tbuckley/cabot-search huggingface dataset:
Best practice alert and cost transparency information for high cost oncology medications.
Authors: Pelin Cinar, Tracy Lin, Kevin Rodondi
Journal: Journal of Clinical Oncology (2018)

323 Background: Oncology medication cost is often absent from therapy decision process until issues arise with payer denial resulting in potential patient financial toxicity. To incorporate cost, Best Practice Alert (BPA) and Cost Transparency Information (CTI) for high cost oncology medication (HCOM) were implemented into prescribing platform as care coordination tools. Methods: Ten HCOM were identified in gastrointestinal (GI) and breast oncology groups for which BPA and CTI were developed. Over a 6 month period, HCOM prescriptions triggered BPAs to alert providers and to place automated referrals to social work (SW). CTI – with drug costs and comparable treatment plan(s) – were posted in prescribing platform. Descriptive analyses examined differences in total payment to hospital and patients out-of-pocket payments (OPP) between treatment plans. Pre- and post-intervention surveys evaluated oncologists’ perception and behavior toward treatment cost. Results: The analysis included 162 patients and 1406 medication claims. In the GI group, BPAs effectively identified treatments incurring higher mean total payment (diff = 46733, p &lt; 0.001) and higher mean OPP (diff = 115, p &lt; 0.001). For the breast group, the impact was mixed. BPAs identified treatments with higher total payment at the 90% quantile (p &lt; 0.001) and higher mean total payment (diff = 72612, p &lt; 0.001), but there was no statistically significant difference in OPP between treatments. Pre-intervention survey (n = 26, 50% response rate) indicated 46% of oncologists rarely discuss medication cost with patients and 35% rarely refer patients to SW. Only 4% of oncologists strongly agreed that they could easily acquire cost information. Post-intervention survey highlighted that CTI improved oncologists’ awareness of medication costs, but BPA exerted no substantial influence on provider behaviors. Conclusions: BPA intervention effectively highlighted treatment cost and accurately identified patients at risk for financial toxicity. The lack of statistically significant difference in oncologists’ behavior and perception may be due to a small sample size. Comments from providers suggest that BPA combined with OPP would be more useful in reducing financial toxicity.
Abstract 10210: Effects of Chronic Treatment With the Phosphodiesterase-5 Inhibitors Sildenafil and Tadalafil on Platelet Aggregation in Patients With Eisenmenger Syndrome
Authors: Nair Y Maeda, Mariana M Clavé, Sonia M Mesquita, Sergio P Bydlowski, Antonio A Lopes
Journal: Circulation (2015)

Background: Patients with pulmonary arterial hypertension (PAH) associated with the Eisenmeger syndrome (ES) frequently have decreased platelet counts and aggregation. This is probably due to chronic endogenous platelet activation and consumption associated with hypoxemia and blood hyperviscosity, with "exhausted" platelets present in circulation. When platelets are analyzed in vitro, decreased response to aggregation inducing agents is generally observed. Purpose: Since phosphodiesterase-5 inhibitors (PDE-5Is) are frequently used in the management of PAH, we investigated, the effects of sildenafil and tadalafil on in vitro platelet aggregation (PA) in adults with ES. Methods: Twenty-three naïve patients aged 28 (22-47) years (median and interquartile range) were randomly assigned to oral treatment with sildenafil (20mg t.i.d., N=11) or tadalafil (single daily dose of 40mg, N=12). Baseline spO 2 , Ht, Hb level and platelet count were 87% (80-92%), 52% (49-60%), 17 (16-20)g/dL and 205 (158-248) x 10 3 pl/μL, respectively. Data were collected at baseline, 90 and 180 days of treatment. Whole blood PA was analyzed by the impedance method. Results are expressed as percent normal. Results: Treatment with PDE-5Is resulted in decrease Ht and Hb level (p&lt;0.001), but no change in platelet count. When patients analyzed as a whole (N=23), ADP-induced PA was 44% (23-91%), 54% (23-87%) and 71% (42-124%) respectively at baseline, 90 and 180 days (p=0.029). Collagen-induced PA was 55% (23-138%), 96% (67-162%) and 146% (62-187%), respectively (p=0.041). When treatment groups were investigated separately at 180 days, collagen-induced PA was 2.7 (1.1-11.1) times baseline in sildenafil-treated patients, and 1.8 (0.6-4.2) times baseline in the tadalafil group. ADP-induced PA was 2.2 (1.3-4.8) times baseline in the sildenafil , but 1.0 (0.7-3.6) time baseline for tadalafil. Conclusion: In ES patients, PDE-5Is therapy is associated with improvement of PA. This may be due to decelerated endogenous platelet activation associated with hemodynamic improvement. However, particularly for sildenafil, some patients may become transiently at a higher risk of thrombotic events, as PA increases far above normal levels.
Advanced care planning and selection of therapy: Influence on hospitalization for patients with metastatic lung cancer.
Authors: Dana Angela Drzayich Jankus, Richard W DeClue, Stephen Stemkowski, Adrianne Waldman Casebeer, Francis Lobo, Bryan A. Loy, Beata Korytowsky
Journal: Journal of Clinical Oncology (2018)

130 Background: Advanced care planning (ACP) allows patients to express preferences for medical treatment toward the end of life. Reduced healthcare resource utilization has been observed with ACP. The association of ACP and hospitalization was assessed among patients who initiated second line (2L) therapy for metastatic non-small cell lung cancer (mNSCLC). Methods: Adults who received 2L treatment for mNSCLC were identified in a retrospective study of claims from Humana Medicare Advantage, following its launch of ACP programs in 2015. In this cohort, patients who participated in ACP programs and patients who did not were matched 2:1 by age, sex, race, population density of residence, and year of 2L termination. Categories of 2L therapy were chemotherapy, immuno-oncology (IO), and targeted therapy. Extent of comorbidity was assessed using the Deyo-Charlson Comorbidity Index (DCCI). The odds of hospitalization in the 12 months following initiation of 2L therapy for patients who participated in ACP programs and patients who did not were assessed with a logistic regression model, offset for patient months of follow-up, and considering therapy category and DCCI. Results: Ninety-eight patients who participated in ACP programs were matched to 196 patients who did not. More than half the cohort was male; median age was 71. There was no difference in therapy category or DCCI by ACP program participation. A greater proportion of patients with no ACP were hospitalized post-2L treatment, 57.7% vs 42.9%, P&lt; 0.001. ACP was associated with a 52.1% decreased odds of hospitalization. Patients treated with IO or targeted therapy had reduced odds of hospitalization, 54.8% and 75.4% respectively, relative to patients treated with chemotherapy. Conclusions: This early assessment of ACP programs in patients with mNSCLC suggests ACP program participants may have fewer hospitalizations near the end of life. Possibly, ACP program participation presents opportunities for staff to identify changes in health status and prevent escalation to hospitalization. Also, because of its potential to reduce hospitalizations, selection of therapy should be considered as a part of ACP.
Abstract 11150: Hyperbaric Oxygenation Enhances Transplanted Cell Graft Survival and Functional Recovery in Critical Limb Ischemia
Authors: Gen Takagi, Masaaki Miyamoto, Sonoko Kirinoki-Ichikawa, Yoshiaki Kubota, Shuhei Tara, Tomohito Hada, Ikuyo Takagi, Wataru Shimizu
Journal: Circulation (2016)

Introduction: One of the major limitations in the application of stem-cell therapy to repair ischemic tissue is the low survival of transplanted cells, possibly due to poor oxygenation. Also the effect of hyperbaric oxygen therapy (HBOT) on bone marrow-derived mesenchymal stem cells (MSCs) is poorly understood. Hypothesis: We hypothesized that HBOT could be used as an adjuvant treatment to augment stem-cell therapy. Therefore, this study aimed to evaluate the effect of HBOT on the engraftment of bone marrow-derived MSCs transplanted in critical limb ischemia (CLI). Methods: Sixty-nine consecutive CLI patients refractory to peripheral revascularization therapy were enrolled. MSC transplantation was performed in all patients. HBOT (given 100% oxygen under 2.8 atmosphere absolute, for 60 min) was administered to 36 patients with and 33 patients without, by 2 weeks after those therapies. These patients were followed up by an outpatient clinic after limb survival. The primary endpoint was tissue oxygen tension of blood flow recovery, and secondary endpoint was adverse event rate (death and major limb amputation), analyzed by intention-to-treat. Results: Mean follow up was 11.4 ± 0.6 years. Limb survival rate was 84.1% and survival was 76.8%. The effect of HBOT was independent of background conditions, such as diabetes and hemodialysis (NS, respectively, Breslow-Day analysis). After 4 weeks, recovery of skin oxygen tension was significantly increased in MSC+HBO group compared to that in MSC group (22.7±16.3 to 34.5±21.4 vs 24.4±15.4 to 28.3±19.6, p = 0.045, odds ratio; 0.194). Surprisingly, in diabetic patients, MSC+HBOT group had significantly lower adverse event rate compared to MSC group (2 vs. 10 cases, p = 0.043, log-rank test, figure). Conclusions: HBOT appears to be a potential and clinically viable non-invasive adjuvant treatment for CLI stem-cell therapy.
Opportunities and Challenges in Cardiovascular Pharmacogenomics
Authors: Dan M. Roden, Sara L. Van Driest, Quinn S. Wells, Jonathan D. Mosley, Joshua C. Denny, Josh F. Peterson
Journal: Circulation Research (2018)

This review will provide an overview of the principles of pharmacogenomics from basic discovery to implementation, encompassing application of tools of contemporary genome science to the field (including areas of apparent divergence from disease-based genomics), a summary of lessons learned from the extensively studied drugs clopidogrel and warfarin, the current status of implementing pharmacogenetic testing in practice, the role of genomics and related tools in the drug development process, and a summary of future opportunities and challenges.
Abstract 16300: Efficacy and Safety of Anticoagulation Following Bioprosthetic Aortic Valve Replacement: A Meta-analysis
Authors: Haris Riaz, Muhammad S Khan, Talha Riaz, Jay Idrees, Irbaz Bin Riaz, Mohammad Q Khan, Vedha Sanghi, Sajjad Raza, Richard Krasuski
Journal: Circulation (2015)

Background: The American College of Cardiology (ACC) guidelines recommend three months of anticoagulation (AC) after replacement of the aortic valve with a bioprosthesis (BP). However, there remains great variability in the current clinical practice and conflicting results from clinical studies. To assist clinical decision making, we pooled the existing evidence to assess whether AC in the setting of a new BP was associated with improved outcomes and/or greater risk of bleeding. Methods: We searched the PubMed database from the inception of these databases until April 2015 to identify original studies (observational studies or clinical trials) that assessed AC with warfarin in comparison with either aspirin or no antiplatelet or anticoagulant therapy. We included the studies if their outcomes included thromboembolism or stroke/transient ischemic attacks (TIA) and bleeding events. Quality assessment was performed in accordance with the Newland Ottawa scale and random effects was used to pool the data from the available studies. I2 testing was done to assess the heterogeneity of the included studies. Results: After screening through 170 papers, a total of 13 studies (cases=6431, controls=18210) were included in the final analyses. Use of warfarin use was associated with a significantly increased risk of overall bleeding (OR= 1.96, 95% CI 1.25-3.08, P&lt;0.0001) or bleeding risk at 3 months (OR= 1.92, 95% CI 1.10-3.34), P&lt;0.0001) compared with aspirin or placebo. With regard to composite primary outcome variables (risk of venous thromboembolism, stroke or TIA) at 3 months, no significant difference was seen with warfarin (OR= 1.13, 95% CI 0.82-1.56, P=0.67). Moreover AC was also not shown to improve outcomes at time interval &gt;3 months (OR= 1.12, 95% CI 0.80-1.58, P=0.79). Conclusion: Contrary to the current guidelines, a meta-analysis of prior studies suggests that AC in the setting of an aortic bioprosthesis significantly increases bleeding risk without a favorable impact on thromboembolic events. Larger, randomized controlled studies should be performed to further guide this clinical practice.
Comparison of health utility values from EQ-5D-3L and EQ-5D-5L in patients with breast cancer in different health states.
Authors: Tiffany Tse, Dongyang Yang, Justine Baek, Mindy Liang, Amy Skitch, Christine Brezden-Masley, M. Catherine Brown, Sofia Torres, Wei Xu, Geoffrey Liu
Journal: Journal of Clinical Oncology (2018)

197 Background: Recently, our group reported Canadian-derived EQ-5D-3L-derived health utility scores for over 20 different cancer sites (PMID: 27567613). However, more recently, a Canadian valuation set for EQ-5D-5L derived health utilities has been reported. As we switch from the 3L to 5L version, we need to evaluate whether the data can be analyzed together across versions, or whether the older cancer valuations need to be replicated. Methods: Breast cancer patients in three health states (primary breast cancer, locoregional recurrence of breast cancer, and metastatic breast cancer) were evaluated using EQ-5D-3L from 2014-2015 and EQ-5D-5L from 2016-2017. Mean (SD) values were compared. We opted not to compare the two versions in the same patients because of recall bias, so we compared two different sets of patients. Results: Of 387 breast cancer patients, 259 (67%) had completed the EQ-5D-5L, while 128 (33%) completed the EQ-5D-3L. The two groups had similar distributions for clinico-demographic data except for ethnicity, where there were more Asian patients in the 5L (22% vs 9%; p &lt; 0.0074). When comparing EQ-5D-5L and EQ-5L-3L within health states, the EQ-5D-5L values were numerically higher for all three health states: for primary breast cancer (mean HUS(SD)/version: 0.85(0.11)/5L vs. 0.81(0.16)/3L) with a p-value of 0.028; locoregional recurrence (0.87(0.08)/5L vs. 0.85(0.20)/5L) with no available p-value due to the small sample size; metastatic disease (0.79(0.15)/5L vs. 0.78(0.13)/3L) with a p-value of 0.78. Histogram distributions appeared different between the two versions. There was greater separation and statistical significance between health states when using the 5L version when compared to the 3L version. The 5L version had a greater variation of values than the 3L, utilizing the entire spectrum of values from 0.0 to 1.0. Conclusions: Though the trends across health states were similar in EQ-5D-5L and EQ-5D-3L health states, values using the 5L were higher and distributions appeared different. There should be extreme caution if considering combining health utility values from 5L and 3L in Canadian breast cancer datasets.
Disability and Access to Care
Authors: Bridget Kuehn
Journal: JAMA (2018)

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The Y Chromosome Regulates BMPR2 Expression via SRY: A Possible Reason “Why” Fewer Males Develop Pulmonary Arterial Hypertension
Authors: Ling Yan, Joy D. Cogan, Lora K. Hedges, Bethany Nunley, Rizwan Hamid, Eric D. Austin
Journal: American Journal of Respiratory and Critical Care Medicine (2018)
Manipulating plant RNA-silencing pathways to improve the gene editing efficiency of CRISPR/Cas9 systems
Authors: Yanfei Mao, Xiaoxuan Yang, Yiting Zhou, Zhengjing Zhang, Jose Ramon Botella, Jian-Kang Zhu
Journal: Genome biology (2018)

The CRISPR/Cas9 system, composed of a single-guide RNA for target recognition and a Cas9 protein for DNA cleavage, has the potential to revolutionize agriculture as well as medicine. Even though extensive work has been done to improve the gene editing activity of CRISPR/Cas9, little is known about the regulation of this bacterial system in eukaryotic host cells, especially at the post-transcriptional level. Here, we evaluate the expression levels of the two CRISPR/Cas9 components and the gene editing efficiency in a set of Arabidopsis mutants involved in RNA silencing. We find that mutants defective in the post-transcriptional gene-silencing pathway display significantly higher Cas9 and sgRNA transcript levels, resulting in higher mutagenesis frequencies than wild-type controls. Accordingly, silencing of AGO1 by introduction of an AGO1-RNAi cassette into the CRISPR/Cas9 vector provides an increase in gene editing efficiency. Co-expression of the viral suppressor p19 from the tomato bushy stunt virus to suppress the plant RNA-silencing pathway shows a strong correlation between the severity of the phenotypic effects caused by p19 and the gene editing efficiency of the CRISPR/Cas9 system for two different target genes, AP1 and TT4. This system has useful practical applications in facilitating the detection of CRISPR/Cas9-induced mutations in T1 plants as well as the identification of transgene-free T2 plants by simple visual observation of the symptom severity caused by p19. Our study shows that CRISPR/Cas9 gene editing efficiency can be improved by reducing RNA silencing in plants.
Transmission of toxigenic Corynebacterium diphtheriae by a fully immunised resident returning from a visit to West Africa, United Kingdom, 2017
Authors: David Edwards, Dianne Kent, Caroline Lester, Colin Stewart Brown, Michael E. Murphy, Nicholas M. Brown, Olajumoke Sule, Alexandra Itani, Meera Chand, Amy Trindall, Callum Pearson, Iain Roddick, Norman K. Fry, Jorg Hoffmann, Nalini Iyanger, Laurence Kemp, Joanne White, Babak Javid, Isobel D. Ramsay, Dominik Zenner, Aliko Ahmed, Gayatri Amirthalingam, Sultan Salimee, David Litt, Mark Reacher
Journal: Eurosurveillance (2018)

In early 2017, a United Kingdom (UK)-born person in their 20s presented with a skin ulcer on the foot 3 weeks after returning from Ghana. The patient had last received a diphtheria-containing vaccine in 2013, completing the recommended course. MALDI-TOF of a cutaneous swab identified Corynebacterium diphtheriae . Real-time PCR ascertained the species and presence of the diphtheria toxin gene. An Elek test confirmed toxigenicity. The isolate was macrolide sensitive and penicillin resistant. The local Public Health England (PHE) Health Protection Team obtained the patient’s clinical history and traced contacts to inform appropriate public health action. One close contact (in their early 80s with uncertain immunisation status who had not recently travelled) had a positive throat swab for toxigenic C. diphtheriae and reported a history of mild coryzal symptoms. Multilocus sequence typing revealed that strains from the index case and contact had Sequence Type 493*. Diphtheria is extremely rare in the UK due to high vaccine coverage and this is the first documented transmission in 30 years. Clinicians and laboratory staff should remain highly suspicious of lesions in overseas travellers, even when patients are fully vaccinated. Older individuals who might not have completed a full immunisation course may have higher diphtheria susceptibility.
Pneumonitis in Non–Small Cell Lung Cancer Patients Receiving Immune Checkpoint Immunotherapy: Incidence and Risk Factors
Authors: Karthik Suresh, Khinh Ranh Voong, Bairavi Shankar, Patrick M. Forde, David S. Ettinger, Kristen A. Marrone, Ronan J. Kelly, Christine L. Hann, Benjamin Levy, Josephine L. Feliciano, Julie R. Brahmer, David Feller-Kopman, Andrew D. Lerner, Hans Lee, Lonny Yarmus, Franco D’Alessio, Russell K. Hales, Cheng Ting Lin, Kevin J. Psoter, Sonye K. Danoff, Jarushka Naidoo
Journal: Journal of Thoracic Oncology (2018)
Experience and outcomes of the Acute Leukemia Shared-Care Program.
Authors: Amanda Wong, Audrey Wong, Cassandra McKay, Bryan Maguire, Mindaugas Mozuraitis, Jonathan Wang, Kim Maki, Sherrie Hertz, C. Tom Kouroukis, Judy Costello
Journal: Journal of Clinical Oncology (2018)

184 Background: Acute leukemia (AL) is a rapidly progressive disease requiring timely and intensive treatment. Historically, care for approximately 50% of AL patients in Ontario, Canada has been centralized resulting in significant resource pressures at the specialized center and travel pressures on patients and caregivers. The AL Shared-Care Program was launched in 2014 to enable delivery of appropriate portions of care at an AL Service Site and Partner Cancer Center closer to the patient’s home. Methods: The impact of the Program was evaluated through provider interviews (n = 22) and the Patient Experience Survey which included 20 non-shared-care (control) and 26 shared-care (intervention) patients. A retrospective analysis of 332 control and 70 intervention patients was used to evaluate the Program’s impact on travel, survival outcomes, and resource utilization. Results: Retrospective analysis revealed that an average intervention group patient saved a median round trip travel distance of 115 km [IQR: 88-179] and time of 91 min [IQR: 62-141]. 91% of health care providers reported that the Program provided person-centered care. Patients reported positive experiences with no statistically significant differences between the intervention and control groups in coordination of care (81% vs 90%, p = 0.39), overall care (88% vs 100%, p = 0.12), and experience (85% vs 90%, p = 0.60). There was no statistically significant correlation between patient satisfaction scores and patient-reported health status (r = 0.10, p = 0.51) and state of health (r = 0.03, p = 0.87). There was no significant difference in survival between groups (HR = 0.73, 95% CI [0.49, 1.13], p = 0.16). Finally, system cost estimated based on emergency department visits, admissions for febrile neutropenia, and follow-up clinic visits showed that there was no statistically significant difference in average monthly cost per patient between the intervention and control groups ($943 vs $1,197 respectively, p = 0.48). Conclusions: The AL Shared-Care Program reduced the travel burden for patients and caregivers without negatively impacting provider and patient experience, survival and system costs. Findings of this work will support the expansion of the Program to additional sites.