tbuckley/cabot-search huggingface dataset:
Can rheumatoid arthritis (RA) registries provide contextual safety data for modern RA clinical trials? The case for mortality and cardiovascular disease
Authors: Kaleb Michaud, Niklas Berglind, Stefan Franzén, Thomas Frisell, Christopher Garwood, Jeffrey D Greenberg, Meilien Ho, Marie Holmqvist, Laura Horne, Eisuke Inoue, Fredrik Nyberg, Dimitrios A Pappas, George Reed, Deborah Symmons, Eiichi Tanaka, Trung N Tran, Suzanne M M Verstappen, Eveline Wesby-van Swaay, Hisashi Yamanaka, Johan Askling
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> We implemented a novel method for providing contextual adverse event rates for a randomised controlled trial (RCT) programme through coordinated analyses of five RA registries, focusing here on cardiovascular disease (CVD) and mortality. <h3>Methods</h3> Each participating registry (Consortium of Rheumatology Researchers of North America (CORRONA) (USA), Swedish Rheumatology Quality of Care Register (SRR) (Sweden), Norfolk Arthritis Register (NOAR) (UK), CORRONA International (East Europe, Latin America, India) and Institute of Rheumatology, Rheumatoid Arthritis (IORRA) (Japan)) defined a main cohort from January 2000 onwards. To address comparability and potential bias, we harmonised event definitions and defined several subcohorts for sensitivity analyses based on disease activity, treatment, calendar time, duration of follow-up and RCT exclusions. Rates were standardised for age, sex and, in one sensitivity analysis, also HAQ. <h3>Results</h3> The combined registry cohorts included 57 251 patients with RA (234 089 person-years)—24.5% men, mean (SD) baseline age 58.2 (13.8) and RA duration 8.2 (11.7) years. Standardised registry mortality rates (per 100 person-years) varied from 0.42 (CORRONA) to 0.80 (NOAR), with 0.60 for RCT patients. Myocardial infarction and major adverse cardiovascular events (MACE) rates ranged from 0.09 and 0.31 (IORRA) to 0.39 and 0.77 (SRR), with RCT rates intermediate (0.18 and 0.42), respectively. Additional subcohort analyses showed small and mostly consistent changes across registries, retaining reasonable consistency in rates across the Western registries. Additional standardisation for HAQ returned higher mortality and MACE registry rates. <h3>Conclusions</h3> This coordinated approach to contextualising RA RCT safety data demonstrated reasonable differences and consistency in rates for mortality and CVD across registries, and comparable RCT rates, and may serve as a model method to supplement clinical trial analyses for drug development programmes.
BEVLiN: Prospective study of the safety and efficacy of first-line bevacizumab (BEV) plus low-dose interferon-α2a (IFN) in patients (pts) with metastatic renal cell carcinoma (mRCC).
Authors: B. Melichar, S. Bracarda, V. Matveev, I. Rusakov, A. Kaprin, A. Zyryanov, R. Janciauskiene, E. Fernebro, G. H. Mickisch, M. E. Gore, A. Schulze, S. Jethwa, V. Sneller, P. Mulders, J. Bellmunt
Journal: Journal of Clinical Oncology (2011)

4546 Background: The phase III AVOREN trial showed that first-line BEV + IFN (9 MIU 3 x weekly [t.i.w]) is effective in pts with mRCC. In a retrospective analysis, efficacy was maintained and IFN-related toxicity improved if IFN dose was reduced to 6 or 3 MIU due to IFN-related toxicity. BEVLiN is the first trial to prospectively assess the safety and efficacy of BEV with low-dose IFN (3 MIU) in mRCC. Methods: 147 nephrectomised pts with previously untreated clear cell mRCC (Motzer score favourable/intermediate) were enrolled (Dec 2008–Feb 2010) into this open-label, single arm, multinational phase II trial. Pts received BEV 10mg/kg q2w + IFN 3 MIU t.i.w until disease progression. Primary endpoints are safety (specific IFN-associated adverse events [AEs] of grade (Gr) ≥3) and progression-free survival (PFS); secondary endpoints are overall survival (OS), overall response rate (ORR) and any Gr ≥3, overall and serious AEs. BEVLiN was designed to allow a cross-trial, descriptive comparison with an AVOREN subgroup (BEV + IFN 9 MIU, pts with favourable/intermediate Motzer score). Initial data cutoff was 20 August 2010 (median follow-up 10.5 months); more mature data will be available in March 2011. Results: BEVLiN baseline pts characteristics are similar to AVOREN BEV + IFN favourable/intermediate Motzer score pts. Median PFS in BEVLiN is 15.6 months (95% CI: 10.1; not reached) versus 10.5 months (95% CI: 10.1; 12.9) in AVOREN subgroup. ORR is 22% in BEVLiN. Incidences of any Gr and Gr ≥3 specific IFN-associated AEs in BEVLiN were lower than in AVOREN subgroup (Table). Conclusions: Incidence of IFN-associated AEs appears reduced with low-dose IFN + BEV without compromising PFS in BEVLiN, compared with a historical control subgroup in AVOREN (15.6 vs 10.5 months, respectively). Protocol predefined IFN-associated AEs. BEVLiN N=146* AVOREN subgroup N=283* AE, % (95% CI) Any Gr Gr ≥3 Any Gr Gr ≥3 Pyrexia 19 (13–27) <1 (<1–4) 45 (39–51) 2 (<1–4) Fatigue 27 (20–35) 4 (2–9) 35 (29–40) 12 (8–16) Asthenia 8 (4–13) 3 (<1–7) 31 (25–36) 9 (6–13) Influenza-like illness 4 (2–9) 0 (0–2) 27 (21–32) 2 (<1–5) Malaise 0 (0–2) 0 (0–2) 3 (1–5) <1 (<1–2) * Treated pts.
Multisequential Transformation of a Pig Cell Line (PFT): Correlations Between Tumorigenicity and Chromosome and Ultrastructural Markers&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: A M Bouillant, A Bundza, P Genest, A S Greig
Journal: JNCI Journal of the National Cancer Institute (1980)

Cells from representative subcultures of a continuous cell line of pig uterine tube (PFT) and carrying none, one, or two chromosome markers were inoculated in athymic nude mice (RCN) to determine the occurrence of the malignant transformation in this line. No tumors developed in mice after implantation of cells from either the 16th and 65th subcultures (no chromosome markers) or the 106th subculture (one chromosome marker, anchorage-dependent). Three adenomas (11.1%) were found in 27 mice that had been inoculated with anchorage-independent cells having one chromosome marker. Of 27 mice inoculated with cells showing two chromosome markers and gap junctions, 23 mice (85.1%) developed undifferentiated carcinomas. Ultrastructural traits and karyotypes of tumors were generally similar to those of the PFT cell inocula. However, annulate lamellae were found in 8 of 13 tumors examined by electron microscopy but were not seen in PFT cell inocula. The occurrence of a multisequential transformation was indicated by serial examination of the first 400 subcultures of the line and by comparison of the markers observed in three successive populations of cells differing in their genetic constitution.
Strain MC29 Avian Leukosis Virus. Myelocytoma, Endothelioma, and Renal Growths: Pathomorphological and Ultrastructural Aspects&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Z. Mladenov, Ursula Heine, Dorothy Beard, J. W. Beard
Journal: JNCI Journal of the National Cancer Institute (1967)

Transmission of strain MC29 avian leukosis virus resulted in a complex spectrum of neoplasms. Host response characterizing the strain was the occurrence of liver epithelial cell tumor described in another report and myelocytomatosis and myelocytomas originating from the most primitive cells of intersinusoidal spaces in the bone marrow. The myelocytomas, pure populations of myelocytes with eosinophilic granules, grew by mitosis of the specific cells and often expanded to form massive neoplasms associated particularly with skull and sternal and pelvic bones. The growth was derived essentially directly from primitive myeloid cells with the morphology of hemocytoblasts without definite transition through the myeloblast stage. Contrary to another avian myeloid neoplasm (myeloblastosis induced by BAI strain A), the disease was not notably leukemic with respect to the specific cells involved. Other associated neoplasms were endothelioma (hemocytoblastoma), erythroblastosis, and renal carcinoma. The pathomorphology and ultrastructure of the conditions were investigated, and the results were compared with analogous findings with neoplasms caused by other leukosis virus strains.
Crisis in London's mental health services
Authors: S. Weich, N. Bouras, G. Holt, A. Beadsmoore, P. Hardy, D. Goldberg, G. Thornicroft, R. Duffett, J. Cookson, L. Lessof, S. Hatch
Journal: BMJ (1997)

<h3>Background</h3> The aseptic preparation of parenteral nutrition (PN) admixtures is a process which is being implemented in many hospital pharmacies throughout Europe. The prescribing, checking and compounding of PN is critical and can be prone to errors if not carefully planned and monitored. <h3>Purpose</h3> To identify critical issues in the prescribing and preparation process of PN admixtures in hospital pharmacies, a national survey on current practices was conducted. Based on the results, standardisation of the preparation methods and products will be initiated. <h3>Material and methods</h3> To identify the PN preparation characteristics, an online survey was designed using Limesurvey consisting of multiple choice and free text questions. It focused on the current practices of PN compounding, use of specific products and opinions of the participants on their automated compounding devices and prescribing software. After review by a multidisciplinary team, the survey was sent via email to hospital pharmacists through the mailing list of the national association of hospital pharmacists. It was requested that only one reply be sent from each hospital pharmacy which prepares PN admixtures. The analysis was conducted with Excel software. <h3>Results</h3> 85 completed surveys were received. Approximately 40% of the pharmacies prepared between 100 and 500 PN products monthly. 72% of the pharmacies prepared the PN with an automated compounding device. Approximately 70% still relied on fax transmission to receive PN prescriptions. The resulting database on the type of automation and electronic documentation used by the individual hospital pharmacies allowed the facilitation of a direct information exchange between users and also newcomers. <h3>Conclusion</h3> The national survey provides an overview of the status quo of PN preparation and shows the necessity for a focus group to create standards in order to jointly optimise the process. <h3>References and/or acknowledgements</h3> Limesurvey, https://www.limesurvey.org/ No conflict of interest
Treatment of cocaine-induced panic disorder
Authors: A K Louie, R A Lannon, T A Ketter
Journal: American Journal of Psychiatry (1989)

The authors describe 10 patients who developed panic attacks only after substantial cocaine use. The timing of the onset of symptoms, i.e., after 1-6 years of cocaine use, and the fact that only one patient had a first-degree relative with panic disorder were more suggestive of acquired than primary panic disorder. The patients' atypical symptoms and responses to medications may be explained in terms of limbic-neuronal hyperexcitability induced by cocaine through a kindling mechanism.
Evaluation of Medical-Technology Strategies
Authors: John P. Bunker, Jinnet Fowles, Ralph Schaffarzick
Journal: New England Journal of Medicine (1982)

This two-part report was submitted to the Congressional Office of Technology Assessment as part of a study entitled "Strategies for Medical Technology Assessment." In Part I we examine the effects of coverage and reimbursement on biomedical innovation. We conclude that the absence of a consistent and explicit policy of reimbursement for new technologies results in the escalation of charges and provides incentives to conceal innovations. The failure to develop a consistent reimbursement policy is attributed to inadequate technology assessment. In Part II we propose the creation of a private institute for healthcare evaluation. The goals of the proposed institute would . . .
Case 5-2008
Authors: Robert L. Sheridan, Daniel P. Ryan, Gennadiy Fuzaylov, Katherine Nimkin, J.A. Jeevendra Martyn
Journal: New England Journal of Medicine (2008)

An 18-month-old Chinese girl was seen for management of a life-threatening neck contracture due to burns to the face and torso at 12 months of age. The wounds had healed with contractures that resulted in fused nares, microstomia, and sleep apnea. Tracheal intubation was impossible because of the fused nares and microstomia, and scar tissue prevented tracheotomy.
Case 30-2011
Authors: John Cunningham, Mukesh G. Harisinghani, Diana Taheri
Journal: New England Journal of Medicine (2011)

A 62-year-old woman with autoimmune overlap syndrome and polymyositis presented to this hospital with anemia, thrombocytopenia, and acute renal failure. Four days before admission, she was found on the floor of her home, confused and minimally conversant.
Consecutive Complete Radical Surgery (Crs) Plus Hyperthermic Intraperitoneal Chemotherapy (Hipec) Procedures in Patients with Peritoneal Carcinomatosis (Pc). Clinical Results and Survival According to Malignancy Type (Spain)
Authors: I. Ramos, O. Crusellas Maña, J. Castellvi, G. Galofre, G. Soler, F. Losa, M. Martin, P. Barrios
Journal: Annals of Oncology (2014)
Counterpoint: Prostate Cancer Life Expectancy Can Not Be Accurately Predicted From Currently Available Tools
Authors: Susan A. McCloskey, Michael R. Kuettel
Journal: Journal of the National Comprehensive Cancer Network (2007)

A large and growing percentage of prostate cancers are diagnosed among men of advanced age. Current guidelines stratify treatment recommendations based on life expectancy; therefore, accurate determination of life expectancy is essential. Evidence shows that patient-related factors, including age, comorbidities, and functional status, are critical determinants of life expectancy. Equally strong evidence supports tumor-related factors, including Gleason score, tumor stage, and prostate-specific antigen, and efficacy of treatment. Currently, no available tools comprehensively consider all pertinent factors in determining life expectancy.
Plasmodesmata Localizing Proteins Regulate Transport and Signaling during Systemic Acquired Immunity in Plants
Authors: Gah-Hyun Lim, M.B. Shine, Laura de Lorenzo, Keshun Yu, Weier Cui, Duroy Navarre, Arthur G. Hunt, Jung-Youn Lee, Aardra Kachroo, Pradeep Kachroo
Journal: Cell Host & Microbe (2016)
Phase 3 randomized double blind placebo controlled trial evaluating Omega-3 in the prevention of Taxane or Platinum Induced Peripheral Sensory Neuropathy.
Authors: Ralph Maroun, Ramy Saleh, Jamil Asselah, Muriel Haziza, Sarkis H. Meterissian, Nathaniel Bouganim
Journal: Journal of Clinical Oncology (2015)

TPS9643 Background: Chemotherapy induced peripheral neurotoxicity (CIPN) is a common and feared side effect of taxanes and platinum based chemotherapy. CIPN often leads to a decrease in dose intensity and or premature discontinuation of chemotherapy. Omega-3 fatty acids (OFA) have beneficial effects on neurological disorders including diabetic neuropathy, primarily by inhibition of the formation of proinflammatory cytokines involved in peripheral neuropathy (PN). A small study by Ghoreishi et al. has shown benefit of OFA in the prevention of taxane induced neuropathy. We hypothesize that the supplementation of OFA should diminish and or delay platinum or taxane induced PN. Methods: Randomized double blind placebo controlled trial to investigate the efficacy of OFA in reducing incidence and severity of taxane or platinum-induced PN. Eligible patients with breast cancer randomly assigned to take mammalian OFA with Vit D3 (provided by Auum Inc) 5cc sublingual tid vs placebo tid for 6 months. Clinical and electrophysiological studies were performed before the onset of chemotherapy and one month after cessation of therapy to evaluate CIPN based on
Case 7-1970
Authors: Richard C. Cabot, Benjamin Castleman, Betty U. McNeely, Mortimer M. Civan, Benjamin Castleman
Journal: New England Journal of Medicine (1970)

Presentation of Case First admission. A sixty-eight-year-old man was admitted to the hospital because of somnolence, vomiting and a movement disorder.Three weeks previously there was the onset of headache, fatigue, anorexia and malaise. The headache increased in severity. Two days before entry he began to have jerking movements of both arms, accompanied by somnolence and vomiting.For many years he had had intermittent severe frontal headaches, for which he took as many as 20 Anacin a day. There was no history of hypertension, diabetes, mental illness, seizures or renal disease. Twenty-seven years previously subtotal thyroidectomy had been performed . . .
216PD: nab-Paclitaxel + carboplatin (nab-P/C) in advanced non-small cell lung cancer (NSCLC): outcomes in elderly patients (pts) with squamous (SCC) histology
Authors: C. Gridelli, A. Ko, M. O'Brien, T.J. Ong, M.A. Socinski, P.E. Postmus
Journal: Journal of Thoracic Oncology (2016)
138PD: Impact of dose adjustment on the safety and efficacy of afatinib in patients (pts) with advanced EGFR mutation-positive non-small cell lung cancer (NSCLC): Post-hoc analyses of LUX-Lung 3 (LL3) and LUX-Lung 6 (LL6)
Authors: M. Schuler, J. Yang, L.V. Sequist, N. Yamamoto, C. Zhou, K. O'Byrne, V. Hirsh, T. Mok, R. Shah, Y.-L. Wu
Journal: Journal of Thoracic Oncology (2016)
PTCT-05CHEMOTHERAPY ADMINISTRATION DIRECTLY INTO THE FOURTH VENTRICLE IN CHILDREN WITH MALIGNANT FOURTH VENTRICULAR BRAIN TUMORS: A PILOT CLINICAL TRIAL
Authors: David I. Sandberg, Michael Rytting, Wafik Zaky, Marcia Kerr, Leena Ketonen, Uma Kundu, Bartlett D. Moore, Grace Yang, Ping Hou, Clark Sitton, Laurence J. Cooper, Vidya Gopalakrishnan, Dean A. Lee, Peter F. Thall, Soumen Khatua
Journal: Neuro-Oncology (2015)

BACKGROUND: We hypothesize that chemotherapy can be safely and repeatedly administered directly into the fourth ventricle to treat recurrent malignant brain tumors in children. METHODS: For the first time in humans, methotrexate was infused into the fourth ventricle in children with recurrent, malignant brain tumors. A catheter was surgically placed into the fourth ventricle under direct visualization and attached to a ventricular access device. Cerebrospinal fluid (CSF) flow was confirmed by CINE MRI postoperatively. Each cycle consisted of 4 consecutive daily methotrexate infusions (2 milligrams). Disease response was monitored with serial MRI scans and CSF cytologic analysis. Trough CSF methotrexate levels were sampled. RESULTS: Five patients (3 with medulloblastoma and 2 with ependymoma) received 18, 18, 12, 9, and 3 cycles, respectively. There were no serious adverse events or new neurological deficits attributed to methotrexate. Two additional enrolled patients were withdrawn prior to planned infusions due to rapid disease progression. Median serum methotrexate level four hours after infusion was 0.04 micromoles per liter (µmol/L). Range was 0.02–0.13 µmol/L. Median trough CSF methotrexate level 24 hours after infusion was 3.18 µmol/L (range 0.53 - 212.36 µmol/L). All three patients with medulloblastoma had partial response or stable disease until one patient had progressive disease after cycle 18. Both patients with ependymoma had progressive disease after 9 and 3 cycles, respectively. CONCLUSIONS: These data establish the safety of neurosurgical implantation of a catheter into the fourth ventricle and direct infusion of low-dose methotrexate into the fourth ventricle. Some patients with recurrent medulloblastoma experience a beneficial anti-tumor effect both within the fourth ventricle and at distant sites. These results support future clinical trials of direct infusion of chemotherapy and novel agents into the fourth ventricle for children with malignant posterior fossa tumors.
Prognosis and treatment of patients with peripheral T-cell lymphoma: The M. D. Anderson Cancer Center experience.
Authors: J. V. Pozadzides, G. Perini, M. Hess, J. E. Romaguera, F. B. Hagemeister, P. McLaughlin, L. Fayad, I. F. Khouri, C. Hosing, B. Pro
Journal: Journal of Clinical Oncology (2010)

8051 Background: Peripheral T-cell lymphomas (PTCLs) are a more aggressive group of diseases and have a poorer prognosis compared with B-cell lymphomas. Although significant progress has been made in treating patients with peripheral T-cell lymphomas, little is known whether the prognosis of patients with PTCLs has improved. Methods: The authors' retrospective study evaluated the clinical outcome of 447 patients with T-cell lymphomas who were treated at The University of Texas M. D. Anderson Cancer Center (Houston, TX) between 1996 and 2009. Cutaneous T-cell lymphoma (mycosis fungoides, Sezary syndrome, cutaneous NK, cutaneous ALCL) patients were excluded from the analysis. Results: Out of 447 patients with T-cell lymphomas, 215 patients with diagnosis of peripheral T-cell lymphoma were included in analysis. Eighty (37%) patients received CHOP therapy, 131 (61%) received intensive therapy (alternating triple therapy, Hyper-CVAD, or Hyper- CVAD-like regimen), and 4 (1.86%) received palliative therapy. Forty-one (19%) patients received autologous stem cell transplant, 13 (6%) received allogeneic stem cell transplant, and 161 (75%) did not receive transplant. At the time of analysis, 113 patients are alive and 102 patients are deceased. Both progression-free survival (PFS) and overall survival (OS) were analyzed in subgroups based on year intervals. For all patients, the 5-year and 10-year PFS are 52% and 42% and OS are 45% and 27%, respectively. Analysis of PFS and OS of year subgroups are shown below (Table). Conclusions: The current data continue to show a poor prognosis for PTLC with a marginal improvement in OS possibly related to better supportive care and new treatments. Progression-free survival p = 0.665 Progression-free survival p Year subgroups 3-year PFS Year subgroups 1996-2000 52% 1996-2000 vs. 2006-2009 0.5528 2001-2005 56% 1996-2000 vs. 2001-2005 0.8968 2006-2009 53% 2001-2005 vs. 2006-2009 0.4382 Overall survival p=0.1022 Overall survival P Year subgroups 3-year OS Year subgroups 1996-2000 46% 1996-2000 vs. 2006-2009 0.0847 2001-2005 65% 1996-2000 vs. 2001-2005 0.0411 2006-2009 60% 2001-2005 vs. 2006-2009 0.3763 No significant financial relationships to disclose.