tbuckley/cabot-search huggingface dataset:
A Randomized Phase II/III Study of Dalotuzumab in Combination With Cetuximab and Irinotecan in Chemorefractory,<i>KRAS</i>Wild-Type, Metastatic Colorectal Cancer
Authors: Francesco Sclafani, Tae Y. Kim, David Cunningham, Tae W. Kim, Josep Tabernero, Hans J. Schmoll, Jae K. Roh, Sun Y. Kim, Young S. Park, Tormod K. Guren, Eliza Hawkes, Steven J. Clarke, David Ferry, Jan-Erik Frödin, Mark Ayers, Michael Nebozhyn, Clare Peckitt, Andrey Loboda, David J. Mauro, David J. Watkins
Journal: JNCI Journal of the National Cancer Institute (2015)

Insulin-like growth factor type 1 receptor (IGF-1R) mediates resistance to epidermal growth factor receptor (EGFR) inhibition and may represent a therapeutic target. We conducted a multicenter, randomized, double blind, phase II/III trial of dalotuzumab, an anti-IGF-1R monoclonal antibody, with standard therapy in chemo-refractory, KRAS wild-type metastatic colorectal cancer. Eligible patients were randomly assigned to dalotuzumab 10mg/kg weekly (arm A), dalotuzumab 7.5mg/kg every alternate week (arm B), or placebo (arm C) in combination with cetuximab and irinotecan. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints included exploratory biomarker analyses. All statistical tests were two-sided. The trial was prematurely discontinued for futility after 344 eligible KRAS wild-type patients were included in the primary efficacy population (arm A = 116, arm B = 117, arm C = 111). Median PFS was 3.9 months in arm A (hazard ratio [HR] = 1.33, 95% confidence interval [CI] = 0.98 to 1.83, P = .07) and 5.4 months in arm B (HR = 1.13, 95% CI = 0.83 to 1.55, P = .44) compared with 5.6 months in arm C. Median OS was 10.8 months in arm A (HR = 1.41, 95% CI = 0.99 to 2.00, P = .06) and 11.6 months in arm B (HR = 1.26, 95% CI = 0.89 to 1.79, P = .18) compared with 14.0 months in arm C. Grade 3 or higher asthenia and hyperglycaemia occurred more frequently with dalotuzumab compared with placebo. In exploratory biomarker analyses, patients with high IGF-1 mRNA tumors in arm A had numerically better PFS (5.6 vs 3.6 months, HR = 0.59, 95% CI = 0.28 to 1.23, P = .16) and OS (17.9 vs 9.4 months, HR = 0.67, 95% CI = 0.31 to 1.45, P = .31) compared with those with high IGF-1 mRNA tumors in arm C. In contrast, in arm C high IGF-1 mRNA expression predicted lower response rate (17.6% vs 37.3%, P = .04), shorter PFS (3.6 vs 6.6 months, HR = 2.15, 95% CI = 1.15 to 4.02, P = .02), and shorter OS (9.4 vs 15.5 months, HR = 2.42, 95% CI = 1.21 to 4.82, P = .01). Adding dalotuzumab to irinotecan and cetuximab was feasible but did not improve survival outcome. IGF-1R ligands are promising biomarkers for differential response to anti-EGFR and anti-IGF-1R therapies.
Uterine Neoplasms
Authors: Benjamin E. Greer, Wui-Jin Koh, Nadeem Abu-Rustum, Michael A. Bookman, Robert E. Bristow, Susana M. Campos, Kathleen R. Cho, Larry Copeland, Marta Ann Crispens, Patricia J. Eifel, Warner K. Huh, Wainwright Jaggernauth, Daniel S. Kapp, John J. Kavanagh, John R. Lurain, Mark Morgan, Robert J. Morgan, C. Bethan Powell, Steven W. Remmenga, R. Kevin Reynolds, Angeles Alvarez Secord, William Small, Nelson Teng
Journal: Journal of the National Comprehensive Cancer Network (2009)
Variations in treatment of lower SES prostate cancer patients at a VA, a county and a private hospital
Authors: S. Costello, M. S. Wolf, E. A. Lyons, P. Ray, M. Kozloff, C. L. Bennett
Journal: Journal of Clinical Oncology (2005)

6072 Background: Previous studies have found that patient treatment choice for localized prostate cancer is primarily dependent on the specialty of the treating physician. Herein, investigators with the Chicago Cohort Study of Prostate Cancer evaluated treatment choice at three multi-modality hospitals. Methods: Newly diagnosed prostate cancer patients (N=150) were approached at diagnosis at a VA, a county and a private hospital. Patients completed demographic and medical questionnaires and were followed to record treatment choice. Results: In a multivariate analysis, controlling for age and stage, hospital site was a significant predictor of treatment via radical prostatectomy at the VA site (AOR: 3.1, 96%CI: 1.4–6.9, p=0.006). However, age less than 65 was also a significant predictor of radical prostatectomy (AOR: 8.6, 95%CI: 1.8–41.5, p=0.008). Hospital site was also a significant predictor or external beam therapy as patients at Ingalls hospital were more likely to receive this treatment (AOR: 10.1, 95%CI: 3.0–33.5, p<0.001). Receiving therapy at the county hospital was also a significant predictor of receiving external beam therapy and hormonal therapy (AOR: 3.1, 95%CI: 1.5–6.5, p=0.002). Conclusions: At multiple modality sites, the specific hospital rather than the treating physician or specific patient characteristics appears to be a predictor of the type of treatment that a patient will receive. No significant financial relationships to disclose.
PTH-025 Which patients tolerate unsedated colonoscopy? a uk bowel cancer screening centre experience
Authors: S Ansari, L-A Smith, R Mayers, C Yu
Journal: Gut (2015)

<h3>Introduction</h3> In the UK Bowel Cancer Screening Programme (BCSP), sedation doses and comfort scoring are used in quality assurance. There is debate whether we should offer unsedated colonoscopy, nitrous oxide being available in many units. This is a double edged sword; endoscopists are using less sedation and analgesia but potentially increase discomfort for patients. There is marked diversity in the Bradford and Airedale area with an approximate 20% South Asian population. We wanted to know if we could predict patients who would choose to have their colonoscopy unsedated. Previous studies within the Bradford and Airedale BCSP have shown differences in uptake related to ethnicity and deprivation indices. Our question was whether these also play a role in the tolerance of colonoscopy. <h3>Method</h3> Retrospective analyses of all BCSP cases performed by a single endoscopist at Bradford Royal Infirmary (BRI) were reviewed between February 2010 and April 2014. This endoscopist routinely offered a choice of sedation to all patients: 1. No medication but Fentanyl and then Midazolam if required 2. Fentanyl at the start then Midazolam if required 3. Combination of Fentanyl and Midazolam Data collected was gender, ethnicity, postcode and deprivation index, Fentanyl and Midazolam doses used. <h3>Results</h3> In total, 453 colonoscopies were performed. Midazolam was not used in 219 cases (48%). Neither drug was used in 20% of cases (80 Males, 9 Females). Only 5 Asian males and no Asian females had a drug-free procedure. In 130 cases (29%), Fentanyl was the only medication used. Just 7% of Asian females had Fentanyl only compared to 27% of Caucasian females. Use of both drugs was highest in Asian females (93%) compared to Caucasian females (67%). Analysis of deprivation index of patients using their postcode showed no difference in sedation uptake. <h3>Conclusion</h3> There was a clear difference in the use of sedation within the group. Several factors may influence patient choice regarding sedation. The first being language barriers; being offered unsedated colonoscopy may be erroneously interpreted as having no option of medication if it becomes uncomfortable. Choosing sedation may be driven by other cultural elements. Colonoscopy is an invasive procedure and may be seen as embarrassing or shameful, these fears are known barriers to screening uptake. Fear of pain and being diagnosed with cancer may also influence choice. However, some are quick to avoid medication when given a choice. Having no sedation or Fentanyl reduces the need for someone to collect or stay with the patient. This was seen more with those who lived on their own, not having to stay with family or friend post procedure. When offering all patients unsedated colonoscopy we should be mindful that not all will tolerate or want it. <h3>Disclosure of interest</h3> None Declared.
Brain metastases in lung cancer
Authors: I. Koko, N. Mullai, J. Samuel, L. P. Hussein
Journal: Journal of Clinical Oncology (2004)

7306 Background: Brain is one of the common areas of metastases occurring in 20–50% of patients with lung cancer. They are seen more often in small cell lung cancer (SCLC) than in non-small cell lung cancer (NSCLC). This study was done to evaluate the incidence of various types of lung cancer causing brain mets in an urban hospital serving predominantly minority patients. Method: A retrospective analysis of records of 90 patients, who received radiation as treatment for brain mets were analyzed. Results: Fifty-three patients were male and thirty-seven were female. Sixty-three percent of patients were in the age group of 41–60 years. Sixty-nine percent of patients were African American. Eighty-eight percent of brain mets were due to NSCLC. In sixty-three percent of these patients, metastases were found before or at the time of diagnosis of lung cancer. Further twenty-six percent of patients developed brain metastases within one year of diagnosis. Only one percent of patients developed brain mets after one year. Conclusion: Lung cancer is one of the common causes of brain metastases. Presentation with brain mets is not an uncommon occurrence. However, this study shows that in eighty-four percent of patients with brain metastases, the mets were detected before or at the time of diagnosis of lung cancer, or within one year of diagnosis, especially in the age group of 41–60 years. Brain mets are generally associated with poor prognosis and median survival after diagnosis is approximately four months. The high incidence of early brain metastases in this patient population with lung cancer stresses the importance of continued education for prevention of risk factors and early diagnosis. This would enable effective utilization of various new modalities in the treatment of lung cancer. No significant financial relationships to disclose.
Pure Red Cell Aplasia In Major ABO Mismatched Allogeneic Hematopoietic Cell Transplantation Is Associated With Severe Pancytopenia
Authors: Fleur M. Aung, Benjamin Lichtiger, Amin Alousi, Sairah Ahmed, Paolo Anderlini, Borje S. Andersson, Qaiser Bashir, Stefan O. Ciurea, Roy B Jones, Partow Kebriaei, Yago Nieto, Betul Oran, Simrit Parmar, Muzaffar H. Qazilbash, Nina Shah, Issa Khouri, Elizabeth J Shpall, Richard E Champlin, Uday R Popat
Journal: Blood (2013)
P247 The Prevalence of Asthma and Level of Treatment in Current or Former Heroin Smokers
Authors: BH Vlies, N Lewis-Burke, L Davies, PP Walker
Journal: Thorax (2015)

<h3>Introduction</h3> We have reported an association between heroin smoking and early onset severe COPD/emphysema and from this screening study reported a COPD prevalence of approximately one third in heroin smokers attending a community drug centre. However, respiratory symptoms were common in people who did not have COPD and a previous report showed a high level of wheeze and bronchial hyper-responsiveness in opiate smokers/insufflators. Therefore, we examined our cohort to determine asthma prevalence and level of symptoms and treatment in this group. <h3>Methods</h3> Current and former heroin smokers were recruited from a community-based drug service in Merseyside and completed spirometry with reversibility testing, MRC and CAT score and smoking, drug use, health and treatment questionnaires. They were not selected because of the presence of symptoms. Asthma was defined by either airflow obstruction that normalised with bronchodilation or airflow obstruction with an FEV1 that improved by ≥9% with bronchodilation (7 subjects), or a diagnosis of asthma before age 25 or before the subject had smoked heroin for 2 years (28 subjects). <h3>Results</h3> 107 heroin smokers completed the study, the majority of whom had also smoked cigarettes, cannabis and crack. 35/107 (33%) met our diagnosis of asthma and we compared them with 42 heroin smokers with neither COPD nor asthma. The asthma subjects had a significantly lower mean FEV1 (3.26 L vs 3.73 L and 83% vs 97% predicted) and FEV1/FVC (0.71 vs 0.81). Mean age was 42 years and duration of cigarette, cannabis and crack smoking was similar as were MRC and CAT scores. Symptoms were very common in the asthma group – cough 23 (66%), wheeze 23 (66%) and breathlessness 26 (74%) but this was similar to the non-asthmatics. Only 11 (31%) were prescribed short-acting beta-agonists and/or inhaled steroids and only 2 (6%) a long-acting beta agonist despite 32 (92%) having a prior diagnosis of asthma. <h3>Conclusions</h3> In an unselected group of current/former heroin smokers the prevalence of asthma was high at 33% and similar to the number diagnosed with COPD. Further detailed assessment of this cohort may be valuable and different methods of engaging with this undertreated and hard-to-reach group worthy of examination.
Therapeutic Modulation of Calcium Dynamics Using Ultrasound and Other Energy-Based Techniques
Authors: Ivan Mauricio Suarez Castellanos, Bogdan Balteanu, Tania Singh, Vesna Zderic
Journal: IEEE Reviews in Biomedical Engineering (2016)

Ultrasound, along with other types of energy-based methods, has been widely investigated for use in various therapeutic applications because of its ability to stimulate specific biological processes. Many of these processes are mediated by calcium (Ca <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2+</sup> ) signaling, thus making modulation of Ca <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2+</sup> dynamics an evident therapeutic target for energy-based techniques. Various diseases have been associated with abnormal Ca <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2+</sup> signaling and could, therefore, benefit from therapeutic approaches trying to regulate the transport of Ca <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2+</sup> across cell membranes. Here, we review published literature on the use of mechanical, electrical, magnetic, and electromagnetic energy in modulating Ca <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2+</sup> transients with particular emphasis on therapeutic ultrasound. We further provide brief discussions on the role of Ca <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2+</sup> in living cells and the use of different experimental techniques to determine and measure its contribution to different biological processes. Finally, we explore the benefits, limitations, and potential clinical applications of different energy-based modalities that can be utilized in modulation of Ca <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2+</sup> signaling.
Reciprocal Relation between Plasma Albumin Level and Hepatic Sulfobromophthalein Removal
Authors: Henry Grausz, Rudi Schmid
Journal: New England Journal of Medicine (1971)

In four patients with hypoalbuminemia due to the nephrotic syndrome, the removal rate of sulfobromophthalein (BSP) was rapid with less than 1 per cent dye retention at 45 minutes. After partial correction of the hypoalbuminemia by intravenous infusion of salt-poor human albumin, dye retention was 4 to 9 per cent at 45 minutes. This reciprocal relation between BSP removal rate and plasma albumin level appears to reflect the degree of dye binding in the plasma that governs the rate of BSP extraction by the liver. The accelerated dye disappearance associated with hypoalbuminemia may have clinical implications in patients with chronic parenchymal liver disease, in whom a low plasma albumin may tend to minimize the extent of BSP retention that would prevail if the albumin level were normal.
Case 17-2004
Authors: Samuel Z. Goldhaber, Eric S. Nadel, Mary Etta King, Amita Sharma
Journal: New England Journal of Medicine (2004)

A woman who had recently fractured her ankle said she had chest pain and then collapsed at home. She had no palpable pulse but was resuscitated and taken to the hospital; additional episodes of pulseless electrical activity occurred. An electrocardiogram showed a rate of 56, atrioventricular dissociation, and a right bundle-branch block. A bedside echocardiogram showed no pericardial tamponade. Despite aggressive resuscitation, her blood pressure and oxygen saturation remained low. A therapeutic procedure was performed.
Efficacy of Deferoxamine in Preventing Complications of Iron Overload in Patients with Thalassemia Major
Authors: Gary M. Brittenham, Patricia M. Griffith, Arthur W. Nienhuis, Christine E. McLaren, Neal S. Young, Eben E. Tucker, Christopher J. Allen, David E. Farrell, John W. Harris
Journal: New England Journal of Medicine (1994)

To determine whether deferoxamine prevents the complications of transfusional iron overload in thalassemia major, we evaluated 59 patients (30 were female and 29 male; age range, 7 to 31 years) periodically for 4 to 10 years or until death.
Hospital-Acquired Enterovirus Infections
Authors: Malcolm S. Artenstein, Louis Weinstein
Journal: New England Journal of Medicine (1962)

HOSPITAL-acquired infections, especially those due to staphylococci, have become of increasing concern in recent years.1 Nosocomial diseases caused by viruses have received relatively little attention, although occasional reports have documented their occurrence.2 3 4 The transmission of enteroviruses in hospitalized persons has been recorded.5 , 6 In general, however, this subject has been of little interest, possibly because the infections are usually benign. Nevertheless, the occasional severe or fatal illness, particularly in neonatal infants,7 suggests the need for further study of this problem.The present study was undertaken for the purpose of determining the frequency of transmission of enteroviruses among children hospitalized on an . . .
Elevated Platelet-Associated IgG in the Thrombocytopenia of Septicemia
Authors: John G. Kelton, Peter B. Neame, Jack Gauldie, Jack Hirsh
Journal: New England Journal of Medicine (1979)

The mechanism of thrombocytopenia, a frequent complication of septicemia, is obscure, but indirect evidence suggests that the immune system may be involved. To investigate this possibility, we quantitated platelet-associated IgG on platelets obtained from 44 patients during 46 episodes of septicemia. Thrombocytopenia occurred in 21 of 46 episodes (46 per cent). Platelet-associated IgG was elevated in eight of 11 episodes of gram-negative septicemia and thrombocytopenia (47.3±11.7 fg of IgG per platelet [mean ± S.E.]) and in one of 20 patients with gram-negative septicemia and normal platelet counts (5.9±1.1) (P<0.001). Elevated levels occurred in eight of 10 patients with gram-positive septicemia and thrombocytopenia (55.3±14.7 fg of IgG per platelet) and in none of 11 patients with gram-positive septicemia and normal platelet counts (5.6±1.7) (P<0.001). Serial testing during the thrombocytopenia and recovery showed an inverse relation between the platelet count and platelet-associated IgG. Thrombocytopenia in some patients with septicemia may be related to the binding of IgG to platelets. (N Engl J Med 300:760–764, 1979)
Home Office fights to conceal details of detainee’s death
Authors: Clare Dyer
Journal: BMJ (2016)

The UK’s Home Office is trying to keep secret a report on the circumstances in which an immigration detainee died after being handcuffed throughout an angioplasty operation in an NHS hospital.

Mohammed Jakaria Chowdhury, who was detained at Harmondsworth immigration removal centre near Heathrow airport, died of heart failure in November 2012 at Harefield Hospital in northwest London. He was handcuffed for almost all of his week long stay in hospital, including while he was sedated during the operation. The handcuffs were removed only seven hours before he died in intensive care.

The charity Medical Justice was …
Abstract 4371: Increase in B-Type Natriuretic Peptide at 24 Hours Predicts 30-day Survival After Transcatheter Aortic Valve Implantation
Authors: Joelle Kefer, Jean Renkin, Parla Astarci, Patrick Montant, Alain Dekleermaker, Amine Matta, David Glineur, Philippe Noirhomme, Gebrine El Khoury, Christophe Beauloye, Jean-Louis Vanoverschelde
Journal: Circulation (2009)

Background: B-type natriuretic peptide (BNP) has been shown to predict outcome after conventional aortic valve replacement (AVR). The aim of the present study was to investigate whether BNP also pr...
Reappraisal of Temporary Levodopa Withdrawal (Drug Holiday) in Parkinson's Disease
Authors: Richard Mayeux, Yaakov Stern, Kevin Mulvey, Lucien Cote
Journal: New England Journal of Medicine (1985)

Transient withdrawal of therapy has been advocated as a method of dealing with the complications of long-term use of levodopa in the treatment of Parkinson's disease. We retrospectively examined the effect of a 10-day period of levodopa withdrawal, or "drug holiday," in 28 patients. We then compared the subsequent clinical course of these patients over one year with that of 30 other randomly selected, similar patients with Parkinson's disease. In both groups the disease progressed; there was no difference in disease severity, capacity for daily living activities, or total amounts of dopamine agonists eventually used. For some patients, it was possible to reduce dopamine agonists used immediately after the drug holiday without causing deterioration, but a pulmonary embolus and other complications occurred. Subsequent complications related to long-term dopamine-agonist therapy during the follow-up period were similar in the two groups. This investigation indicates that a drug holiday carries some risk and does not improve the efficacy of levodopa therapy or prevent the problems that occur with long-term administration. (N Engl J Med 1985; 313:724–8.)
Phase II double-blind placebo-controlled randomized study of armodafinil for brain radiation-induced fatigue
Authors: Brandi R Page, Edward G Shaw, Lingyi Lu, David Bryant, David Grisell, Glenn J Lesser, Drew C Monitto, Michelle J Naughton, Stephen R Rapp, Steven R Savona, Sunjay Shah, Doug Case, Michael D Chan
Journal: Neuro-Oncology (2015)

Background.Common acute-term side effects of brain radiotherapy (RT) include fatigue, drowsiness, decreased physical functioning, and decreased quality of life (QOL).We hypothesized that armodafinil (a wakefulness-promoting drug known to reduce fatigue and increase cognitive function in breast cancer patients receiving chemotherapy) would result in reduced fatigue and sleepiness for patients receiving brain RT.Methods.A phase II, multi-institutional, placebo-controlled randomized trial assessed feasibility of armodafinil 150 mg/day in participants receiving brain RT, from whom we obtained estimates of variability for fatigue, sleepiness, QOL, cognitive function, and treatment effect.Results.From September 20, 2010, to October 20, 2012, 54 participants enrolled with 80% retention and 94% self-reported compliance.There were no grade 4-5 toxicities, and the incidence of grade 2 -3 toxicities was similar between treatment arms, the most common of which were anxiety and nausea (15%), headaches (19%), and insomnia (20%).There were no statistically significant differences in end-RT or 4 week post-RT outcomes between armodafinil and placebo in any outcomes (Functional Assessment of Chronic Illness Therapy [FACIT]-Fatigue, Brief Fatigue Inventory, Epworth Sleepiness Scale, FACT-Brain, and FACIT-cognitive function).However, in participants with more baseline fatigue, those treated with armodafinil did better than those who received the placebo on the end-RT assessments for several outcomes. Conclusion.Armodafinil 150 mg/day was well tolerated in primary brain tumor patients undergoing RT with good compliance.While there was no overall significant effect on fatigue, those with greater baseline fatigue experienced improved QOL and reduced fatigue when using armodafinil.These data suggest that a prospective, phase III randomized trial is warranted for patients with greater baseline fatigue.