tbuckley/cabot-search huggingface dataset:
A phase II trial of pegylated liposomal doxorubicin, rituximab, cyclophosphamide, vincristine, and prednisone (DR-COP) in aggressive B-cell non-Hodgkin’s lymphoma
Authors: A. Tulpule, C. A. Duran, D. L. Smith, N. E. Berman, L. Buchanan, G. Gorospe, W. Boswell, B. Nathwani, A. M. Levine
Journal: Journal of Clinical Oncology (2005)

6634 Background: The R-CHOP regimen (rituxan, cyclosphosphamide, doxorubicin, vincristine and prednisone) has become the standard of care for treatment of patients with aggressive B-cell lymphomas. R-CHOP is associated with higher complete remission rates compared with CHOP alone in elderly patients. Pegylated liposomal doxorubicin (Doxil) has an improved pharmacokinetic profile over conventional doxorubicin with decreased cardiotoxicity. We substituted Doxil for conventional doxorubicin in the R-CHOP regimen to define the toxicity profile and obtain data on efficacy. Methods: Patients were treated with Doxil, 40 mg/m2, cyclophosphamide, 750 mg/m2, vincristine, 2.0 mg, all given IV on day 1; prednisone, 100 mg given orally on days 1–5. Rituxan, 375 mg/m2 IV day 1 was added to the regimen starting cycle 2. Chemotherapy cycles were repeated every 21 days and given until 2 cycles beyond complete remission for a maximum of 8 cycles. Results: To date, 34 patients with a median age of 51 years have been accrued. All patients were CD20+ positive with diffuse large cell lymphoma in 27, high grade in 4, and follicular in 4. Two patients had stage III and 27 had stage IV disease. Fifteen had elevated serum LDH levels. 23 patients had an intermediate or high risk IPI score. Toxicities have been primarily hematologic with transient grade 3 or 4 neutropenia in 20 patients; grade 3 or 4 anemia in 9 patients; and grade 3 or 4 thrombocytopenia in 4 patients. Six patients experienced grade 2 or 3 palmer-planter erythrodysesthesia (PPE) and two patients experienced grade 3 mucositis. Other non-hematologic side effects were grade 1 or 2 in severity. Of the 26 evaluable patients, 20 have had a complete or clinical complete remission (76.9%) and 5 had a partial remission (19.2%); one of these went on to stem cell transplant. Median duration of response was 8.3 months (range 0.7 to 18.9 months). Five patients were inevaluable for response and the remaining 4 patients are too early to evaluate. Conclusions: Our preliminary results show that pegylated liposomal doxorubicin (Doxil) substituted for conventional doxorubicin in the R-CHOP regimen is an active regimen for aggressive NHL. No significant financial relationships to disclose.
Elotuzumab Therapy for Relapsed or Refractory Multiple Myeloma
Authors: Sagar Lonial, Meletios Dimopoulos, Antonio Palumbo, Darrell White, Sebastian Grosicki, Ivan Spicka, Adam Walter-Croneck, Philippe Moreau, Maria-Victoria Mateos, Hila Magen, Andrew Belch, Donna Reece, Meral Beksac, Andrew Spencer, Heather Oakervee, Robert Z. Orlowski, Masafumi Taniwaki, Christoph Röllig, Hermann Einsele, Ka Lung Wu, Anil Singhal, Jesus San-Miguel, Morio Matsumoto, Jessica Katz, Eric Bleickardt, Valerie Poulart, Kenneth C. Anderson, Paul Richardson
Journal: New England Journal of Medicine (2015)

Elotuzumab, an immunostimulatory monoclonal antibody targeting signaling lymphocytic activation molecule F7 (SLAMF7), showed activity in combination with lenalidomide and dexamethasone in a phase 1b-2 study in patients with relapsed or refractory multiple myeloma.In this phase 3 study, we randomly assigned patients to receive either elotuzumab plus lenalidomide and dexamethasone (elotuzumab group) or lenalidomide and dexamethasone alone (control group). Coprimary end points were progression-free survival and the overall response rate. Final results for the coprimary end points are reported on the basis of a planned interim analysis of progression-free survival.Overall, 321 patients were assigned to the elotuzumab group and 325 to the control group. After a median follow-up of 24.5 months, the rate of progression-free survival at 1 year in the elotuzumab group was 68%, as compared with 57% in the control group; at 2 years, the rates were 41% and 27%, respectively. Median progression-free survival in the elotuzumab group was 19.4 months, versus 14.9 months in the control group (hazard ratio for progression or death in the elotuzumab group, 0.70; 95% confidence interval, 0.57 to 0.85; P<0.001). The overall response rate in the elotuzumab group was 79%, versus 66% in the control group (P<0.001). Common grade 3 or 4 adverse events in the two groups were lymphocytopenia, neutropenia, fatigue, and pneumonia. Infusion reactions occurred in 33 patients (10%) in the elotuzumab group and were grade 1 or 2 in 29 patients.Patients with relapsed or refractory multiple myeloma who received a combination of elotuzumab, lenalidomide, and dexamethasone had a significant relative reduction of 30% in the risk of disease progression or death. (Funded by Bristol-Myers Squibb and AbbVie Biotherapeutics; ELOQUENT-2 ClinicalTrials.gov number, NCT01239797.).
Process improvement in breast cancer care: Is mammography volume associated with a greater need for process improvement?
Authors: Teena L. Francois, Christine B. Weldon, Julia Rachel Trosman, Danielle Dupuy, Elizabeth A. Marcus, Betty Roggenkamp, Julian C. Schink, David Ansell, Anne Marie Murphy
Journal: Journal of Clinical Oncology (2013)

45 Background: Chicago black women are 62% more likely to die from breast cancer than white women. Previous data from 39 Chicago hospitals suggested significant variation in mammography quality (Chicago Breast Cancer Quality Consortium, 2010). We developed process improvement recommendations for sites that participated in our care process assessment (Weldon CB, et al, ASCO-Abstract-6120-2012). This study was funded through a generous grant from the Susan G. Komen for the Cure Foundation. We compared improvement needs between high and low patient volume institutions. Methods: Using Deming’s PDCA cycle for continuous improvement, we created care process improvement recommendations for 25 Chicago institutions with the patient base averaging more than 50% minority patients (20 community, 3 academic and 2 public hospitals). Low mammography volume (&lt; 5,000 mammograms/ year) was reported by 12 of the 25 sites. Recommendations are based on analysis across sites, literature, and input from institution staff. Thematic and statistical analyses were performed using simple frequencies and Fisher's exact test. Results: Improvement recommendations are classified into nine areas (see Table). We found that 100% (12/12) of low mammography volume institutions have specific improvement needs in 6 or more process improvement areas, as compared to 23% (3/13) of the high mammography volume institutions (p value &gt; 0.0001). Conclusions: Lower volume mammography sites have a larger need for breast cancer care process improvements. [Table: see text]
Black medicine: an observational study of doctors’ coffee purchasing patterns at work
Authors: Karlmeinrad Giesinger, David F Hamilton, Matthias Erschbamer, Bernhard Jost, Johannes M Giesinger
Journal: BMJ (2015)

To evaluate doctors' coffee consumption at work and differences between specialties.Single centre retrospective cohort study.Large teaching hospital in Switzerland.766 qualified doctors (425 men, 341 women) from all medical specialties (201 internal medicine, 76 general surgery, 67 anaesthetics, 54 radiology, 48 orthopaedics, 43 gynaecology, 36 neurology, 23 neurosurgery, 96 other specialties).Staff purchasing history from staff canteens' electronic payment system linked to separate anonymised personal data from the human resource database.Numbers of coffees purchased per person per year.84% (644) of doctors purchased coffee at one of the hospital canteens. 70 772 coffees were consumed by doctors in 2014. There was a significant association between specialty and yearly coffee purchasing (F=12.45; P<0.01). On average orthopaedic surgeons purchased the most coffee per person per year (mean 189, SD 136) followed by radiologists (177, SD 191) and general surgeons (167, SD 138). Anaesthetists purchased the least coffee (39, SD 48). Male doctors bought significantly more coffees per person per year (128 (SD 140) v 86 (SD 86), t=-4.66, P<0.01) and twice as many espressos as female doctors (mean 27 (SD 46) v 10 (SD 19), t=-6.54, P<0.01). Hierarchical position was associated with coffee purchasing (F=4.55; P=0.04). Senior consultants (>5 years' experience) bought most coffees per person per year (140, SD 169) and junior doctors and registrars bought fewest (95, SD 85). Propensity of buying rounds also increased with hierarchical position (χ(2)=556.24; P<0.01), with heads of departments buying more rounds than junior doctors (30% v 15%).Doctors commonly use coffee as a stimulant. Substantial variation exists between specialties. Surgeons drink notably more coffee than physicians, with orthopaedic surgeons consuming the greatest amount in the communal cafeteria setting, though this might reflect social tendencies rather than caffeine dependency. Hierarchical position is positively correlated with coffee consumption and generosity with regard to buying rounds of coffee.
Design of Catalytic Peptides and Proteins Through Rational and Combinatorial Approaches
Authors: Yoshiaki Maeda, Olga V. Makhlynets, Hiroshi Matsui, Ivan V. Korendovych
Journal: Annual Review of Biomedical Engineering (2016)

This review focuses on recent progress in noncomputational methods to introduce catalytic function into proteins, peptides, and peptide assemblies. We discuss various approaches to creating catalytic activity and classification of noncomputational methods into rational and combinatorial classes. The section on rational design covers recent progress in the development of short peptides and oligomeric peptide assemblies for various natural and unnatural reactions. The section on combinatorial design describes recent advances in the discovery of catalytic peptides. We present the future prospects of these and other new approaches in a broader context, including implications for functional material design.
Relation of rates of self referral to A&amp;E departments to deprivation
Authors: S. Hull, I. R. Jones, K. Moser
Journal: BMJ (1998)

Editor—Carlisle et al report an association between markers of social deprivation derived from the 1991 census and out of hours contacts with both general practice services and accident and emergency departments.1

We undertook a related study in east London, based on 63 000 attendances by adults at accident and emergency departments.2 This showed that factors related to social deprivation accounted for 48% of the variation in total adult attendance rates between practices. This was so even in an area of consistently high deprivation where the practices’ underprivileged area (Jarman) scores ranged from 30.4 to 62.1 (median value 42.5). In contrast to Carlisle et al, we included in the multivariate analysis explanatory variables relating to practice size and resources, since organisational factors are often cited as causes of high use of accident and emergency departments among inner city populations.3 We found that practice characteristics (partnership size, female partner, practice manager, nurse, training status, and computer) did not predict rates of attendance, while markers of deprivation did. Distance from the hospital was negatively correlated with attendance rates in the univariate analysis but not in the multivariate analysis. 

Carlisle et al’s paper mentioned another intriguing finding: wide variation in out of hours use of both general practitioners and accident and emergency departments between practices serving populations from the same wards. We recently completed a study examining the outcomes of all attendances at an accident and emergency department by patients from two practices over seven months.4 The practices were in Tower Hamlets, had similar underprivileged area scores, were in close proximity to each other, and were within 2 km of the nearest hospital.4 While the attendance rates at accident and emergency departments from the two practices were significantly different, the outcomes, in terms of the proportions of patients admitted and referred on to outpatients, were similar (table). This suggests that case mix and severity vary between apparently similar practice populations. 

If practice based budgets are to be based on an equitable allocation of scarce resources it is important to develop robust markers of variations in case mix among practices, which can contribute to the debate on resource allocation in primary care.
Abstract 19858: Higher Prevalence of Insulin Resistance among Asian Americans despite Lower Body Mass Index
Authors: Jia Pu, Robert Romanelli, Beinan Zhao, Sukyung Chung, Vani Nimbal, Latha Palaniappan
Journal: Circulation (2014)

Background: This study aims to identify racial/ethnic differences in the relationship between BMI and insulin resistance across Asian American subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese), Mexicans, non-Hispanic blacks (NHBs), and non-Hispanic whites (NHWs) in a large, mixed payer ambulatory care setting in northern California. Study Design: This cross-sectional study examined electronic health records of patients aged 18 years or older from 2000-2012. Insulin resistance was indicated by TG/HDL ratio>3. Overweight or obesity was defined as BMI≥25. Results: Although Asian Americans had the lowest rate of overweight and obesity, they had the highest prevalence of insulin resistance in both normal weight (19%, 9,262 of 49,981) and overweight/obese groups (43%, 15,742 of 36,496), followed by Mexicans (normal: 12%, 197 of 1,590; overweight: 39%, 2,106 of 5,377), NHWs (normal: 9%, 6,271 of 65,921; overweight: 32%, 33,475 of 103,695) and NHBs (normal: 6%, 46 of 716; overweight: 16%, ...
Abstract MP19: Serum 25-hydroxyvitamin D is associated with incident heart failure in whites but not blacks: The Atherosclerosis Risk in Communities Study (ARIC)
Authors: Pamela L Lutsey, Erin D Michos, James S Pankow, Elizabeth Selvin, Laura R Loehr, W.H. L Kao, John H Eckfeldt, Myron D Gross, Aaron R Foslom
Journal: Circulation (2014)

Background: Suboptimal 25-hydroxyvitamin D [25(OH)D] is a potential cardiovascular risk factor, likely influencing cardiovascular events via established risk factors, namely hypertension, diabetes, and inflammation. Emerging evidence also suggests that the association between 25(OH)D and cardiovascular risk is stronger in whites than blacks, but these preliminary findings need further confirmation. Hypotheses: Serum 25(OH)D is inversely associated with incident heart failure, and (a) partly mediated by traditional cardiovascular risk factors and (b) stronger among whites than blacks. Methods: A total of 12,215 ARIC Study participants free of heart failure at baseline in 1990-92 (median age 56, 24% black) were followed through 2010. Total serum 25(OH)D was measured in stored samples at baseline using LCMS. Month of blood draw was accounted for. Incident heart failure events were identified via active surveillance and defined by a hospital discharge code of ICD9-428 and parallel ICD codes for deaths. Multivariable Cox proportional hazards regression models were employed. Results: During a median of 17 years of follow-up, there were 1,799 incident heart failure events. Median 25(OH)D was 26.2 and 19.0 ng/mL in whites and blacks, respectively. The association between 25(OH)D and heart failure varied by race (p-interaction = 0.01). Among whites, those in the lowest quintile of 25(OH)D were at 2-fold greater risk of heart failure relative to those in the highest quintile ( Table ). The HR was attenuated, but remained statistically significant after multivariable adjustment. In blacks there was no association between 25(OH)D and heart failure. Results were similar when race-specific quintiles were used. Conclusions: Low serum 25(OH)D was independently associated with risk of incident heart failure among whites, but not among blacks in this community-based population. Further work is needed to determine what mechanisms underlie racial variation in the association between vitamin D status and risk of heart failure.
Disease Progression in Pulmonary Arterial Hypertension
Authors: J. Eduardo Rame, Anjali Vaidya
Journal: JACC Heart Failure (2014)

Pulmonary arterial hypertension (PAH) is a progressive syndrome of right heart failure that encompasses multiple etiologies and risk factors. The presentation, clinical progression, and response to therapeutic intervention are variable across patients, and much interest has been directed in clinical
Polymorphism of nucleotide excision repair genes as predictors for clinical outcome in advanced gastric cancer patients treated with oxaliplatin-based chemotherapy
Authors: H. Hur, K. Song, C. Park, Y. Hong, H. Chun, H. Jeon
Journal: Journal of Clinical Oncology (2009)

4565 Background: The individual variations in treatment response and the toxicity of combination regimen of oxaliplatin and 5-fluorouracil with leucovorin (FOLFOX) for advanced gastric cancer patients have been reported. The aim of this study is to evaluate the influence of polymorphism of nucleotide excision repair genes that are involved in the metabolism of cisplatin on the clinical outcomes of gastric cancer patients treated with modified FOLFOX-6 chemotherapy. Methods: From March 2006 to December 2007, eighty-two patients with advanced gastric cancer were treated with modified FOLFOX-6 as the primary chemotherapy in our institution. Of these patients, 55 patients who were available for peripheral blood sampling before starting chemotherapy were enrolled in this study. Genomic DNA was extracted from mononuclear cells of patients’ blood. Four polymorphisms were investigated in three genes, ERCC, GSTP and XRCC. Results: The overall response rate (RR) was 40.0%. Median time to progression (TTP) and overall survival (OS) was 6 months (C.I.: 5.0 - 7.0 months) and 15.0 months (C.I.: 9.7 - 20.3 months). Grade 3 or 4 hematologic toxicities were presented in 17 patients (30.9%), gastrointestinal toxicities in 5 patients (9.1%), peripheral neuropathy in 5 patients (9.1%) and hepato-toxicity in 4 patients (7.3%). Most common types of polymorphism were G/G (67.3%) in XRCC1 Arg399Gln, A/A (74.5%) in GSTP1 Ile105Val, C/C (60.0%) in ERCC1 Asn118Asn and C/A (49.1%) in ERCC1 C8092A. The RR was significantly lower in patients with C/C type in ERCC1 C8092A gene than those with other type (25.0% vs 51.6%, p=0.046). However, there were no differences of TTP and OS among the polymorphisms in three genes. The rate of grade 3 or 4 hematologic toxicity was higher in patients with C/T or T/T in ERCC1 codon 118 gene than those with C/C type (45.5% vs 21.2%, p=0.057). Conclusions: We demonstrated that modified FOLFOX-6 chemotherapy was effective and tolerable. The polymorphism of C/C type in ERCC1 C8092A gene was found to be a predictive marker of the poor response and C/C type in ERCC1 Asn118Asn gene was to be a predictive marker of the hematologic toxicity. No significant financial relationships to disclose.
Phase II study of sorafenib and docetaxel in men with metastatic castration resistant prostate cancer (mCRPC)
Authors: J. P. Cetnar, M. A. Rosen, D. J. Vaughn, N. B. Haas, A. B. Troxel, H. Song, G. Adluru, K. T. Flaherty, P. J. O'Dwyer, R. K. Amaravadi
Journal: Journal of Clinical Oncology (2009)

e16055 Background: Previous trials of the antiangiogenic kinase inhibitor sorafenib in mCRPC have reported PSA elevation accompanying radiographic response, and evidence that sorafenib may potentiate docetaxel (dxl) myelosuppression. To assess the safety, antivascular effects, and activity of sorafenib and dxl in mCRPC, a phase II trial with dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) was conducted. Methods: Eligible men had mCRPC and no prior chemotherapy. Treatment consisted of dxl 75 mg/m 2 (day 1) and sorafenib (days 2–19) of a 21 day cycle. Patients received 7 days of sorafenib before cycle 1. Six patients received sorafenib 200mg BID and remaining patients received sorafenib 400 mg BID if &lt;4/6 patients had grade 4 neutropenia. DCE-MRI was performed at baseline, days 8 and 28. The primary endpoint was PSA response rate (&gt;50% PSA decline). Secondary endpoints were vascular response rate (&gt;20% decline in area under the gadolinium curve [AUC60]), toxicity rates, and time to progression (TTP). PSA-only progression (2 consecutive PSA rises) was confirmed by a third PSA rise or radiographic progression after a 21-day drug holiday. Sample size of 69 patients in 1 stage was designed to maximize detection of significant correlations between DCE-MRI and clinical outcomes. Results: Six of 13 enrolled patients (46%) had a PSA response. A median PSA increase of 37% was observed in 73% of patients after 1 week of sorafenib. The median TTP was 8+ months. Two patients had complete disappearance of bone lesions. Grade 3 adverse events were neutropenia (77%), hand-foot syndrome (23%), anemia (15%), nausea (8%), and rash (8%). A median AUC60 decline of 40% from baseline was observed after 7 days of sorafenib, and only a 6% decline on day 28 during a scheduled sorafenib holiday. Conclusions: Sorafenib 400 mg po bid and dxl 75 mg/m2 are tolerable in men with mCRPC. Elevated PSA values in men treated with sorafenib and dxl does not always reflect disease progression. DCE-MRI can capture sorafenib's impairment of tumor vasculature in osseous metastases and rebound angiogenesis during drug holidays. Bone responses and TTP data provide evidence of encouraging activity. No significant financial relationships to disclose.