tbuckley/cabot-search huggingface dataset:
Cost implications to Medicare of recombinant erythropoietin therapy for the anemia of end-stage renal disease.
Authors: N R Powe, R I Griffiths, E B Bass
Journal: Journal of the American Society of Nephrology (1993)

The purpose of this study was to estimate the net cost effect to Medicare of the increasing use of recombinant human erythropoietin (EPO) instead of red blood cell transfusions or androgens in the management of anemia for the approximately 100,000 hemodialysis patients in the U.S. End-Stage Renal Disease (ESRD) program. A computerized decision model that takes into account the effectiveness and possible side effects of transfusions, androgens, and EPO and predicts 1- and 5-yr direct medical costs to Medicare associated with each therapy was constructed. Probability estimates for clinical events were derived from the literature. Costs were assigned by use of the amounts Medicare pays providers of ESRD care for: (1) use of EPO, transfusions, and androgens; and (2) health care services related to the treatment of anemia (including complications of treatment and possible reductions in morbidity). For every 10,000 hemodialysis patients treated with EPO, net Medicare expenditures will be much greater than if only transfusions are used by $42,530,000 at 1 yr (6% of ESRD program costs) and by $118,050,000 at 5 yr and also much greater than if androgens are used (by $42,700,000 at 1 yr and $118,370,000 at 5 yr). The increase in cost was highly sensitive to the dose of EPO; moderately sensitive to changes in estimated anemia response rates for EPO, frequency of EPO-induced vascular access clotting, and reduction in cardiovascular or overall morbidity; and slightly sensitive to transfusion rates, estimated anemia response rates for androgens, frequency of EPO-induced seizure or hypertensive complications (stroke, myocardial infarction), frequency of transfusion-related viral infection, and frequency of androgen-induced virilization. Considering both effectiveness and side effects of alternative treatments for the anemia of ESRD, it was projected that the increasing use of EPO will markedly increase the cost to Medicare of ESRD medical care.
Familial cancer, emotional distress, and low natural cytotoxic activity in healthy women
Authors: D.H. Bovbjerg, H. Valdimarsdottir
Journal: Annals of Oncology (1993)

We investigated the possibility that healthy individuals with a family history of cancer may have lower levels of natural cytotoxic activity and examined the possible contribution of distress-induced immune suppression.Forty-three healthy women, recruited without regard to their family histories of cancer, came to the laboratory on two consecutive days. On each day, subjects completed questionnaires and provided blood samples for assessment of natural cytotoxic activity.1) Women with a history of cancer in one or more first degree relatives had lower levels of natural cytotoxic activity than women without cancer in first degree relatives. 2) There were no differences in demographic, health, or behavioral variables, but we could not rule out differences in emotional distress. 3) Independent of family history, women with higher levels of distress had lower natural cytotoxic activity. 4) When the contribution of this distress-induced immune suppression was statistically removed, natural cytotoxic activity remained lower in women with cancer in first degree relatives.These findings raise the possibility that reductions in systemic natural cytotoxic activity, in conjunction with heritable defects in the preneoplastic cell, may contribute to increased cancer risk in individuals with a family history of cancer.
Severe thrombocytopenia after the first cycle of temozolomide: Who is at risk?
Authors: K. Elandt, M. R. Hassler, S. Oberndorfer, T. Brücke, C. C. Zielinski, C. Marosi
Journal: Journal of Clinical Oncology (2008)

13019 Background: Temozolomide (TMZ) is an oral alkylating agent that has significantly improved survival of patients with glioblastoma multiforme (GBM). However, sporadic patients develop severe hematological toxicity very early, even after the first exposure to TMZ. Methods: By chart review, we identified 11 patients out of more than 300 patients treated with TMZ with the 200mg/m2 on days 1–5 regimen and 6 patients of near 200 treated with the concomitant regimen of 75 mg/m2 and radiation, who developed severe hematological toxicities (HT) after the first cycle of TMZ. The patients were 9 women and 8 men, aged 32 to 77. We checked concomitant medications (antiepileptic treatment, low molecular heparins, steroids etc.) and controlled other patient characteristics in order to detect common features. Results: All 17 patients were chemotherapy naïve before TMZ treatment. None was frail or presented with impairments of hepatic or renal function. The blood count nadir occurred mostly from day 21 to day 28 (range 11–43) and recovered usually within 2 weeks. Thrombocytopenia lasted in median for 7.5 weeks. The management of thrombocytopenia necessitated hospitalization for more than a week in all patients. Two patients developed febrile neutropenia concomitantly (one fatal). One patient did not recover from the haematological toxicity and required substitution with thrombocytes (36 units) and red cells (20 units) until week 42 when he died from progressive disease. Sixteen patients were substitutied with thrombocytes, some also red cells (n=6) and G-CSF (n=12). 10/17 patients were under antiepileptic prevention with enzyme inducing anti-epileptic drugs and 14 had thrombosis prophylaxis with low molecular weight heparin 9 patients had both. Conclusions: Our findings indicate that close meshed blood controls after the first treatment cycle with TMZ identifies the rare patients who develop early severe HT. Under treatment with TMZ, antiepileptic prophylaxis with enzyme inducing drugs should only be maintained if other AEDs are contraindicated, as thromboembolic prophylaxis with low molecular weight heparin postoperatively remains indispensable in high-grade glioma patients. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Mundipharma, Novartis, Schering-Plough
Monoclonal Antibodies Raised Against Cell Membrane Components of Human Bladder Tumor Tissue Recognizing Subpopulations in Normal Urothelium&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: I C Summerhayes, R A McIlhinney, B A Ponder, R J Shearer, R D Pocock
Journal: JNCI Journal of the National Cancer Institute (1985)

Monoclonal antibodies to human bladder carcinoma membrane antigens were produced by fusion of MOPC-21 NS/1 mouse myeloma cells with spleen cells from BALB/c mice immunized against a crude membrane extract from a metastatic bladder carcinoma. Hybrids were screened for antibody production in a solid-phase radioimmunoassay and selected for their reactivity with subpopulations of urothelial cells on normal bladder tissue sections. Three antibody groups were defined: Group I (4-72-2) was urothelium specific and stained the basal and intermediate cells in normal urothelium; group II (3-48-2, 48-1, and 3-50-3) showed reactivity with intermediate and superficial cells; group III (8-30-3, 77-1, 2-94-2, 3-71-1, and 94-3) was restricted to antigens on the luminal membrane of superficial cells. All antibodies recognized antigenic determinants in fixed paraffin-embedded material and within groups showed a range of staining patterns in other tissues. Studies on sections representing different stages of neoplastic progression showed disruption in the antibody-staining pattern in urothelium and, in all cases, a strong distinct staining of invasive tumor areas and metastatic secondary tumors. Biochemical analysis of the antigens defined at least three antigenic systems, two of which consisted of molecules having Mr of 250,000 and 300,000 as judged by Western blot analysis. Antigenic determinants recognized by some antibodies (3-48-2, 48-1, 3-50-3, 8-30-3, 77-1, and 3-71-1) were shown to be carbohydrate by reactivity with glycolipid fraction and suggest that antibodies within groups recognize different epitopes on the same molecule.
John Rodney Ellis Dathan
Authors: Brian Leatherdale, Gill Turner
Journal: BMJ (2015)

John Rodney Ellis Dathan—or “Rod,” as we all know him—qualified at the London Hospital. His junior medical training, on the medical unit, under Professors Jack Ledingham and Clifford Wilson, led to his MD under their supervision. He was instrumental in establishing the hospital’s renal dialysis unit. While a medical student he captained the football team during a very successful period.

Rod was appointed initially at the remarkably young age of 30 as a consultant renal physician to Southampton and Portsmouth, but he moved quickly to take up a full time post in Southampton and south west Hampshire. As part of this job and in addition to his Southampton role, he took over clinical responsibility for the tiny Lymington New …
Radiotherapy plus concurrent irinotecan (CPT-11) and capecitabine (CAP) as preoperative downstaging treatment for locally advanced inoperable rectal cancer: A phase I/II study
Authors: S. W. Gollins, S. Myint, E. Levine, J. Bishop, B. Haylock, S. Susnerwala, M. Saunders, A. Biswas
Journal: Journal of Clinical Oncology (2006)

13519 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 (lower limit within 12 cm of the anal verge) which on MRI was 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 weeks 1, 2, 3 and 4. Doses of CAP and CPT-11 were gradually escalated in cohorts of three patients. Results: The most common DLT was diarrhoea. Initially dose level (D/L) 3 was chosen as the recommended dose for phase II. However, unacceptable toxicity was encountered in the first 12 patients treated at D/L 3 (see Table). Thus D/L 2 is now being expanded to 60 patients for phase II. 40 patients have thus far potentially been eligible for resection: 5 (13%) could not be resected (2 deteriorated, 2 developed metastases, 1 died during treatment), 32 (80%) had R0 and 3 (7%) R1 resection. 9 (25%) had a pathological complete response (pCR) and 7 (20%) ‘near’ pCR. 5 (9%) of 57 patients had a defunctioning stoma pre-RT. Conclusions: The RD for this regime is 60 mg/m 2 i.v. CPT-11 weeks 1, 2, 3, 4 and 650 mg/m 2 bd of oral CAP daily. This demonstrates promising signs of efficacy. The RD is currently being studied in an expanded phase II cohort of 60 patients. D=diarrhea; F=febrile neutropenia; A=anorexia; L=lethargy; N=nausea/vomiting. [Table: see text] No significant financial relationships to disclose.
Molecular tumor imaging with <sup>99m</sup>Tc radiopharmaceuticals using software fusion SPECT-CT.
Authors: L. B. Delgado, J. P. Gambini, M. Nuñez, J. Noble, E. Corchs, A. Quagliata, P. Cabral, R. Fresco, E. Savio, O. Alonso
Journal: Journal of Clinical Oncology (2010)

e21060 Background: Evaluation of tumor biology is essential for patient management. Although PET-CT with 18F-FDG has set a new standard for tumor evaluation, the discovery of new 99mTc-based single photon radiotracers in oncology is an attractive alternative due to its lower cost and better availability. SPECT-CT fusion imaging software allows fusing anatomical with functional images that were performed in different equipments and time, obtaining complementary information than the one provided from each study separately. 99mTc-HYNIC Octretoide (99mTc-OCT) images somatostatin receptor expression and distribution. 99mTc-Glucarate (99mTc-GLU) has tumoral affinity and 99mTc- methyldiphosphonate (MDP) detects bone metastasis. The objective of this study was targeting tumors with different 99mTc radiopharmaceuticals by means of SPECT-CT fusion software. Methods: SPECT-CT fusion imaging was performed with 99mTc-OCT in 2 patients (pts) with metastatic neuroendocrine tumors (NT) with unknown primary location and 3 pts with recurrent thyroid cancer (ThyC) and elevated thyroglobulin with negative 131I whole body scan, using 99mTc-GLU in 1 patient (pt) with a larynx tumor and 1 pt with local relapse from basocellular carcinoma and with 99mTc-MDP in 1 pt with thyroid bone metastasis. Once written informed consent was obtained, SPECT of the region of interest was performed. Three-dimensional images were co-registered with CT scans. Results: 99mTc-OCT in ThyC pts allowed the detection of lesions not visualized in CT (n=2) and the detection of asyntomatic unknown metastatic lesions (n=1). In NT it allowed the detection of primary location in both pts. 99mTc-GLU allowed the detection of primary larynx tumor (n=1) and of local relapse from previously resected sclerosant basocellular carcinoma in right nasogenian fold (n=1). 99mTc-MDP detected a T9 metastatic ThyC vertebral lesion. In the entire studied pts, SPECT-CT image fusion was able to obtain information that allowed a better detection and localization of the described lesions. Conclusions: SPECT-CT software fusion images with different 99mTc radiopharmaceuticals can be considered to visualize tumor biology and as a complementary diagnostic option to the existing ones. No significant financial relationships to disclose.
Abstract 16099: Influence of Nutritional Status on Depressive Symptoms and Quality of Life in Patients With Heart Failure
Authors: Miyuki Tsuchihashi-Makaya, Arata Fukushima, Shintaro Kinugawa, Yoshiharu Kinugasa, Taisuke Ono, Hisashi Matsuo, Akiko Okada, Masahiko Kato, Kazuhiro Yamamoto, Hiroyuki Tsutsui
Journal: Circulation (2014)

Introduction: The important goal of heart failure (HF) management is to improve quality of life (QoL) and psychological status. Nutrition is a key component of HF management, but information on the impact of nutrition in HF is limited. Moreover, there is little evidence that nutritional status affects QoL and psychological status. Hypothesis: This study tested the hypothesis that nutritional status is associated with QoL and depressive symptoms in HF patients. Methods: A cross-sectional study was conducted in 102 HF patients (mean age: 68.4 ±13.1 years, male: 66%). QoL and depressive symptoms were assessed by the Minnesota Living with Heart Failure (MLWHF) questionnaire and Patient Health Questionnaire-9 (PHQ-9), respectively. Nutritional status was assessed by the Mini Nutritional Assessment (MNA) long version and patients were categorized as well nourished (≥24 points), at risk of malnutrition (17-23.5 points), or malnourished (&lt;17 points). Data on sociodemographic and clinical characteristics were also collected. Multiple linear regression analysis was performed to evaluate the association of nutritional status with depression and QoL. Results: In total, 50% patients were at risk of malnutrition and 2% were malnourished. HF patients at risk of malnutrition were more likely to have a history of valve surgery, implantable cardiac defibrillation (ICD), or smoking. Risk of malnutrition was not associated with left ventricular ejection fraction (LVEF) or brain natriuretic peptide (BNP) (P = 0.100 and P = 0.173, respectively). Malnourished patients or those at risk of malnutrition had significantly lower QoL and more depressive symptoms than well-nourished patients (QoL: 14.2 ± 13.9 vs 23.2 ± 17.9, P = 0.007; depressive symptoms: 4.49 ± 4.7 vs 2.02 ± 2.9, P = 0.002). In multiple linear regression analysis, these significant associations remained after controlling for age, sex, HF etiology, smoking, ICD therapy, LVEF, and BNP. Conclusions: Risk of malnutrition was associated with lower QoL and higher depressive symptoms in HF patients. This study confirmed that good nutrition was an important goal in HF management. Further research is required to identify key nutrients and dietary habits affecting QoL and psychological status in HF patients.
California doctor convicted of murder in overdose deaths is sentenced to 30 years
Authors: Michael McCarthy
Journal: BMJ (2016)

<h3>Background</h3> In the UK demand for emergency ambulances is increasing. To deal with this increase, Ambulance Service Trusts must use resources effectively and ensure that they are deployed appropriately. <h3>Aim</h3> The aim of this study was to gain an understanding of factors influencing resource dispatchers9 (RD) decision-making processes when managing ambulance resources attending out-of-hospital cardiac arrest (OOHCA) and how these decisions might impact on resource availability. <h3>Method</h3> Utilising a generic qualitative approach, nine RDs participated in semi structured interviews which were recorded and transcribed verbatim. Data analysis was performed using a template style of thematic analysis. <h3>Findings</h3> OOHCA generally takes priority over other emergency calls regardless of clinical need or likely prognosis. Participants stated that they would probably drive past a critically ill patient to attend a patient in cardiac arrest even if they believed them to be beyond help. A significant amount of time was spent dealing with deceased patients, especially when waiting for police to attend. This may affect resource availability and subsequently delay treatment of other critically ill and injured patients. <h3>Limitations</h3> Dispatching processes may differ between Trusts so further studies are required to enhance transferability of findings. <h3>Conclusions</h3> OOHCA is almost always prioritised above other time critical emergencies despite the view that other patients may benefit more from a priority response. Decisions are made rapidly, under pressure and with very little clinical information to hand. <h3>Recommendations for change</h3> Further research is required before substantive recommendations can be made but preliminary indications infer that resource efficiency may be improved by applying simple changes to every day practice including dialogue between lead clinician and dispatcher to optimise staff skill mix in attendance to calls and improved liaison between police and ambulance controls to facilitate the prompt stand down of ambulance resources dealing with deceased patients.
Safety analysis of FOLFOX4 treatment in advanced/recurrent or adjuvant colorectal cancer in Asian and Western patients.
Authors: K. Sugihara, A. Ohtsu, Y. Shimada, N. Mizunuma, P. Lee, A. De Gramont, R. M. Goldberg, M. L. Rothenberg, T. Andre, S. Brienza
Journal: Journal of Clinical Oncology (2010)

3611 Background: FOLFOX4 is a standard regimen for the treatment of advanced/recurrent and adjuvant colorectal cancer. In order to support the Japanese colorectal cancer adjuvant indication, its safety profile was evaluated in both Asian and Western patients (Pts) in 6 FOLFOX4 studies. Methods: A total of 3,359 colorectal cancer Pts, 1,515 Asian and 1,844 Western, treated by FOLFOX4 were included from 2 Asian (J-PMS [Jpn Post Marketing Surveillance] and adjuvant MASCOT) and 4 Western (de Gramont first-line phase III [EFC2962], Goldberg first-line phase III [N9741], Rothenberg second-line phase III [EFC4584] and adjuvant MOSAIC) studies. All AEs were graded by NCI-CTC, except neurosensory by specific scales, re-coded by MedDRA ver 9.0, and analyzed by SAS ver 8.1. Results: Pts received FOLFOX4 for 6-12 cycles over 16-28 weeks. Dose intensities of L- OHP, bolus, and infusion 5-FU were 33-36, 297-338, and 467-510 mg/m2/wk, respectively. In both populations, the most common AEs included haematologic, gastrointestinal, and neurologic disorders. The frequencies of typical AEs (grade ≥3) were as follows. Conclusions: There was no evidence that Asian Pts experienced worse toxicity than Western Pts and trends toward reduced diarrhea and neurotoxicity among Asian Pts were observed. J-PMS J-PMS MASCOT EFC2962 N9741 EFC4584 MOSAIC Line 1st ≥2nd Adjuvant 1st 1st 2nd Adjuvant Pt No. 222 1,134 159 209 259 268 1,108 Median cycles 8 6 12* 12 10 7 12* Neutropenia % 42.8 37.2 52.2 44.5 55.6 46.3 41.1 Diarrhea % 1.4 1.7 6.3 12.0 13.9 11.2 10.8 Neurosensory % 2.7 1.9 4.4 18.7 18.1 9.3 12.4 Allergic reaction % 2.3 0.6 3.1 1.9 1.5 1.1 3.0 * Max 12 cycles Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Debiopharm Amgen, Bristol-Myers Squibb, Genentech, sanofi-aventis, Yakult Honsha Baxter International, Chugai Pharma, sanofi-aventis, Taiho Pharmaceutical, Yakult Honsha Amgen, Daiichi Sankyo, Genentech, sanofi-aventis, Yakult Honsha
Evaluation of soluble KIT (sKIT) as a potential surrogate marker for TTP in sunitinib malate (SU)-treated patients (pts) with advanced GIST
Authors: M. Blackstein, X. Huang, G. D. Demetri, P. G. Casali, C. R. Garrett, P. Schöffski, M. H. Shah, J. Verweij, C. M. Baum, S. E. DePrimo
Journal: Journal of Clinical Oncology (2007)

10007 Background: SU is an oral, multitargeted tyrosine kinase inhibitor of KIT, PDGFRs, VEGFRs, RET and FLT3, approved multinationally for the treatment of imatinib (IM)-resistant/-intolerant GIST. Preliminary analysis in a SU phase I/II GIST study suggested that a decline in plasma sKIT levels may correlate with measures of clinical benefit. We evaluated the potential of sKIT as a surrogate marker for TTP using samples obtained in a randomized, double-blind, placebo-controlled phase III study of SU in pts with IM-resistant/-intolerant GIST, clinical results of which have been reported previously. Methods: 312 pts were randomized (2:1) to receive SU 50 mg (n=207) or placebo (n=105) daily in 6-wk cycles (4 wks on treatment, 2 wks off), respectively. The primary endpoint was TTP as per RECIST. Levels of sKIT in plasma samples were measured in cycle 1 on days 1, 14 and 28 and in cycles 2 and 3 on days 1 and 28 using a performance-validated ELISA. Prentice Criterion, Cox models and the Proportion of Treatment Effect (PTE) were used to analyze the results (PTE of 1 = ideal surrogate). Results: Numbers of pts with matched pairs of baseline and on-study plasma samples varied from 228 pts at cycle 1, day 14 to 106 pts at the end of cycle 3. After 4 wks of treatment (cycle 1, day 28), plasma sKIT levels began to exhibit a significant decrease (P&lt;0.0001) in response to SU treatment; at the same time, changes in the level of sKIT (decreases vs. increases) also became indicators of TTP (HR=0.53; 95% CI, 0.37–0.75; P=0.0003), with decreases associated with longer TTP. This trend continued throughout the sampling period, with the effect persisting off treatment. Although the impact of SU on plasma sKIT levels continued to be seen after 2 cycles, sKIT changes became a better indicator of TTP than initial treatment group by cycle 2, day 28 (PTE = 0.62; HR=0.51; 95% CI, 0.38–0.69; P&lt;0.0001), and at cycle 3, day 1 (PTE = 0.64; HR=0.42; 95% CI, 0.29–0.60; P&lt;0.0001). Conclusion: These preliminary findings suggest that circulating sKIT may be a surrogate marker for TTP in GIST pts after 2 cycles of SU treatment. Further studies are warranted to confirm these findings and to establish whether sKIT can be used as a general surrogate marker of clinical outcomes in GIST pts with SU or other therapies. [Table: see text]