tbuckley/cabot-search huggingface dataset:
Clinical and Cost Effectiveness of Online Cognitive Behavioral Therapy in Children With Functional Abdominal Pain Disorders
Authors: Maria Lalouni, Brjánn Ljótsson, Marianne Bonnert, Richard Ssegonja, Marc Benninga, Johan Bjureberg, Jens Högström, Hanna Sahlin, Magnus Simrén, Inna Feldman, Erik Hedman-Lagerlöf, Eva Serlachius, Ola Olén
Journal: Clinical Gastroenterology and Hepatology (2018)

Scalable and effective treatments are needed for children with functional abdominal pain disorders (FAPDs). We performed a randomized controlled trial of the efficacy and cost effectiveness of cognitive behavioral therapy delivered online (Internet-CBT) compared with usual therapy.We studied children (age, 8-12 y) diagnosed with FAPDs, based on the Rome IV criteria, in Sweden from September 2016 through April 2017. The patients were assigned randomly to groups that received 10 weeks of therapist-guided, internet-delivered cognitive behavioral therapy (Internet-CBT, n = 46) or treatment as usual (treatments within the health care and school systems, including medications and visits to doctors and other health care professionals; n = 44). The primary outcome was global child-rated gastrointestinal symptom severity assessed using the Pediatric Quality of Life Gastrointestinal Symptom scale. All outcomes were collected from September 2016 through January 2018. Secondary outcomes included quality of life, gastrointestinal-specific anxiety, avoidance behaviors, and parental responses to children's symptoms. Societal costs and costs for health care consumption were collected during the treatment.Children who received Internet-CBT had a significantly larger improvement in gastrointestinal symptom severity with a medium effect size (Cohen's d = 0.46; 95% CI, 0.05-0.88; number needed to treat, 3.8) compared with children who received the treatment as usual. The children's quality of life, gastrointestinal-specific anxiety, avoidance behaviors, and parental responses to children's symptoms also improved significantly in the Internet-CBT group compared with the treatment as usual group. The effects of Internet-CBT persisted through 36 weeks of follow-up evaluation. Children who received Internet-CBT had significantly less health care use than children who received treatment as usual, with an average cost difference of US $137 (P = .011). We calculated a cost savings of US $1050 for every child treated with Internet-CBT compared with treatment as usual.In a randomized trial of pediatric patients with FAPDs, we found Internet-CBT to be clinically cost effective compared with treatment as usual. Internet-CBT has the potential to increase the availability of treatment for a number of patients and reduce health care costs. ClinicalTrials.gov: NCT02873078.
Apoptosis of A549 cells by small interfering RNA targeting survivin delivery using poly-β-amino ester/guanidinylated O-carboxymethyl chitosan nanoparticles
Authors: Yue Tang, Yun Liu, Yuwen Xie, Jing Chen, Yushun Dou
Journal: Asian Journal of Pharmaceutical Sciences (2018)

Gene-based therapeutics has emerged as a promising approach for human cancer therapy. Among a variety of non-viral vectors, polymer vectors are particularly attractive due to their safety and multivalent groups on their surface. This study focuses on guanidinylated O-carboxymethyl chitosan (GOCMCS) along with poly-β-amino ester(PBAE) for siRNA delivery. Binding efficiency of PBAE/siRNA/GOCMCS nanoparticles were characterized by gel electrophoresis. The siRNA-loaded nanoparticles were found to be stable in the presence of RNase A, serum and BALF respectively. Fine particle fraction (FPF) which was determined by a two-stage impinger (TSI) was 57.8% ± 2.6%. The particle size and zeta potential of the nanoparticles were 153.8 ± 12.54 nm and + 12.2 ± 4.94 mV. In vitro cell transfection studies were carried out with A549 cells. The cellular uptake was significantly increased. When the cells were incubated with siSurvivin-loaded nanoparticles, it could induce 26.83% ± 0.59% apoptosis of A549 cells and the gene silencing level of survivin expression in A549 cells were 30.93% ± 2.27%. The results suggested that PBAE/GOCMCS nanoparticle was a very promising gene delivery carrier.
Prevalence of Elective and Ruptured Abdominal Aortic Aneurysm Repairs by Age and Sex From 2003 to 2016 in Ontario, Canada
Authors: Konrad Salata, Mohamad A. Hussain, Charles de Mestral, Elisa Greco, Muhammad Mamdani, Thomas L. Forbes, Deepak L. Bhatt, Subodh Verma, Mohammed Al-Omran
Journal: JAMA Network Open (2018)

<h3>Importance</h3> Age and sex are important considerations in assessing and individualizing therapy for abdominal aortic aneurysm (AAA) repair. <h3>Objective</h3> To determine the prevalence of open and endovascular elective AAA (EAAA) and ruptured AAA (RAAA) repair by age and sex. <h3>Design, Setting, and Participants</h3> In this retrospective, population-based, cross-sectional, time-series analysis in Ontario, Canada, from April 1, 2003, to March 31, 2016, all patients undergoing AAA repair who were older than 39 years were included. <h3>Exposures</h3> Elective AAA and RAAA repair with open surgical repair (OSR) or endovascular aortic repair (EVAR). <h3>Main Outcomes and Measures</h3> Age- and sex-standardized rates of EAAA and RAAA repair with OSR and EVAR. <h3>Results</h3> From 2003 to 2016, 19 489 EAAA repairs (12 232 [63%] OSR and 7257 [37%] EVAR) and 2732 RAAA repairs (2466 [90%] OSR and 266 [10%] EVAR) were identified. The mean (SD) age was 72.7 (8.1) years in the EAAA subgroup and 73.5 (8.9) years in the RAAA subgroup; 15 813 patients (81%) in the EAAA subgroup and 2178 (80%) in the RAAA subgroup were men. The rates of EAAA by age quintile and sex decreased over the study period except among patients older than 79 years (1.3 per 100 000 population in 2003 to 2.2 per 100 000 population in 2016; 70% increase;<i>P</i> &lt; .001). The rates of elective OSR decreased across all age and sex subgroups (range, 38%-74% decrease;<i>P</i> ≤ .009 for all subgroups) except among patients older than 79 years (1.3 per 100 000 population at baseline to 0.56 per 100 000 population in the second quarter of 2016; 53% decrease;<i>P</i> = .05). The rates of elective EVAR significantly increased across all age and sex subgroups (range, 566%-1585% increase;<i>P</i> ≤ .04 for all subgroups). Elective EVAR became the dominant treatment approach for aneurysms in men around 2010, whereas it maintained parity among women in 2016. The RAAA repair rate decreased over the study period in all subgroups (range, 32%-91% decrease;<i>P</i> ≤ .001 for all subgroups), but the decrease was not significant among women (80% decrease;<i>P</i> = .08). Similarly, the rates of ruptured OSR decreased among all subgroups (range, 47%-91% decrease;<i>P</i> &lt; .001), but the decrease was not significant among women (87% decrease;<i>P</i> = .54). Ruptured EVAR showed significant uptake in all subgroups. <h3>Conclusions and Relevance</h3> Among patients with AAA in Ontario, Canada, use of EVAR appeared to increase from 2003 to 2016, whereas OSR use appeared to decrease. These findings were most pronounced among elective procedures for men and older patients. The delayed increase in the use of EVAR among women may reflect continued anatomical constraints for women seeking elective repair.
Estimating the Effects of PM2.5 on Life Expectancy Using Causal Modeling Methods
Authors: Joel D. Schwartz, Yan Wang, Itai Kloog, Ma’ayan Yitshak-Sade, Francesca Dominici, Antonella Zanobetti
Journal: Environmental Health Perspectives (2018)

Background: Many cohort studies have reported associations between PM2.5 and the hazard of dying, but few have used formal causal modeling methods, estimated marginal effects, or directly modeled the loss of life expectancy. Objective: Our goal was to directly estimate the effect of PM2.5 on the distribution of life span using causal modeling techniques. Methods: We derived nonparametric estimates of the distribution of life expectancy as a function of PM2.5 using data from 16,965,154 Medicare beneficiaries in the Northeastern and mid-Atlantic region states (129,341,959 person-years of follow-up and 6,334,905 deaths). We fit separate inverse probability-weighted logistic regressions for each year of age to estimate the risk of dying at that age given the average PM2.5 concentration at each subject's residence ZIP code in the same year, and we used Monte Carlo simulations to estimate confidence intervals. Results: The estimated mean age at death for a population with an annual average PM2.5 exposure of 12 μg/m3 (the 2012 National Ambient Air Quality Standard) was 0.89 y less (95% CI: 0.88, 0.91) than estimated for a counterfactual PM2.5 exposure of 7.5 μg/m3. In comparison, life expectancy at 65 y of age increased by 0.9 y between 2004 and 2013 in the United States. We estimated that 23.5% of the Medicare population would die before 76 y of age if exposed to PM2.5 at 12 μg/m3 compared with 20.1% if exposed to an annual average of 7.5 μg/m3. Conclusions: We believe that this is the first study to directly estimate the effect of PM2.5 on the distribution of age at death using causal modeling techniques to control for confounding. We find that reducing PM2.5 concentrations below the 2012 U.S. annual standard would substantially increase life expectancy in the Medicare population. https://doi.org/10.1289/EHP3130
OWE-039 Nurse inpatient endoscopy coordinator: interim analysis of a quality improvement project
Authors: Sister Rebecca Ullah, Sampath Kumar, Anuj Gandagule, Simon Everett, Ruchit Sood, Jo Corrigan
Journal: Endoscopy (2018)

<h3>Introduction</h3> The Gastroenterology department at Leeds Teaching Hospitals is large tertiary referral centre with a catchment area of more than 8 00 000 people. Several issues have been identified that have impacted on the timely provision of an inpatient endoscopy service such as incomplete pre-endoscopy ward checklists, incomplete bowel preparation for lower gastrointestinal endoscopy, non-adherence to fasting guidelines and last-minute cancellations as a result. We introduced a nurse inpatient endoscopy coordinator (NIC) with the aim of improving efficiency and quality of our inpatient endoscopy service. <h3>Methods</h3> The quality improvement project (QIP) was conducted at St. James's University Hospital over a 3 month period between November 2017 and January 2018. We collected data for 180 inpatient endoscopy procedures of which 50 were seen by the NIC prior to the procedure. The role of the NIC was to ensure completion of the pre-endoscopy checklist, provision of written information regarding the procedure, ensure patient consent was obtained on the ward, and provide guidance to the ward staff with regards to fasting and/or bowel preparation if indicated. <h3>Results</h3> Data was collected for 180 inpatient procedures. The table shows the comparison of the quality assessment outcomes if seen by the NIC compared with when the patient was not seen by the NIC. There were 7 procedures cancelled after arrival in the endoscopy department when not seen by the NIC versus no procedures cancelled when seen by the NIC (p=0.19). One procedure was cancelled by the NIC prior to arrival in the endoscopy unit as they were deemed too unwell to have the procedure undertaken. A patient satisfaction questionnaire showed that 100% of patients seen by the NIC were 'very satisfied' in several aspects of their care, such as provision of verbal and written information, in being well informed about their procedure and that their procedure was completed in a timely manner. <h3>Conclusion</h3> This QIP has shown that the introduction of a NIC can have a significant impact on improving efficiency and quality in an inpatient endoscopy service.
Anti-tumor macrophages activated by ferumoxytol combined or surface-functionalized with the TLR3 agonist poly (I : C) promote melanoma regression
Authors: Jiaojiao zhao, Zhengkui Zhang, Yaxian Xue, Guoqun Wang, Yuan Cheng, Yuchen Pan, Shuli Zhao, Yayi Hou
Journal: Theranostics (2018)

Macrophages orchestrate inflammation and control the promotion or inhibition of tumors and metastasis.Ferumoxytol (FMT), a clinically approved iron oxide nanoparticle, possesses anti-tumor therapeutic potential by inducing pro-inflammatory macrophage polarization.Toll-like receptor 3 (TLR3) activation also potently enhances the anti-tumor response of immune cells.Herein, the anti-tumor potential of macrophages harnessed by FMT combined with the TLR3 agonist, poly (I:C) (PIC), and FP-NPs (nanoparticles composed of amino-modified FMT (FMT-NH2) surface functionalized with PIC) was explored.Methods: Proliferation of B16F10 cells co-cultured with macrophages was measured using immunofluorescence or flow cytometry (FCM).Phagocytosis was analyzed using FCM and fluorescence imaging.FP-NPs were prepared through electrostatic interactions and their properties were characterized using dynamic light scattering, transmission electron microscopy, and gel retardation assay.Anti-tumor and anti-metastasis effects were evaluated in B16F10 tumor-bearing mice, and tumor-infiltrating immunocytes were detected by immunofluorescence staining and FCM.Results: FMT, PIC, or the combination of both hardly impaired B16F10 cell viability.However, FMT combined with PIC synergistically inhibited their proliferation by shifting macrophages to a tumoricidal phenotype with upregulated TNF-α and iNOS, increased NO secretion and augmented phagocytosis induced by NOX2-derived ROS in vitro.Combined treatment with FMT/PIC and FMT-NH2/PIC respectively resulted in primary melanoma regression and alleviated pulmonary metastasis with elevated pro-inflammatory macrophage infiltration and upregulation of pro-inflammatory genes in vivo.In comparison, FP-NPs with properties of internalization by macrophages and accumulation in the lung produced a more pronounced anti-metastatic effect accompanied with decreased myeloid-derived suppressor cells, and tumor-associated macrophages shifted to M1 phenotype.In vitro mechanistic studies revealed that FP-NPs nanoparticles barely affected B16F10 cell viability, but specifically retarded their growth by steering macrophages to M1 phenotype through NF-κB signaling.Conclusion: FMT synergized with the TLR3 agonist PIC either in combination or as a nano-composition to induce macrophage activation for primary and metastatic melanoma regression, and the nano-composition of FP-NPs exhibited a more superior anti-metastatic efficacy.
Expression of Myeloma Cell and Soluble B-Cell Maturation Antigen (BCMA) in Relapsed and Refractory Multiple Myeloma Patients Treated with GSK2857916 in BMA117159
Authors: E.J. Dettman, Fabio Rigat, Josh Albert, Ruth Barnard, Mary Birchler, Yan Deghenhardt, Stephen DeWall, Boyenoh Gaye, Zangdong He, Veronica Liu, Joanna Opalinska
Journal: Blood (2018)
A feasibility study of the Physician Orders for Life-Sustaining Treatment for patients with terminal cancer.
Authors: Su-Jin Koh, Ho Jung An, Hyun Jung Jun, Sang Hoon Chun, Kyung Hee Lee, Hee Kyung Ahn, Hyun Ae Jung, Kim Ju Hee, Min-Ho Kim
Journal: Journal of Clinical Oncology (2018)

8 Background: Terminally ill patients can decide end-of-life preferences with physicians in Physician Orders for Life-Sustaining Treatment (POLST) form. We did multi-center, prospective study to assess the feasibility of completing the POLST form in real oncologic practice. Methods: The inclusion criteria were patients with terminal cancer, age ≥20, and sufficient to communicate. The primary end point was the completion rate of the POLST. The questionnaire about the barriers from physicians or patients was asked to whom refused the POLST discussion. Results: From June to December 2017, 336 patients were enrolled from seven hospitals. The median age was 66 (20–94) years, 52.7% were male, 60.4% showed ECOG 3/4, and hepato-pancreato-biliary (26.2%) was the most common origin, followed by lung (23.2%) and gastro-intestinal (19.9%). Patients were in various situations: hospice care (41.2%), after progression (37.9%), under active treatment (15.8%), or just diagnosed as cancer (5.1%). The expected survival duration was 10.6 ±7.3 months. The POLST forms were introduced in 60.1%, and 31.3% signed the form. The barriers from physicians were reluctance of family members (49.7%), lack of rapport (44.8%), patients’ denial of prognosis (34.3%); lack of time (22.7%), guilty feeling (21.5%), prognostic (21.0%) or time (16.6%) uncertainty. The barriers from patients were lack of knowledge/understanding in 41.3% for each, denial of prognosis (14.3%), emotional discomfort (63.5%), and difficulty in making decision by themselves (66.7%). Conclusions: One-third of patients completed the POLST forms, and various barriers were found. To overcome those barriers, social engagement, education, and systemic support might be necessary.
Cannabinoid‐1 Receptor Antagonism Improves Glycemic Control and Increases Energy Expenditure Through Sirtuin‐1/Mechanistic Target of Rapamycin Complex 2 and 5′Adenosine Monophosphate–Activated Protein Kinase Signaling
Authors: Jie Liu, Grzegorz Godlewski, Tony Jourdan, Ziyi Liu, Resat Cinar, Keming Xiong, George Kunos
Journal: Hepatology (2018)

Endocannabinoids promote energy conservation in obesity, whereas cannabinoid‐1 receptor (CB 1 R) blockade reverses body weight gain and insulin resistance and increases energy expenditure. Here we investigated the molecular mechanisms of the catabolic effects of CB 1 R blockade in the liver. Exposure of primary mouse hepatocytes and HepG2 cells to the CB 1 R agonist arachidonyl‐2'‐chloroethylamide inhibited the expression of Sirtuin‐1 (Sirt1) and Rictor, a component of mechanistic target of rapamycin complex 2 (mTORC2) and suppressed insulin‐induced Akt phosphorylation at serine 473. These effects were reversed by peripheral CB 1 R antagonist JD5037 in control hepatocytes but not in hepatocytes deficient in Sirt1 and/or Rictor, indicating that these two proteins are required for the CB 1 R‐mediated inhibition of insulin signaling. Feeding C57BL/6J mice a high‐fat diet (HFD) inhibited hepatic Sirt1/mTORC2/Akt signaling, and the inhibition was reversed by rimonabant or JD5037 in wild‐type but not liver‐specific Sirt1 ‐/‐ (Sirt1‐LKO) mice, to levels observed in hepatocyte‐specific CB 1 R ‐/‐ mice. A similar attenuation of hyperglycemia and hyperinsulinemia in wild‐type mice with obesity but not in Sirt1‐LKO mice could be attributed to insufficient reversal of HFD‐induced mitochondrial reactive oxygen species generation in peripheral tissues in the latter. In contrast, JD5037 treatment was equally effective in HFD‐fed wild‐type and Sirt1‐LKO mice in reducing hepatic steatosis, increasing fatty acid β‐oxidation, and activating 5′adenosine monophosphate–activated protein kinase (AMPK) through liver kinase B1 (LKB1), resulting in a similar increase in total energy expenditure in the two strains. Conclusion: Peripheral CB 1 R blockade in mice with obesity improves glycemic control through the hepatic Sirt1/mTORC2/Akt pathway, whereas it increases fatty acid oxidation through LKB1/AMPK signaling.
EGFR-Mutant SCLC Exhibits Heterogeneous Phenotypes and Resistance to Common Antineoplastic Drugs
Authors: Chih-An Lin, Sung-Liang Yu, Hsuan-Yu Chen, Huei-Wen Chen, Shr-Uen Lin, Chia-Ching Chang, Chong-Jen Yu, Pan-Chyr Yang, Chao-Chi Ho
Journal: Journal of Thoracic Oncology (2018)
Mutagenesis in Norovirus in Response to Favipiravir Treatment
Authors: Christopher Ruis, Li-An K Brown, Sunando Roy, Claire Atkinson, Rachel Williams, Siobhan O Burns, Erika Yara-Romero, Michael Jacobs, Richard Goldstein, Judith Breuer, David M Lowe
Journal: New England Journal of Medicine (2018)

2.A.(1) Drug substance 2.A.(1).1) Characterization (a) General propertiesThe determined physicochemical properties of the drug substance include description, X-ray powder diffraction, solubility, hygroscopicity, melting point and thermal analysis, dissociation constant, partition coefficient, and crystalline polymorphism.The drug substance is a white to light yellow powder.It is sparingly soluble in acetonitrile and in methanol, and slightly soluble in water and in ethanol (99.5).It is slightly soluble at pH 2.0 to 5.5 and sparingly soluble at pH 5.5 to 6.1.The drug substance is not hygroscopic at 25°C/51% to 93%RH.The melting point is 187°C to 193°C, and the dissociation constant (pKa) is 5.1 due to the hydroxyl group of favipiravir.Measurement results on the partition ratio of favipiravir in water/octanol at 25°C indicate that favipiravir tends to be distributed in the 1-octanol phase at pH 2 to 4 and in the water phase at pH 5 to 13. (b) Structure determinationThe structure of the drug substance is supported by elemental analysis, ultraviolet-visible spectrophotometry, infrared spectrophotometry, nuclear magnetic resonance spectroscopy ( 1 H-NMR, 13 C-NMR), mass spectrometry, and single crystal crystallography. (c) Crystalline polymorphism
Regional Hyperthermia With Neoadjuvant Chemotherapy for Treatment of Soft Tissue Sarcoma—Reply
Authors: Ulrich Mansmann, Lars H. Lindner, Rolf Issels
Journal: JAMA Oncology (2018)

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