tbuckley/cabot-search huggingface dataset:
Evaluation of the implementation of the Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) across the province of Ontario.
Authors: Farzana Haji, Lisa Catherine Barbera, Heidi Amernic, Jenna Evans, Zahra Ismail, Michael Donald Brundage
Journal: Journal of Clinical Oncology (2018)

188 Background: EPIC-CP, a prostate cancer Patient-Reported Outcome Measure (PROM), was implemented across Ontario’s 14 Regional Cancer Centres (RCCs) using a phased roll-out approach. This approach enabled implementation and evaluation in enrolled centres, with the aim of using the results to improve implementation in both the enrolled regions and those preparing to implement. The objective was to analyze formative evaluation results and identify opportunities for improvement in implementation. Methods: Surveys were developed for patients and providers to capture attitudes and experiences regarding EPIC-CP. Data collection was initiated approximately three months post-implementation, with three RCCs evaluated concurrently in ‘waves’. Descriptive analyses were performed to summarize the survey data. Results: To date, nine RCC’s have completed the formative evaluation with 104 providers and 517 patients responding to the surveys. Providers reported challenges with data flow (44% always or mostly received EPIC-CP results in a timely manner) and with responding to specific symptoms (27% and 29% reported that they are very confident in treating/managing sexual function and emotional issues respectively). Although 54% of providers acknowledged that using EPIC-CP should be part of their role, 46% indicated that it has added little or no value to their practice. In contrast, 75% of patients reported that EPIC-CP made it easier to communicate symptoms to their care team, which suggests that patients find EPIC adds value. Patient comments identified gaps such as educational resources for symptom management and additional support when completing the PROM. Conclusions: Opportunities to improve the patient and provider experience with EPIC-CP include: developing educational resources, addressing issues with technology and data flow, and identifying factors that influence provider uptake. These results will be used to design resources and support to improve the process for implementing EPIC-CP in later waves.
Examining patient burden and drivers of delayed care in patients undergoing surgical treatment of primary lung cancer.
Authors: Caleb Barnhill, Charles Hillenbrand, Stephen Kaplan, Madhan Kuppusamy, Michal Hubka
Journal: Journal of Clinical Oncology (2018)

153 Background: Patients’ geographic location can impact access to specialty care and affect the appropriateness and timeliness of evaluation leading to primary surgical treatment of lung cancer. Cancer care coordination has long been speculated to lead to greater efficiency in oncologic care, yet objective measures demonstrating the utility of such healthcare team members is lacking. We aimed to study the impact of patients’ residence on healthcare encounters, travel burden and the distribution of physiologic and oncologic workup leading to delays in care at a specialty cancer center. Methods: We conducted a single center retrospective cohort study of 103 patients undergoing workup of primary lung cancer between January 2015 and August 2017. The shortest route between patient residence and treating medical center was measured in miles and classified as: urban ( &lt; 40 miles); rural (40.1 – 100 miles); and regional (100.1 – 1,000 miles). Average total miles traveled (i.e. travel burden), total number of healthcare encounters, and the distribution of physiologic and oncologic evaluations as drivers of delay in care were examined. Results: Patients were categorized as urban n = 80 (77.7%); rural n = 12 (11.7%); and regional n = 11 (10.7%). Median travel burden (urban = 100 miles [interquartile range, IQR 56-216.8]; rural = 385.7 [127.1 – 769]; regional = 780 [560 – 1936]; p &lt; 0.001) and median total healthcare encounters (urban = 7 [6-9]; rural = 9 [7-9.5]; regional = 10 [7-12]; p = 0.3) increased with greater distance of patient residence from treating medical center. Additional necessary physiologic workup was associated with delayed care and greater burden in the rural and regional patients compared to those residing in urban locations (urban = 21% increase; rural = 152%; regional = 162%). Additional oncologic workup was associated with delayed care in the regional group only (49% increase). These trends remained even when controlling for clinical stage. Conclusions: These findings demonstrate the need for better cancer care coordination for rural and regional lung cancer patients to improve efficiency, appropriateness and timeliness of care while decreasing patient-related burdens.
Long-Term Persistence of Anti-HIV Broadly Neutralizing Antibody-Secreting Hematopoietic Cells in Humanized Mice
Authors: Anne-Sophie Kuhlmann, Kevin G. Haworth, Isaac M. Barber-Axthelm, Christina Ironside, Morgan A. Giese, Christopher W. Peterson, Hans-Peter Kiem
Journal: Molecular Therapy (2018)
Uptake and effectiveness of influenza vaccine in those aged 65 years and older in the United Kingdom, influenza seasons 2010/11 to 2016/17
Authors: Richard G Pebody, Fiona Warburton, Nick Andrews, Mary Sinnathamby, Ivelina Yonova, Arlene Reynolds, Chris Robertson, Simon Cottrell, Muhammad Sartaj, Rory Gunson, Matthew Donati, Catherine Moore, Joanna Ellis, Simon de Lusignan, Jim McMenamin, Maria Zambon
Journal: Eurosurveillance (2018)

BackgroundIn 2016/17, seasonal influenza vaccine was less effective in those aged 65 years and older in the United Kingdom. We describe the uptake, influenza-associated mortality and adjusted vaccine effectiveness (aVE) in this age group over influenza seasons 2010/11-2016/17. Methods: Vaccine uptake in 2016/17 and five previous seasons were measured using a sentinel general practitioners cohort in England; the test-negative case-control design was used to estimate pooled aVE by subtype and age group against laboratory-confirmed influenza in primary care from 2010-2017. Results: Vaccine uptake was 64% in 65-69-year-olds, 74% in 70-74-year-olds and 80% in those aged 75 and older. Overall aVE was 32.5% (95% CI: 11.6 to 48.5); aVE by sub-type was 60.8% (95% CI: 33.9 to 76.7) and 50.0% (95% CI: 21.6 to 68.1) against influenza A(H1N1)pdm09 and influenza B, respectively, but only 5.6% (95% CI: - 39.2 to 35.9) against A(H3N2). Against all laboratory-confirmed influenza aVE was 45.2% (95% CI: 25.1 to 60.0) in 65-74 year olds; - 26.2% (95% CI: - 149.3 to 36.0) in 75-84 year olds and - 3.2% (95% CI: - 237.8 to 68.5) in those aged 85 years and older. Influenza-attributable mortality was highest in seasons dominated by A(H3N2). Conclusions: Vaccine uptake with non-adjuvanted, normal-dose vaccines remained high, with evidence of effectiveness against influenza A(H1N1)pdm09 and B, though poor against A(H3N2), particularly in those aged 75 years and older. Forthcoming availability of newly licensed vaccines with wider use of antivirals can potentially further improve prevention and control of influenza in this group.
Creating value: Institution of outpatient infusional EPOCH-based chemotherapy at a safety-net hospital.
Authors: Arjun Gupta, Mary C. Hon, Neil Keshvani, Eileen M. Marley, David H. Johnson, Navid Sadeghi, Hsiao Ching Li
Journal: Journal of Clinical Oncology (2018)

128 Background: EPOCH-based chemotherapy regimens are traditionally administered inpatient because they include a continuous 96-hour infusion. These admissions are costly, and disruptive to patients’ lives. We transitioned EPOCH-based chemotherapy regimens to an ambulatory infusion model at our safety-net hospital (Parkland Health and Hospital System, Dallas, TX), where patients visit the infusion center daily for 5 days. Methods: Guidelines for chemotherapy administration and educational materials were developed through a multidisciplinary collaboration with physicians, nursing, and pharmacy. Data were collected through chart review and the finance department. Project costs included purchase of portable infusion pumps and increasing outpatient infusion clinic capacity. Patient satisfaction with home infusions compared to hospitalization was measured on a Likert-type scale via direct-to-patient survey. Results: From 1/30/2017 through 1/30/2018, a total of 87 cycles of EPOCH-based chemotherapy were administered to 23 unique patients. 61 (70%) of these cycles were administered in the outpatient setting to 18 unique patients. There was a 58% reduction in drug costs in the outpatient setting due to lower drug acquisition cost. An estimated 336 days of hospital stay were avoided. There were no inappropriate prophylactic antimicrobial prescriptions and daily blood draws in the outpatient setting. 88% of survey responders reported &gt; 3 (scale, 1 to 5) on a Likert-type scale for both overall experience with home infusions, and likelihood they would use home infusions again. No chemotherapy spills or extravasation occurred; 1 cycle was complicated by pump failure where chemotherapy was given at a slower rate than intended. Conclusions: Multiday EPOCH-based regimens were successfully and safely administered in an ambulatory setting at our safety net urban hospital. Patients reported satisfaction with the experience, and received less unnecessary interventions in the outpatient setting. Significant cost savings from avoided hospitalization and decreased drug acquisition cost were demonstrated.
Epacadostat Plus Pembrolizumab in Patients With Advanced Solid Tumors: Phase I Results From a Multicenter, Open-Label Phase I/II Trial (ECHO-202/KEYNOTE-037)
Authors: Tara C. Mitchell, Omid Hamid, David C. Smith, Todd M. Bauer, Jeffrey S. Wasser, Anthony J. Olszanski, Jason J. Luke, Ani S. Balmanoukian, Emmett V. Schmidt, Yufan Zhao, Xiaohua Gong, Janet Maleski, Lance Leopold, Thomas F. Gajewski
Journal: Journal of Clinical Oncology (2018)

Tumors may evade immunosurveillance through upregulation of the indoleamine 2,3-dioxygenase 1 (IDO1) enzyme. Epacadostat is a potent and highly selective IDO1 enzyme inhibitor. The open-label phase I/II ECHO-202/KEYNOTE-037 trial evaluated epacadostat plus pembrolizumab, a programmed death protein 1 inhibitor, in patients with advanced solid tumors. Phase I results on maximum tolerated dose, safety, tolerability, preliminary antitumor activity, and pharmacokinetics are reported.
Abstract 19124: Impaired Mitochondrial Respiration in the Large Cerebral Arteries in Rats With Type 2 Diabetes
Authors: Ivan Merdzo, Ibolya Rutkai, Prasad V Katakam, Catherine A McNulty, Sanjay V Wunnava, David W Busija
Journal: Circulation (2016)

The involvement of mitochondria in the pathophysiology of the metabolic syndrome is unclear. We have previously shown that mitochondrial respiration levels assessed by the Seahorse XFe24 analyzer i...
Abstract 19898: Systemic Nitroglycerin Administration Mitigates the Protective Effects of Inhaled Nitric Oxide During Cardiac Ischemia-Reperfusion
Authors: Ming Wu, Maarten Vanhaverbeke, Piet Claus, Arief Wibowo, Denise Veltman, Hilde Gillijns, Peter Sinnaeve, Peter Pokreisz, Stefan Janssens
Journal: Circulation (2017)

Introduction: Inhaled nitric oxide (iNO) reduces infarct size during experimental myocardial ischemia-reperfusion (I/R). Concomitant intra-arterial administration of nitroglycerin (NTG) during perc...
Improving patient-centered oral chemotherapy at an academic cancer center.
Authors: Charles Henry Lim, Jennifer Petronis, Sabrina Mellor, Monika K. Krzyzanowska
Journal: Journal of Clinical Oncology (2018)

212 Background: Despite established standards for prescribing and monitoring oral anti-cancer medications (OAC) and validated tools supporting OAC patient education, substantial quality gaps remain. Methods: To identify local gaps in care for patients receiving OAC, we used a patient survey in the GI and Endocrine medical oncology clinic. Providers were also interviewed. The survey consisted of 23 questions addressing three domains (treatment plan (T) education, self-management (S) education and health team communication (C) as well as a single question overall satisfaction score. A composite average score encompassing all 23 questions was generated. Questions were derived from ASCO chemotherapy standards and validated patient communication instruments and scored on a 5-point Likert scale. Subsequently, individualized drug-specific written care plans guiding patient education were developed and tested in iterative PDSA cycles. The aim was to improve the composite average patient survey score by 10%. The same patient survey was used to assess the impact of the change ideas. Results: We collected 32 patient surveys, 21 pre- and 11 post-intervention. Baseline surveys indicated lowest scores in the C domain. Providers reported variation in education content and communication techniques used. Care plans with standardized content for 8 OAC agents were tested in simulated and clinic settings in a stepwise fashion, with implementation beginning in Feb 2018. Providers received training on integrating the care plans into clinic workflow. The composite average score for all 23 items improved from 4.18 to 4.29. The single question overall satisfaction score improved from 4.17 to 4.45. Improvement was noted across all 3 domains (T: 4.31 → 4.41, S: 4.26 → 4.36, C: 4.00 → 4.15). For balancing measures, provider teaching time per patient initially rose following implementation before returning to baseline. Conclusions: The intervention led to improvement in the patient experience when starting OAC. Standardized content and a framework guiding provider communication were key elements of the change ideas. To meet the study aim, further PDSA cycles integrating teach back methodology and proactive phone follow up are ongoing.
The effect of 3,3’-diindolylmethane (DIM) on plasma cytokine levels in healthy human subjects
Authors: Cheryl Rockwell, Gregory Reed
Journal: Cancer Research (2008)

504  3,3’-Diindolylmethane (DIM), a spontaneously-formed dimer of indole-3-carbinol (I3C), is the major circulating product following oral administration of I3C to humans. I3C is produced by cruciferous vegetables, including cabbage, cauliflower, and broccoli. Both I3C and DIM have been shown to have chemopreventive effects in a number of different animal models and to promote apoptosis in human tumor cells, supporting investigations of these compounds as potential chemopreventive supplements. Recent studies reported by Xue et al. have shown that DIM stimulates function in isolated murine immune cells and also induces cytokine production in mice in vivo, but the effect of DIM on immune function in humans has not yet been reported. As such, the purpose of the present study was to determine the effect of DIM on plasma cytokine levels in humans. The study agent was nutritional-grade, absorption-enhanced 3, 3’-diindolylmethane,a product of BioResponse, LLC (Boulder, CO). Groups of 4 healthy human subjects, randomized to 3 active DIM and 1 placebo, were orally administered single doses of DIM (50, 100, 150, 200, or 300 mg) after which plasma was collected 12 and 24 hr later (in addition to a baseline plasma sample). The 300 mg dose was repeated in a second group of subjects. Profiling of cytokines and other inflammatory mediators was then performed by multiplex suspension bead array. VEGF, IL-10, IL-13, FGFβ, and GM-CSF levels were largely undetectable at all time points and doses tested. DIM administration had little effect upon TNFα, IL-1β, IL-2, MCP-1, MIP-1β, IL-17, IL-12 (p70), IL-7, IL-5, IL-4, IFNγ, G-CSF, and eotaxin levels, irrespective of dose and/or time points measured. While increased IL-6 levels (2 - 12 pg/ml) were detected 12 hr after DIM administration in nearly half of the subjects who received moderate to high doses (100 - 300 mg), the increases in IL-6 did not correlate with DIM dose or resulting plasma levels. The elevated IL-6 levels detected in the aforementioned individuals also correlated with increased IL-8 plasma levels. Collectively, these data suggest that most cytokines/chemokines are not affected by acute DIM treatment, as measured at 12 and 24 hr after administration, but further studies are needed to fully characterize the overall effects of DIM on cytokine production in humans. Supported by NCI Contract N01-CN-35008.
Are we really good to go? Can we do better?
Authors: Katie Magni, Janet Bagley, Jeffrey Durney, Rachel A Wolfberg, Melissa Perna, Richard Crifasi
Journal: Journal of Clinical Oncology (2018)

251 Background: ASCO/ONS (2016) stated that health care continues to see errors regarding chemotherapy administration. ASHP (2015) recommends that institutions establish checkpoints to ensure that chemotherapy orders are correct. These critical safety checks involve stakeholders on the frontline. The institute uses the pharmacy intervention program to combat this critical need. Pharmacy interventions are reviewed monthly and defined as any medication order that pharmacy reviews and recognizes a discrepancy, requiring follow up. An interdisciplinary workgroup of pharmacists and nurses was established to address pharmacy interventions identified. Methods: The workgroup met over two months to revise the existing medication administration criteria and developed a standardized Good to Go worksheet. A mandatory training video was assigned to infusion nurses. The worksheets were piloted over three weeks and reviewed for completion and notes. Pharmacy interventions were collected prior to and during implementation to track compliance and improvement to patient safety. Nurses and pharmacists were identified as team members. Daily debriefing huddles were held during implementation with feedback incorporated and revisions made to the worksheet for the following day(s). This project was approved by the DFCI IRB as a Quality Improvement Project. Results: The pilot unit had a pharmacy intervention rate of 8.8 % for one week prior to implementation. During week one of the pilot the pharmacy interventions decreased to 4.1% and one month after pilot the rate was 4.6% and 4.7%. The most recent pharmacy interventions were communicated to staff. May data showed a further reduction to 2.8%. Nurses reported feeling better organized and more focused, while pharmacists report less phone calls to infusion. Statements from frontline staff and leadership including the positive results of the pilot were added to the training video. Conclusions: With the positive impact on patient safety, the Good to Go project will be implemented throughout the institute in the summer of 2018. Team members will include infusion nurses and pharmacists from all units. A standardized team approach to chemotherapy administration has the potential to minimize medication errors.
Amino functionalized chiral mesoporous silica nanoparticles for improved loading and release of poorly water-soluble drug
Authors: Xin Wang, Chang Li, Na Fan, Jing Li, Haotian Zhang, Lei Shang, Zhonggui He, Jin Sun
Journal: Asian Journal of Pharmaceutical Sciences (2018)

In the present paper, chiral mesoporous silica nano-cocoon (A-CMSN) functionalized with amino group was synthesized, and its loading and release of indomethacin (IMC), a poorly soluble drug, was studied. Due to the use of chiral anionic surfactants as a template, A-CMSN possessed 2D hexagonal nano-cocoon morphology with curled channels on its surface, which was quite different from another 2D hexagonal mesoporous silica nanoparticles (MCM-41) with straightway channels. After being loaded into the two silica carriers by hydrogen bond, crystalline IMC converted to amorphous form, leading to the improved drug dissolution. And IMC loading capacity of A-CMSN was higher than MCM-41 because curled loading process originating from curvature chiral channels can hold more drug molecules. Compared with IMC, IMC loaded A-CMSN presented obviously fast release throughout the in vitro release experiment, while IMC loaded MCM-41 released faster than IMC at the initial 5 h then showed controlled slow release afterwards, which was closely related to the mesoporous silica nanoparticles and different channel mesostructures of these two carriers. A-CMSN possessed nano-cocoon morphology with curled 2D hexagonal channel and its channel length was shorter than MCM-41, therefore IMC molecules can easily get rid of the constraint of A-CMSN then to be surrounded by dissolution medium.
Phase 1 safety and pharmacokinetic study on the use of pioglitazone in critically ill patients with sepsis: a randomized clinical trial
Authors: Jennifer M. Kaplan, Basilia Zingarelli, Kelli Krallman, Sonya Tang Girdwood, Denise Lagory, Tomoyuki Mizuno, Lin Fei, Hector R. Wong, Alexander A. Vinks
Journal: Intensive Care Medicine (2018)
Outcomes following stereotactic radiosurgery for small to medium-sized brain metastases are exceptionally dependent upon tumor size and prescribed dose
Authors: Fabio Y Moraes, Jeff Winter, Eshetu G Atenafu, Archya Dasgupta, Hamid Raziee, Catherine Coolens, Barbara-Ann Millar, Normand Laperriere, Maitry Patel, Mark Bernstein, Paul Kongkham, Gelareh Zadeh, Tatiana Conrad, Caroline Chung, Alejandro Berlin, David B Shultz
Journal: Neuro-Oncology (2018)

At our institution, we have historically treated brain metastasis (BM) ≤2 cm in eloquent brain with a radiosurgery (SRS) lower prescription dose (PD) to reduce the risk of radionecrosis (RN). We sought to evaluate the impact of this practice on outcomes.We analyzed a prospective registry of BM patients treated with SRS between 2008 and 2017. Incidences of local failure (LF) and RN were determined and Cox regression was performed for univariate and multivariate analyses (MVAs).We evaluated 1533 BM ≤2 cm. Median radiographic follow-up post SRS was 12.7 months (1.4-100). Overall, the 2-year incidence of LF was lower for BM treated with PD ≥21 Gy (9.3%) compared with PD ≤15 Gy (19.5%) (sub-hazard ratio, 2.3; 95% CI: 1.4-3.7; P = 0.0006). The 2-year incidence of RN was not significantly higher for the group treated with PD ≥21 Gy (9.5%) compared with the PD ≤15 Gy group (7.5%) (P = 0.16). MVA demonstrated that PD (≤15 Gy) and tumor size (>1 cm) were significantly correlated (P < 0.05) with higher rates of LF and RN, respectively. For tumors ≤1 cm, when comparing PD ≤15 Gy with ≥21 Gy, the risks of LF and RN are equivalent. However, for lesions >1 cm, PD ≥21 Gy is associated with a lower incidence of LF without significantly increasing the risk of RN.Our results indicate that rates of LF or RN following SRS for BM are strongly correlated with size and PD. Based on our results, we now, depending upon the clinical context, consider increasing PD to 21 Gy for BM in eloquent brain, excluding the brainstem.