tbuckley/cabot-search huggingface dataset:
Funding model for stem cell transplant.
Authors: Julia Monakova, Huma Tariq, Sherrie Hertz, Tom Kouroukis, Irene Blais
Journal: Journal of Clinical Oncology (2017)

22 Background: A call for development of a new model for funding Stem Cell Transplant (SCT) services in Ontario led to a costing initiative described below. The new model needed to be in alignment with current costs and clinical practices, and to avoid over or under-funding the required components of care for all types of transplant (autologous, allogeneic-related, allogeneic un-related). Methods: The patient care path was broken down by transplant type into the following phases: Pre-Transplant, Graft Harvesting or Procurement, Transplant, and Follow-Up. The following Canadian and Ontario data sources were used for fiscal year 2013/14 and 2014/15 to identify costs of care: -Case Costing data submitted by the six hospitals providing SCT services, -Discharge Abstract Database (DAD), -National Ambulatory Care Reporting System (NACRS), -Other data sources, as needed (e.g. Specialized Services Oversight Information System, Health Indicator Tool). Additionally, the costs for high cost drugs, infrastructure, psychosocial support, and pathology services components were specifically identified. Broad consultation with clinical, administrative, and costing experts ensured the data was complete and appropriate to patient care needs. Once the costs for each component and phase were estimated, the funding model was developed using the bundling approach where the costs of specific activities and/or phases were bundled together for the purposes of funding. Results: The SCT Funding Model developed based on this costing initiative consists of the following four bundles covering the continuum of a patient’s care from pre-transplant to post-transplant care follow-up: 1.) Pre-Transplant, 2.)Graft Acquisition, 3.)Transplant (includes transplant and follow-up), and 4.) High Cost Drugs. Conclusions: The new SCT Funding Model reflects up-to-date costs and addresses the gaps of the previous approach. It has been implemented and is widely supported due to the extensive stakeholder engagement throughout the process. It is an important component of provincial-level planning for SCT service delivery.
Therapeutic treatment of Marburg and Ravn virus infection in nonhuman primates with a human monoclonal antibody
Authors: Chad E. Mire, Joan B. Geisbert, Viktoriya Borisevich, Karla A. Fenton, Krystle N. Agans, Andrew I. Flyak, Daniel J. Deer, Herta Steinkellner, Ognian Bohorov, Natasha Bohorova, Charles Goodman, Andrew Hiatt, Do H. Kim, Michael H. Pauly, Jesus Velasco, Kevin J. Whaley, James E. Crowe, Larry Zeitlin, Thomas W. Geisbert
Journal: Science Translational Medicine (2017)

A single mAb is an effective therapy in nonhuman primates infected with Marburg or Ravn virus.
Lanreotide depot/autogel (LAN) in intestinal and pancreatic neuroendocrine tumors (NETs) according to body mass index (BMI): Subgroup analyses from the CLARINET study.
Authors: Edward M. Wolin, Martyn E. Caplin, Marianne E. Pavel, Jaroslaw B Cwikla, Alexandria T. Phan, Markus Raderer, Eva Sedlackova, Guillaume Cadiot, Jaume Capdevila, Lucy Wall, Guido Rindi, Alison Langley, Edda Gomez-Panzani, Philippe B. Ruszniewski
Journal: Journal of Clinical Oncology (2015)

e15182 Background: CLARINET showed antitumor effects with LAN 120 mg in metastatic intestinal/pancreatic NETs. Here, we characterize treatment effects within subgroups defined post hoc by baseline BMI. Methods: CLARINET was a 96-wk randomized trial of patients with metastatic grade 1/2 (Ki-67 <10%) non-functioning intestinal/pancreatic NETs (NCT00353496). Patients received LAN 120 mg (N=101) or placebo (PBO; n=103) every 4 wks. Patient subgroups are based on well-known WHO BMI categories. Median progression-free survival (PFS) [95% CI] was determined by Kaplan–Meier method, and HRs and CIs with Cox proportional hazards model with single term for treatment (both intent-to-treat population); summary statistics were used for adverse events (AEs) (safety population). PFS analyses investigated only consistency of treatment effects across subgroups as the study was not otherwise powered for such analyses. Results: LAN median PFS was not reached in any BMI subgroup (vs 13–24 months for PBO); HRs favored LAN and were generally consistent with the overall population (Table). Incidences of AEs overall were similar across BMI and treatment groups; the most common AE was diarrhea (Table). Conclusions: CLARINET subgroup analyses suggest LAN has antitumor effects and a favorable safety/tolerability profile regardless of patient BMI. Clinical trial information: NCT00353496. BMI* 18.5–<25.0 18.5–<25.0 25.0–<30.0 25.0–<30.0 ≥30.0 ≥30.0 LAN PBO LAN PBO LAN PBO n 34 38 38 29 24 27 PFS Median [95% CI] PFS, months NC 13.0 [12.0,18.2] NC 24.4 [18.0,NC] NC 17.6 [9.0,24.5] HR for PD/death [95% CI] 0.33 [0.16,0.67] 0.71 [0.32,1.57] 0.45 [0.19,1.05] Any AE, n (%) 30 (88) 35 (92) 32 (84) 26 (90) 22 (92) 24 (89) (Severe/moderate/ mild/missing, %) (32/29/24/3) (32/39/21/0) (16/55/13/0) (34/41/14/0) (25/46/17/4) (22/52/15/0) Treatment-related AEs 17 (50) 8 (21) 18 (47) 10 (34) 12 (50) 9 (33) SAEs, n (%) 9 (29) 14 (37) 8 (21) 9 (31) 4 (17) 6 (22) Treatment-related SAEs 0 0 1 (3) 0 1 (4) 1 (4) Withdrawals due to AEs, n (%) 3 (9) 0 0 3 (10) 0 0 *BMI <18.5 kg/m2 omitted as n=5. HR, hazard ratio for PD/death with LAN vs. PBO; NC, not calculable; PD, progressive disease. Note: HR for overall population: 0.47 [0.30,0.73] (Caplin, 2014).
Breast cancer patients co-expressing estrogen receptor alpha and/or progesterone receptors and HER2/neu: Response to adjuvant therap
Authors: F. Gago, D. R. Ciocca
Journal: Journal of Clinical Oncology (2004)

699 Background: In breast cancer patients ERα/PR (HR) predict the response to endocrine therapy (mainly tamoxifen: Tx), and HER2/neu predicts the response to trastuzumab. These molecules are inversely correlated (not all reports agree on this), however, in a few cases they are co-expressed. Some but not all studies suggest that HR+/HER2/neu+ patients have poor response to Tx making this special group a matter of debate. In this prospective study we report the response to adjuvant therapy in a relatively small subgroup of patients co-expressing HR and HER2/neu. Methods: We have analysed the data from our patients: n=516, follow-up: 5–10 years, consecutive stage I-II cases, tumor biopsies studied by immunohistochemistry to integrate the molecular markers ERα, PR, PCNA, HER2/neu, p53 and P170 with the clinicopathological data to obtain prognostic information (J Steroid Biochem Mol Biol 67:431–437, 1998). ERα/PR+: nuclear receptors in ≥ 10% of cancer cells, HER2/neu+: membrane staining in >1% of cancer cells (in previous studies this expression level correlated with western blot and southern blot). Results: Fifty one (10.4%) patients co-expressed HR and HER2/neu, from these, 21 patients received adjuvant therapy with Tx alone (20 mg/day). Lymph node-negative patients treated with Tx alone showed survival curves similar to the patients that were HR+/HER2/neu negative (n=106). In contrast, lymph node positive patients (HR+/HER2/neu+) treated with Tx alone had shorter survival (p=0.002), the treatment with poly-chemotherapy followed by Tx did not improved significantly the survival of these patients. Conclusions: Breast cancer patients co-expressing HR and HER2/neu may be treated with adjuvant therapy with Tx alone if they are lymph node negative. In contrast, Tx alone should not be used in HR+/HER2/neu+ patients with lymph node-positive tumors (treatment with poly-chemotherapy followed by Tx did not improved the survival, in these cases perhaps trastuzumab should be added). No significant financial relationships to disclose.
Clinical features at presentation, C-kit, and Her2/<i>neu</i> overexpression as prognostic factors in elderly patients with lung carcinoma
Authors: A. Panwalkar, A. Potti
Journal: Journal of Clinical Oncology (2004)

9636 Purpose: To determine the clinical predictors of survival and significance of C-kit and Her2/neu overexpression as prognostic markers in elderly males (age =/>65 years) with lung carcinoma (LC). Methods: After approval from the institutional review board, a retrospective chart review was performed to obtain demographic/clinical data on elderly males with a biopsy-proven LC. C-kit and Her2/neu overexpression was also assessed using immunohistochemical techniques (IHC). Results: 64 elderly males (mean age: 73.75 years; range: 65–87 years) were included in our study. 12/64 patients (18.75%) had small cell lung cancer (SCLC) and 48 (75%) had non-small cell lung cancer (NSCLC). 4 patients (6.25%) refused diagnostic biopsies. The most common diagnostic procedures were CT-guided biopsy (n=38, 59.37%) and transbronchial biopsy (n=12, 18.75%). Of the 64 patients studied, 24 (37.5%) presented with cough, 16 (25%) as an incidental finding and 8 (12.5%) with dyspnea. Cox regression analysis revealed that patients with dyspnea at presentation had a 4.25 greater odds (95% CI 1.8–10, p=0.01) of early demise as compared with cough. With increasing performance status (from ECOG 0 to 4), the hazards of dying increased by 1.27 times the previous level (p=0.005). Interestingly, of the 12 patients with SCLC, 4 (33.3%) revealed C-kit overexpression, while none of the NSCLC specimens revealed overexpression. Also, after adjusting for confounding variables, C-kit overexpression was associated with a significant survival advantage (p=0.018) in SCLC, using the Log rank test. In contrast, presence of Her2/neu identified in 4 patients with SCLC (33.3%) and 9 NSCLC patients (18.75%) had an insignificant effect on survival (p=0.87) in elderly males with LC. Conclusions: Elderly males with LC represent a select subgroup with characteristic clinical and pathologic features. Her2/neu overexpression seen in NSCLC and SCLC lacks prognostic significance in elderly males. Interestingly, however, c-kit overexpression, seen in ∼30% of the SCLC cohort seems to confer a survival advantage. Further larger studies are needed to validate our findings. No significant financial relationships to disclose.
Screening for specific anti-angiogenic agents
Authors: Anshu Roy, Lynn Rasmussen, Ling Zhai, Clinton Maddox, E. Lucile White, Judith Hobrath, Murray Stackhouse, Adam Keeton, Gary Piazza, Rongbao Li, Subramaniam Ananthan, Namita Bansal, Kochurani Jacob, Joseph Maddry, Zhican Qu
Journal: Cancer Research (2008)

1543  Imbalance in angiogenesis is involved in many pathological conditions, such as cancer, rheumatoid arthritis, and inflammation. Targeting angiogenesis has recently emerged as a proven therapeutic strategy for treatment of cancer and age-related macular degeneration. To understand the underlying biological signaling pathways of angiogenesis and to develop potential anti-angiogenic therapy, we have developed a system to discover small molecular probes that can selectively inhibit endothelial cell activation, and thereby block excessive angiogenesis. First, a high throughput screening (HTS) assay was developed for screening large libraries of chemical compounds against both primary human endothelia and fibroblasts to identify compounds with differential inhibitory activity against the endothelial cells versus fibroblasts. Second, HTS dose response-based EC50 values were determined to identify lead compounds with selectivity and potency against human endothelial activation. Third, a number of selected lead compounds were studied for their activities in endothelial cell tube-formation and migration, and to elucidate their mechanisms of action. Fourth, the selective compounds are being further studied in vivo by embryo CAM assay and mouse Matrigel plug assay. A number of compounds that exhibited specific inhibitory activities against human endothelial cells were identified from an 86,000 compound library screening. Analysis of structural clusters of the initial hits led to the identification of several chemical scaffolds as interesting leads. Structure-activity relationship (SAR) analyses and synthetic efforts on selected scaffolds for lead optimization are in progress. Our progress toward identification of specific anti-angiogenic agents will be presented.
A phase II study of nilutamide in men with prostate cancer following failure of flutamide or bicalutamide therapy
Authors: N. B. Davis, C. W. Ryan, W. M. Stadler, N. J. Vogelzang
Journal: Journal of Clinical Oncology (2004)

4669 Background: Determine PSA response, time to PSA progression and, in a subset with measurable disease at baseline, the objective response rate and time to radiographic progression in men with prostate cancer refractory to bicalutamide and/or flutamide therapy. Methods: Eligibility included histologically confirmed prostate cancer not amenable to curative therapy with either radiation or surgery and progressive disease demonstrated by radiographic or PSA criteria. Patients progressing on bicalutamide therapy must have undergone a 6-week anti-androgen withdrawal period while those progressing on flutamide were eligible following a 4-week withdrawal. All subjects received nilutamide, 150 mg/day orally, for a minimum of 8 weeks; patients were evaluable for PSA and radiographic response after 4 and 8 weeks, respectively. A baseline PSA, CXR, bone scan and abdominal/pelvic CT were obtained; re-evaluation included PSA every 4 weeks and repeat radiographic imaging for those with baselines abnormalities. A 50% PSA decline without radiographic progression was considered a partial response. CXR was repeated for any pulmonary symptoms. Results: To date, 13 men have been enrolled and 11 are evaluable. Median Gleason's score at diagnosis was 7 (range 6–9). Median number of prior therapies was 3 (range 1–5). Median baseline PSA was 16.7 ng/ml (range 4.9–151 ng/ml). 8 subjects had diffuse bone metastases and 3 had other radiographically measurable disease. Of these, 2 are not yet radiographically evaluable (on study < 8 weeks) and one has radiographic stable disease at 8 weeks. There have been no grade 3/4 toxicities; the most common grade 1/2 toxicities were constipation (2), sensory neuropathy (3), fatigue (3), and visual changes (2) involving transient change in color vision and sensitivity to light, respectively. Responses include 2 (18%) PR and 5 (45%) PD. Those progressing did so after 8 weeks of therapy and by PSA criteria only. Conclusions: Nilutamide is well tolerated and leads to PSA responses following bicalutamide or flutamide failure. Ongoing study will determine the response rate and duration of response for this third line hormonal approach. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis
Abstract P365: Effects of a Health Partner Intervention on Arterial Health
Authors: Heval Mohamed Kelli, Robert Heinl, Jamal Hajjari, Samantha Noreen, Yi-An Ko, Muhammad Hammadah, Ayman Samman-Tahhan, Pratik Sandesara, Talal Alghamdi, Kaavya Chivukula, Frank Corrigan, Ibhar Al Mheid, Thomas Ziegler, Greg Gibson, Michelle Lampl, Kenneth Brigham, Viola Vaccarino, Greg Martin, Arshed A Quyyumi
Journal: Circulation (2017)

Introduction: Lifestyle modification is effective for cardiovascular disease prevention. Whether lifestyle intervention also preserves vascular health is less clear. Our study examined the role of a Health Partner-administered lifestyle intervention on vascular function. Hypothesis: Lifestyle intervention improves and preserves vascular function. Methods: A total of 711 university employees (48±11 years, 66% women, 22.5% Black) enrolled in a program that promoted healthier lifestyles at Emory University. Participants collaborated with a Health Partner to generate a personalized plan focused on achieving ideal health metrics. Anthropometric, laboratory and vascular function measurements were performed at baseline and at 1-year and 2-years of follow-up. Arterial stiffness was assessed by carotid-femoral pulse wave velocity and radial tonometry-derived central augmentation index. Microvascular function was assessed as digital reactive hyperemia index. Flow-mediated dilation was measured using ultrasound. The sample was divided into individuals within the lowest tertile and those in the upper two tertiles for vascular function at baseline. Paired t-test was used to assess the changes in vascular functions at 1 and 2 years of follow-up compared to baseline. Results: At each of the 1-year and 2-year follow-up visits, vascular function improved in the group within the abnormal tertile at baseline. Flow-mediated dilation increased by 1.6% and 2.0% (P&lt;0.001) respectively, pulse wave velocity decreased by 0.85 m/s and 0.93 m/s (P&lt;0.001), central augmentation index was lower by 3.4 and 3.2 (P&lt;0.001), and microvascular function assessed by reactive hyperemia index improved by 0.48 and 0.52 (P&lt;0.001). In those within the upper two tertiles, pulse wave velocity did not significantly change, but flow-mediated dilation and reactive hyperemia index showed significant decline at 2 years of follow up. Conclusion: A personalized, goal directed Health Partner intervention was associated with better vascular stiffness, endothelial and microvascular function in those with baseline abnormal values. These effects were evident at 1 year following enrollment and were sustained for 2 years. Whether the impact of Health Partner intervention on vascular function improves long-term morbidity and mortality needs further investigation in a controlled design.
Practices should be able to keep money saved from putting patients on low carbohydrate diet, GP says
Authors: Jane Feinmann
Journal: BMJ (2017)

GPs who advise patients on the benefits of a low carbohydrate diet to manage type 2 diabetes should be entitled to keep all or part of any resulting savings in their drugs bill, an independent forum of MPs and peers has heard.

David Unwin, a GP in Southport and the Royal College of General Practitioners’ champion for collaborative care and support planning in obesity and diabetes, made the proposal on 28 March at the All Party Parliamentary Food and Health Forum. The forum is conducting a hearing on diabetes and diet, chaired by the Labour peer and former London GP Nicolas Rea.

Unwin said that his practice’s spending on type 2 diabetes drugs (excluding insulin) was £4194 (€4940; $5260) less per 1000 …
Quality of life (QOL) results of a randomized study of intravenous (IV) paclitaxel and cisplatin vs IV paclitaxel, intraperitoneal (IP) cisplatin and IP paclitaxel in optimal stage III epithelial ovarian cancer (OC): A Gynecologic Oncology Group trial
Authors: L. B. Wenzel, H. Huang, D. Armstrong, J. Walker, D. Cella
Journal: Journal of Clinical Oncology (2004)

5026 Background: A study examining IP therapy in optimal stage III OC patients suggested improvement in relative risk of recurrence for patients in that arm (ASCO, 2002). An important secondary outcome was assessment of QOL. Methods: 415 patients were randomly allocated to receive Regimen 1 (R1): IV paclitaxel 135mg/m2/24h and IV cisplatin 75mg/m2 or Regimen 2 (R2): IV paclitaxel 135mg/m2/24h followed by IP cisplatin (100mg/m2), plus IP paclitaxel 60mg/m2 on day 8, with cycles repeated every 21 days x 6. Using the FACT-O, GOG-NTX, and pain measure (PAIN), QOL was assessed: prior to randomization (baseline), prior to cycle 4, and 3–6 weeks and 12 months post-treatment. Multivariate analysis was used to compare baseline FACT-O scores with NTX and PAIN subscales. Follow-up assessments were analyzed using a Linear Mixed Model with unstructured covariance and baseline scores, age and performance status as covariates. Results: Mean FACT-O and PAIN scores were significantly different between treatment arms, with R2 patients reporting worse QOL and pain prior to cycle 4 (p<0.0001) and worse QOL 3–6 weeks post-treatment (p=0.0035). Neurotoxicity was also significantly worse in R2 3–6 weeks after completing chemotherapy (p=0.0004), and one year later (p=0.0018). However, there were no significant QOL or PAIN score differences between arms one year post-treatment. Conclusions: Patients who received higher dose IP therapy (R2) experienced more QOL disruption, pain and NTX when compared to those who received more conventional dose IV therapy (R1). However, R2 patients experienced better recurrence-free survival. This trade-off should be considered when discussing treatment options with patients. Studies to reduce the added burden of regimens such as R2 are encouraged. No significant financial relationships to disclose.
Development of a risk prediction model among professional hockey players with visible signs of concussion
Authors: Jared M Bruce, Ruben J Echemendia, Willem Meeuwisse, Michael G Hutchison, Mark Aubry, Paul Comper
Journal: British Journal of Sports Medicine (2017)

Little research examines how to best identify concussed athletes. The purpose of the present study was to develop a preliminary risk decision model that uses visible signs (VS) and mechanisms of injury (MOI) to predict the likelihood of subsequent concussion diagnosis.Coders viewed and documented VS and associated MOI for all NHL games over the course of the 2013-2014 and 2014-2015 regular seasons. After coding was completed, player concussions were identified from the NHL injury surveillance system and it was determined whether players exhibiting VS were subsequently diagnosed with concussions by club medical staff as a result of the coded event.Among athletes exhibiting VS, suspected loss of consciousness, motor incoordination or balance problems, being in a fight, having an initial hit from another player's shoulder and having a secondary hit on the ice were all associated with increased risk of subsequent concussion diagnosis. In contrast, having an initial hit with a stick was associated with decreased risk of subsequent concussion diagnosis. A risk prediction model using a combination of the above VS and MOI was superior to approaches that relied on individual VS and associated MOI (sensitivity=81%, specificity=72%, positive predictive value=26%).Combined use of VS and MOI significantly improves a clinician's ability to identify players who need to be evaluated for possible concussion. A preliminary concussion prediction log has been developed from these data. Pending prospective validation, the use of these methods may improve early concussion detection and evaluation.
Thirty Miles at Sea — Providing Consistent Care in an Inconsistent Environment
Authors: Margot Hartmann, Jason Graziadei
Journal: New England Journal of Medicine (2017)

Interview with Dr. Heather Kovich on the challenges facing patients and physicians in rural areas of the United States. (10:07)Download Nantucket Cottage Hospital, a 19-bed facility and one of the smallest hospitals in Massachusetts, has to navigate the complexity of operating on an island 30 miles offshore, where the year-round population of 15,000 swells to more than 60,000 during the summer months.