tbuckley/cabot-search huggingface dataset:
Abstract 19672: Comparison of Major-bleeding Risk and Health Care Costs Among Treatment-naïve Non-valvular Atrial Fibrillation Patients Initiating Apixaban, Dabigatran, Rivaroxaban or Warfarin
Authors: Alpesh Amin, Allison Keshishian, Lin Xie, Onur Baser, Kwanza Price, Lien Vo, Prianka Singh, Amanda Bruno, Jack Mardekian, Wilson Tan, Shalabh Singhal, Chad Patel, Kevin Odell, Jeffrey Trocio
Journal: Circulation (2015)

Objective: The study aim was to compare major bleeding risk and health care costs after initiating oral anticoagulants (OACs) for treatment-naïve non-valvular atrial fibrillation (NVAF) patients. Methods: Patients in the Medicare advantage population prescribed apixaban, rivaroxaban, dabigatran or warfarin were selected from the Optum Research Database 01JAN2013-31DEC2014. The first OAC prescription date was designated as the index date. Patients were required to have a NVAF diagnosis, continuous health plan enrollment for 6 months and no OAC claims before the index date. Patients were classified into four cohorts based on their index OAC prescription. Major bleeding events, identified by the Cunningham algorithm plus additional bleeding sites, were compared using a Cox proportional hazards model. Health care costs were calculated per patient per month and compared using generalized linear models. Results: The study included 36,260 patients: 3,762 apixaban, 2,677 dabigatran, 8,740 rivaroxaban, and 21,081 warfarin patients. CHA2DS2-VASc score was higher in apixaban patients (4.2) compared to dabigatran and rivaroxaban (both 4.0; p&lt;0.001), but lower than in warfarin patients (4.3; p&lt;0.001). After adjusting for baseline characteristics, apixaban patients were significantly less likely to have a major-bleeding event within one year of treatment initiation compared to rivaroxaban (HR=0.69; 95% CI=0.59-0.81) and warfarin (HR=0.71; 95% CI=0.61-0.82) patients and trended towards numerically lower major bleeding compared to dabigatran patients (HR=0.87; 95% CI=0.72-1.06). Major bleeding-related medical costs were lower in apixaban patients ($53) compared to rivaroxaban ($111) and warfarin ($138) patients (p&lt;0.001) and similar to dabigatran patients ($44, p=0.370). Furthermore, apixaban patients incurred lower all-cause medical costs ($1,646) compared to dabigatran ($1,974, p=0.02), rivaroxaban ($1,909, p=0.002) and warfarin ($2,162, p&lt;0.001) patients. Conclusion: In a large national Medicare advantage population, treatment-naïve NVAF patients treated with apixaban were significantly less likely to have a major-bleeding event compared to those prescribed rivaroxaban or warfarin and had significantly lower medical costs.
Teens who use cannabis show higher risk of taking other illicit drugs
Authors: Zosia Kmietowicz
Journal: BMJ (2017)

Teenagers who use cannabis are more likely to smoke, drink in a harmful way, and take other illicit drugs in early adulthood than non-users, a study has found. Although the study was observational, researchers from the University of Bristol concluded that more should be done to reduce young people’s cannabis exposure.1

Cannabis has often been cited as a “gateway” to other drug use, said the researchers, but the evidence for this has been inconsistent.

To explore the link they used data from the Avon Longitudinal Study of Parents and Children (ALSPAC), …
Bone grafts and biomaterials substitutes for bone defect repair: A review
Authors: Wenhao Wang, Kelvin W.K. Yeung
Journal: Bioactive Materials (2017)

Bone grafts have been predominated used to treat bone defects, delayed union or non-union, and spinal fusion in orthopaedic clinically for a period of time, despite the emergency of synthetic bone graft substitutes. Nevertheless, the integration of allogeneic grafts and synthetic substitutes with host bone was found jeopardized in long-term follow-up studies. Hence, the enhancement of osteointegration of these grafts and substitutes with host bone is considerably important. To address this problem, addition of various growth factors, such as bone morphogenetic proteins (BMPs), parathyroid hormone (PTH) and platelet rich plasma (PRP), into structural allografts and synthetic substitutes have been considered. Although clinical applications of these factors have exhibited good bone formation, their further application was limited due to high cost and potential adverse side effects. Alternatively, bioinorganic ions such as magnesium, strontium and zinc are considered as alternative of osteogenic biological factors. Hence, this paper aims to review the currently available bone grafts and bone substitutes as well as the biological and bio-inorganic factors for the treatments of bone defect.
Single Cell Bisulfite Sequencing Defines Epigenetic Diversification in Chronic Lymphocytic Leukemia
Authors: Dan A. Landau, Kendell Clement, Hongcang Gu, Evan Biederstedt, Divy Kangeyan, Steven Hill, Lili Wang, Martin Aryee, Andreas Gnirke, Alex Meissner, Catherine J Wu
Journal: Blood (2016)
Childhood factors associated with complete and clinical asthma remission at 25 and 49 years
Authors: Orestes A. Carpaij, Maartje A.E. Nieuwenhuis, Gerard H. Koppelman, Maarten van den Berge, Dirkje S. Postma, Judith M. Vonk
Journal: European Respiratory Journal (2017)

Asthma can go into remission later in life in approximately 35% of all patients [1]. Asthma remission is associated with childhood onset of asthma [2, 3], the male sex, smoking cessation, initially less severe airway obstruction and, notably, more severe bronchial hyperresponsiveness (BHR) [4, 5]. Unfortunately, patients in asthma remission may show relapse later in life. Data regarding childhood factors that predict clinical asthma remission in adulthood are sparse, and even fewer data on complete asthma remission [6] or the persistence of asthma remission throughout the lifespan are presently available. Therefore, the aim of the current study is to explore whether asthma remission persists in children, followed from childhood up to an average age of 49 years. Furthermore, we determined which factors in childhood are associated with clinical and/or complete asthma remission that persists during adulthood. Asthma remission is rare but strictly defined complete asthma remission is persistent in most cases <http://ow.ly/g0ZK30b1ACC>
Validity of 1% hormonal positivity cutoff by American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines at Georgia Cancer Center.
Authors: Houssein Talal Abdul Sater, Ramses F. Sadek, Li fang Zhang, Aaron Gopal, Jean-Pierre Blaize, David Yashar, Reena Patel, Swetha Aribindi, Hiral S Patel, Shou-Ching Tang
Journal: Journal of Clinical Oncology (2017)

1094 Background: Hormone Receptor Status (HS) in breast cancer (BC) is a universally accepted biomarker. ASCO/CAP 2010 guidelines set the threshold of Estrogen and Progesterone Receptor positivity to 1 %. BC with 1-9% HS expression remains controversial with recent data disputing these guidelines. The objective of this retrospective study was to validate these guidelines at Georgia Cancer Center (GCC) with high percentage of black race. Methods: All female patients with invasive BC diagnosed between 2005-2010 at GCC (11y follow-up) were chart reviewed. We used Cox proportional hazards model to explore survival among three HS groups ( &lt; 1%, 1-9%, ≥10%) adjusting for standard prognostic factors. Hazard ratios (HR) and 95% confidence intervals (CI) were also reported. 1-9 %, and ≥10% groups were further explored using same method to test survival difference with or without hormone therapy (HT). Fischer’s Exact test was used to evaluate response to HT in these groups. Results: 400 patients (all stages) with mean age of 59, were 24.75% HS &lt; 1%, 17.5% HS1-9%, and 57.75% HS≥10%. Race was 43.75% Black, and 54% White. Disease stages were 84.4% early (I-IIIA) and 15.56% late (IIIB-IV). Grades were 51.42% low (1-2) and 48.58% high (3). The 2 groups (1-9%, ≥10%) received chemotherapy (42.86%, 39.83%), and HT (58.57%, 80.52%) respectively while 70.71% of &lt; 1% HS group had chemotherapy. Mortality in HS &lt; 1% was significantly higher than HS ≥10% (HR 1.8, 95% CI 1.07-3.02), while mortality between HS 1-9% and HS ≥10% was not different (HR 1.05, 95% CI 0.48-2.30). Treated (HT) subjects had lower mortality than untreated subjects in the 1-9% group (HR 0.10, 95% CI 0.01-0.85). 100% of HT group had no evidence of tumor at last follow up compared to 87.5% in non-treatment group (p = 0.048). There was no significant difference in mortality between treated (HT) 1-9% and ≥10% groups. Conclusions: Hormone receptor expression as low as 1-9% was found to be equi-prognostic to ≥10% expression. It also predicted response to hormonal therapy. Whether other factors as lympho-vascular invasion, grade, and other parameters change the behavior of the 1-9% HS group remain to be explored.
Effect of genetic polymorphisms on erlotinib pharmacokinetics and toxicity in Japanese patients with non-small cell lung cancer.
Authors: Sho Saeki, Jiichiro Sasaki, Norihiro Iwamoto, Megumi Inaba, Sunao Ushijima, Hiroto Kishi, Shinji Fujii, Hiroshi Semba, Kosuke Kashiwabara, Shinya Sakata, Yuki Kai, Yukari Tsubata, Takeshi Isobe, Chihiro Endo-Tsukude, Hirotsugu Kohrogi, Hideyuki Saito, Akinobu Hamada
Journal: Journal of Clinical Oncology (2015)

e19104 Background: Erlotinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, which has been shown to be effective in non-small cell lung cancer (NSCLC) patients. Several population pharmacokinetics (PK) analyses have reported large inter-individual variabilities in erlotinib blood exposure and its toxicities. Here, aiming to develop a optimal dose regimen, we analyzed single nucleotide polymorphisms (SNPs) of PK-related genes and investigated the relationships between genotypes and inter-individual variabilities in the PK and adverse effects. Methods: We performed a multicenter study of 50 patients treated with 150 mg erlotinib as a second-line or later treatment. For PK analyses, blood samples were collected from 28 patients at 5 to 18 time points, and trough blood samples were collected from 20 patients at 1 time point. SNPs in genes encoding metabolizing enzymes or efflux transporters (CYP1A1, CYP1A2, CYP2D6, CYP3A4, CYP3A5, UGT1A1, UGT2B7, GSTM1, GSTT1, ABCB1, and ABCG2) were analyzed. Population PK analyses were carried out using NONMEM. SNPs were tested as covariates in a population PK model. The effects of these SNPs and erlotinib exposure on toxicity were evaluated. Results: A 2-compartment model with first order absorption and linear elimination described the erlotinib PK. Only the ABCB1 1236C > T polymorphism was a statistically significant covariate for CL/F, showing a 29.4% decrease in CL/F for the TT genotype as compared with the CC and the CT genotypes. The inter-individual variability in CL/F decreased by 10.6% after inclusion of the TT genotype as a covariate in the model. This result indicates that a dose reduction to 100 mg for the TT genotype group could equalize the erlotinib exposure between each genotype group. A higher incidence of adverse effects (mainly diarrhea) was observed in the TT genotype group. Conclusions: Of the 20 SNPs that are related to erlotinib PK, only ABCB1 1236C > T influenced the exposure of erlotinib. Individual dosing based on ABCB1 genotype might reduce the adverse effects. Further clinical trials are needed to investigate the toxicity and the clinical outcome of this dose regimen.
Decitabine Combined with Haag Regimen Is an Effective Salvage Treatment for Advanced Acute Myeloid Leukemia
Authors: XiaoWen Tang, Wei Cui, Zhengming Jin, Xiaming Zhu, Aining Sun, Huiying Qiu, Miao Miao, Jing Cao, Dandan Guo, Depei Wu
Journal: Blood (2016)
ImmunoCAP cellulose displays cross-reactive carbohydrate determinant (CCD) epitopes and can cause false-positive test results in patients with high anti-CCD IgE antibody levels
Authors: Wolfgang Hemmer, Friedrich Altmann, Friedrich Holzweber, Clemens Gruber, Felix Wantke, Stefan Wöhrl
Journal: Journal of Allergy and Clinical Immunology (2017)
A population model to predict progression free survival in breast cancer patients treated with neoadjuvant chemotherapy ñ vaccines based on tumour growth inhibition metrics.
Authors: Belen P.Solans, Diego Salas, Marta Abengozar, Luis Javier Pina, Arlette Elizalde, Maria Cruz Martinez Cosgaya, Susana De La Cruz, Esteban Salgado Pascual, Ignacio Gil-Bazo, Jose Manuel Aramendia, Inaki F Troconiz, Marta Santisteban
Journal: Journal of Clinical Oncology (2017)

e12114 Background: Breast cancer (BC) is the most commonly diagnosed malignancy in women. Neoadjuvant chemotherapy selects patients with optimal pathological responses and increases tumorectomy versus total mastectomy. Changes in tumor size (CTS) are related to an early clinical benefit and to Progression Free Survival (PFS) and Overall Survival (OS) in BC patients. Thus, the identification of new prognostic factors in the neoadjuvant scenario is crucial. Objectives:To assess the link between tumor growth inhibition metrics (TGI) and progression free survival (PFS) based on data obtained from BC patients with neoadjuvant therapy Methods: Data were obtained from 218 patients with BC treated at the University Clinic of Navarra, diagnosed from January 2008 to February 2016, with a median age of 49 years (range 25 to 84). Classification of molecular subtypes was based on IHC and found as follows: Her2 (6%), LA ( 23%), LB ( 36%), LB-Her2 (10%) and TN ( 25%). Patients were treated with ddECx 4 followed Docetaxel x 4. Her2 patients had therapy with Trastuzumab. 18% of the patients (LB and TN) received vaccination with dendritic cells. Data were analysed under the population approach with NONMEN 7.3. A model accounting for the dynamics of tumor growth and antitumor effect of the neoadjuvant therapy was developed. The model describes tumor size as the sum of the longest diameters of target lesions as a function of time and drug exposure. A PFS model was developed to describe the PFS time distribution as a function of covariates Results: The TGI was able to individually and accurately describe the tumor shrinkage. Vaccinated patients had an increased shrinkage rate of 36% (p &lt; 0.001) than those who were not (p &lt; 0.001). PFS (months) was best described by a Weibull model, and greater tumor size at diagnosis (p &lt; 0.05), smaller CTS (p &lt; 0.05) and TN subtype (p &lt; 0.001) were identified as poor prognostic factors Conclusions: A PFS model that uses a model-based estimate of tumor growth to predict the PFS of BC patients receiving neoadjuvant therapy has been developed. This model helps to gain early understanding of potential clinical benefit to facilitate go/no-go decision making.
VIDEO ANALYSIS OF ACUTE INJURIES DURING THE 24TH MEN'S HANDBALL WORLD CHAMPIONSHIP 2015 IN QATAR
Authors: Stig H. Andersson, Roald Bahr, Marco Cardinale, Nebojsa Popovic, Tone Bere, Grethe Myklebust
Journal: British Journal of Sports Medicine (2017)

Background Handball is a contact sport with a high prevalence of acute injuries. Injuries often occur during high-speed movements involving several players, making it difficult to describe the exact mechanism of injury. Objective Describe the mechanisms of injury in elite male handball. Design Prospective video analysis. Setting During the men´s handball world championship 2015, 132 injuries were reported through on-site injury surveillance by team medical staff. Based on the injury reports, two operators accessed the videos of each game and identified the specific injury situations using video analysis software (ProzoneHANDBALL v.1.0.0.14, ProzoneSports, Leeds, UK). Video analysis A total of 97 injury videos were identified; 42 were excluded, as the injury situation was not visible. Five handball experts performed an individual analysis of the 55 included videos based on a specific form developed to describe the injury situations and causes, followed by a consensus meeting. Main Outcome Measurements The form included variables related to the playing situation, landing situation, action of attacker and defender at time of injury and localization of tackle/hit. Results The most common injury location was the head and face (n=17, 31%), followed by the ankle (n=6, 11%). The most frequent injury cause was opponent contact (n=27, 49%), followed by landing trauma subsequent to opponent contact (n=8, 15%). The injuries were equally distributed between attackers (n=29, 53%) and defenders (n=26, 47%), but time-loss injuries (49%) were more common among attackers (68%). The most frequent playing action performed by injured attackers was a jump shot (n=9, 31%); tackles were most often to their throwing arm (n=7, 30%). Conclusions Acute injuries in elite male handball are equally distributed between attackers and defenders. However, attackers sustain more severe injuries. The most frequent injury causes are direct opponent contact and landing trauma after opponent contact.
High-quality de novo assembly of the apple genome and methylome dynamics of early fruit development
Authors: Nicolas Daccord, Jean-Marc Celton, Gareth Linsmith, Claude Becker, Nathalie Choisne, Elio Schijlen, Henri van de Geest, Luca Bianco, Diego Micheletti, Riccardo Velasco, Erica Adele Di Pierro, Jérôme Gouzy, D Jasper G Rees, Philippe Guérif, Hélène Muranty, Charles-Eric Durel, François Laurens, Yves Lespinasse, Sylvain Gaillard, Sébastien Aubourg, Hadi Quesneville, Detlef Weigel, Eric van de Weg, Michela Troggio, Etienne Bucher
Journal: Nature Genetics (2017)

Using the latest sequencing and optical mapping technologies, we have produced a high-quality de novo assembly of the apple (Malus domestica Borkh.) genome. Repeat sequences, which represented over half of the assembly, provided an unprecedented opportunity to investigate the uncharacterized regions of a tree genome; we identified a new hyper-repetitive retrotransposon sequence that was over-represented in heterochromatic regions and estimated that a major burst of different transposable elements (TEs) occurred 21 million years ago. Notably, the timing of this TE burst coincided with the uplift of the Tian Shan mountains, which is thought to be the center of the location where the apple originated, suggesting that TEs and associated processes may have contributed to the diversification of the apple ancestor and possibly to its divergence from pear. Finally, genome-wide DNA methylation data suggest that epigenetic marks may contribute to agronomically relevant aspects, such as apple fruit development.
Externally validated improved 5-factor prognostic model in patients (pts) receiving salvage systemic therapy for advanced urothelial carcinoma (UC).
Authors: Guru Sonpavde, Gregory Russell Pond, Jonathan E. Rosenberg, Dean F. Bajorin, Ashley Marie Regazzi, Stephanie A. Mullane, Guenter Niegisch, Peter Albers, Andrea Necchi, Giuseppe di Lorenzo, Ronan Fougeray, Yoo-Joung Ko, Antonio Rozzi, Kazumasa Matsumoto, Jae-Lyun Lee, Hiroshi Kitamura, Haruki Kume, Matthew I. Milowsky, Toni K. Choueiri, Joaquim Bellmunt
Journal: Journal of Clinical Oncology (2015)

4527 Background: Prognostic factors in pts receiving salvage systemic therapy for advanced UC include performance status (PS), liver metastasis (LM), hemoglobin (Hb) and time from prior chemotherapy (TFPC). We investigated the impact of neutrophil count (N), lymphocytes (L), platelets (PLT) and albumin (Alb). Methods: Patient level data from phase II trials of salvage therapy on N, L, PLT and Alb were required in addition to TFPC, Hb, PS and LM status. Cox proportional hazards regression was used to evaluate their association with overall survival (OS). An optimal regression model was constructed using forward stepwise selection and risk groups defined using number of adverse factors. Trial was a stratification factor. External validation of significant factors was conducted in a separate dataset of 5 salvage phase II trials including 167 pts. Results: Data for discovery was obtained from 10 trials accruing 708 pts. After adjustment for TFPC < 3 months (mo), Hb < 10 g/dl, PS > 0 and LM status, PLT > ULN (upper limit of normal) and Alb < LLN were significant poor prognostic factors (Table). Only the addition of Alb < LLN was externally validated. Based on the 5 factor risk model, the median OS (mo) is 8.9, 6.4, 4.5 for 0-1, 2, 3+ risk factors (n = 207, 171, 113) in discovery dataset (n = 491), and 10.6, 10.0, 7.0 with n = 73, 47, 47 in the validation dataset (n = 167). The c-index improved from 0.631 to 0.638 in the discovery set and from 0.601 to 0.632 in the validation set by adding Alb < LLN to the previously identified 4 factors. Conclusions: A 5-factor model including TFPC < 3 mo, Hb < 10 g/dL, PS > 0, LM status and Alb < LLN was externally validated and enhanced the Bellmunt prognostic model in pts receiving salvage systemic therapy for advanced UC. Table Factor Discovery (n = 491) Validation (n = 167) HR (95% CI) p-value HR (95% CI) p-value TFPC < 3 months 1.49 (1.19, 1.87) < 0.001 1.35 (0.87, 2.08) 0.18 ECOG PS > 0 1.39 (1.16, 1.67) < 0.001 1.58 (1.06, 2.35) 0.023 Liver Metastases 1.45 (1.16, 1.81) < 0.001 1.26 (0.83, 1.90) 0.27 Hb < 10 g/dl 1.73 (1.27, 2.35) < 0.001 1.35 (0.94, 1.96) 0.10 Alb < LLN 1.61 (1.20, 2.15) 0.002 1.90 (1.27, 2.85) 0.002