tbuckley/cabot-search huggingface dataset:
Abstract 316: Emergency Medical Services Response Time to Cardiac Arrest May be Delayed When Using European Emergency Phone Number in the Czech Republic
Authors: Anatolij Truhlar, Tomas Jezek, Maaret Castrén, Michal Plodr, Jiri Masek, Vladimir Cerny, Nikolaos I Nikolaou
Journal: Circulation (2013)

Introduction: Survival of people in cardiac arrest depends on EMS response time. Laypeople may use both national (155) and European (112) phone numbers for requesting EMS in the Czech Republic. The 155 medical dispatchers deal with the request directly while 112 fire-brigade operators have to transfer the call to EMS. It was unclear, whether use of the different systems may cause any delay when calling for help. This study was aimed to compare times needed for contacting medical dispatch. Methods: A prospective observational study was performed during a 1-month period in the Hradec Kralove region (0.55 mil.) as a part of the EUROCALL study conducted on behalf of ERC. The 180 test calls (6 per day) were simulating request for EMS and randomly distributed to follow diurnal distribution, day of the week, use of a landline or a mobile phone, and 155 or 112 numbers. Multiple successive time intervals were recorded with an online timer. Data analysis was performed using Prism 6.0 for Mac OS X (GraphPad, La Jolla, USA). Results: There were no differences in response times until the first 155 or 112 operator answered the call (11.9 ± 0.4 vs. 11.5 ± 0.3 seconds, p = 0.42). However, the 155 operators were all qualified paramedics/nurses able to provide dispatcher-assisted CPR and (pre)alarm appropriate response teams immediately, while the 112 operators had to transfer the calls to EMS dispatch. The overall time interval “number dialed - call answered by medical dispatcher” was faster if a direct number (155) was used (11.9 ± 0.4 vs. 62.0 ± 1.8 seconds, p &lt; 0.0001). Difference between means was 50.2 ± 1.9 seconds. The longest recorded connection times were 24.5, and 117.5 seconds respectively. There were no differences between landline and mobile phone calls. No call was aborted. A location of the caller service provided by 112 worked precisely especially if public phone-boxes were used. However, location misunderstandings appeared when connections of landline calls were technically performed via internet access. Conclusion: When requesting EMS, laypeople should (be taught to) use national emergency phone number when response time is critical, e.g. cardiac arrest. The European number 112 causes delay but may be used as an alternative in specific situations (e.g. foreigners, no SIM card).
Abstract P238: Long-Term Survival Trends in Hospitalized Heart Failure Patients
Authors: Lindsay G Smith, A. Selcuk Adabag, Alan K Berger, Russell V Luepker
Journal: Circulation (2012)

Background: Long-term survival data on patients with heart failure (HF) in community-based populations are limited. Preserved ejection fraction (PEF) is present in 50-60% of HF patients. We examined whether trends in long-term survival differed between HF patients with preserved (ejection fraction &gt;/= 45) and reduced ejection fraction (REF) in the context of modern treatment. Methods: The Minnesota Heart Survey, a community-based population study conducted in the Minneapolis-St. Paul metropolitan area, abstracted a random sample of hospital records for patients aged 35-84 with a discharge diagnosis of HF in 1995 and 2000. In the absence of a gold standard diagnosis of HF, hospitalization records that met at least four of six published classification algorithm definitions were considered HF related. Mortality was ascertained from medical records and by linkage to death certificates from the Department of Health. Kaplan-Meier was used for unadjusted survival and Cox proportional hazards regression was used to calculate adjusted hazard ratios (HR). Results: In 1995 1269 HF patients (PEF, n = 423; REF, n = 846) and in 2000 1103 HF patients (PEF, n = 413; REF, n = 690) were identified. The prevalence of hypertension, diabetes mellitus and hyperlipidemia were significantly higher in 2000; the utilization of ACE-Inhibitors, beta-blockers and revascularization were also significantly greater in 2000. In 1995, the unadjusted 9-year survival was 21% in REF and 28% in PEF; in 2000 these numbers were 28% in REF and 29% in PEF (Figure). After adjustment for sex and age the HR for 9-year mortality in 1995 was 0.77 (95% CI: 0.68 - 0.89) for HF patients with PEF compared to REF, p = 0.0003; in 2000 the adjusted HR for 9-year mortality in patients with PEF compared to REF was 0.95 (95%CI: 0.82 - 1.10), p = 0.48. Conclusion: Survival after a HF related hospitalization is low with less than 30% of patients surviving nine years. The increased utilization of ACE-Inhibitors and beta-blockers may partially explain the improved survival among HF patients with REF.
In women with terminal cancer does having a family meeting affect the place of death?
Authors: R. Shields, W. Young, L. Bilodeau, W. Bergren, D. Dizon
Journal: Journal of Clinical Oncology (2009)

e20516 Background: An important objective of the patient self determination act is for patients to see their wishes fulfilled, particularly at the end of life. Studies by Tiernan et al have shown that up to 80% of patients prefer to die at home however only a small proportion of patients actually die at home. Our work on support care networks show that a large proportion of women with cancer rely on multiple persons for health care proxy roles and for primary support. Given this, we sought to determine whether conducting a formal family meeting predicts whether a patient's preferred place of death corresponds with their actual place of death. Methods: We conducted a retrospective review of 105 women seen at Women &amp; Infants’ Hospital within the last 12 weeks of their death and stratified patients between those who had a documented family meeting and those who did not. Results: Seventy-two percent (n= 105) of the study sample had family meetings in the last 12 weeks of life. Of those who had family meetings, 61% of patients whose preference of place of death coincide with their actual place of death (p&lt;0.0001). In the sample of patients whose wishes coincide with their family meetings (n=76), almost 60% died at home and 34% died at inpatient hospice. Of those who did not have family meetings, 89% had unknown preferences of place of death, 48% died at the nursing home, 24% died in the hospital and 24% died at home. These results reached statistical significance (p= 0.001). Conclusions: Women who had a family meeting within the last 12 weeks of life were significantly more likely to die at home or with hospice services as compared to those who did not. This highlights the importance of including a patient's support networks into any communication between those dying from cancer and their healthcare providers. A larger study is warranted to determine whether this experience is specific to women with terminal cancer or is applicable to all patients with cancer facing the end of life. No significant financial relationships to disclose.
Correlation of <sup>18</sup>F-fluoride PET response to dasatinib in castration-resistant prostate cancer bone metastases with progression-free survival: Preliminary results from ACRIN 6687.
Authors: Evan Y. Yu, Fenghai Duan, Mark Muzi, Jeremy Gorelick, Bennett Chin, Joshi J. Alumkal, Mary-Ellen Taplin, Ben Herman, Celestia S. Higano, Robert K Doot, Donna M Hartfeil, Phillip G. Febbo, David A. Mankoff
Journal: Journal of Clinical Oncology (2013)

5003 Background: Dasatinib is a SRC kinase inhibitor that decreases bone turnover in men with metastatic castration-resistant prostate cancer (mCRPC). 18 F-fluoride PET was used to evaluate differential response between normal and tumor bone to dasatinib. Methods: Patients with bone mCRPC underwent dynamic 18 F-flouride PET imaging prior to and 12 weeks after dasatinib treatment. Up to 5 bone metastases with matching normal bone regions were selected for analysis by SUV max , K i , K 1 and Patlak flux. Their pre-treatment values and change from pre-treatment to post-treatment values were evaluated via generalized estimating equations to predict skeletal-related events (SRE) and via Cox proportional hazards modeling to predict progression-free survival (PFS) with Prostate Cancer Working Group 2 criteria, overall survival and time to SRE. Results: Eighteen patients treated with dasatinib underwent baseline 18 F-flouride PET imaging; 12 had follow-up scans allowing assessment of changes due to therapy. Median age for all patients was 69 (range 48-86) years. Significant decrease in SUV max (p=0.0002) occurred in bone metastases with dasatinib while significant increases in Patlak flux (p=0.0033) occurred in normal bone. Significant differences in changes from tumor bone compared to normal bone in response to dasatinib were noted for SUV max (p&lt;0.0001). Of 18 patients, 17 have either met progression criteria or death by the time of this analysis. Decrease in tumor bone SUV max (p=0.019), K i (p=0.022), and Patlak flux (p=0.034) from pre-treatment to post-treatment correlates with longer PFS. Conclusions: 18 F-fluoride PET indicates differential effect of dasatinib on tumor compared to normal bone in men with mCRPC. In patients undergoing pre- and post-dasatinib 18 F-fluoride PET imaging a decrease in bone mCRPC fluoride uptake in response to treatment correlates with PFS. Clinical trial information: NCT00936975.
Pivotal Study of Iodine I 131 Tositumomab for Chemotherapy-Refractory Low-Grade or Transformed Low-Grade B-Cell Non-Hodgkin’s Lymphomas
Authors: Mark S. Kaminski, Andrew D. Zelenetz, Oliver W. Press, Mansoor Saleh, John Leonard, Louis Fehrenbacher, T. Andrew Lister, Robert J. Stagg, George F. Tidmarsh, Stew Kroll, Richard L. Wahl, Susan J. Knox, Julie M. Vose
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To evaluate the efficacy and safety of tositumomab and iodine I 131 tositumomab (Bexxar; Corixa Corp, Seattle, WA, and GlaxoSmithKline, Philadelphia, PA) in patients with chemotherapy-refractory low-grade or transformed low-grade non-Hodgkin’s lymphoma (NHL) and to compare its efficacy to the patients’ last qualifying chemotherapy (LQC) regimens. PATIENTS AND METHODS: Sixty patients who had been treated with at least two protocol-specified qualifying chemotherapy regimens and had not responded or progressed within 6 months after their LQC were treated with a single course of iodine I 131 tositumomab. RESULTS: Patients had received a median of four prior chemotherapy regimens. A partial or complete response (CR) was observed in 39 patients (65%) after iodine I 131 tositumomab, compared with 17 patients (28%) after their LQC (P &lt; .001). The median duration of response (MDR) was 6.5 months after iodine I 131 tositumomab, compared with 3.4 months after the LQC (P &lt; .001). Two patients (3%) had a CR after their LQC, compared with 12 (20%) after iodine I 131 tositumomab (P &lt; .001). The MDR for CR was 6.1 months after the LQC and had not been reached with follow-up of more than 47 months after iodine I 131 tositumomab. An independent review panel verified that 32 (74%) of the 43 patients with nonequivalent durations of response (&gt; 30 days difference) had a longer duration of response after iodine I 131 tositumomab (P &lt; .001). Only one patient was hospitalized for neutropenic fever. Five patients (8%) developed human antimurine antibodies, and one (2%) developed an elevated TSH level after treatment. Myelodysplasia was diagnosed in four patients in follow-up. CONCLUSION: A single course of iodine I 131 tositumomab was significantly more efficacious than the LQC received by extensively pretreated patients with chemotherapy-refractory, low-grade, or transformed low-grade NHL and had an acceptable safety profile.
Phase I and pharmacokinetic study of VEGF Trap administered subcutaneously (sc) to patients (pts) with advanced solid malignancies
Authors: J. Dupont, L. Schwartz, J. Koutcher, D. Spriggs, M. Gordon, D. Mendelson, J. Murren, A. Lucarelli, J. Cedarbaum
Journal: Journal of Clinical Oncology (2004)

3009 Background: Vascular Endothelial Growth Factor (VEGF) Trap is a potent angiogenesis inhibitor that binds VEGF-A 100- to 1000- fold more tightly than monoclonal antibodies (Kd <1pM) and inactivates all circulating and tissue VEGF-A isoforms plus placental growth factor. VEGF Trap is comprised of portions of the human VEGF receptor VEGFR1 (Flt-1) and VEGFR2 (KDR) extracellular domains fused to human IgG1 Fc. Methods: In this phase I trial, successive cohorts of pts with relapsed or refractory solid tumors received a single sc dose of VEGF Trap, followed 4 weeks later by 6 weekly doses. Pts without disease progression subsequently entered a long-term extension study. Study endpoints included safety, pharmacokinetics, and immunogenicity. Anti-tumor activity was assessed by CT scan. Results: A total of 30 pts have been treated across 6 dose levels to date: 0.025, 0.05, 0.1, 0.2, 0.4 and 0.8 mg/kg. Drug-related grade 3 AEs have included hypertension (HTN; n=4), proteinuria (n=1), and afebrile neutropenia (n=1). Other than HTN, No dose-related pattern of adverse events (AEs) has emerged. However, the maximum tolerated dose has not yet been reached, and no pts have died due to an AE. No pts have developed anti-VEGF Trap antibodies, including 14 pts treated for ≥ 4 mos. Free plasma VEGF Trap levels associated with anti-tumor activity in animal models were approached at, but not below, the 0.8 mg/kg dose level. Objective partial or complete responses have not yet been achieved, but 14 of 24 evaluable pts, including 5 of 6 pts treated with 0.8 mg/kg, maintained stable disease (SD) for at least 10 weeks and entered the extension study. Conclusions: VEGF Trap has a favorable safety and tolerability profile and does not appear to elicit an antibody response. Consistent with previous findings with an anti-VEGF antibody, VEGF Trap may be associated with dose-dependent hypertension. Five of 6 evaluable pts treated with 0.8 mg/kg, compared with 9 of 18 evaluable pts who received lower doses, maintained SD at the end of the 10-week study. Evaluation of higher dose levels is ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Regeneron Pharmaceuticals, Inc. Regeneron Pharmaceuticals, Inc. Regeneron Pharmaceuticals, Inc. Regeneron Pharmaceuticals, Inc.
Epigenomic annotation of gene regulatory alterations during evolution of the primate brain
Authors: Marit W Vermunt, Sander C Tan, Bas Castelijns, Geert Geeven, Peter Reinink, Ewart de Bruijn, Ivanela Kondova, Stephan Persengiev, Ronald Bontrop, Edwin Cuppen, Wouter de Laat, Menno P Creyghton
Journal: Nature Neuroscience (2016)
Agreement of airway resistance measurements by two different techniques of body-plethysmography and impulse oscillometry in asthmatic patients
Authors: Akbar Sharifi, Khalil Ansarin
Journal: European Respiratory Journal (2011)

Background: Airway resistance can be measured by different techniques of body-plethysmography and impulse oscillometry (IOS). So far there has been no systematic study comparing validity of these techniques in relation to clinical condition of the patients reported.

Aims and objectives: We investigated correlation between these techniques in assessment of airway resistance and asthma control test.

Methods: In 92 patients with asthma selected on the basis of ATS criteria for diagnosis of asthma and GINA asthma control test (ACT) questionnaire completed. Pulmonary function tests including body-plethysmography with airway resistance measurement and impulse oscillometry measuring total airway resistance at 5 Hz and 20Hz was done using IOS.

Results: ACT score has a significant correlation with a r value of - 0.34 with total airway resistance measured by body-plethysmography (p=0.003) and also significant correlation with r value of - 0.31 (p=0.002) with airway resistance measured by IOS at 5Hz but no significant correlation with airway resistance measured by IOS at 20 Hz. There is a significant correlation between airway resistance measured by body plethysmography and airway resistance measured by IOS at 5 Hz and at 20 Hz.

Conclusion: These finding indicates a good correlation of total airway resistance measured by body plethysmography and by IOS at 5 Hz as well as 20 Hz, which is stronger with the first, Also significant negative correlation between ACT score and airway resistance centered in peripheral airways measured by IOS at 5 Hz but not with the resistance at central airways measured mainly by IOS at 20Hz.
Irestatin, a potent inhibitor of IRE1α and the unfolded protein response, is a hypoxia-selective cytotoxin and impairs tumor growth
Authors: D. Feldman, A. C. Koong
Journal: Journal of Clinical Oncology (2007)

3514 Background: The unfolded protein response (UPR) is an adaptive response to the toxic accumulation of misfolded proteins in the endoplasmic reticulum (ER), and is activated in solid tumors. IRE1a is a core component of the UPR and responds to ER stress through activation of its dual kinase and endonuclease domains. The IRE1a endonuclease splices the mRNA for XBP-1, generateing a potent transcription factor that is required for tumor growth. Methods: We developed a fibrosarcoma cell line expressing a fusion of unprocessed XBP-1 inserted upstream of firefly luciferase. Under ER stress, IRE1a catalyzes the removal of a 26-nt intronic sequence from the XBP-1 mRNA, introducing a shift in reading frame that permits translation of luciferase. We screened a chemical library of 66,000 small molecules for inhibitors of XBP-luciferase activity and identified 12 molecules, termed irestatins, which consistently inhibited the IRE1a signaling module without affecting the activity of a control CMV-luciferase reporter. We pursued several of the most potent irestatins, including irestatin 9389, which inhibited XBP-luciferase activity with an IC50 of ∼25 nM. Results: Irestatin-mediated inhibition of the IRE1a endonuclease impairs the growth of malignant myeloma cells and inhibits the survival of oxygen-starved tumor cells in vitro. Exposure to irestatin 9389 (2.5 μM) had a negligible effect on the survival of HT1080 cells cultured under normal oxygen conditions. However, in cells cultured under hypoxia for 48 hours, irestatin 9389 inhibited colony formation by nearly 80-fold (48% vs. 0.62%). A two-week course of treatment with single-agent irestatin 9389 (50 mg/kg) administered every other day by i.p. bolus injection was well tolerated and strongly inhibited the growth of subcutaneous HT1080 tumor xenografts (1790 ± 380 mm 3 vs. 480 ± 210 mm 3 ; P&lt;0.01). Conclusion: Irestatins define a novel class of hypoxia- and ER stress-selective agents targeted to the underlying physiological response to the tumor microenvironment. Intratumoral inhibition of the UPR can potentiate cell death and impair tumor growth. Molecular intervention against central components of the UPR may represent an effective therapeutic strategy in cancer treatment. No significant financial relationships to disclose.
Profound Postinitiation Enhancement by Short-Term Severe Methionine, Choline, Vitamin B&lt;sub&gt;12&lt;/sub&gt;, and Folate Deficiency of Hepatocarcinogenesis in F344 Rats Given a Single Low-Dose Diethylnitrosamine Injection&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: K. L. Hoover
 4, P. H. Lynch, L. A. Poirier
Journal: JNCI Journal of the National Cancer Institute (1984)

The potential promoting and/or complete carcinogenic activity of a methyl group-deficient (MD) diet lacking methionine, choline, vitamin B12, and folate on liver tumor induction in weanling male F344/NCr rats was examined. Each of 50 rats per group received one injection 20 mg diethylnitrosamine [(DENA) CAS: 55-18-5; N-nitrosodiethylamine]/kg body weight at 4 weeks of age, and then each was maintained on a methyl group-adequate (MA) diet for 52 weeks (groups 2 and 5) or on an MD diet for 15 weeks followed by the MA diet for 37 weeks (group 4). Controls received injections of saline and were maintained on the same two respective diet regimens (groups 1 and 3, respectively). Histologic results from sacrifices at 6, 10, 15, 22, 39, and 52 weeks revealed early development of foci of eosinophilic gamma-glutamyltransferase (GGT)-positive hepatocytes by week 6 in DENA-MD diet-treated rats, with subsequent development of a diffuse hyperplasia of hepatocytes, oval cell proliferation, cholangiofibrosis, nodular cirrhosis, and neoplastic nodule (NN) formation and, at 52 weeks, hepatocellular carcinomas (HCC) in 13 of 15 rats. Similar but significantly fewer lesions were observed at slightly later sacrifice times in the livers of saline-MD diet-treated rats, with development of NN in 5 of 12 rats and an HCC in 1 of 12 rats at 52 weeks. DENA-treated rats on MA diets developed relatively few GGT-positive foci, and none developed any neoplastic lesions. Except for basophilic foci, areas and foci of cellular alteration containing glycogen-rich hepatocytes frequently exhibited diminished uptake of injected iron and decreased glucose-6-phosphatase and ATPase contents focally or throughout. This study indicates that a relatively brief exposure of both untreated and DENA-treated weanling rats to a severely MD diet produces classical preneoplastic and neoplastic lesions in their livers.
Eastern Cooperative Oncology Group randomized trials of observation versus maintenance therapy for patients with metastatic breast cancer in complete remission following induction treatment.
Authors: G Falkson, R S Gelman, K J Pandya, C K Osborne, D Tormey, F J Cummings, G W Sledge, M D Abeloff
Journal: Journal of Clinical Oncology (1998)

PURPOSE To investigate the value of maintenance treatment for patients with metastatic breast cancer whose disease is in complete remission (CR). PATIENTS AND METHODS One hundred ninety-five women (141 eligible) whose disease was in CR or in CR except for bone metastases following six cycles (6 months) of doxorubicin-containing induction treatment were randomized to receive cyclophosphamide, methotrexate, fluorouracil, prednisone, tamoxifen, and halotestin [CMF(P)TH] or observation. In a previous pilot study, patients in CR after 24 months of induction treatment were randomized to continue chemotherapy for 4 more years or stop chemotherapy. RESULTS Among patients randomized to CMF(P)TH, life-threatening toxicity included leukopenia in 3%, thrombocytopenia in 3%, cardiac in 2%, and diabetes in 1%. The median time to relapse from randomization was 18.7 months on CMF(P)TH and only 7.8 months on observation (P &lt; .0001). The median time to death was 32.2 months on CMF(P)TH and 28.7 months on observation (P=.74). Similar results were seen in the pilot study (median time to relapse, 12.6 and 6.4 months; median survival, 37.7 and 24.2 months; study too small for statistical significance). Maintenance treatment was always the most significant covariate in time-to-relapse models. CONCLUSION There is definite toxicity associated with CMF(P)TH maintenance treatment. When CR was obtained on induction, maintenance treatment with CMF(P)TH was never significant in survival models. However, maintenance treatment was always the most significant covariate in the time-to-relapse models, which motivates its consideration for appropriately informed patients.
Early use of azithromycin may reduce severity of wheezing, study finds
Authors: J. Wise
Journal: BMJ (2015)

Giving azithromycin to children with a history of recurrent severe lower respiratory tract illness may reduce the severity of further episodes, a randomised double blind placebo controlled trial published in JAMA has found,1 although experts warn that widespread use of such a strategy could result in increased antibiotic resistance.

The researchers randomised 607 children aged 12-71 months with a history of recurrent severe lower respiratory tract infection to receive azithromycin (12 mg/kg/day) for five days or placebo at the onset of symptoms that had previously …