tbuckley/cabot-search huggingface dataset:
A phase I study of EC145 administered weeks 1 and 3 of a 4-week cycle in patients with refractory solid tumors
Authors: E. Sausville, P. LoRusso, M. Quinn, K. Forman, C. Leamon, D. Morganstern, S. Bever, R. Messmann
Journal: Journal of Clinical Oncology (2007)

2577 Background: Folic acid is internalized via two main pathways; a reduced folate carrier (RFC) or a folate-specific receptor (FR). While FR is minimally distributed in normal tissues, it is over-expressed in many human tumors, including cancers of the ovary, lung and kidney. Experimental data indicate that EC145, a conjugate of folic acid and the vinca alkaloid desacetylvinblastine hydrazide (DAVLBH), is a high-affinity ligand for the folate receptor (FR) but not for RFC. EC145 is also highly active against FR-positive KB tumors in vivo. This phase I trial assessed the safety and pharmacokinetics (PK) of escalating bolus doses of EC145. Methods: The phase I study treated eligible patients with EC145 as an intravenous bolus according to a ‘flat dose‘ escalation plan on days 1, 3, 5 (week 1) and 15, 17, 19 (week 3) of a 4-week cycle. Endpoints included determination of a safe and tolerable EC145 dose, development of a PK model, and identification of antitumor activity. Results: As of Dec 2006, 16 patients had received bolus EC145 (1.2, 2.5 or 4 mg; n = 3, 11 and 2, respectively). EC145 was generally well tolerated at bolus doses &lt; 2.5 mg with one patient continuing on study for 6 cycles. Overall, the most common side effects were fatigue (n = 9), constipation (n = 7) and neuropathy (n = 6). DLT at 4 mg included reversible ileus and neuropathy. Formal PK analysis will be available at the time of presentation. One patient has had a minor response and another has exhibited disease stabilization &gt; 5 months (both ovarian cancer patients). Upon declaration of the bolus MTD, the trial was amended to explore the utility of a 1-hour EC145 infusion to take full advantage of potential high affinity interaction between EC145 and the FR to effect drug targeting. As of Jan 2, 2007, three patients had been accrued to a dose level of 2.5 mg over 1 hr, and all tolerated the therapy without significant toxicity. Conclusions: EC145 may be administered safely as a 2.5 mg intravenous bolus dose on days 1, 3, 5 (week 1) and 15, 17, 19 (week 3) of a 28-day schedule. No significant financial relationships to disclose.
PTU-120 Impact of ledipasvir/sofosbuvir treatment for of chronic hepatitis c gt1 patients on the economic productivity in the united kingdom
Authors: W Rosenberg, A Brown, A Srivastava, N Smith, M Stepanova, Z Younossi
Journal: Gut (2015)

<h3>Introduction</h3> Hepatitis C genotype 1 (GT1) is most common in the United Kingdom (UK). Chronic hepatitis C (CHC) related work impairment, manifested as increased presenteeism and absenteeism presents an economic burden for both employers and society. Treatment with Ledipasvir/Sofosbuvir (LDV/SOF) demonstrates high efficacy, excellent tolerability profiles and significant QOL improvement. An economic model was created to evaluate the impact of LDV/SOF treatment <i>vs</i>no treatment for patients with GT1 HCV infection on work productivity in UK. <h3>Method</h3> This cost-analysis model integrates epidemiologic and economic data to estimate CHC GT1 patients’ productivity impairment per annum across two scenarios: treatment with LDV/SOF <i>vs</i>no treatment. We estimated the total number of CHC GT1 patients in the workforce in the British population using employment rate for HCV patients, GT1 prevalence (45.0%) and vireamic prevalence (0.4%). Absenteeism and presenteeism rates were obtained from ION trials; rates were assumed to remain unchanged from baseline in patients not achieving SVR. The cost of total work hours per patient was calculated using national working hours per year and labour costs. Sensitivity analyses were performed to assess impact of a 20% reduction in labour costs and of differing employment rates by fibrosis stage observed for the European ION trials participants. <h3>Results</h3> Treating British GT1 patients with LDV/SOF could result in estimated productivity gains of £17M annually (£202.6 per patient) (Table 1). Results from the sensitivity analyses using reduced labour costs among HCV patients showed estimated productivity gains of £13.6M (£162.1 per patient) (Table 1). Using the differential employment rates by cirrhotic status showed that although patient level gains are higher in cirrhotic (£332.9) than in non-cirrhotic patients (£238.5), overall population level gains are higher for non-cirrhotic patients (£16.8M million pounds <i>vs</i>£4.6M), as non-cirrhotic patients represent 84% of the GT1 CHC population. <h3>Conclusion</h3> Treatment with LDV/SOF for GT1 CHC patients could provide substantial economic gains associated with work productivity increases in UK, both at patient and population level, which would need to be offset against treatment cost. <h3>Disclosure of interest</h3> W. Rosenberg Consultant for: Eisai, GSK, Speaker Bureau of: Gilead, Janssen, Conflict with: Janssen, MSD, Gilead, A. Brown Consultant for: Abbvie, BMS, Gilead, Janssen, Merck, Speaker Bureau of: Abbvie, BMS, Gilead, Janssen, Merck, A. Srivastava: None Declared, N. Smith: None Declared, M. Stepanova: None Declared, Z. Younossi Consultant for: Gilead, BMS, Intercept, Abbvie, Salix, Merck, GSK.
P0983 : Association between macro-nutrient intake and presence of nonalcoholic fatty liver disease in the Rotterdam study: a population-based study
Authors: B.J. Veldt, J.C. Kiefte-de Jong, B.E. Hansen, H.L. Janssen, E.P. Plompen, B.H. Stricker, A. Hofman, O.H. Franco, R.J. de Knegt, H.J. Metselaar, S. Darwish Murad
Journal: Journal of Hepatology (2015)
New Horizons in Allergen Immunotherapy
Authors: Robert A. Wood
Journal: JAMA (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Case 34-1976
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, Walter T. St. Goar, Michael J. Gallagher
Journal: New England Journal of Medicine (1976)

Presentation of CaseA 52-year-old woman was admitted to the hospital because of hypercalcemia.She was well until several months previously, when polyuria and polydipsia developed. Ten days before entry there was the onset of cough, fever, progressive weakness, lethargy, muscle cramps, constipation and polyarthralgia. Six days later she entered another hospital, where she was found to be confused and dyspneic, with rales at both lung bases. The temperature was 36.9°C. The urine gave a +++ test for protein; the sediment contained 10 white cells, numerous red cells and ++++ bacteria per high-power field. The hematocrit was 38.6 per cent; . . .
High Court is expected to hear challenges to junior doctor contract in June
Authors: Clare Dyer
Journal: BMJ (2016)

Two High Court challenges to the lawfulness of the health secretary’s decision to go ahead with the new contract for junior doctors in England are expected to be heard in June, The BMJ has learnt.

The timing means that a court ruling on the contract’s lawfulness should be delivered before the health secretary, Jeremy Hunt, proceeds with his plan to introduce the contract as doctors move into new jobs from August.

The news came as it emerged that the United Kingdom’s watchdog on equal rights, the Equality and Human Rights Commission, had advised a United Nations committee that the proposed contract discriminated against …
EXPERIMENTAL RICKETS IN RATS
Authors: Alfred F. Hess, Lester J. Unger, Joseph M. Steiner
Journal: The Journal of Experimental Medicine (1922)

Rats on a low phosphorus diet cannot be protected from the development of rickets by exposures to soft Roentgen rays such as were employed in this study. Furthermore, rats on a diet containing phosphate in an amount adequate to prevent rickets were not rendered rachitic by exposure to massive doses of Roentgen rays of an intensity sufficient to produce marked destruction of the blood-forming cells of the marrow.
Quantitative Comparison of BCG Strains and Preparations in Immunotherapy of a Rat Sarcoma2
Authors: N. Willmott, M. V. Pimm, R. W. Baldwin
Journal: JNCI Journal of the National Cancer Institute (1979)

Ten preparations of BCG, six clinical vaccines, and four experimental preparations were compared for suppression of tumor growth by regional application. The preparations differed widely in their proportions of viable bacterial units and in bacterial unit:dry weight ratios. As assessed by their ability to suppress tumor development following direct admixtures with cell inocula of a rat sarcoma, one of the six clinical vaccines (Connaught) was significantly superior to Glaxo on any parameter (dry weight, No. of total units, or No. of viable units), immuno BCG Pasteur F was superior to Glaxo on two parameters (dry weight and No. of viable units), and Pasteur scarification was superior to Glaxo only on a viable unit basis. The Tice and Rijks Institute vaccines were not significantly different from Glaxo on any basis. Experimental vaccines from the Trudeau Mycobacterial Collection, stored as frozen liquid suspensions, showed a less marked variation in physical properties; here too, the Pasteur strain was superior to two other Trudeau preparations examined (Tice and Phipps). Viable organisms were not essential for tumor suppression, gamma-radiation-sterilized vaccine being equally effective. Tests with pulmonary tumor deposits, treated by iv BCG, and tests with pleural deposits, treated by intrapleural BCG, indicated that agents identified as superior in the subcutaneous screening system were also superior in the treatment of thoracic deposits.
Dexamethasone and High-Dose Methotrexate Improve Outcome for Children and Young Adults With High-Risk B-Acute Lymphoblastic Leukemia: A Report From Children’s Oncology Group Study AALL0232
Authors: Eric C. Larsen, Meenakshi Devidas, Si Chen, Wanda L. Salzer, Elizabeth A. Raetz, Mignon L. Loh, Leonard A. Mattano, Catherine Cole, Alisa Eicher, Maureen Haugan, Mark Sorenson, Nyla A. Heerema, Andrew A. Carroll, Julie M. Gastier-Foster, Michael J. Borowitz, Brent L. Wood, Cheryl L. Willman, Naomi J. Winick, Stephen P. Hunger, William L. Carroll
Journal: Journal of Clinical Oncology (2016)

Survival for children and young adults with high-risk B-acute lymphoblastic leukemia has improved significantly, but 20% to 25% of patients are not cured. Children's Oncology Group study AALL0232 tested two interventions to improve survival.Between January 2004 and January 2011, AALL0232 enrolled 3,154 participants 1 to 30 years old with newly diagnosed high-risk B-acute lymphoblastic leukemia. By using a 2 × 2 factorial design, 2,914 participants were randomly assigned to receive dexamethasone (14 days) versus prednisone (28 days) during induction and high-dose methotrexate versus Capizzi escalating-dose methotrexate plus pegaspargase during interim maintenance 1.Planned interim monitoring showed the superiority of the high-dose methotrexate regimens, which exceeded the predefined boundary and led to cessation of enrollment in January 2011. At that time, participants randomly assigned to high-dose methotrexate during interim maintenance 1 versus those randomly assigned to Capizzi methotrexate had a 5-year event-free survival (EFS) of 82% versus 75.4% (P = .006). Mature final data showed 5-year EFS rates of 79.6% for high-dose methotrexate and 75.2% for Capizzi methotrexate (P = .008). High-dose methotrexate decreased both marrow and CNS recurrences. Patients 1 to 9 years old who received dexamethasone and high-dose methotrexate had a superior outcome compared with those who received the other three regimens (5-year EFS, 91.2% v 83.2%, 80.8%, and 82.1%; P = .015). Older participants derived no benefit from dexamethasone during induction and experienced excess rates of osteonecrosis.High-dose methotrexate is superior to Capizzi methotrexate for the treatment of high-risk B-acute lymphoblastic leukemia, with no increase in acute toxicity. Dexamethasone given during induction benefited younger children but provided no benefit and was associated with a higher risk of osteonecrosis among participants 10 years and older.
Phase II study of weekly carboplatin/gemcitabine + concurrent thoracic radiotherapy (RT) followed by consolidation carboplatin/gemcitabine for inoperable stage III non-small cell lung cancer (NSCLC).
Authors: Manuel Domine, Cristina Carames Sanchez, Francisco Lobo, Tatiana Carolina Hernandez Guerrero, Ana Leon, Victoria Casado, Gustavo Rubio, Jose Ignacio Martin-Valades, Yann Izarzugaza, Juan Luis Arranz, Irene Moreno, Andrea Correa Noguera, Victor Zenzola, Miriam Dorta, Susana Casado, Ana Ruperez, Roberto Hernandez Lopez, Victor Moreno, Jesus Garcia-Foncillas
Journal: Journal of Clinical Oncology (2015)

e18515 Background: Concurrent chemo- and radiotherapy (CT+RT) is standard of care for inoperable stage IIIA/B NSCLC. Optimal CT + concurrent RT regimen and schedule remain undefined. This trial evaluated carboplatin –gemcitabine + concurrent RT followed by consolidation carboplatin – gemcitabine. Methods: Treatment schedule during CT-RT phase: weekly carboplatin (AUC 2) + gemcitabine (200mg/m2) for 6 weeks + concurrent RT (60 Gy). CT consolidation phase: carboplatin (AUC 3) gemcitabine (2500 mg/m2) every two weeks for 3 cycles. Primary endpoint was security and secondary response rate, time to progression (TTP) and overall survival (OS). Results: 24 patients were enrolled: Sex 18 male, 6 female. Histology: 12 adenocarcinoma, 8 squamous, 4 undifferentiated large cell carcinoma. Stage: IIIB: 20, IIIA: 4. ECOG 0-1: 23, ECOG 2: 1. All the patients completed concurrent CT-RT and 22 consolidation CT. Toxicity: CT- RT phase: No grade 4 toxicity was observed. Grade 3: Neutropenia 0, anemia 4.1%, thrombocytopenia 12.5%, esophagitis 16.6%. CT consolidation phase: Grade 3-4 toxicity: Neutropenia 16.6%, Anemia 21%, Thrombocytopenia 16.6% of the patients.. 3 patients required red blood cell transfusion and 1 patient died for febrile neutropenia grade 4 during consolidation. Efficacy: Response Rate: 75% (Partial: 50% Complete: 22%), Stable disease 21% Progression 4%. Median TTP: 11 months (95% CI 7-17) and median OS: 18 months (95% CI 16.2- 20.5) Conclusions: Concurrent carboplatin – gemcitabine with thoracic RT is feasible with a favorable profile showing less hematologic toxicity and esophagitis than other CT-RT regimens. CT consolidation showed severe hematological toxicity. This regimen is active and could be a good option to combine with concurrent RT.
Mechanical Thrombectomy and Functional Outcomes After Stroke
Authors: Islam Y. Elgendy, Deepak L. Bhatt, Anthony A. Bavry
Journal: JAMA (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Efficacy of hematopoietic cell transplantation in metachromatic leukodystrophy: the Dutch experience
Authors: Diane F. van Rappard, Jaap J. Boelens, Martje E. van Egmond, Jurgen Kuball, Peter M. van Hasselt, Kim J. Oostrom, Petra J. W. Pouwels, Marjo S. van der Knaap, Carla E. M. Hollak, Nicole I. Wolf
Journal: Blood (2016)
Safety and immunogenicity of an investigational maternal trivalent group B streptococcus vaccine in healthy women and their infants: a randomised phase 1b/2 trial
Authors: Shabir A Madhi, Clare L Cutland, Lisa Jose, Anthonet Koen, Niresha Govender, Frederick Wittke, Morounfolu Olugbosi, Ajoke Sobanjo-ter Meulen, Sherryl Baker, Peter M Dull, Vas Narasimhan, Karen Slobod
Journal: The Lancet Infectious Diseases (2016)
Specialised services “swallow up” increasing share of NHS budget
Authors: Anne Gulland
Journal: BMJ (2016)

The financial watchdog could not say whether the commissioning of specialised services by NHS England was good value for money.

In a review of how NHS England commissioned the 146 specialised services provided in England—for example for kidney disease, specific mental health problems, and rare cancers—the National Audit Office found that the budget for these services in 2015-16 was £14.6bn, 14% of the total NHS budget.1

This year spending was set to increase by 7% to £15.6bn, double the rate of increase of the NHS budget as a whole.

Since NHS England took responsibility for commissioning specialist services in April 2013 the agency has not been able to stay within budget, …
Abstract 13988: Novel Quantitative Assessment of Whole Blood Thrombogenicity in Patients Treated With Anticoagulants Undergoing Radiofrequency Catheter Ablation for Atrial Fibrillation
Authors: Miwa Ito, Koichi Kaikita, Daisuke Sueta, Masanobu Ishii, Yuichiro Arima, Satomi Iwashita, Aya Takahashi, Tadashi Hoshiyama, Hisanori Kanazawa, Kenji Sakamoto, Eiichiro Yamamoto, Kenichi Tsujita, Kenichi Tsujita, Tomoko Tanaka, Megumi Yamamuro, Sunao Kojima, Sunao Kojima, Seiji Hokimoto, Hiroshige Yamabe, Hisao Ogawa
Journal: Circulation (2015)

Introduction: Non-vitamin K antagonist oral anticoagulants (NOACs) are equivalent to warfarin in preventing thromboembolism in patients with atrial fibrillation (AF). Recently, Total Thrombus-formation Analysis System (T-TAS) was developed as an easy-to-use system for quantitative analysis of thrombus formation using microchips with thrombogenic surfaces (collagen, PL chip; collagen plus tissue factor, AR chip). Hypothesis: We evaluated the efficacy and safety of NOACs using the T-TAS in AF patients undergoing radiofrequency catheter ablation (RFCA). Methods: After exclusion of 19 from 121 consecutive patients undergoing RFCA for AF, the remaining 102 patients were divided into two groups; AF patients treated with warfarin (n=28), and NOACs (n=74). Blood samples obtained on the day (anticoagulant-free point), 3 days and 1 month after RFCA were used in T-TAS to compute the thrombus formation area under the curve (AUC) (PL24-AUC10, AUC for PL chip; AR10-AUC30, for AR chip). Results and Conclusion: The AR10-AUC30 and PL24-AUC10 levels were identical between the warfarin and NOACs groups on the day of RFCA (1708.5±162.1 vs 1757.5±138.0 in AR10-AUC30, p=0.13 and 389.1±95.5 vs 391.7±76.0 in PL24-AUC10, p=0.94, respectively). AR10-AUC30, but not PL24-AUC10 levels, was significantly lower in warfarin and NOACs groups at 3 days and 1 month after RFCA. Multiple logistic regression analysis identified AR10-AUC30 levels on the day of RFCA as a significant predictor of bleeding events in the period of three months after RFCA [odds ratio (OR) 20.6; 95% confidence interval (95%CI): 2.46 to 172.6; p=0.005]. Receiver-operating characteristic analysis showed that AR10-AUC30 levels on the day of RFCA significantly predicted bleeding events [AUC 0.849 (95%CI: 0.719-0.979; p&lt;0.001)]. The cut-off levels of AR10-AUC30 were 1647.6 for identification of bleeding events within three months after RFCA. These results suggested that AR10-AUC30 level determined by T-TAS is a potentially useful marker for assessment of the efficacy and safety of anti-coagulant therapy including warfarin and NOACs, in AF patients undergoing RFCA.
Lenalidomide in Combination with R-ESHAP (LR-ESHAP) in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma Who Are Candidates for Autologous Stem-Cell Transplantation: A Phase 2 Study from the Spanish Group Geltamo
Authors: Alejandro Martín, Mónica Baile, Guillermo Rodríguez, Ivan Dlouhy, Juan Manuel Sancho, Isidro Jarque, Eva González-Barca, Antonio Salar, Manuel Espeso, Carlos Grande, Juan Bergua, Santiago Montes-Moreno, Armando Lopez-Guillermo, Dolores Caballero
Journal: Blood (2016)
Support for Academic Medical Centers — Revisiting the 1997 Balanced Budget Act
Authors: John K. Iglehart
Journal: New England Journal of Medicine (1999)

With many academic medical centers reeling from the combined financial pressures of managed care and the Balanced Budget Act of 1997, their advocates have descended on Washington seeking relief. They stand a reasonable chance of winning some relief from Medicare's largest reductions in expenditures for hospitals in the program's history, but it is almost certain to fall short of what they are seeking. Moreover, longer-term questions will continue to plague these institutions, because the federal government is divided over how and at what level it should support graduate medical education and care for indigent patients in a market-oriented health care . . .
Retroviral-Mediated Gene Transfer of gp91phox Into Bone Marrow Cells Rescues Defect in Host Defense Against Aspergillus fumigatus in Murine X-Linked Chronic Granulomatous Disease
Authors: Helga Björgvinsdóttir, Chunjin Ding, Nancy Pech, Mary A. Gifford, Ling Lin Li, Mary C. Dinauer
Journal: Blood (1997)
An unusual localized laterally spreading tumor
Authors: Erika Macedo, Fernanda Martins, Gustavo de Paulo, Angelo Ferrari
Journal: Endoscopy (2015)

A 54-year-old man was referred for a screening colonoscopy. He had no family history of colorectal cancer and no significant prior history, except for mild arterial blood hypertension that was well controlled with beta blockers (atenolol 50 mg/day). Physical examination results were normal and colon preparation was uneventful. Colonoscopy showed several diverticula in the left colon; otherwise findings were normal up to the terminal ileum. During scope withdrawal, careful examination of the sigmoid colon revealed a flat-type laterally spreading tumor with a small area of protruding lesion ([Fig. 1]). A better look at the lesion with colonic distension showed that the tumor involved the entire surface of a single diverticulum ([Figs. 2, 3]). Because of the location and the low risk of the surgery to the patient, the lesion was tattooed ([Fig. 4] gray areas) and the patient was referred for a laparoscopic left colectomy, which was successfully performed with no complications. Histological analysis revealed the presence of an adenoma with low grade dysplasia. The patient is now having regular colonoscopic surveillance.