bluuebunny/crossref_metadata_2025_split huggingface dataset:
Individual and environmental determinants of burnout among nurses
Authors: Rees Clare S. , Eley Robert , Osseiran-Moisson Rebecca , Francis Karen , Cusack Lynette , Heritage Brody , Hegney Desley 
Published: July 2019

Objective Burnout is a significant problem affecting the nursing workforce and is associated with significant personal suffering and high rates of nurse turnover. Efforts to further understand the variables that explain burnout are needed. The aim of this cross-sectional study was to examine both environmental and individual factors that may explain burnout among nurses. Method We recruited 1848 Australian nurses to complete several online questionnaires measuring the practice environment (Practice Environment Scale of the Nursing Work Index), burnout (Professional Quality of Life Scale), trait negative affect ( Spielberger State-Trait Anxiety Inventory form Y2) and resilience (Connor Davidson Resilience Scale). Correlational analysis as well as hierarchical regression was used to determine the relative importance of variables in explaining burnout scores. Results All of the practice environment scales were significantly related to burnout in the negative direction, and these relationships were above .3 for all except the relationship scale ( r = –.256) and the participation in hospital affairs scale ( r = –.285). Overall, the regression model accounted for 62% of the variance in nurse burnout scores. Trait negative affect, resilience and two aspects of practice environment (Manager sub-scale and Staffing sub-scale) all explained significant variance in burnout scores. The largest contribution came from the two individual variables (resilience and trait negative affect) that together explained 55% of the variance in burnout scores. Conclusions Findings suggest that health service administrators should provide nursing staff with education and support to build individual resilience. Workplaces that attend to staffing and resource issues and have managers who provide high levels of support to their staff appear to be essential strategies to help prevent nurse burnout.
Comparison of T2*GRE and DSC-PWI for hemorrhage detection in acute ischemic stroke patients: Pooled analysis of the EPITHET, DEFUSE 2, and SENSE 3 stroke studies
Authors: Amukotuwa Shalini A , Fischbein Nancy J , Albers Gregory W , Davis Stephen , Donnan Geoffrey A , Andre Jalal B , Bammer Roland 
Published: July 2019

Aims The objective of this study was to compare the diagnostic performance of the baseline pre-contrast images of dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) with conventional T2*gradient recalled echo (GRE) imaging for detection of hemorrhage in acute ischemic stroke patients. Material and methods T2*GRE and DSC-PWI from 393 magnetic resonance imaging scans from 221 patients enrolled in three prospective stroke studies were independently evaluated by two readers blinded to clinical and other imaging data. Agreement between T2*GRE and DSC-PWI for the presence of hemorrhage, and acute hemorrhagic transformation, was assessed using the kappa statistic. Inter-reader agreement was also assessed using the kappa statistic. Results Agreement between the baseline images of DSC-PWI and T2*GRE regarding the presence of hemorrhage was almost perfect (kreader 1 : 0.90, 95% confidence interval 0.86–0.95 and kreader 2 : 0.91, 95% confidence interval 0.87–0.96). Agreement between the sequences was still higher for detection of acute hemorrhagic transformation (kreader 1 : 0.94, 95% confidence interval 0.91–0.98 and kreader 2 : 0.95, 95% confidence interval 0.92–0.98). Inter-reader agreement for detection of hemorrhage was also almost perfect for both T2*GRE (k: 0.95, 95% confidence interval 0.91–0.98) and DSC-PWI (k: 0.96, 95% confidence interval 0.93–0.99). Acute hemorrhagic transformation detected on T2*GRE was missed on DSC-PWI by one or both readers in 5/393 (1.3%) scans. Conclusion The almost perfect statistical agreement between DSC-PWI and conventional T2*GRE suggests that DSC-PWI is sufficient for hemorrhage screening prior to thrombolysis in stroke patients. T2*GRE can therefore be omitted when DSC-PWI is included, thereby shortening the acute ischemic stroke magnetic resonance imaging protocol and expediting treatment. Trial registration: ClinicalTrials.gov Identifier: NCT02586415.
The endonuclease APE1 processes miR-92b formation, thereby regulating expression of the tumor suppressor LDLR in cervical cancer cells
Authors: Sun Yi , Feng Yun , Zhang Guiqian , Xu Ya 
Published: July 2019

Background: The molecular mechanisms underlying cervical cancer require elucidation to identify novel therapeutic targets. Apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) is a multifunctional apurinic/apyrimidinic (AP) endonuclease that influences the transcription of many cancer-related genes via microRNome regulation. Herein, we examine the role of miR-92b-3p (hereinafter miR-92b), whose processing may be regulated by APE1, in cervical cancer progression. Methods: APE1’s processing of miR-92b from its pri-miR form was measured by a quantitative reverse transcription polymerase chain reaction (qRT-PCR)-based ratio. APE1’s endonuclease activity was measured with AP-site incision assays. APE1-DROSHA interaction was studied with immunofluorescence, confocal and proximity ligation analyses. The miR-92b’s targeting of low-density lipoprotein receptor (LDLR) was investigated with luciferase reporter assays. The miR-92b mimics and shRNA-based miR-92b silencing, as well as LDLR overexpression and short interfering RNA (siRNA)-based LDLR silencing, were employed in CaSki and SiHa cervical cancer cells. Cell proliferation and chemosensitivity to paclitaxel and cisplatin were assayed. Cell-cycle progression and apoptosis were assessed by flow cytometry. Tumor growth was studied in a murine xenograft model. Results: APE1’s endonuclease activity, via association with the DROSHA-processing complex, is necessary for processing mature miR-92b, thereby regulating expression of miR-92b’s direct target LDLR. The miR-92b promotes cell proliferation in vitro and in vivo, promotes cell-cycle progression, and reduces apoptosis and chemosensitivity. LDLR silencing recapitulated miR-92b’s transformative effects, while LDLR overexpression rescued these effects. Conclusions: APE1 enhances miR-92b processing, thereby suppressing LDLR expression and enhancing cervical carcinoma progression. Our identification of the novel APE1-miR-92b-LDLR axis improves our understanding of the complex pathogenesis of cervical carcinoma and reveals a novel therapeutic strategy for combating this disease.
The Use of Bone Grafts, Bone Graft Substitutes, and Orthobiologics for Osseous Healing in Foot and Ankle Surgery
Authors: Peterson Jonathan R. , Chen Fangyu , Nwankwo Eugene , Dekker Travis J. , Adams Samuel B. 
Published: July 2019

Achieving fusion in osseous procedures about the foot and ankle presents unique challenges to the surgeon. Many patients have comorbidities that reduce osseous healing rates, and the limited space and high weightbearing demand placed on fusion sites makes the choice of bone graft, bone graft substitute, or orthobiologic agent of utmost importance. In this review, we discuss the essential characteristics of grafts, including their osteoconductive, osteoinductive, osteogenic, and angiogenic properties. Autologous bone graft remains the gold standard and contains all these properties. However, the convenience and lack of donor site morbidity of synthetic bone grafts, allografts, and orthobiologics, including growth factors and allogenic stem cells, has led to these being used commonly as augments. Level of Evidence: Level V, expert opinion.
Consensus criteria for diagnosis, staging, and treatment response assessment of T-cell prolymphocytic leukemia
Authors: Staber Philipp B. , Herling Marco , Bellido Mar , Jacobsen Eric D. , Davids Matthew S. , Kadia Tapan Mahendra , Shustov Andrei , Tournilhac Olivier , Bachy Emmanuel , Zaja Francesco , Porkka Kimmo , Hoermann Gregor , Simonitsch-Klupp Ingrid , Haferlach Claudia , Kubicek Stefan , Mayerhoefer Marius E. , Hopfinger Georg , Jaeger Ulrich , Dearden Claire 
Published: July 2019

Abstract
In a Special Report, the T-PLL International Study group presents consensus criteria for the diagnosis, staging, and treatment response assessment of patients with T-cell prolymphocytic leukemia.
Triglyceride-glucose index is associated with symptomatic coronary artery disease in patients in secondary care
Authors: da Silva Alessandra , Caldas Ana Paula Silva , Hermsdorff Helen Hermana Miranda , Bersch-Ferreira Ângela Cristine , Torreglosa Camila Ragne , Weber Bernardete , Bressan Josefina 
Published: July 2019

Abstract
Background
The triglyceride-glucose index (TyG index) is a tool for insulin resistance evaluation, however, little is known about its association with coronary artery disease (CAD), which is the major cardiovascular death cause, and what factors may be associated with TyG index.

Objective
To evaluate the association between the TyG index and the prevalence of CAD phases, as well as cardiovascular risk factors.

Methods
The baseline data of patients in secondary care in cardiology from Brazilian Cardioprotective Nutritional Program Trial (BALANCE Program Trial) were analyzed. Anthropometric, clinical, socio-demographic and food consumption data were collected by trained professionals. The TyG index was calculated by the formula: Ln (fasting triglycerides (mg/dl) × fasting blood glucose (mg/dl)/2) and regression models were used to evaluate the associations.

Results
We evaluated 2330 patients, which the majority was male (58.1%) and elderly (62.1%). The prevalence of symptomatic CAD was 1.16 times higher in patients classified in the last tertile of the TyG index (9.9 ± 0.5) compared to those in the first tertile (8.3 ± 0.3). Cardiometabolic risk factors were associated with TyG index, with the highlight for higher carbohydrate and lower lipid consumption in relation to recommendations that reduced the chance of being in the last TyG index tertile.

Conclusion
The TyG index was positively associated with a higher prevalence of symptomatic CAD, with metabolic and behavioral risk factors, and could be used as a marker for atherosclerosis.
Trial registration ClinicalTrials.gov identifier: NCT01620398. Registered 15 June, 2012
Suicidal risk factors in major affective disorders
Authors: Baldessarini Ross J. , Tondo Leonardo , Pinna Marco , Nuñez Nicholas , Vázquez Gustavo H. 
Published: July 2019

BackgroundRates and risk factors for suicidal behaviour require updating and comparisons among mood disorders.AimsTo identify factors associated with suicidal risk in major mood disorders.MethodWe considered risk factors before, during and after intake assessments of 3284 adults with/without suicidal acts, overall and with bipolar disorder (BD) versus major depressive disorder (MDD), using bivariate comparisons, multivariable regression modelling and receiver operating characteristic (ROC) analysis.ResultsSuicidal prevalence was greater in BD versus MDD: ideation, 29.2 versus 17.3%; attempts, 18.8 versus 4.78%; suicide, 1.73 versus 0.48%; attempts/suicide ratio indicated similar lethality, 10.9 versus 9.96. Suicidal acts were associated with familial BD or suicide, being divorced/unmarried, fewer children, early abuse/trauma, unemployment, younger onset, longer illness, more dysthymic or cyclothymic temperament, attention-deficit hyperactivity disorder (ADHD), substance misuse, mixed features, hospital admission, percentage time unwell, less antidepressants and more antipsychotics and mood stabilisers. Logistic regression found five independent factors: hospital admission, more depression at intake, BD diagnosis, onset age ≤25 years and mixed features. These factors were more associated with suicidal acts in BD than MDD: percentage time depressed/ill, alcohol misuse, >4 pre-intake depressions, more dysthymic/cyclothymic temperament and prior abuse/trauma. ADHD and total years ill were similar in BD and MDD; other factors were more associated with MDD. By ROC analysis, area under the curve was 71.3%, with optimal sensitivity (76%) and specificity (55%) with any two factors.ConclusionsSuicidal risks were high in mood disorders: ideation was highest with BD type II, attempts and suicides (especially violent) with BD type I. Several risk factors for suicidal acts differed between BD versus MDD patients.Declaration of interestNo author or immediate family member has financial relationships with commercial entities that might appear to represent potential conflicts of interest with the information presented.
The importance of surgical margins in dedifferentiated liposarcoma survival.
Authors: Albagoush Sara , Gootee Jonathan , Nguyen Kevin , Aurit Sarah J , Curtin Christina , Silberstein Peter T. 
Published: July 2019

e22528 Background: Among the types of soft tissue sarcomas (STS), liposarcoma is the most common malignant STS. Considering therapeutic options, surgical resection is the most utilized therapeutic option. In this study, we aim to explore the effects of varying degrees of surgical margins on survival in patients with dedifferentiated liposarcoma. Methods: The National Cancer Database (NCDB) was used to select patients with dedifferentiated liposarcoma to determine if surgical margins and other variables were associated with worse overall survival after accounting for age, gender, race, Charlson-Deyo score, anatomic site, treatment approach, tumor size, tumor grade, and presence of metastases through multivariable analysis. Results: Of the 1,004 patients, 64.4% were male, 87.0% were white, and the median age was 63 years. Approximately 95% had no metastases at the time of diagnosis, and 91.5% had high grade liposarcoma. For the status of surgical margins, 50.8% had no residual tumors, 26.1% had microscopic residual tumors, and 4.3% had macroscopic residual tumors. In general, the risk of death was higher for older males (25.8% increased risk of mortality) and those with metastases (312.9% increased risk of mortality) as well as patients with high grade liposarcoma (112.4% increased risk of mortality). When compared to no residual tumor after surgery, patients with macroscopic residual tumors, had a 96.7% increased risk of death (HR 95% CI:1.24 to 3.13; p= 0.004). Conclusions: Older age, presence of metastasis, male patients, retroperitoneal/abdomen primary site, high grade tumors, and macroscopic or residual tumor present after surgery led to an increased risk of mortality.
CheckMate 384: Phase IIIb/IV trial of nivolumab (nivo) 480 mg Q4W versus 240 mg Q2W after ≤ 12 months of nivo in previously treated advanced NSCLC.
Authors: Garon Edward B. , Reinmuth Niels , Falchero Lionel , Garcia Garcia Yolanda , Hureaux José , Gore Ira , Harris Ronald P. , Bidoli Paolo , Baldini Editta , Ros Silverio , Laack Eckart , Mitchell Paul , Wolf Martin , O'Byrne Kenneth John , Zibdawi Labib , Jao Kevin , Spigel David , Li Ang , Rabindran Sridhar K. , Pichon Eric 
Published: July 2019

100 Background: Nivo is approved as 240 mg Q2W in the EU and Japan and 240 mg Q2W or 480 mg Q4W in the US and Canada for second-line treatment (tx) of advanced NSCLC. Pharmacokinetic modeling in various tumors predicts that exposure, efficacy and safety can be maintained with less frequent Q4W dosing, which may provide a more convenient tx option. We present an interim analysis of efficacy and safety from CheckMate 384 (NCT02713867), an international, open-label, randomized phase 3b/4 trial evaluating less frequent nivo dosing (480 mg Q4W vs 240 mg Q2W) in patients (pts) with advanced NSCLC and prior Q2W nivo tx. Methods: Pts (N = 329) with previously treated histologically confirmed stage IIIB/IV or recurrent NSCLC, ECOG performance status 0–2, and prior tx with nivo 3 mg/kg or 240 mg Q2W for ≤12 mo, with ≥2 consecutive assessments of complete / partial response or stable disease, were randomized 1:1 to nivo 480 mg Q4W or 240 mg Q2W over a 30-min infusion. Co-primary endpoints: post-randomization (RND) progression-free survival rates (PFS) at 6 mo and 1 y. Secondary endpoints included safety. Due to tx landscape changes in NSCLC, statistical analyses were amended for a reduced sample size. One-sided 95% CIs were generated to compare PFS rates; presented data analyses are descriptive. Results: Of 166 and 163 pts randomized to 480 mg Q4W and 240 mg Q2W, 164 and 161 pts were treated, respectively. Median follow-up was 9.5 mo (480 mg Q4W) and 10.2 mo (240 mg Q2W). Baseline characteristics were balanced between tx arms. Stratified PFS rates post-RND were comparable between tx arms at 6 mo and 1 y (Table). Safety profiles were similar; any grade tx-related adverse events (TRAEs) and TRAEs leading to discontinuation were reported in 48% vs 61% and 6% vs 9% of pts with 480 mg Q4W vs 240 mg Q2W. No tx-related deaths were reported. Conclusions: Nivo 480 mg Q4W showed similar efficacy and safety to 240 mg Q2W in pts with disease control on nivo, supporting the potential use of 480 mg Q4W as a more convenient dosing option for second-line NSCLC tx. Clinical trial information: NCT02713867. [Table: see text]
Outcome, costs and dollar value of anticancer drugs in non-small cell lung cancer with emphasis on pembrolizumab.
Authors: Guirgis Helmy M. 
Published: July 2019

104 Background: Drug outcomes were analyzed in 9 clinical studies of advanced/metastatic non-small-cell lung cancer (NSCLC). Overall survivals were not reached in some studies. Objective: Weigh hazard ratios (HR), costs and dollar value of each drug vs. its control with emphasis on pembrolizumab (pembro). Methods: Protocols were followed, and parent company costs quoted. yearly-costs of pembro, bevacizumab (bev), pemetrexed (peme) and docetaxel (doc) were calculated. Probability of survival (PoS) was defined as (1.0-HR) and dollar value as cost/PoS. Results: Doc and bev carried black box warnings with estimated grade 3/4 adverse events > 20% compared with pembro <10% and peme < 15%. Doc costs were $63,648. In second-line, estimated HR of doc versus supportive care was 0.70 and value $212,169. Pembro costs at 2mg/Kg x 80 Kg q3 weeks were $125,770. Compared with doc, pembro HR in PD-L1 > 1.0% tumor proportion score (TPS) was 0.71 and value $433,690. Using the 200mg total dose, costs were $157,213 and value $542,114. In first-line, pembro versus chemo in > 1.0% chemo demonstrated HR 0.81, and value $827,439, improving in > 50% to 0.69 and $507,139 respectively. Pembro + chemo versus chemo in < 1.0% were 0.59 and $383,446 improving in > 50% to 0.42 and $271,057. Bev costs were $132,314, HR 0.79 and value $630,067. Peme were $97,947, 0.63-0.78 and $264,722-$445,213. Conclusions: Pembro at 160 mg total dose in 80 Kg patients reduced the 200 mg costs by 20% with proportionate savings at lower weights. Pembro dollar value were enhanced by dose adjustment, PD-L1 enrichment and chemotherapy.
A phase Ia/Ib study of an anti-TIM-3 antibody (LY3321367) monotherapy or in combination with an anti-PD-L1 antibody (LY3300054): Interim safety, efficacy, and pharmacokinetic findings in advanced cancers.
Authors: Harding James J. , Patnaik Amita , Moreno Victor , Stein Mark , Jankowska Anna M. , Velez de Mendizabal Nieves , Tina Liu Zhuqing , Koneru Mythili , Calvo Emiliano 
Published: July 2019

12 Background: Combined targeting of both the TIM-3 and PD-L1 immune checkpoint pathways may improve efficacy. LY3321367 mAb targets TIM-3 on immune cells and LY3300054 mAb targets PD-L1 on tumor cells and tumor-infiltrating immune cells. This analysis presents safety, efficacy, pharmacokinetic (PK) and pharmacodynamics/soluble target engagement (TE) results from LY3321367 (anti-TIM-3) monotherapy and in combination with LY3300054 (anti-PD-L1) in patients (pts) with advanced cancer. Methods: This ongoing, open-label phase 1a/1b, dose escalation and expansion study enrolled pts with histologically confirmed advanced relapsed/refractory solid tumors. Pts received IV infusions of 3mg-1200mg LY3321367 Q2W monotherapy (Arm A) or 70mg-1200mg LY3321367 + 200mg-700mg LY3300054 Q2W combination therapy (Arm B). Primary objectives assessed safety and tolerability and determined the RP2D. PK, soluble target TE, anti-drug antibodies (ADAs), and clinical efficacy (RECIST v1.1) were also evaluated. Results: At data cutoff (3 August 2018), LY3321367 monotherapy was administered to 23 pts (Arm A); 18 pts received LY3321367 combination therapy (Arm B) as phase 1a dose escalation (3 mths median follow-up). Treatment-related AEs observed in Arms A and B were mild (Gr ≤2), except for 1 pt with Gr 3 anemia in Arm B (200 mg LY3321367 + 700 mg LY3300054). No dose limiting toxicities, dose limiting-equivalent toxicities, treatment-related SAEs, or deaths were observed in Arm A or B. For LY3321367, 68.2% (Arm A) and 88.2% (Arm B) of pts were positive for treatment-emergent ADAs. Despite ADAs, no effect on PK was noted; ADA titers were low, except for 1 pt with an infusion-related reaction. LY3321367 t1/2 was ~22 days. Full TE was maintained 2 wks after 1200 mg dose; 600 mg Q2W maintained TE at steady-state. In Arm A, 2 pts had > 20% tumor regression, 1 of which was later confirmed as a PR in a post-PD-1 SCLC pt. Conclusions: LY3321367 is well tolerated as a monotherapy and in combination with LY3300054. The RP2D for LY3321367 combination therapy is 1200 mg IV infusions Q2W for cycles 1-2; 600 mg infusions Q2W starting at cycle 3 onward. Clinical trial information: NCT03099109.
Mixed response to immunotherapy in lung cancer.
Authors: Baldeo Candice , Kaleem Tasneem , Paz-Fumagalli Ricardo , Copland John A. , Menefee Michael E. 
Published: July 2019

122 Background: Mixed response (MR) to systemic therapy is common and associated with a poor prognosis. MR often represents a therapeutic dilemma resulting in the discontinuation of a therapy to which a portion of the tumor is still sensitive, due to the emergence of resistance in other metastatic deposits. We hypothesize that discordant responses in patients receiving immunotherapy may be associated with genomic variation within discordant tumors. Methods: We defined MR with the following criteria: 1) At least one tumor has increased in size while another tumor has decreased; 2) One or more tumors have remained stable while another has increased; 3) One or more tumors have remained stable while another has decreased. 4) A new tumor has developed while other tumors have decreased or remained stable. Between 2012 and 2017, we identified 112 patients with a MR. Two patients with metastatic lung cancer, treated with nivolumab underwent paired, simultaneous sampling of discordant tumors. Results: Both patients treated with nivolumab demonstrated genomic heterogeneity between discordant tumors on next-generation sequencing, including one patient with SCLC. Conclusions: MR remains a common and challenging therapeutic quandary. Genomic heterogeneity and differences in TMB of metastatic tumors demonstrating a MR, may be factors that contribute to this phenomenon. Further characterization of genomic discrepancies in MR may provide insights into mechanisms of emerging resistance, as well as, more rational and effective combinatorial therapies.[Table: see text]