tbuckley/cabot-search huggingface dataset:
Efficacy, Acceptability, and Tolerability of Antipsychotics in Treatment-Resistant Schizophrenia
Authors: Myrto T. Samara, Markus Dold, Myrsini Gianatsi, Adriani Nikolakopoulou, Bartosz Helfer, Georgia Salanti, Stefan Leucht
Journal: JAMA Psychiatry (2016)

In treatment-resistant schizophrenia, clozapine is considered the standard treatment. However, clozapine use has restrictions owing to its many adverse effects. Moreover, an increasing number of randomized clinical trials (RCTs) of other antipsychotics have been published.To integrate all the randomized evidence from the available antipsychotics used for treatment-resistant schizophrenia by performing a network meta-analysis.MEDLINE, EMBASE, Biosis, PsycINFO, PubMed, Cochrane Central Register of Controlled Trials, World Health Organization International Trial Registry, and clinicaltrials.gov were searched up to June 30, 2014.At least 2 independent reviewers selected published and unpublished single- and double-blind RCTs in treatment-resistant schizophrenia (any study-defined criterion) that compared any antipsychotic (at any dose and in any form of administration) with another antipsychotic or placebo.At least 2 independent reviewers extracted all data into standard forms and assessed the quality of all included trials with the Cochrane Collaboration's risk-of-bias tool. Data were pooled using a random-effects model in a Bayesian setting.The primary outcome was efficacy as measured by overall change in symptoms of schizophrenia. Secondary outcomes included change in positive and negative symptoms of schizophrenia, categorical response to treatment, dropouts for any reason and for inefficacy of treatment, and important adverse events.Forty blinded RCTs with 5172 unique participants (71.5% men; mean [SD] age, 38.8 [3.7] years) were included in the analysis. Few significant differences were found in all outcomes. In the primary outcome (reported as standardized mean difference; 95% credible interval), olanzapine was more effective than quetiapine (-0.29; -0.56 to -0.02), haloperidol (-0. 29; -0.44 to -0.13), and sertindole (-0.46; -0.80 to -0.06); clozapine was more effective than haloperidol (-0.22; -0.38 to -0.07) and sertindole (-0.40; -0.74 to -0.04); and risperidone was more effective than sertindole (-0.32; -0.63 to -0.01). A pattern of superiority for olanzapine, clozapine, and risperidone was seen in other efficacy outcomes, but results were not consistent and effect sizes were usually small. In addition, relatively few RCTs were available for antipsychotics other than clozapine, haloperidol, olanzapine, and risperidone. The most surprising finding was that clozapine was not significantly better than most other drugs.Insufficient evidence exists on which antipsychotic is more efficacious for patients with treatment-resistant schizophrenia, and blinded RCTs-in contrast to unblinded, randomized effectiveness studies-provide little evidence of the superiority of clozapine compared with other second-generation antipsychotics. Future clozapine studies with high doses and patients with extremely treatment-refractory schizophrenia might be most promising to change the current evidence.
Detection of Epstein-Barr virus messenger RNA in Reed-Sternberg cells of Hodgkin's disease by in situ hybridization with biotinylated probes on specially processed modified acetone methyl benzoate xylene (ModAMeX) sections [see comments]
Authors: P Brousset, S Chittal, D Schlaifer, J Icart, C Payen, F Rigal-Huguet, JJ Voigt, G Delsol
Journal: Blood (1991)
The cost of treating pulmonary embolisms following surgery for gynecological malignancies
Authors: T. P. Boren, M. A. Martino, E. Williamson, P. Twitty, J. Fiorica
Journal: Journal of Clinical Oncology (2005)

8250 Background: Pulmonary embolism is one of the most common causes of postoperative morbidity and mortality in women treated for gynecologic malignancy. This study evaluates the cost of three common treatment options following the diagnosis of postoperative pulmonary embolism. Methods: Twenty patients were identified at our institution over a two year period that were diagnosed with a postoperative pulmonary embolism. Three treatment arms were evaluated. Two patients were treated with IVC Filter only, eight patients were treated with an IVC filter and anticoagulation consisting of lovenox and/or coumadin, and twelve patients were treated with anticoagulation therapy only. The cost of the hospital stay was factored into the total cost of treatment. The cost of each treatment option was obtained from the billing department at our institution. Results: In the first treatment arm involving IVC filter placement only, the average hospital stay was 3.5 days with an average cost of inpatient and outpatient treatment of $7,897.50. In the second treatment arm consisting of anticoagulation therapy and IVC filter placement, the average hospital stay was 6.3 days with an average overall cost of treatment totaling $9,721.35. Anticoagulation therapy alone resulted in an average hospital stay of 14.8 days, with a cost a treatment averaging $21,905.90. The length of hospital stay mentioned above reflects the hospital days after the PE diagnosis. The average cost for each treatment arm reflects both the inpatient and outpatient treatment costs of the parameters specified following PE diagnosis. Conclusion: This study determines the average cost of treating a pulmonary embolism in the post-operative period using three separate treatment options. The increased cost of anticoagulation therapy alone may result from continued inpatient management and the need for outpatient lab testing. Randomized studies are warranted to evaluate the cost/benefit analysis, safety, and outcome with a pre-operative anti-coagulation preventative management algorithm. No significant financial relationships to disclose.
Implementation Science
Authors: Elliott S. Fisher, Stephen M. Shortell, Lucy A. Savitz
Journal: JAMA (2016)

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Identifying the effect of patient sharing on between-hospital genetic differentiation of methicillin-resistant Staphylococcus aureus
Authors: Hsiao-Han Chang, Janina Dordel, Tjibbe Donker, Colin J. Worby, Edward J. Feil, William P. Hanage, Stephen D. Bentley, Susan S. Huang, Marc Lipsitch
Journal: Genome Medicine (2016)

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common healthcare-associated pathogens. To examine the role of inter-hospital patient sharing on MRSA transmission, a previous study collected 2,214 samples from 30 hospitals in Orange County, California and showed by spa typing that genetic differentiation decreased significantly with increased patient sharing. In the current study, we focused on the 986 samples with spa type t008 from the same population. We used genome sequencing to determine the effect of patient sharing on genetic differentiation between hospitals. Genetic differentiation was measured by between-hospital genetic diversity, F ST , and the proportion of nearly identical isolates between hospitals. Surprisingly, we found very similar genetic diversity within and between hospitals, and no significant association between patient sharing and genetic differentiation measured by F ST . However, in contrast to F ST , there was a significant association between patient sharing and the proportion of nearly identical isolates between hospitals. We propose that the proportion of nearly identical isolates is more powerful at determining transmission dynamics than traditional estimators of genetic differentiation (F ST ) when gene flow between populations is high, since it is more responsive to recent transmission events. Our hypothesis was supported by the results from coalescent simulations. Our results suggested that there was a high level of gene flow between hospitals facilitated by patient sharing, and that the proportion of nearly identical isolates is more sensitive to population structure than F ST when gene flow is high.
Mechanisms of Acquired Resistance to AZD9291
Authors: Tae Min Kim, Ahnah Song, Dong-Wan Kim, Soyeon Kim, Yong-Oon Ahn, Bhumsuk Keam, Yoon Kyung Jeon, Se-Hoon Lee, Doo Hyun Chung, Dae Seog Heo
Journal: Journal of Thoracic Oncology (2015)

AZD9291, a third-generation and mutation-selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is active against patients with EGFR-mutant non-small-cell lung cancer (NSCLC) who failed prior treatment with EGFR TKIs. However, acquired resistance to AZD9291 is inevitable. In this study, we identified the mechanisms of acquired resistance to AZD9291 in EGFR-mutant NSCLC.Four NSCLC patients with both an EGFR exon 19 deletion and the EGFR mutation after developing acquired resistance to first-generation EGFR TKIs received AZD9291 at doses of 20 to 80 mg/day in a phase I trial (NCT01802632). Paired tumor samples before and after treatment were obtained to evaluate EGFR modifications, alternative pathway activation, and histologic transformation. Genetic alterations were analyzed using Sanger sequencing, fluorescence in situ hybridization, real-time polymerase chain reaction, and targeted exome sequencing.All four patients achieved a partial response (median duration of response, 9 months [range, 9-11 months]) and subsequently showed resistance to AZD9291. EGFR-mutant clones depopulated AZD9291-resistant tumors to below 1% (baseline, 14%-36%) in three patients with progression: one with the loss of EGFR-double mutant clones and two accompanied by transformation to small-cell carcinoma and focal fibroblast growth factor receptor 1 (FGFR1) amplification, respectively. EGFR-mutant clones remained and the EGFR ligand was overexpressed in one patient with focal progression to AZD9291.Acquired resistance mechanisms of AZD9291 in patients with EGFR-mutant NSCLC who failed treatment with first-generation EGFR TKIs include the loss of EGFR-mutant clones plus alternative pathway activation or histologic transformation and EGFR ligand-dependent activation.
Clinical, pathological and immunistochemistry characterization of primary breast cancer metastasizing to the central nervous system (CNS): Analysis of time to development of CNS metastasis
Authors: A. F. Ferreira Filho, S. Saueressig, D. L. da Silva, M. P. dos Santos, A. P. Wunder, R. Santana, C. Zetler
Journal: Journal of Clinical Oncology (2007)

2051 Background: The characterization of breast cancer patients (BCP) with high risk of developing CNS metastases still remains a challenge. The identification of these patients could enable new strategies of prevention, early detection and innovative treatments. Methods: We analyzed the records of 950 BCP treated at our institutions during 1997 to 2003 and found that 38 (4%) of these patients developed CNS metastases. In these 38 patients, we reviewed the clinical course, initial pathology and the primary tumor immunohistochemistry profile of hormone receptors, HER-2, p53, as well as microvessel density by the Chalkey count technique by the anti-CD105 antibody E-9. Results: Median age was 54 years (30–75), 11% &lt; 40 years, median tumor size was 3.5 cm (1.2–17). Median number of positive axillary nodes was 6 (0–27) and axillary lymph nodes were negative in 10 patients (29%). Only two patients (5%) had grade 1 tumors. The median survival after the development of CNS metastases was of 4.5 months (0.5 - 27 months), with 8% of patients living longer than one year. Treatment consisted of whole brain radiotherapy in 79% of the patients. Hormone negative receptor status was found in 24 patients (63%), HER-2 was overexpressed in 26 patients (68%) and p53 was positive in 16 patients (46%). Mean Microvessel density was &gt; 7 in 23 patients (59%). For the whole group of patients, the median time to the development of CNS metastases was 22 months (5–96). Patients with p53 positive tumors had a lower time to development of CNS metastasis (19.3 versus 34.6 months, p = 0.005), as compared to p53 negative tumors. No differences were found between subgroups of patients, as defined by tumor grade, microvessel density, hormone receptors and HER-2 status, or positivity of axyllary lymph nodes. Conclusions: The primary tumors of BCP who developed CNS metastases showed a high percentage of hormonoreceptor negativity (63%), overexpression of HER-2 (68%), and high counts of microvessel density . While the role of CD 105 expression and the development of CNS metastases in BC patients deserve further research, p53 positivity may be a marker of risk of early development of CNS metastases in BCP. No significant financial relationships to disclose.
Early COPD diagnosis during a smoking cessation (SC) program increases smoking cessation rates
Authors: Eleni Ischaki, Eleni Litsiou, Vassiliki Saltagianni, Filipos Filippidis, Aikaterini Tsoutsa, Ioanna Nikoloutsou, Andreas Asimakos, Spyridon Zakynthinos, Paraskevi Katsaounou
Journal: European Respiratory Journal (2014)

Introduction: Diagnosing COPD at early stages is crucial since the prognosis can be modified. Nevertheless most COPD pts are diagnosed at stages III&IV due to absence of respiratory symptoms at early stages. A smoking cessation program could help in identifying COPD pts by performing spirometry and increase smoking cessation rates using COPD diagnosis as a motive.

Aim: 1)To evaluate the rates of undiagnosed early COPD pts (stage I&II according GOLD) in our smoking cessation program.

2) To assess the effectiveness of COPD diagnosis as a motivational tool for quitting smoking.

Methods: 551 current smokers (>18yrs), attended voluntarily our outpatient smoking cessation clinic. All smokers performed Spirometry. Behavioral counseling and pharmacotherapy with varenicline were administered.

Results: 1) 86 of 551 smokers were COPD patients (81 first diagnosed) with minor symptoms that were underestimated

View this table:

SMOKING CESSATION RATES ACCORDING TO COPD STAGES





. 2) Smoking abstinence rates at 3m was significantly higher in first diagnosed COPD pts (95% vs. 55%)

View this table:

SMOKING CESSATION RATES ACCORDING TO COPD STAGES





Conclusion: A SC program is an opportunity to identify undiagnosed COPD pts. COPD diagnosis can be used effectively as a motive for quitting smoking. SC combined with adequate pharmacological treatment and vaccination can reduce the rate of yearly FEV1 decline and exacerbations and thus improve health related quality of life.
Evaluation of the Immune Marker in Post-Auto Hsct Patient with Malignant Lymphoma
Authors: Kaori Ito, Masataka Okamoto, Maiko Ando, Akinao Okamoto, Yoko Inaguma, Masutaka Tokuda, Satoko Morishima, Toshiyasu Makihara, Shigeki Yamada, Nobuhiko Emi
Journal: Annals of Oncology (2014)
Liposomal pegilated doxorubicin in pediatric patients with bone sarcomas and soft tissue sarcomas: Preliminary report.
Authors: R. Rivera-Luna, Rocio Cardenas-Cardos, Liliana Velasco-Hidalgo, Armando Martinez-Avalos, Araceli Castellanos-Toledo
Journal: Journal of Clinical Oncology (2010)

e20000 Background: Liposomal pegilated doxorubicinwas designed to increase the therapeutic efficacy and decrease the cardiotoxicity. Methods: Pediatric patients with bone sarcomas and soft tissue sarcomas treated with liposomal pegilated doxorubicin as part of their treatment program are included. A dose of 40 mg/m2 was used and escalated to 10 mg/m2 per course until reaching 50 mg/m2 in patients with rhabdomyosarcoma and Ewing sarcoma. In patients with osteosarcoma the top dose was 60 mg/m2. Twenty-four hours prior to the administration of the anthracycline the patients were premedicated with ranitidine, dexamethasone and cloropiramine. The pegilated doxorubicin was diluted in 400 ml/m2 of dextrose 5% solution and administered as IV infusion in 3 hours. The doxorubicin was administered every 4-6 weeks depending upon the tumor protocol. All the patients had an initial and subsequent evaluation including routine laboratory tests, chest CT scan, electrocardiogram and echocardiogram. Results: 16 patients from April to November 2009 were included. Age average was 8.1 years (range 2-16 years). There were 6 patients with osteosarcoma, 7 with rhabdomyosarcoma and 3 with Ewing sarcoma. 14 patients had no prior chemotherapy treatment, one patient presented as a second malignancy and no prior exposure to anthracyclines and 2 patients had a relapse prior to the exposure to anthracyclines. No acute infusion reactions, adverse reactions including hand-foot syndrome and cardiac toxicity were documented. Partial and complete response was in 14 (87.5%) patients, 2/6 (12.5%) patients with osteosarcoma had progressive disease. Among the 16 patients, 30 courses of this anthracycline were administered. Neutropenia grade IV was seen in 13 patients. Infectious and none infectious mortality was not present in either of these cases. Conclusions: This presentation of Anthracycline was well tolerated, with good therapeutic efficacy. It is required further follow up in order to determine response rate and the incidence of cardiotoxicity as a late effect. No significant financial relationships to disclose.
Abstract 12113: STAT1 Transcription Factor is Required for the Delayed Protection Against Cardiomyocyte Apoptosis by Ischemic Preconditioning
Authors: Roberto Bolli, Yanqing Zhu, Ou-Li Wang, Yiru Guo, Gregg Rokosh, Adam B Stein, Buddhadeb Dawn, Yu-Ting Xuan
Journal: Circulation (2013)

Apoptosis accounts for significant cardiomyocyte loss during myocardial infarction. Although STAT1 is known to play a predominantly proapoptotic role in many cells and tissues, the role of STAT1 si...
Phase I/II trial in patients with metastatic breast cancer (MBC) previously treated with a taxane and an anthracycline: Final safety data
Authors: L. T. Vahdat, J. Klimovsky, C. A. Bunnell
Journal: Journal of Clinical Oncology (2006)

10528 Background: Ixabepilone, a semi-synthetic analog of the natural product epothilone B, has shown anti-tumor activity in a broad range of tumor types including breast cancer. Preclinical studies suggest synergy between ixabepilone and capecitabine in breast cancer models and has fuelled interest in the clinical setting. Methods: This open-label Phase I/II study was conducted to determine the recommended Phase II (and III) doses of ixabepilone and capecitabine using a 3-hour infusion of ixabepilone given on Day 1 (Schedule A) or a 1-hour infusion of ixabepilone given for 3 days (Schedule B) in combination with capecitabine given orally on Days 1–14 every 21 days in patients (pts) with MBC previously treated with a taxane and an anthracycline. Eligible pts were aged ≥18 years with pathologic diagnosis of breast cancer and evidence of MBC, who had received prior treatment with a taxane and an anthracycline in the adjuvant or metastatic setting. Pts were excluded if they had received &gt;3 prior chemotherapy regimens in the metastatic setting or had ≥Grade 2 neuropathy. Toxicity was continuously monitored using NCI CTC v2. Results from the 62 pts treated with 40 mg/m 2 as a 3 hr-infusion ixabepilone and 2000 mg/m 2 capecitabine are shown here. Results: 56 of the 62 pts (90%) were aged &lt;65 years. 80% of pts had visceral disease; 44% were ER/PR/HER-2 negative. 44% of pts had received ≥ two prior chemotherapies in the metastatic setting. Grade 3 neuropathy (sensory and motor) was reported in 12 pts and 1 pt (19%, 2%), respectively. Hand-foot syndrome, reported in 39 pts (63%), was primarily Grade 2 (26%) or 3 (34%). Hematologic toxicities included Grade 4 leukopenia (7 pts, 12%) and Grade 4 neutropenia (16 pts, 26%). Dose reductions were used to manage sensory neuropathy and hematologic abnormalities. Conclusions: The recommended Phase II (and III) doses are 40 mg/m 2 ixabepilone (3-hour infusion on Day 1 every 21 days) and 2000 mg/m 2 capecitabine (divided BID on Days 1–14 every 21 days). This ixabepilone/capecitabine combination demonstrated a manageable safety profile and promising clinical anti-tumor activity in pts with MBC previously treated with a taxane and an anthracycline. [Table: see text]
Effects of Nicotine Patch vs Varenicline vs Combination Nicotine Replacement Therapy on Smoking Cessation at 26 Weeks
Authors: Timothy B. Baker, Megan E. Piper, James H. Stein, Stevens S. Smith, Daniel M. Bolt, David L. Fraser, Michael C. Fiore
Journal: JAMA (2016)

<h3>Importance</h3> Smoking cessation medications are routinely used in health care; it is vital to identify medications that most effectively treat this leading cause of preventable mortality. <h3>Objective</h3> To compare the efficacies of varenicline, combination nicotine replacement therapy (C-NRT), and the nicotine patch for 26-week quit rates. <h3>Design, Setting, and Participants</h3> Three-group randomized intention-to-treat clinical trial occurring from May 2012 to November 2015 among smokers recruited in the Madison, Wisconsin, and Milwaukee, Wisconsin, communities; 65.5% of smokers offered the study (2687/4102) refused participation prior to randomization. <h3>Interventions</h3> Participants were randomized to one of three 12-week open-label smoking cessation pharmacotherapy groups: (1) nicotine patch only (n = 241); (2) varenicline only (including 1 prequit week; n = 424); and (3) C-NRT (nicotine patch + nicotine lozenge; n = 421). Six counseling sessions were offered. <h3>Main Outcomes and Measures</h3> The primary outcome was carbon monoxide–confirmed self-reported 7-day point-prevalence abstinence at 26 weeks. Secondary outcomes were carbon monoxide–confirmed self-reported initial abstinence, prolonged abstinence at 26 weeks, and point-prevalence abstinence at weeks 4, 12, and 52. <h3>Results</h3> Among 1086 smokers randomized (52% women; 67% white; mean age, 48 years; mean of 17 cigarettes smoked per day), 917 (84%) provided 12-month follow-up data. Treatments did not differ on any abstinence outcome measure at 26 or 52 weeks, including point-prevalence abstinence at 26 weeks (nicotine patch, 22.8% [55/241]; varenicline, 23.6% [100/424]; and C-NRT, 26.8% [113/421]) or at 52 weeks (nicotine patch, 20.8% [50/241]; varenicline, 19.1% [81/424]; and C-NRT, 20.2% [85/421]). At 26 weeks, the risk differences for abstinence were, for patch vs varenicline, −0.76% (95% CI, −7.4% to 5.9%); for patch vs C-NRT, −4.0% (95% CI, −10.8% to 2.8%); and for varenicline vs C-NRT, −3.3% (95% CI, −9.1% to 2.6%). All medications were well tolerated, but varenicline produced more frequent adverse events than did the nicotine patch for vivid dreams, insomnia, nausea, constipation, sleepiness, and indigestion. <h3>Conclusions and Relevance</h3> Among adults motivated to quit smoking, 12 weeks of open-label treatment with nicotine patch, varenicline, or C-NRT produced no significant differences in biochemically confirmed rates of smoking abstinence at 26 weeks. The results raise questions about the relative effectiveness of intense smoking pharmacotherapies. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT01553084