bluuebunny/crossref_metadata_2025_split huggingface dataset:
A 6-year comparative economic evaluation of healthcare costs and mortality rates of Dutch patients from conventional and CAM GPs
Authors: Baars Erik W , Kooreman Peter 
Published: August 2014

ObjectivesTo compare healthcare costs and mortality rates of Dutch patients with a conventional (CON) general practitioner (GP) and patients with a GP who has additionally completed training in complementary and alternative medicine (CAM).DesignComparative economic evaluation.SettingDatabase from the Dutch insurance company Agis.Participants1 521 773 patients (98.8%) from a CON practice and 18 862 patients (1.2%) from a CAM practice.Main outcome measuresAnnual information on five types of healthcare costs for the years 2006–2011: care by GP, hospital care, pharmaceutical care, paramedic care and care covered by supplementary insurance. Healthcare costs in the last year of life. Mortality rates.ResultsThe mean annual compulsory and supplementary healthcare costs of CON patients are respectively €1821 (95% CI 1813 to 1828) and €75.3 (95% CI 75.1 to 75.5). Compulsory healthcare costs of CAM patients are €225 (95% CI 169 to 281; p<0.001; 12.4%) lower and result mainly from lower hospital care costs (€165; 95% CI 118 to 212; p<0.001) and lower pharmaceutical care costs (€58; 95% CI 41 to 75; p<0.001), especially in the age categories 25–49 and 50–74 years. The costs in the last year of life of patients with CAM, GPs are €1161 (95% CI −138 to 2461; p<0.1) lower. This difference is entirely due to lower hospital costs (€1250; 95% CI 19 to 2481; p<0.05). The mean annual supplementary costs of CAM patients are €33 (95% CI 30 to 37; p<0.001; 44%) higher. CAM patients do not have lower or higher mortality rates than CON patients.ConclusionsDutch patients whose GP additionally completed training in CAM on average have €192 (10.1%) lower annual total compulsory and supplementary healthcare costs and do not live longer or shorter than CON patients.
Parent skills training for parents of children or adults with developmental disorders: systematic review and meta-analysis protocol
Authors: Reichow Brian , Kogan Cary , Barbui Corrado , Smith Isaac , Yasamy M Taghi , Servili Chiara 
Published: August 2014

IntroductionDevelopmental disorders, including intellectual disability and autism spectrum disorders, may limit an individual's capacity to conduct daily activities. The emotional and economic burden on families caring for an individual with a developmental disorder is substantial, and quality of life may be limited by a lack of services. Therefore, finding effective treatments to help this population should be a priority. Recent work has shown parent skills training interventions improve developmental, behavioural and family outcomes. The purpose of this review protocol is to extend previous findings by systematically analysing randomised controlled trials of parent skills training programmes for parents of children with developmental disorders including intellectual disabilities and autism spectrum disorders and use meta-analytic techniques to identify programme components reliably associated with successful outcomes of parent skills training programmes.Methods and analysisWe will include all studies conducted using randomised control trials designs that compare a group of parents receiving a parent skills training programme to a group of parents in a no-treatment control, waitlist control or treatment as usual comparison group. To locate studies, we will conduct an extensive electronic database search and then use snowball methods, with no limits to publication year or language. We will present a narrative synthesis including visual displays of study effects on child and parental outcomes and conduct a quantitative synthesis of the effects of parent skills training programmes using meta-analytic techniques.Ethics and disseminationNo ethical issues are foreseen and ethical approval is not required given this is a protocol for a systematic review. The findings of this study will be disseminated through peer-reviewed publications and international conference presentations. Updates of the review will be conducted, as necessary, to inform and guide practice.Trial registration numberPROSPERO (CRD42014006993).
Cost and turn-around time display decreases inpatient ordering of reference laboratory tests: a time series
Authors: Fang Daniel Z , Sran Gurmeet , Gessner Daniel , Loftus Pooja D , Folkins Ann , Christopher John Y , Shieh Lisa 
Published: August 2014

ObjectiveReference tests, also known as send-out tests, are commonly ordered laboratory tests with variable costs and turn-around times. We aim to examine the effects of displaying reference laboratory costs and turn-around times during computerised physician order entry (CPOE) on inpatient physician ordering behaviour.DesignWe conducted a prospective observational study at a tertiary care hospital involving inpatient attending physicians and residents. Physician ordering behaviour was prospectively observed between September 2010 and December 2012. An intervention was implemented to display cost and turn-around time for reference tests within our CPOE. We examined changes in the mean number of monthly physician orders per inpatient day at risk, the mean cost per order, and the average turn-around time per order.ResultsAfter our intervention, the mean number of monthly physician orders per inpatient day at risk decreased by 26% (51 vs 38, p<0.0001) with a decrease in mean cost per order (US$146.50 vs US$134.20, p=0.0004). There were no significant differences in mean turn-around time per order (5.6 vs 5.7 days, p=0.057). A stratified analysis of both cost and turn-around time showed significant decreases in physician ordering. The intervention projected a mean annual savings of US$330 439. Reference test cost and turn-around time variables were poorly correlated (r=0.2). These findings occurred in the setting of non-significant change to physician ordering in a control cohort of non-reference laboratory tests.ConclusionsDisplay of reference laboratory cost and turn-around time data during real-time ordering may result in significant decreases in ordering of reference laboratory tests with subsequent cost savings.
Improving Sepsis Management in the Acute Admissions Unit
Authors: Adcroft Laura 
Published: August 2014

AbstractSepsis is a common condition with a major impact on healthcare resources and expenditure. We therefore wanted to investigate and improve how the acute admission unit (AAU) at the Great Western Hospital (GWH) is managing patients who present directly to the unit with sepsis. In order to obtain this information, an audit was undertaken against the College of Emergency Medicine standards used by the emergency department within GWH and across the UK. Data was retrospectively collected for 30 patients with a diagnosis of severe sepsis or septic shock. The notes were scrutinized with regard to the implementation of College of Emergency Medicine standards for the management of sepsis. This meant that performance in the AAU was compared against the emergency department at GWH and national figures.The data collected shows performance is below national standards with regard to documentation of high flow oxygen use (AAU: 24%, ED 100%; national median: 50%; CEM standard 95%), crystalloid fluid boluses (AAU: 52%; ED: 90%; national median: 83%; CEM standard 100%), lactate measurements (AAU: 66%, ED: 93%; national median: 80%; CEM standard 95%), and obtainment of blood cultures (AAU: 52%; ED 73%; national median: 77%; CEM standard: 95%). Only 3% of patients received all six parts of the sepsis bundle.Since auditing in 2012/2013 we have introduced a sepsis proforma based on a current proforma being used within Severn Deanery. This proforma uses the ‘Sepsis Six’ bundle appropriate to ward based care. We have raised awareness of sepsis implications and management through the creation of a ‘sepsis working group’ to educate both junior doctors and nurses. In turn, this has led to education through the use of posters, pocket reference cards, and teaching sessions. Re-audit shows significant improvement in administering all parts of the Sepsis Six bundle and an 8% improvement in patients receiving all six of the bundle.
Compliant neurovascular balloon catheters may not be compatible with liquid embolic materials: intraprocedural rupture of the protecting balloon during tumor embolization using n-butyl cyanoacrylate and lipiodol mixture
Authors: Park Soonchan , Hwang Seon Moon , Lim Ok Kyun , Hwang Changmo , Lee Deok Hee 
Published: August 2014

BackgroundSimultaneous use of balloon catheters with embolic materials can cause unwanted rupture of the balloon occlusion catheters, which might cause a serious problem. Therefore, knowledge of the compatibility of occlusion balloon catheters with liquid embolic materials is important in various interventional procedures.ObjectiveTo determine the compatibility of occlusion balloon catheters with commonly used embolic materials in vitro.MethodsWe used three types of occlusion balloon catheters (Scepter C, Microvention, Tustin, California, USA; Hyperform, Covidien, Irvine, California, USA; and Ascent, Codman Neurovascular, Raynham, Massachusetts, USA) to test their tolerances to Lipiodol, n-butyl cyanoacrylate (NBCA; Histoacryl; B Braun, Melsungen, Germany), and dimethyl sulfoxide (DMSO) with Onyx. The balloon was inflated just as it is in an endovascular procedure, then put on a Petri dish to observe its morphological change after one drop of liquid embolic material was added using a 1 mL syringe. The presence of rupture and the time to rupture were evaluated by constant video monitoring. Additionally, we observed morphological changes of the balloon catheter surface after contact with embolic materials with a scanning electron microscope.ResultsLipiodol or a 33% NBCA–Lipiodol mixture dropping onto the three types of balloon catheter resulted in ruptures of all three. All three types of balloon catheter were tolerant to NBCA and to DMSO followed by Onyx.ConclusionsGlue embolization should not be performed with all three kinds of balloon catheter on the market, but DMSO and Onyx are compatible with those balloon catheters.
Arthroscopic Fixation of Cell Free Polymer-Based Cartilage Implants with a Bioinspired Polymer Surface on the Hip Joint: A Cadaveric Pilot Study
Authors: Lahner Matthias , Duif Christian , Ficklscherer Andreas , Kaps Christian , Kalwa Lukas , Seidl Tobias 
Published: August 2014

This study investigates the adhesion capacity of a polyglycolic acid- (PGA-) hyaluronan scaffold with a structural modification based on a planar polymer (PM) surface in a cadaver cartilage defect model. Two cadaver specimens were used to serially test multiple chondral matrices. In a cadaver hip model, cell free polymer-based cartilage implants with a planar bioinspired PM surface (PGA-PM-scaffolds) were implanted arthroscopically on 10 mm × 15 mm full-thickness femoral hip cartilage lesions. Unprocessed cartilage implants without a bioinspired PM surface were used as control group. The cartilage implants were fixed without and with the use of fibrin glue on femoral hip cartilage defects. After 50 movement cycles and removal of the distraction, a rearthroscopy was performed to assess the outline attachment and integrity of the scaffold. The fixation techniques without and with fibrin fixation showed marginal differences for outline attachment, area coverage, scaffold integrity, and endpoint fixation after 50 cycles. The PGA-PM-scaffolds with fibrin fixation achieved a higher score in terms of the attachment, integrity, and endpoint fixation than the PGA-scaffold on the cartilage defect. Relating to the outline attachment, area coverage, scaffold integrity, and endpoint fixation, the fixation with PGA-PM-scaffolds accomplished significantly better results compared to the PGA-scaffolds(P=0.03752, P=0.03078, P=0.00512, P=0.00512). PGA-PM-scaffolds demonstrate increased observed initial fixation strength in cadaver femoral head defects relative to PGA-scaffold, particularly when fibrin glue is used for fixation.
Metastatic Heterogeneity of Breast Cancer Cells Is Associated with Expression of a Heterogeneous TGFβ-Activating miR424–503 Gene Cluster
Authors: Li Yun , Li Wei , Ying Zhe , Tian Han , Zhu Xun , Li Jun , Li Mengfeng 
Published: August 2014

Abstract
TGFβ signaling is known to drive metastasis in human cancer. Under physiologic conditions, the level of TGFβ activity is tightly controlled by a regulatory network involving multiple negative regulators. At metastasis, however, these inhibitory mechanisms are usually overridden so that oncogenic TGFβ signaling can be overactivated and sustained. To better understand how the TGFβ inhibitors are suppressed in metastatic breast cancer cells, we compared miRNA expression profiles between breast cancers with or without metastasis and found that the miR424–503 cluster was markedly overexpressed in metastatic breast cancer. Mechanistic studies revealed that miR424 and miR503 simultaneously suppressed Smad7 and Smurf2, two key inhibitory factors of TGFβ signaling, leading to enhanced TGFβ signaling and metastatic capability of breast cancer cells. Moreover, antagonizing miR424–503 in breast cancer cells suppressed metastasis in vivo and increased overall host survival. Interestingly, our study also found that heterogeneous expression of the miR424–503 cluster contributed to the heterogeneity of TGFβ activity levels in, and metastatic potential of, breast cancer cell subsets. Overall, our findings demonstrate a novel mechanism, mediated by elevated expression of the miR424–503 cluster, underlying TGFβ activation and metastasis of human breast cancer. Cancer Res; 74(21); 6107–18. ©2014 AACR.
Zfx Facilitates Tumorigenesis Caused by Activation of the Hedgehog Pathway
Authors: Palmer Colin J. , Galan-Caridad Jose M. , Weisberg Stuart P. , Lei Liang , Esquilin Jose M. , Croft Gist F. , Wainwright Brandon , Canoll Peter , Owens David M. , Reizis Boris 
Published: August 2014

Abstract
The Hedgehog (Hh) signaling pathway regulates normal development and cell proliferation in metazoan organisms, but its aberrant activation can promote tumorigenesis. Hh-induced tumors arise from various tissues and they may be indolent or aggressive, as is the case with skin basal cell carcinoma (BCC) or cerebellar medulloblastoma, respectively. Little is known about common cell-intrinsic factors that control the development of such diverse Hh-dependent tumors. Transcription factor Zfx is required for the self-renewal of hematopoietic and embryonic stem cells, as well as for the propagation of acute myeloid and T-lymphoblastic leukemias. We report here that Zfx facilitates the development of experimental BCC and medulloblastoma in mice initiated by deletion of the Hh inhibitory receptor Ptch1. Simultaneous deletion of Zfx along with Ptch1 prevented BCC formation and delayed medulloblastoma development. In contrast, Zfx was dispensable for tumorigenesis in a mouse model of glioblastoma. We used genome-wide expression and chromatin-binding analysis in a human medulloblastoma cell line to characterize direct, evolutionarily conserved targets of Zfx, identifying Dis3L and Ube2j1 as two targets required for the growth of the human medulloblastoma cells. Our results establish Zfx as a common cell-intrinsic regulator of diverse Hh-induced tumors, with implications for the definition of new therapeutic targets in these malignancies. Cancer Res; 74(20); 5914–24. ©2014 AACR.
Promoting Thiol Expression Increases the Durability of Antitumor T-cell Functions
Authors: Kesarwani Pravin , Al-Khami Amir A. , Scurti Gina , Thyagarajan Krishnamurthy , Kaur Navtej , Husain Shahid , Fang Quan , Naga Osama S. , Simms Patricia , Beeson Gyda , Voelkel-Johnson Christina , Garrett-Mayer Elizabeth , Beeson Craig C. , Nishimura Michael I. , Mehrotra Shikhar 
Published: August 2014

Abstract
Ex vivo–expanded CD8+ T cells used for adoptive immunotherapy generally acquire an effector memory-like phenotype (TEM cells). With regard to therapeutic applications, two undesired features of this phenotype in vivo are limited persistence and reduced antitumor efficacy, relative to CD8+ T cells with a central memory-like phenotype (TCM cells). Furthermore, there is incomplete knowledge about all the differences between TEM and TCM cells that may influence tumor treatment outcomes. Given that TCM cells survive relatively longer in oxidative tumor microenvironments, we investigated the hypothesis that TCM cells possess relatively greater antioxidative capacity than TEM cells. Here, we report that TCM cells exhibit a relative increase compared with TEM cells in the expression of cell surface thiols, a key target of cellular redox controls, along with other antioxidant molecules. Increased expression of redox regulators in TCM cells inversely correlated with the generation of reactive oxygen and nitrogen species, proliferative capacity, and glycolytic enzyme levels. Notably, T-cell receptor–transduced T cells pretreated with thiol donors, such as N-acetyl cysteine or rapamycin, upregulated thiol levels and antioxidant genes. A comparison of antitumor CD8+ T-cell populations on the basis of surface thiol expression showed that thiol-high cells persisted longer in vivo and exerted superior tumor control. Our results suggest that higher levels of reduced cell surface thiols are a key characteristic of T cells that can control tumor growth and that profiling this biomarker may have benefits to adoptive T-cell immunotherapy protocols. Cancer Res; 74(21); 6036–47. ©2014 AACR.
Ceramide Kinase Promotes Tumor Cell Survival and Mammary Tumor Recurrence
Authors: Payne Ania W. , Pant Dhruv K. , Pan Tien-Chi , Chodosh Lewis A. 
Published: August 2014

Abstract
Recurrent breast cancer is typically an incurable disease and, as such, is disproportionately responsible for deaths from this disease. Recurrent breast cancers arise from the pool of disseminated tumor cells (DTC) that survive adjuvant or neoadjuvant therapy, and patients with detectable DTCs following therapy are at substantially increased risk for recurrence. Consequently, the identification of pathways that contribute to the survival of breast cancer cells following therapy could aid in the development of more effective therapies that decrease the burden of residual disease and thereby reduce the risk of breast cancer recurrence. We now report that ceramide kinase (Cerk) is required for mammary tumor recurrence following HER2/neu pathway inhibition and is spontaneously upregulated during tumor recurrence in multiple genetically engineered mouse models for breast cancer. We find that Cerk is rapidly upregulated in tumor cells following HER2/neu downregulation or treatment with Adriamycin and that Cerk is required for tumor cell survival following HER2/neu downregulation. Consistent with our observations in mouse models, analysis of gene expression profiles from more than 2,200 patients revealed that elevated CERK expression is associated with an increased risk of recurrence in women with breast cancer. In addition, although CERK expression is associated with aggressive subtypes of breast cancer, including those that are estrogen receptor–negative, HER2+, basal-like, or high grade, its association with poor clinical outcome is independent of these clinicopathologic variables. Together, our findings identify a functional role for Cerk in breast cancer recurrence and suggest the clinical utility of agents targeted against this prosurvival pathway. Cancer Res; 74(21); 6352–63. ©2014 AACR.
The Retinoblastoma Tumor Suppressor Modulates DNA Repair and Radioresponsiveness
Authors: Thangavel Chellappagounder , Boopathi Ettickan , Ciment Steve , Liu Yi , O' Neill Raymond , Sharma Ankur , McMahon Steve B. , Mellert Hestia , Addya Sankar , Ertel Adam , Birbe Ruth , Fortina Paolo , Dicker Adam P. , Knudsen Karen E. , Den Robert B. 
Published: August 2014

Abstract
Purpose: Perturbations in the retinoblastoma pathway are over-represented in advanced prostate cancer; retinoblastoma loss promotes bypass of first-line hormone therapy. Conversely, preliminary studies suggested that retinoblastoma-deficient tumors may become sensitized to a subset of DNA-damaging agents. Here, the molecular and in vivo consequence of retinoblastoma status was analyzed in models of clinical relevance.
Experimental Design: Experimental work was performed with multiple isogenic prostate cancer cell lines (hormone sensitive: LNCaP and LAPC4 cells and hormone resistant C42, 22Rv1 cells; stable knockdown of retinoblastoma using shRNA). Multiple mechanisms were interrogated including cell cycle, apoptosis, and DNA damage repair. Transcriptome analysis was performed, validated, and mechanisms discerned. Cell survival was measured using clonogenic cell survival assay and in vivo analysis was performed in nude mice with human derived tumor xenografts.
Results: Loss of retinoblastoma enhanced the radioresponsiveness of both hormone-sensitive and castrate-resistant prostate cancer. Hypersensitivity to ionizing radiation was not mediated by cell cycle or p53. Retinoblastoma loss led to alteration in DNA damage repair and activation of the NF-κB pathway and subsequent cellular apoptosis through PLK3. In vivo xenografts of retinoblastoma-deficient tumors exhibited diminished tumor mass, lower PSA kinetics, and decreased tumor growth after treatment with ionizing radiation (P &lt; 0.05).
Conclusions: Loss of retinoblastoma confers increased radiosensitivity in prostate cancer. This hypersensitization was mediated by alterations in apoptotic signaling. Combined, these not only provide insight into the molecular consequence of retinoblastoma loss, but also credential retinoblastoma status as a putative biomarker for predicting response to radiotherapy. Clin Cancer Res; 20(21); 5468–82. ©2014 AACR.
Identification of Differentially Expressed Long Noncoding RNAs in Bladder Cancer
Authors: Peter Stefan , Borkowska Edyta , Drayton Ross M. , Rakhit Callum P. , Noon Aidan , Chen Wei , Catto James WF 
Published: August 2014

Abstract
Purpose: Loss of epigenetic gene regulation through altered long noncoding RNA (lncRNA) expression seems important in human cancer. LncRNAs have diagnostic and therapeutic potential, and offer insights into the biology disease, but little is known of their expression in urothelial cancer. Here, we identify differentially expressed lncRNAs with potential regulatory functions in urothelial cancer.
Experimental Design: The expression of 17,112 lncRNAs and 22,074 mRNAs was determined using microarrays in 83 normal and malignant urothelial (discovery) samples and selected RNAs with qPCR in 138 samples for validation. Significantly differentially expressed RNAs were identified and stratified according to tumor phenotype. siRNA knockdown, functional assays, and whole-genome transcriptomic profiling were used to identify potential roles of selected lncRNAs.
Results: We observed upregulation of many lncRNAs in urothelial cancer that was distinct to corresponding, more balanced changes for mRNAs. In general, lncRNA expression reflected disease phenotype. We identified 32 lncRNAs with potential roles in disease progression. Focusing upon a promising candidate, we implicate upregulation of AB074278 in apoptosis avoidance and the maintenance of a proproliferative state in cancer through a potential interaction with EMP1, a tumor suppressor and a negative regulator of cell proliferation.
Conclusions: We report differential expression profiles for numerous lncRNA in urothelial cancer. We identify phenotype-specific expression and a potential mechanistic target to explain this observation. Further studies are required to validate lncRNAs as prognostic biomarkers in this disease. Clin Cancer Res; 20(20); 5311–21. ©2014 AACR.