improved OS was found with the use of ablative techniques and BRAF/MEK tyrosine kinase inhibitor (TKI) post diagnosis of BM. In BRAF mutant patients (n = 117) who were TKI naïve at diagnosis of BM (n = 60), the median OS was 9 (6.2–11.8) months versus 5 (1.1–8.9) months in patients who developed BM on TKI treatment (P = 0.001). A complete intracranial response rate occurred in 12% of patients who had immunotherapy (n = 65) with all but two patients receiving stereotactic radiosurgery and no deaths have occurred in this group.ConclusionsThe outcomes of those with BM remain poor, particularly of those with BRAF mutant MM who fail TKI therapy with new BM. Most patients present with multiple BM and death is frequently due to neurological progressive disease. The use of ablative techniques and TKI use confers a longer OS in selected patients.
UGT1A1*6 and UGT1A1*28 polymorphisms are correlated with irinotecan‐induced toxicity: A meta‐analysis
Authors: Yang Yuwei , Zhou MengMeng , Hu Mingjun , Cui Yanjie , Zhong Qi , Liang Ling , Huang Fen 
Published: June 2018

AbstractBackgroundPrevious articles explored the role of UGT1A1 polymorphism on predicting irinotecan‐induced toxicity, but the conclusions were still inconsistent and not comprehensive. We performed this meta‐analysis to investigate the association between UGT1A1 polymorphism and irinotecan‐induced toxicity.MethodsPubMed and Web of Science were searched for articles before July 2017. Inclusion and exclusion criteria were set to select eligible articles, and corresponding data were extracted from those articles. Subgroup analyses based on different cancer categories, doses and races were carried out to achieve comprehensive results. Statistical analyses were conducted using STATA 11.0.ResultsA total of 38 studies with 6742 cases were included after reading full text. Both UGT1A1*6 and UGT1A1*28 polymorphism are significantly associated with severe irinotecan‐induced toxicity. Both Asian and Caucasian cancer patients with UGT1A1*28 variant had an increased risk. Compared with heterozygous variant, patients with homozygous variant suffered from a higher risk of toxicity. The effect of UGT1A1*28 polymorphism on diarrhea was less than on neutropenia. Subgroup analysis exhibited that for UGT1A1*6 polymorphism, patients treated with low‐dose irinotecan were at a notable risk of toxicity. Moreover, the association between UGT1A1*6 polymorphism and irinotecan‐induced toxicity was found in patients suffering from respiratory system cancers.ConclusionsBoth UGT1A1*6 and UGT1A1*28 polymorphisms can be considered as predictors of irinotecan‐induced toxicity, with effect varying by race, cancer type and irinotecan dose.
Long‐term effect of exemestane therapy on bone mineral density supported by bisphosphonates: Results of 5‐year adjuvant treatment in postmenopausal women with early‐stage breast cancer
Authors: Hirano Akira , Inoue Hiroaki , Ogura Kaoru , Hattori Akinori , Yukawa Hiroko , Sakaguchi Shiho , Matsuoka Aya , Tanaka Natsuko , Kodera Asaka , Kamimura Mari , Naritaka Yoshihiko , Shimizu Tadao 
Published: June 2018

AbstractPurposeUnlike anastrozole, the effect of long‐term exemestane (EXE) therapy on bone mineral density (BMD) is still unknown. We assessed changes in BMD from baseline to 5 years of EXE treatment.MethodsPostmenopausal women with endocrine‐responsive breast cancer receiving EXE as adjuvant therapy were enrolled in this study. EXE was administered for 5 years. The BMD of the lumbar spine (LS) and femoral neck (FN) was assessed by dual‐energy X‐ray absorptiometry at baseline and after 6 months and 1, 2, 3, 4, 5 and 6 years. Oral bisphosphonate (Bis) treatment was initiated when patients were diagnosed with osteoporosis with a T‐score of −2.5 or lower.ResultsEighty‐one patients were enrolled in the study between 2005 and 2010. The median follow‐up period was 54.9 months. Forty‐two patients were administered Bis. Overall, the BMD of the LS increased by 7.3% from baseline and that of the FN increased by 3.4% with 5 years of EXE treatment. At the sixth year (i.e. 1 year after the treatment), BMD of the LS increased by 7.2% and that of the FN increased by 5.7%. Furthermore, the BMD of the FN increased by 12.0% in patients treated upfront with Bis and by 1.2% in those not treated with Bis (P = 0.0262). Fractures developed in nine patients (11.1%) and seven (8.6%) had fragility fractures.ConclusionOral Bis improves BMD of the FN in patients with osteoporosis. Five‐year EXE treatment with proper addition of Bis helps maintain the BMD of the LS and FN at the sixth year.
Hypoxia regulates placental angiogenesis via alternatively activated macrophages
Authors: Zhao Hui , Kalish Flora S. , Wong Ronald J. , Stevenson David K. 
Published: June 2018

ProblemUterine and placental macrophages play critical roles in maintaining a normal pregnancy. The majority of these macrophages are believed to be alternatively activated macrophages (M2).Method of StudyMouse bone marrow cells were differentiated into macrophages and polarized to M2 in vitro by treatment with IL‐4 [M2a] or IL‐10 [M2c] and M1 with LPS/IFN‐γ as controls. Macrophage subtypes were confirmed by surface markers and characterized by gene expression profiles.ResultsCompared to M1, M2 showed strong pro‐angiogenic activity by expressing higher mRNA for angiogenic‐associated factors (Cxcl12, Vegfa, PlGF, Mmp2). M2c produced the highest levels of PlGF, Mmp2, and Cxcr4. To mimic the normal placental microenvironment, M2 were exposed to hypoxia and sex hormones (progesterone, estrogen). In both M2c and M2a, severe hypoxic (1%‐3% O2) exposure significantly suppressed PlGF, Cxcl12, and Mmp2 mRNA, but not Vegfa, compared to normoxia (21% O2) or physiological hypoxia (5% O2). mRNA expression returned to normal when hypoxic cells were returned to normoxia. Hypoxia (1%) reduced antioxidant levels in M2 and re‐exposure to normoxia significantly increased superoxide dismutase (Sod1, Sod2) and heme oxygenase‐1 (HO‐1) levels in M2a, and only glutathione peroxidase (Gpx1, Gpx3, Gpx4) in M2c. However, progesterone and estrogen treatment had minimal effects on angiogenic factor expression in M2.ConclusionM2, particularly M2c, displayed strong pro‐angiogenic potential, which decreased under severe hypoxia such as in early pregnancy. Thus, conditions that alter the placental oxygen microenvironment or macrophage response in early pregnancy might cause aberrant angiogenesis and vascular remodeling, and lead to abnormal placental vascular development.
Left bundle branch block: Epidemiology, etiology, anatomic features, electrovectorcardiography, and classification proposal
Authors: Pérez‐Riera Andrés R. , Barbosa‐Barros Raimundo , de Rezende Barbosa Marianne P. C. , Daminello‐Raimundo Rodrigo , de Abreu Luiz C. , Nikus Kjell 
Published: June 2018

AbstractIn left bundle branch block (LBBB), the ventricles are activated in a sequential manner with alterations in left ventricular mechanics, perfusion, and workload resulting in cardiac remodeling. Underlying molecular, cellular, and interstitial changes manifest clinically as changes in size, mass, geometry, and function of the heart. Cardiac remodeling is associated with progressive ventricular dysfunction, arrhythmias, and impaired prognosis. Clinical and diagnostic notions about LBBB have evolved from a simple electrocardiographic alteration to a critically important finding affecting diagnostic and clinical management of many patients. Advances in cardiac magnetic resonance imaging have significantly improved the assessment of patients with LBBB and provided additional insights into pathophysiological mechanisms of left ventricular remodeling. In this review, we will discuss the epidemiology, etiologies, and electrovectorcardiographic features of LBBB and propose a classification of the conduction disturbance.
Use of prescription drugs among women diagnosed with epithelial ovarian cancer in Denmark
Authors: Pottegård Anton , Friis Søren , Verdoodt Freija , Dehlendorff Christian , Hallas Jesper , Kjær Susanne K. 
Published: June 2018

AbstractIntroductionEpithelial ovarian cancer patients often suffer from chronic diseases requiring drug treatment. We assessed temporal patterns of drug use among women with ovarian cancer.Material and methodsWe identified all postmenopausal women with epithelial ovarian cancer in Denmark 2005‐2012 and a comparison cohort of age‐matched women without cancer. We calculated rates of new drug treatment and total drug use and examined use of new and prevalent drugs before and after diagnosis. Analyses were stratified by histological type and stage of epithelial ovarian cancer.ResultsWe identified 2742 patients. The rate of new drug treatment increased from 3 to 5 months before diagnosis and peaked in the first month after diagnosis at 99 new types of drug therapy per 100 individuals (mainly antiemetics, proton‐pump inhibitors, hypnotics, and opioids). Although declining, the rate of new drug use remained substantially higher among epithelial ovarian cancer patients than among controls throughout the 3‐year postdiagnosis follow‐up period. The number of prevalent drugs increased slightly from a median of 4 drugs (interquartile range 2‐7) before diagnosis to 5 drugs (interquartile range 2‐8) shortly after the diagnosis. The use of preventive drugs decreased only slightly after diagnosis. In stratified analyses, we found limited variation according to histological type, whereas patterns were slightly more pronounced among women with nonlocalized disease compared with localized disease.ConclusionsDrug use among postmenopausal women with epithelial ovarian cancer was substantial and varied considerably in relation to the time of cancer diagnosis, although only limited changes were seen in the use of preventive medicines.
Threshold Regression to Accommodate a Censored Covariate
Authors: Qian Jing , Chiou Sy Han , Maye Jacqueline E. , Atem Folefac , Johnson Keith A. , Betensky Rebecca A. 
Published: June 2018

Summary
In several common study designs, regression modeling is complicated by the presence of censored covariates. Examples of such covariates include maternal age of onset of dementia that may be right censored in an Alzheimer's amyloid imaging study of healthy subjects, metabolite measurements that are subject to limit of detection censoring in a case-control study of cardiovascular disease, and progressive biomarkers whose baseline values are of interest, but are measured post-baseline in longitudinal neuropsychological studies of Alzheimer's disease. We propose threshold regression approaches for linear regression models with a covariate that is subject to random censoring. Threshold regression methods allow for immediate testing of the significance of the effect of a censored covariate. In addition, they provide for unbiased estimation of the regression coefficient of the censored covariate. We derive the asymptotic properties of the resulting estimators under mild regularity conditions. Simulations demonstrate that the proposed estimators have good finite-sample performance, and often offer improved efficiency over existing methods. We also derive a principled method for selection of the threshold. We illustrate the approach in application to an Alzheimer's disease study that investigated brain amyloid levels in older individuals, as measured through positron emission tomography scans, as a function of maternal age of dementia onset, with adjustment for other covariates. We have developed an R package, censCov, for implementation of our method, available at CRAN.
Soluble syndecans: biomarkers for diseases and therapeutic options
Authors: Bertrand Jessica , Bollmann Miriam 
Published: June 2018

Syndecans are important mediators of signalling by transmitting external stimuli into the cells. This role in signal transduction has been attributed mainly to the membrane‐bound syndecans. In the last years, however, the soluble ectodomain of syndecans generated by shedding has come into the focus of research as this process has been show to modulate the syndecan‐dependent signalling pathways, as well as other pathways. This review summarizes the current knowledge about the induction of syndecan shedding and the different pathways modulated by shed syndecan proteins. This review summarizes the known and putative sheddases for each syndecan and describes the exemplary conditions of sheddase activity for some syndecans. This review summarizes the proposed use of shed syndecans as biomarkers for various diseases, as the shedding process of syndecans depends crucially on tissue‐ and disease‐specific activation of the sheddases. Furthermore, the potential use of soluble syndecans as a therapeutic option is discussed, on the basis of the current literature.Linked ArticlesThis article is part of a themed section on Translating the Matrix. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.1/issuetoc
Post‐surgical versus post‐intravitreal injection endophthalmitis: changing patterns in causative flora
Authors: Ong Aaron PC , Angbue Te Nikki , Zagora Sophia L , Symes Richard J , Yates William , Chang Andrew A , McCluskey Peter J , Simunovic Matthew P 
Published: June 2018

AbstractImportanceEndophthalmitis is a serious complication of intraocular procedures: knowledge of its causative organisms and outcomes may guide prevention and treatment.BackgroundTo determine the outcomes and spectrum of causative organisms in acute post‐procedural endophthalmitis.DesignA retrospective observational case series performed at a tertiary referral hospital during the period 1 July 2012 to 31 July 2017.ParticipantsTwo hundred and forty‐eight patients diagnosed with acute (≤ 6 weeks post‐inciting event) endophthalmitis.MethodsChart review of microbiological and clinical data.Main Outcome MeasuresThe main outcome measure was odds of any improvement in visual acuity (3 months versus presentation). Secondary outcomes included causative organism, likelihood of vitrectomy and likelihood of evisceration.ResultsOne hundred and ninty cases were post‐cataract surgery or post‐intravitreal injection (49 and 141, respectively). Causative organisms were identified in 45% of post‐cataract surgery and 54% of post‐injection cases (OR = 0.69; P = 0.61). Staphylococcus epidermidis was the most frequent causative organism. Streptococcus species accounted for 32% of post‐surgical and 7% of culture‐positive post‐injection cases (OR = 6.63; P = 0.02). At 3 months, 81% of post‐surgical and 84% of post‐injection cases had improved BCVA over presentation (OR 0.59; P = 0.61).Conclusions and RelevanceS. epidermidis is the most common causative organism. In contrast to other studies, we did not find evidence for an increased odds of Streptococcus spp. endophthalmitis following intravitreal injection. This may in turn reflect guideline‐driven changes in practice.