tbuckley/cabot-search huggingface dataset:
National surveillance of pandemic influenza A(H1N1) infection-related admissions to intensive care units during the 2009–10 winter peak in Denmark: two complementary approaches
Authors: S Gubbels, A Perner, P Valentiner-Branth, K Mølbak
Journal: Eurosurveillance (2010)

Surveillance of 2009 pandemic influenza A(H1N1) in Denmark was enhanced during the 2009–10 winter season with a system monitoring the burden of the pandemic on intensive care units (ICUs), in order to inform policymakers and detect shortages in ICUs in a timely manner. Between week 46 of 2009 and week 11 of 2010, all 36 relevant Danish ICUs reported in two ways: aggregate data were reported online and case-based data on paper. Cases to be reported were defined as patients admitted to an ICU with laboratory-confirmed 2009 pandemic influenza A(H1N1) infection or clinically suspected illness after close contact with a laboratory-confirmed case. Aggregate numbers of cases were reported weekly: during weeks 48-51 (the peak), reporting was daily. The case-based reports contained demographic and clinical information. The aggregate surveillance registered 93 new cases, the case-based surveillance 61, of whom 53 were laboratory confirmed. The proportion of beds used for influenza patients did not exceed 4.5% of the national capacity. Hospitals with cases used a median of 11% of bed capacity (range: 3–40%). Of the patients for whom information was available, 15 of 48 patients developed renal insufficiency, 19 of 50 developed septic shock and 17 of 53 died. The number of patients with pandemic influenza could be managed within the national bed capacity, although the impact on some ICUs was substantial. The combination of both reporting methods (collecting aggregate and case-based data) proved to be useful for monitoring the burden of the pandemic on ICUs.
Testing in prison is uncommon
Authors: H. Maguire, K. Birthistle, D. Carrington, T. McManus
Journal: BMJ (1995)

<h3>Introduction</h3> The proportion of older acute care physicians (ACPs) has been steadily increasing. Ageing is associated with physiological changes and prospective research investigating how such age-related physiological changes affect clinical performance, including crisis resource management (CRM) skills, is lacking. There is a gap in the literature on whether physician’s age influences baseline CRM performance and also learning from simulation. We aim to investigate whether ageing is associated with baseline CRM skills of ACPs (emergency, critical care and anaesthesia) using simulated crisis scenarios and to assess whether ageing influences learning from simulation-based education. <h3>Methods and analysis</h3> This is a prospective cohort multicentre study recruiting ACPs from the Universities of Toronto and Ottawa, Canada. Each participant will manage an advanced cardiovascular life support crisis-simulated scenario (pretest) and then be debriefed on their CRM skills. They will then manage another simulated crisis scenario (immediate post-test). Three months after, participants will return to manage a third simulated crisis scenario (retention post-test). The relationship between biological age and chronological age will be assessed by measuring the participants CRM skills and their ability to learn from high-fidelity simulation. <h3>Ethics and dissemination</h3> This protocol was approved by Sunnybrook Health Sciences Centre Research Ethics Board (REB Number 140–2015) and the Ottawa Health Science Network Research Ethics Board (#20150173–01H). The results will be disseminated in a peer-reviewed journal and at scientific meetings. <h3>Trial registration number</h3> NCT02683447; Pre-results.
Results of Treatment for Soft Tissue Sarcoma in Childhood and Adolescence: A Final Report of the German Cooperative Soft Tissue Sarcoma Study CWS-86
Authors: Ewa Koscielniak, Dieter Harms, Günter Henze, Herbert Jürgens, Helmut Gadner, Manfred Herbst, Thomas Klingebiel, Bernhard F. Schmidt, Mary Morgan, Robert Knietig, Jörn Treuner
Journal: Journal of Clinical Oncology (1999)

PURPOSE: The goal of the second German Soft Tissue Sarcoma Study CWS-86 (1985 to 1990) was to improve the prognosis in children and adolescents with soft tissue sarcoma by means of a clinical trial comprising intensive chemotherapy and risk-adapted local therapy. PATIENTS AND METHODS: There were 372 eligible patients. A staging system based on the postsurgical extent of disease was used. Chemotherapy consisted of vincristine, dactinomycin, doxorubicin, and ifosfamide. Radiotherapy was administered early at 10 to 13 weeks simultaneously with the second chemotherapy cycle (32 Gy or 54.4 Gy). The single dose was reduced to 1.6 Gy and given twice daily (accelerated hyperfractionation). RESULTS: The event-free survival (EFS) and overall survival rates at 5 years were 59% ± 3% and 69% ± 3%, respectively. The 5-year EFS rate according to stage was as follows: stage I, 83% ± 5%; stage II, 69% ± 6%; stage III, 57% ± 4%; and stage IV, 19% ± 6%. The outcome for patients with stage III disease who required radiotherapy was much better in the CWS-86 study compared with the CWS-81 study (5-year EFS, 60% ± 5% v 44% ± 6%; P = .053). The most common treatment failure was isolated local relapse, with 14% of patients relapsing at the primary tumor site. CONCLUSION: The improved design of the study incorporating risk-adapted radiotherapy allowed treatment to be reduced for selected groups of patients without compromising survival.
Exome Array Analysis Identifies a Common Variant in <i>IL27</i> Associated with Chronic Obstructive Pulmonary Disease
Authors: Brian D. Hobbs, Margaret M. Parker, Han Chen, Taotao Lao, Megan Hardin, Dandi Qiao, Iwona Hawrylkiewicz, Pawel Sliwinski, Jae-Joon Yim, Woo Jin Kim, Deog Kyeom Kim, Peter J. Castaldi, Craig P. Hersh, Jarrett Morrow, Bartolome R. Celli, Victor M. Pinto-Plata, Gerald J. Criner, Nathaniel Marchetti, Raphael Bueno, Alvar Agustí, Barry J. Make, James D. Crapo, Peter M. Calverley, Claudio F. Donner, David A. Lomas, Emiel F. M. Wouters, Jorgen Vestbo, Peter D. Paré, Robert D. Levy, Stephen I. Rennard, Xiaobo Zhou, Nan M. Laird, Xihong Lin, Terri H. Beaty, Edwin K. Silverman, Michael H. Cho
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Rationale: Chronic obstructive pulmonary disease (COPD) susceptibility is in part related to genetic variants. Most genetic studies have been focused on genome-wide common variants without a specific focus on coding variants, but common and rare coding variants may also affect COPD susceptibility.Objectives: To identify coding variants associated with COPD.Methods: We tested nonsynonymous, splice, and stop variants derived from the Illumina HumanExome array for association with COPD in five study populations enriched for COPD. We evaluated single variants with a minor allele frequency greater than 0.5% using logistic regression. Results were combined using a fixed effects meta-analysis. We replicated novel single-variant associations in three additional COPD cohorts.Measurements and Main Results: We included 6,004 control subjects and 6,161 COPD cases across five cohorts for analysis. Our top result was rs16969968 (P = 1.7 × 10−14) in CHRNA5, a locus previously associated with COPD susceptibility and nicotine dependence. Additional top results were found in AGER, MMP3, and SERPINA1. A nonsynonymous variant, rs181206, in IL27 (P = 4.7 × 10−6) was just below the level of exome-wide significance but attained exome-wide significance (P = 5.7 × 10−8) when combined with results from other cohorts. Gene expression datasets revealed an association of rs181206 and the surrounding locus with expression of multiple genes; several were differentially expressed in COPD lung tissue, including TUFM.Conclusions: In an exome array analysis of COPD, we identified nonsynonymous variants at previously described loci and a novel exome-wide significant variant in IL27. This variant is at a locus previously described in genome-wide associations with diabetes, inflammatory bowel disease, and obesity and appears to affect genes potentially related to COPD pathogenesis.
Phase II trial of nitrogen mustard, vincristine, and procarbazine in patients with recurrent glioma: North Central Cancer Treatment Group results.
Authors: E Galanis, J C Buckner, P A Burch, P L Schaefer, R P Dinapoli, P J Novotny, B W Scheithauer, K M Rowland, A M Vukov, J A Mailliard, R F Morton
Journal: Journal of Clinical Oncology (1998)

PURPOSE Previous investigators have reported responses in 52% of patients treated with mechlorethamine (nitrogen mustard), vincristine, and procarbazine (MOP) for recurrent glioma. To confirm these promising results, we conducted a phase II prospective study. PATIENTS AND METHODS Sixty-three patients with histologic confirmation of recurrent glioma were treated with the MOP regimen. Patients with or without prior chemotherapy received nitrogen mustard 3 mg/m2 or 6 mg/m2, respectively, intravenously on days 1 and 8 plus vincristine 2 mg/m2 intravenously on days 1 and 8, and procarbazine 100 mg/m2 orally on days 1 to 14. Cycles were repeated every 28 days. RESULTS Of 61 patients assessable for response, eight responded (13%), with one complete response (CR). Responses were as follows: low-grade gliomas, 19%; anaplastic astrocytomas, 11%; anaplastic oligodendrogliomas or oligoastrocytomas, 25%; and glioblastomas, 4.3%. The most common toxicity was myelosuppression with leukocyte nadirs less than 1,000/microL in 23% and platelet nadirs less than 25,000/microL in 13% of patients. Two patients died of infection in the setting of neutropenia. Nonhematologic toxicity included neurosensory changes in 21% of patients (severe in 3%) and severe dermatologic reactions in 8%. In multivariate analysis, Eastern Cooperative Oncology group (ECOG) performance status (PS) was the best predictor for response to chemotherapy (P=.01) and time to progression (P=.008), while PS and grade were the most important predictors of survival (P=.002 and .05, respectively). CONCLUSION This study did not confirm the high response rate previously reported in recurrent gliomas. Patients with recurrent anaplastic oligodendrogliomas or oligoastrocytomas and recurrent low-grade gliomas had the highest response rates (25% and 19%, respectively). In multivariate analysis, ECOG PS was the best predictor of response, while PS and tumor grade were the most important predictors of survival.
Polymorphisms in genes of folate metabolism and effects of high-dose methotrexate in patients with primary central nervous system lymphoma
Authors: S. Knop, M. Guenther, J. Loeffler, C. Meisner, A. Korfel, M. Weller, H. Hebart, U. Herrlinger
Journal: Journal of Clinical Oncology (2006)

7558 Background: The antifolate methotrexate (MTX) is the single most effective agent in primary central nervous system lymphoma (PCNSL) when given intravenously in high doses. MTX inhibits 5,10-methylentetrahydrofolate reductase (MTHFR) as well as thymidylate synthase (TYMS) in target cells what eventually results in decreased DNA synthesis. Intracellular uptake of folates is mediated by the reduced folate carrier (RFC). Two common MTHFR single nucleotide polymorphisms (SNPs) affect enzyme activity: 677 C→T and 1298A→C. A 28 base pair (bp) tandemly repeated sequence in the TYMS enhancer region (5’-UTR) containing either 2 or 3 repeats alters enzyme activity as does a 6 bp deletion (del) polymorphism in the 3’-UTR of TYMS. An RFC SNP (80G→A) is known to influence folate and MTX transport. We hypothesized that these polymorphisms may be directly linked to toxicity in PCNSL patients receiving high-dose MTX. Methods: Genomic DNA was prospectively collected from patients (pts) who received high-dose (HD) MTX 4 g/m 2 every 2 weeks after enrolment onto the German multicenter G-PCNSL-SG1 trial. Genotyping of the two MTHFR and the RFC SNPs was performed by melting point analysis using the Light Cycler technology. Genotyping of the TYMS 28bp polymorphism was performed by conventional PCR followed by agarose gel electrophoresis. The TYMS 6bp del polymorphism was analyzed by PCR, restriction enzyme digest and agarose gel electrophoresis. Response, hematologic (Hb, WBC, ANC, platelets) as well as cumulative incidence of non-hematologic toxicity (renal, pulmonary, mucositis) were assessed prospectively. Results: 123 pts are evaluvable for clinical parameters. Relative risk of any °III/IV toxicity was 26-fold higher for pts with 677TT when compared to CT or CC genotype (p = 0.009). °III/IV non-hematologic toxicity for TT was 10-fold higher than with CT or CC (p = 0.02). Significant differences for hematologic values were restricted to WBC and ANC and found to be associated with RFC 80 GG vs. AG/AA (p = 0.047). Conclusions: Pharmacogenetic studies may identify PCNSL pts who are at risk for severe hematologic and non-hematologic toxicity when treated with HD-MTX. No significant financial relationships to disclose.
Therapy for localized Ewing's sarcoma of bone.
Authors: F A Hayes, E I Thompson, W H Meyer, L Kun, D Parham, B Rao, M Kumar, M Hancock, L Parvey, L Magill
Journal: Journal of Clinical Oncology (1989)

Fifty-two previously untreated patients with localized Ewing's sarcoma of bone were treated with nonintensive chemotherapy in combination with surgery or radiation therapy (RT). RT was delivered to limited volumes in a dose dependent on the initial response to induction chemotherapy (30 to 35 Gy v 50 to 55 Gy). Fifty of the 52 patients achieved complete or partial responses with induction chemotherapy, with one nonresponding patient rendered free of tumor with surgery. Fifty patients were evaluable for local control of tumor and overall response to protocol therapy. Seventeen relapses have occurred; three metastatic, four local plus metastatic, and ten local. Two factors predicted worse disease-free survival: high WBC count (P = .03) and size of primary tumor (P = .05). Of the 14 local recurrences, 12 occurred in 28 patients who presented with primary tumors greater than 8 cm in size while only two of 22 patients with lesions less than 8 cm had local recurrence. The Kaplan-Meier estimate of disease-free survival at 3 years is 82% for those with small lesions and 64% for those with larger lesions. Site of primary was of no prognostic value (P = .27). The 5-year survival estimate for all patients is 80% (median time on study, 3.3 years).
Clinical features and outcomes of testicular choriocarcinoma: A single cancer center experience.
Authors: Jue Wang
Journal: Journal of Clinical Oncology (2015)

401 Background: Pure choriocarcinoma (PC) is a very rare entity and the most aggressive subtype of nonseminomatous germ cell tumor. There is limited published data regarding treatment outcomes in this group of patients. In this series, we report our experience of sixteen patients treated at a single cancer center. Methods: The hospital tumor registry was utilized to retrospectively identify patients with the diagnosis of testicular cancer between 1997-2011. Clinical pathological, radiographic, treatment, and outcome data were retrospectively reviewed and descriptive statistical analysis was performed. Results: Sixteen patients were identified containing choriocarcinoma as component in 120 testicular cancer patients. Four patients (3.3%) had PC and twelve (10%) had mixed choriocarcinoma (MC). The median age of entire cohort was 25 years (range 21–41). Patients with PC was younger (p &lt; 0.001); more advanced stage (IIIC stage 100% vs. 41.7%; p &lt; 0.001), higher rate of lung metastasis (100% vs. 12%; p &lt; 0.001), higher rate of brain metastasis (70% vs. 16.7%; p &lt; 0.001), received more aggressive therapies: RPLND (50% vs. 33.3%; p &lt; 0.001); &gt;2 lines chemotherapy (75% vs. 16.7%; p &lt; 0.001); high dose chemotherapy with stem cell transplant (HDCT) (50% vs. 8.3%; p &lt; 0.001); in comparison with patients with MC. All four PC patients (100%) were classified as poor risk group at diagnosis according to the IGCCCG prognostic classification system. One PC patient died before receiving any therapy, three had standard first and second line chemotherapies (BEP and viep). Two PC patients underwent HDCT (one as third and another as fourth line). One PC patient had pulmonary resection of chemo-resistant disease after HDCT with long term survival. At a median follow-up of 40 months (range 0.2 - 189), three PC (75%) and two MC (16.7%) patients have died in last follow-up. Three-year survival was 25% and 80% in PC and MC, respectively. Conclusions: PC is associated with advanced disease and high rate of pulmonary and brain metastases. The prognoses of these patients remain poor despite of receiving more aggressive therapy, in comparison with patients with MC. Novel therapeutic strategies are urgently needed for patients with this rare cancer.
Chemotherapy (C) and survival among 21,441 elderly (E) patients (pts) with advanced (adv) NSCLC: Analysis of SEER-Medicare claim data 1997-2002
Authors: M. Tang, A. J. Davidoff, C. D. Mullins, D. McNally, B. Seal, M. J. Edelman
Journal: Journal of Clinical Oncology (2008)

8090 Background: C improves quality of life and survival in adv (Stage 3B w/ effusion and stage 4) NSCLC in clinical trials. Little is known about actual patterns of C and survival effects among E. Methods: Pts, aged ≥66 yrs with adv. NSCLC from 1997 to 2002 were identified from SEER registries; Medicare claims provided treatment data. An algorithm distinguished 1st, 2nd, and 3rd line C. Logit models were used to estimate 1-yr survival of 1st line C (doublet-platinum, doublet-non-platinum, singlet), controlling for age, race, income, substage, histology, comorbidities, registry, yr, and claim- based indicators of poor performance status. Microsimulation generates predicted 1 yr adjusted survival rates. Results: Among 21,441 pts w/ adv NSCLC, 6,459 (30.1%) received C, with mean time to initiation = 68 days, mean length = 66 days. 1st line regimens included platinum-taxane doublets (50.9%), platinum-other doublets (17.9% overall; w/ gemcitabine 9.6%, etoposide 3.8%, vinorelbine 2.3%), non-platinum doublets (5.8%) and singlet (25.4% overall; vinorelbine 10.1%, taxane 6.1%, gemcitabine 4.2%). Second line C was identified for 2,338 (36.2%) of patients with any C, with a mean gap between lines = 92 days. Single agents were most common for 2nd line (59.2% overall; gemcitabine 19%, docetaxel 19%, vinorelbine 15%). Platinum based 2nd line regimens were received by 27%. Doublet w/o platinum was received by 13.4%. Third line C was received by 12%, or 1/3 of those with a 2nd line C. One yr survival was 15.7% overall, 31.6% (8.9%) for pts receiving any C; 33.6%, 31.6 %, and 27.3% when C=doublet-platinum, doublet-non-platinum, or singlet respectively. The survival of doublets (platinum or non-platinum) vs singlet was superior (p<.001). Conclusions: 1.Most E pts with adv NSCLC do not receive C. 2. Platinum-based doublet is the most common 1st line C. 3. Singlet is the most common C in the 2nd line. 4. Use of platinum-based doublet improves survival relative to singlet in 1st line C. Further analyses will use propensity score and instrumental variable techniques to control for effect of patient selection on survival estimates. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration sanofi-aventis sanofi-aventis sanofi-aventis sanofi-aventis sanofi-aventis
Routine molecular profiling of patients with advanced non-small-cell lung cancer: results of a 1-year nationwide programme of the French Cooperative Thoracic Intergroup (IFCT)
Authors: Fabrice Barlesi, Julien Mazieres, Jean-Philippe Merlio, Didier Debieuvre, Jean Mosser, Hervé Lena, L'Houcine Ouafik, Benjamin Besse, Isabelle Rouquette, Virginie Westeel, Fabienne Escande, Isabelle Monnet, Antoinette Lemoine, Rémi Veillon, Hélène Blons, Clarisse Audigier-Valette, Pierre-Paul Bringuier, Régine Lamy, Michèle Beau-Faller, Jean-Louis Pujol, Jean-Christophe Sabourin, Frédérique Penault-Llorca, Marc G Denis, Sylvie Lantuejoul, Franck Morin, Quân Tran, Pascale Missy, Alexandra Langlais, Bernard Milleron, Jacques Cadranel, Jean-Charles Soria, Gérard Zalcman
Journal: The Lancet (2016)
Abstract 20624: Coronary Revascularization Procedures in Children: A Review of the Pediatric Cardiac Care Consortium
Authors: Kalpana Thammineni, Jeffrey Vinocur, Brian Harvey, James St Louis, Lazaros Kochilas
Journal: Circulation (2014)

Introduction: Coronary revascularization via coronary arterial bypass grafting (CABG) or percutaneous coronary intervention/stents (PCI) is rarely required in children. We report frequency, indications, in-hospital mortality and follow-up of coronary revascularization procedures from a registry of pediatric cardiac centers. Methods: Retrospective cohort study (1982-2007) from the Pediatric Cardiac Care Consortium for CABG or PCI in children (<18 years). We collected age at procedure, primary diagnosis, indication, timing relative to other procedures, in-hospital mortality, and long term follow up data. Results: We identified 109 patients with coronary revascularization procedures (males 64, females 45). Of them, 92 were primary CABG (median age 8.4 years, range 3 days - 17.4 years) and 17 primary PCI (median age 10.2 years, range 77 days-17.0 years). In total, 79 were performed for surgical heart diseases and 30 for various medical conditions (e.g. Kawasaki disease, heart transplantation). The most common...
Choosing geriatric assessment tools for elderly in clinical trials
Authors: M. B. Rodin, S. Gupta, K. Kuball
Journal: Journal of Clinical Oncology (2005)

4728 Background: Over 65% of cancer patients are > 65, yet elderly are underrepresented in clinical trials. To evaluate representative elderly in clinical trials, a few brief, reliable and sensitive measures of functional status will be critical. We piloted measures of physical performance used in geriatric assessment on a sample of breast and prostate cancer patients. We present here results regarding the potential value of selected measures. Methods: An on-going study of elderly cancer patients enrolled any breast (BrCa) or prostate (CaP) patient scheduled for adjuvant cytotoxic or hormonal therapy. Assessments included self-report and directly observed measures (DOM) of performance. Patients with age > 50, MMSE ≥ 23 and no previous cancer diagnosis or chemotherapy were consented. Assessments were performed at baseline, but before therapy, at 6 months and are planned at 2 years. Results: Complete baseline data are available on 47 BrCa patients, 27 with 6-month followup; 21 CaP baseline and 11 with 6-month followup. The 2 groups did not differ by age (mean 69.7; 69.8), MMSE (mean 27.9; 28.7), self-reported IADL dependency (mean 13; 14) or number of co-morbidities (mean 2.6; 2.7). DOM included the Berg Balance Scale BBS (56 points, < 40 = fall risk) and Timed Up and Go TUG (nl = 15 sec. or less) either raw time or scored (1–4). At baseline 9/47 BrCa and 11/21 CaP scored high risk for falls on the BBS; at 6-mo, 4/27 BrCA AND 5/11 CaP were fall risks. TUG scores in sec 5/46 BrCa at baseline and 3/27 at 6-months had slowed gait speed. Among CaP 2/21 at base and 1/11 at 6-months had slowed gait. A paired analysis revealed no change in individuals’ classification over the 6 months of observation. The TUG takes about 1 minute, the BBS about 15 min to complete, requiring a stop watch, tape measure, chair and little other equipment. Published norms for age and sex are available. Conclusions: DOM identified 10–48% of patients with functional impairments, whereas self-report measures identified none in this small sample. Classification remained stable over time indicating either good treatment tolerance or test insensitivity to small changes. Larger samples are needed to assess the sensitivity and predictive value of these measures for elderly cancer patients in clinical trials. No significant financial relationships to disclose.
‘Stealth’ nanoparticles evade neural immune cells but also evade major brain cell populations: Implications for PEG-based neurotherapeutics
Authors: Stuart I. Jenkins, Daniel Weinberg, Arwa F. al-Shakli, Alinda R. Fernandes, Humphrey H.P. Yiu, Neil D. Telling, Paul Roach, Divya M. Chari
Journal: Journal of Controlled Release (2016)