tbuckley/cabot-search huggingface dataset:
Abstract 256: Accuracy of Manual Shock by Paramedics
Authors: Dana A Yost, Amy Moorhead, Jim Whitney, Adrian Whorton, Robert G Walker
Journal: Circulation (2014)

Background: Limited data exist on the accuracy of rhythm interpretation and manual shocks during out-of-hospital cardiac arrest (OHCA). A prior study, based on data collected before the advent of contemporary high-performance CPR, reported that 21% of manual shocks by paramedics during OHCA were inappropriately delivered to non-shockable rhythms. The current emphasis on minimizing pre-shock pause can reduce the time available for an accurate rhythm determination, and thus might increase inappropriate shocks. We sought to characterize inappropriate shocks in a paramedic service after adoption of high-performance CPR aimed at limiting pre-shock pauses. Methods: We analyzed defibrillator records from all OHCA cases from 10/2009 to 12/2012 in an EMS system providing care for a community of 270,000 persons. Three paramedics independently reviewed continuous ECG and impedance data from all cases with at least one manual shock to assess pre-shock rhythm and categorize each shock as appropriate, inappropriate, or...
Teniposide plus cytarabine as intensification therapy and in continuation therapy for advanced nonlymphoblastic lymphomas of childhood.
Authors: P T Maluf, V Odone Filho, L M Cristofani, J L Britto, M T Almeida, E Pontes, J G Maksoud, A Manissadjian
Journal: Journal of Clinical Oncology (1994)

PURPOSE AND METHODS Thirty-nine consecutive children (age, 2 to 11 years) with nonlymphoblastic (NL) lymphomas were treated uniformly with chemotherapy based on the LNH-II-85 protocol. The protocol consisted of a remission-induction phase that lasted 30 days and started with cyclophosphamide (CTX) 1.2 g/m2 on day 1, followed by vincristine (VCR) 1.5 mg/m2 on days 3, 10, 17, and 24, daunomycin (DAUNO) 60 mg/m2 on days 12 and 13, and prednisone 40 mg/m2/d for 30 days. If a complete remission was achieved, an intensification regimen was given that consisted of eight courses of teniposide (VM-26) 165 mg/m2 plus cytarabine (ARA-C) 300 mg/m2 every 4 days according to bone marrow tolerance. A continuation phase was subsequently started, with alternating courses of thioguanine (6-TG) 300 mg/m2/d for 4 days plus CTX 1.2 g/m2 on day 5; hydroxyurea 2.5 g/m2/d for 4 days plus DAUNO 45 mg/m2 on day 5; VCR 1.5 mg/m2 plus methotrexate (MTX) 120 mg/m2 (24 hours apart); mercaptopurine (6-MP) 500 mg/m2/d for 4 days plus MTX 40 mg/m2; and VM-26 plus ARA-C for 3 courses (4 days apart), by the end of 48 weeks. CNS prophylaxis consisted of intrathecal administration of MTX, ARA-C, and dexamethasone according to age, administered three times during remission induction and every 6 weeks afterwards. RESULTS By the end of the analysis in July 1991, 38 of 39 patients had attained a complete remission and 36 were event-free survivors. Two failures that occurred after completion of therapy were second malignancies (acute lymphocytic leukemia and acute nonlymphocytic leukemia). CONCLUSION These results are significantly better than those obtained with less intensive former regimens performed in our institution before the availability of VM-26. The favorable impact of an intense consolidation phase with VM-26 is remarkably exemplified by three additional patients not included in this study whose families withdrew them from therapy after the intensification phase, all three of whom have been in remission.
Doctors face compulsory system to declare gifts and hospitality from drug companies
Authors: Adrian O’Dowd
Journal: BMJ (2015)

Doctors will be forced to declare any gifts or trips they have received from drug companies from next year, under new government plans.

The health secretary, Jeremy Hunt, has said that he plans to extend the existing rules and regulations over gifts and hospitality in connection with the promotion of medicines to anyone able to supply or prescribe them.

The government intends to introduce a new “sunshine rule”—which refers to shining a light on, or transparency over, doctors’ dealings with the drug and medical device industries next year. The new rule means that NHS staff found to be abusing their position by taking extravagant gifts or hospitality and lobbying for unnecessary or overly expensive medicines or procedures would face serious action.

NHS organisations will have to maintain a hospitality register where staff must declare gifts and hospitality that they receive from drug companies and medical device manufacturers. It will be the responsibility of NHS organisations, such as hospitals and clinical commissioning groups, …
Simultaneous gastrointestinal stromal tumor (GIST) and desmoid fibromatosis (DF)
Authors: A. G. Dumont, D. Lev, A. Lazar, H. Joensuu, J. Trent
Journal: Journal of Clinical Oncology (2009)

10568 Background: Desmoid Fibromatosis (DF) is one of a group of rare fibrous tissue proliferations (2–4 cases per year per million) which tend to be locally aggressive but have no propensity for metastasis. Gastrointestinal Stromal Tumor (GIST) is the most common mesenchymal tumors of the gastrointestinal tract and also rare (15–20 cases per year per million). Anecdotal reports of individuals with both diseases led us to investigate the number of patients at our institute with both types of cancer and their clinical, and histopathologic features. Methods: We identified four cases of GIST associated with DF at the M. D. Anderson Cancer Center between 1995 and 2008 using an IRB-approved protocol. Two more cases were identified from the patient database at the University of Helsinki. Results: Our patients were three men and three women aged from 39 to 66. Two patients were African Americans and 3 were Caucasians. In 5 cases, the GIST was diagnosed prior to the DF while one case had both tumors synchronous at presentation. The primary site of the GIST was gastric in 4 cases and the others were jejunal and mesenteric. Three patients had their DF occur in the surgical incision site mimicking a recurrence of GIST. The 3 others were intra-abdominal DF. There were no cases of DF occurring outside of the GI tract. One GIST patient was metastatic at presentation and one developed metastasis before DF was diagnosed. In 5 cases, imatinib mesylate was administered to the patients with partial response. In all cases KIT expression was observed immunohistochemically for GIST and but not for DF. Additionally, all cases of DF but no cases of GIST were found to have beta-catenin expression by immunohistochemistry. Conclusions: Our findings suggest that concurrent DF may occur in patients with GIST. Additionally, DF may mimic the recurrence of GIST or imatinib resistance. The association of these two sarcomas should be further explored. No significant financial relationships to disclose.
Pemetrexed (Pem)/gemcitabine (Gem) as front-line therapy for advanced NSCLC: A randomized, phase II trial of three schedules
Authors: A. A. Adjei, S. Nair, N. Reuter, S. Mandrekar, S. Kuross, K. M. Rowland, P. Steen, S. Hillman, S. Schild, J. Jett
Journal: Journal of Clinical Oncology (2004)

7070 Background : The combination of the novel multitargeted antifolate, Pem and Gem is broadly active, and is in phase III trials. Conflicting pre-clinical sequence-dependent synergy data prompted further investigation of the optimal schedule of administration. Purpose: A randomized phase II study was undertaken to assess tumor response rates and compare toxicities among pts receiving 3 different schedules of Pem 500 mg/m2 plus Gem 1250 mg/m2. Method: Pts with stage IV (88%) or stage IIIB (12%) NSCLC and a PS ≤ 1 received 3 schedules of Pem and Gem administered 90 minutes apart, on a q21 day cycle as follows: Schedule A: Pem followed by Gem on d1, Gem on d8; Schedule B : Gem followed by Pem on d1, Gem on d8; Schedule C: Gem on d1, Pem followed by Gem on d8. Results: 148 eligible pts (58 arm A, median age 66; 30 Arm B, median age 59.5; 60 Arm C, median age 65) were treated. Median number of treatment cycles was 5 (arm A), 2.5 (arm B) and 4 (arm C). Arm B was permanently closed at interim analysis for inferior efficacy (< 3 responses in first 19 pts). Overall, 74% pts experienced grade 3+ hematologic toxicity and 62% pts experienced grade 3+ non hematologic toxicity of which fatigue (17.6%), dyspnea (11.5%) and rash ( 8.1%) were the most common. There were significant differences in the rate of grade 3+ febrile neutropenia (A = 5%, B = 20%, C = 5%, p = 0.03). Pts on arm A had less severe toxicity than arm C (grade 3+ events: 86% vs. 93%; grade 4+ event: 40% vs. 50%). All patients were evaluable for response. Arm A with a PR of 29% (95% CI 18–42%) met the protocol defined efficacy criteria, whereas arm C with PR of 17% (95% CI 10–32%) did not. Survival data will be presented (current median follow up ∼ 7 months). Conclusion: Sequence and schedule of administration is a critical determinant of the efficacy and toxicity of Pem and Gem combinations. Preliminary efficacy and toxicity data indicate that schedule A is optimal, and should be tested in future studies. No significant financial relationships to disclose.
Ascorbic acid appears to increase the <b><i>in vitro</i></b> specificity and sensitivity of arsenic trioxide to the inhibition of primary myeloid colonies from patients with myelofibrosis with myeloid metaplasia
Authors: R. A. Mesa, A. Tefferi, H. Powell, T. Lasho, S. H. Kaufmann
Journal: Journal of Clinical Oncology (2004)

6619 Background: Myelofibrosis with myeloid metaplasia (MMM) is a hematopoietic stem cell disorder with no effective medical therapy. We have reported the use of in vitro inhibition of myeloid colony growth as a screen for novel therapeutic agents in MMM (Leukemia 2003;17(5):849.). Arsenic trioxide (ATO) was of interest in MMM because it's mechanisms of action (pro-apoptotic and anti-angiogenic), and activity against other myeloid diseases (APL and MDS), suggest possible activity in MMM. Recently it has been shown that the depletion of glutathione (with ascorbic acid (AA)) may augment the efficacy of ATO(Leukemia 2003;17:931.). We used our in vitro model to evaluate ATO (with and without AA) in primary MMM cells. Methods: Peripheral blood mononuclear cells (PBMC) were isolated from 12 MMM patients and 15 controls (normal n=10, polycythemia vera n=3, essential thrombocythemia n=2). PBMC were plated on the Methocult (StemCell technologies) colony assay media. Serial dilutions of ATO (0–10 μM) (clinically sustained ATO concentrations of >1 μM (Blood 1997;89(9):3354) with and without AA (100 μM) were added. Myeloid colonies were assessed after 14 days. Results: ATO demonstrated activity inhibiting myeloid colony growth in the MMM patients with a mean IC50 of 1.05 μM. However, ATO demonstrated similar activity in suppressing normal myeloid colony growth with an IC50 of 1.25 μM. Intriguingly the depletion of glutathione (through the addition of AA) demonstrated an increase in specificity for the in vitro effects of the ATO. Specifically, the IC50 for MMM decreased to 0.7 μM with the addition of AA whereas the IC50 for normals increased to 1.97μM. Control patients with other myeloproliferative disorders demonstrated an increased sensitivity to ATO with the addition of AA, mirroring our results with MMM. Conclusions: ATO demonstrates in vitro activity against MMM myeloid progenitors in clinically achievable concentrations. The addition of AA to ATO may increase the activity and specificity of the agent. Pilot studies of combination ATO plus AA may be warranted in MMM. No significant financial relationships to disclose.
Survey provides more evidence that patients don’t want Sunday GP appointments
Authors: Ingrid Torjesen
Journal: BMJ (2015)

Evidence is mounting against the need for Sunday GP appointments, after a survey of more than 800 000 patients in England found that only 2.2% would rather see their GP on a Sunday than a Saturday.

The survey found that four fifths of patients were happy with the current opening times of their general practice.1 And most patients (74%) who said that they could not make weekday appointments said that they would prefer to attend on Saturdays. 

The results …
Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2015 Treatment Recommendations for Psoriatic Arthritis
Authors: Laura C. Coates, Arthur Kavanaugh, Philip J. Mease, Enrique R. Soriano, Maria Laura Acosta‐Felquer, April W. Armstrong, Wilson Bautista‐Molano, Wolf‐Henning Boehncke, Willemina Campbell, Alberto Cauli, Luis R. Espinoza, Oliver FitzGerald, Dafna D. Gladman, Alice Gottlieb, Philip S. Helliwell, M. Elaine Husni, Thorvardur J. Love, Ennio Lubrano, Neil McHugh, Peter Nash, Alexis Ogdie, Ana‐Maria Orbai, Andrew Parkinson, Denis O'Sullivan, Cheryl F. Rosen, Sergio Schwartzman, Evan L. Siegel, Sergio Toloza, William Tuong, Christopher T. Ritchlin
Journal: Arthritis & Rheumatology (2016)

Objective To update the 2009 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations for the spectrum of manifestations affecting patients with psoriatic arthritis (PsA). Methods GRAPPA rheumatologists, dermatologists, and PsA patients drafted overarching principles for the management of PsA, based on consensus achieved at face‐to‐face meetings and via online surveys. We conducted literature reviews regarding treatment for the key domains of PsA (arthritis, spondylitis, enthesitis, dactylitis, skin disease, and nail disease) and convened a new group to identify pertinent comorbidities and their effect on treatment. Finally, we drafted treatment recommendations for each of the clinical manifestations and assessed the level of agreement for the overarching principles and treatment recommendations among GRAPPA members, using an online questionnaire. Results Six overarching principles had ≥80% agreement among both health care professionals (n = 135) and patient research partners (n = 10). We developed treatment recommendations and a schema incorporating these principles for arthritis, spondylitis, enthesitis, dactylitis, skin disease, nail disease, and comorbidities in the setting of PsA, using the Grading of Recommendations, Assessment, Development and Evaluation process. Agreement of &gt;80% was reached for approval of the individual recommendations and the overall schema. Conclusion We present overarching principles and updated treatment recommendations for the key manifestations of PsA, including related comorbidities, based on a literature review and consensus of GRAPPA members (rheumatologists, dermatologists, other health care providers, and patient research partners). Further updates are anticipated as the therapeutic landscape in PsA evolves.
PWE-093 Splitting The Normal Daily Dose Of Thioguanine May Be Efficacious Treatment For Inflammatory Bowel Disease And Avoid Hepatic Toxicity
Authors: P Pavlidis, A Ansari, J Duley, I Oancea, T Florin
Journal: Gut (2014)

<h3>Introduction</h3> 6-thioguanine (TG) is a treatment for inflammatory bowel disease (IBD). However, its association with nodular regenerative hyperplasia (NRH) and portal hypertension has restricted its utilisation. A murine model has provided evidence that splitting a normal daily dose of TG could prevent exposure of the liver to harmful levels of TG; furthermore safety has not been an issue in human studies with low dose TG. <h3>Methods</h3> We report from two centres on a retrospective experience of the safety and efficacy of an oral split-daily TG dose regimen, to avoid any individual dose &gt;0.3 mg/kg, in 62 IBD patients who were unresponsive or had suffered adverse drug reactions to conventional therapies including thiopurines (60), biologics (18) and calcineurin inhibitors (17). Clinical response was measured using the Harvey Bradshaw Index for Crohn’s, or the Simple Clinical Colitis Score for ulcerative and indeterminate colitis. Patients were followed regularly in clinic with bloods, liver biopsy (9) and progress ultrasound at 6 months (21) or MR imaging (2). <h3>Results</h3> Median duration of TG treatment was 7.8 (0.3–45) months. Median TG dose used was 0.6 (0.3–1) mg/kg/d. Of patients attaining 6 months of TG therapy, 91% (19/21) of Crohn’s patients and 71% (27/38) with ulcerative or indeterminate colitis had a clinically significant response, off steroids. At study end, 33 (53%) patients maintained their good clinical response off steroids; 12 of these had continued with concomitant biologic or calcineurin inhibitor therapy. Previous thiopurine-related adverse reactions were not encountered. 29 (47%) patients withdrew from the study because of loss to follow-up (5), medical adverse events (2) or surgery (22). Possible early NRH was found on liver biopsy in 1 patient who was heterozygote-deficient for thiopurine methyltransferase (TPMT); the patient continued TG at a lower dose. TG was discontinued in a patient found to have NRH and concomitant anti-phospholipid syndrome. There was one successful term pregnancy; cord blood and breast milk TG were low. <h3>Conclusion</h3> A split-dose regimen of TG appeared well-tolerated, efficacious and safe for selected IBD patients. Close monitoring, knowledge of TPMT and exclusion of risk factors for NRH prior to treatment are warranted to maximise safety. <h3>References</h3> Dubinsky MC, Vasiliauskas EA, Singh H, <i>et al</i>. 6-thioguanine can cause serious liver injury in inflammatory bowel disease patients. Gastroenterology 2003:125:298–303 Oancea I, Png CW, Das I, <i>et al</i>. A novel mouse model of veno-occlusive disease provides strategies to prevent thioguanine-induced hepatic toxicity. Gut 2013:62:594–605 <h3>Disclosure of Interest</h3> None Declared.
Phase I study of radiotherapy (RT) plus concurrent irinotecan (CPT-11) and capecitabine (CAP) as preoperative downstaging treatment for locally advanced inoperable rectal cancer
Authors: S. W. Gollins, S. Myint, E. Levine, J. Morris, B. Haylock, S. Susnerwala, M. Saunders, A. Biswas
Journal: Journal of Clinical Oncology (2005)

3565 Background: Preoperative downstaging chemoradiation has become standard treatment for locally advanced unresectable rectal cancer. Oral CAP is potentially more convenient as a radiation sensitiser than infusional fluoropyrimidine regimes. This study evaluated the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended dose (RD) of daily CAP plus weekly i.v. CPT-11 when used in combination with RT in locally advanced rectal cancer. Methods: Patients had an adenocarcinoma of the rectum that was considered to be inoperable because of involvement of the surgical excision plane on MRI scanning. On MRI, tumours were either T3 within 2 mm of the mesorectal outer edge, T4, or any T3 within 5 cm of the anal verge. There were no distant metastases on staging investigations. Patients received planned pelvic RT to 45 Gy in 25 daily fractions over five weeks, concurrent with oral CAP daily throughout RT (including weekends) and a 60 minute infusion of i.v. CPT-11 during weeks 1, 2, 3 and 4 of RT. Doses of CAP and CPT-11 were gradually escalated in cohorts of three patients. Results: There was no grade 4 toxicity. The most common DLT was diarrhoea. Two of six patients encountered DLT at dose level 4 (one grade 3 diarrhoea and one grade 3 neutropenic infection-see table below). The RD chosen was dose level 3. 20 patients were eligible for resection at the time of writing: 3 could not be resected (1 developed liver metastases and 2 deteriorated post chemoradiation) and 17 patients were resected (16 histologically R0 and one R1). 4 patients had a complete pathological response (PCR) and 4 a ‘near’ PCR. Conclusions: The RD for this regime is 60 mg/m2 i.v. CPT-11 weeks 1, 2, 3, 4 and 825 mg/m2 bd of oral CAP daily including weekends, concurrent with RT. This is tolerable and demonstrates promising early signs of efficacy. The RD is currently being studied in an expanded phase II cohort of 50 patients. No significant financial relationships to disclose.
Abstract 19099: The Fractional Excretion of Urea is Substantially Altered by Diuretics in Heart Failure Patients: Implications for its Use in the Evaluation of Worsening Renal Function
Authors: Susan J Cheng, Olga Laur, Alexander J Kula, Chukwuma O Onyebeke, Steven G Coca, Mark A Perazella, Jeffrey M Testani
Journal: Circulation (2014)

Background: In the setting of acute decompensated heart failure (ADHF), significant renal dysfunction (RD) is a common both at presentation and during treatment. The fractional excretion of urea (FeUrea) is often recommended to differentiate “pre-renal” from intrinsic RD in patients receiving diuretics. However, the intra-renal physiology regulating urea reabsorption theoretically should be affected by high dose loop diuretics which are commonly utilized in ADHF. Methods: Heart failure patients presenting to the Yale Transition Care Clinic who received treatment with loop diuretics were enrolled (n=64). Urine was collected at baseline and 60-90 minutes following administration of loop diuretics. Possible AKI was defined as a presenting serum creatinine ≥0.3 mg/dl above the lowest outpatient level in the prior 12 months. Results: Overall, 75.9% of the cohort had an estimated glomerular filtration rate &lt; 60 ml/min/1.73m^2 and 66.7% met criteria for possible AKI. As would be expected in a sodium avid HF population, the mean pre-diuretic FeUrea was 31.9 ± 10.2%. This was below the “pre-renal” FeUrea cutoff (&lt;35%) in 62.5% of patients. Following administration of 160 mg (50 to 280) of IV furosemide equivalents, FeUrea increased by an average of 7.3 ±8.5% (p&lt;0.0001). After diuretics, the percentage of patients with a “pre-renal” FeUrea decreased to 37.7% which translated into 42.5% of initially “pre-renal” patients no longer being classified as “pre-renal.” The change in FeUrea was unrelated to the diuretic induced urine output (r=0.19 p=0.14) or the dose of diuretic (r=0.17, p=0.20). There was significant individual variability in the change in FeUrea induced by loop diuretics (Figure) such that a loop diuretic “correction factor” would not be appropriate. Conclusion: Contrary to traditional wisdom, FeUrea does not appear to be a reliable tool to workup changes in renal function in ADHF patients receiving treatment with high dose loop diuretics.
Abstract 15261: Comparison of Left Atrial Mechanics Between Different Techniques of Two-Dimensional Speckle Based Strain in Patients with Atrial Fibrillation: Velocity Vector Imaging versus 2-Dimensional Strain
Authors: Hirohiko Motoki, Andrew C To, Mandeep Bhargava, Oussama M Wazni, Walid I Saliba, Thomas H Marwick, Allan L Klein
Journal: Circulation (2011)

Background: Speckle tracking measurement of left atrial (LA) strain (e) allows evaluation of contractile, reservoir, and conduit function. We sought to compare LA e with velocity vector imaging (VV...