tbuckley/cabot-search huggingface dataset:
Dectin-1 Contributes to Myocardial Ischemia/Reperfusion Injury by Regulating Macrophage Polarization and Neutrophil Infiltration
Authors: Qin Fan, Rong Tao, Hang Zhang, Hongyang Xie, Lin Lu, Ting Wang, Min Su, Jian Hu, Qi Zhang, Qiujing Chen, Yoichiro Iwakura, Weifeng Shen, Ruiyan Zhang, Xiaoxiang Yan
Journal: Circulation (2019)

Macrophage-associated immune response plays an important role in myocardial ischemia/reperfusion (IR) injury. Dectin-1, expressed mainly on activated myeloid cells, is crucial for the regulation of immune homeostasis as a pattern recognition receptor. However, its effects and roles during the myocardial IR injury remain unknown. Genetic ablation, antibody blockade, or Dectin-1 activation, along with the adoptive bone marrow transfer chimeric model, was used to determine the functional significance of Dectin-1 in myocardial IR injury. Immune cell filtration and inflammation were examined by flow cytometry, quantitative real-time polymerase chain reaction, and immunohistochemistry. Moreover, Dectin-1+ cells were analyzed by flow cytometry in the blood of patients with ST-segment-elevation myocardial infarction and stable patients with normal coronary artery (control). We demonstrated that Dectin-1 expression observed on the bone marrow-derived macrophages is increased in the heart during the early phase after IR injury. Dectin-1 deficiency and antibody-mediated Dectin-1 inhibition led to a considerable improvement in cardiac function, accompanied by a reduction in cardiomyocyte apoptosis, which was associated with a decrease in M1 macrophage polarization and Ly-6C+ monocyte and neutrophil infiltration. Activation of Dectin-1 with its agonist had the opposite effects. Furthermore, Dectin-1 contributed to neutrophil recruitment through the regulation of Cxcl1 and granulocyte colony-stimulating factor expression. In addition, Dectin-1-dependent interleukin-23/interleukin-1β production was shown to be essential for interleukin-17A expression by γδT cells, leading to neutrophil recruitment and myocardial IR injury. Furthermore, we demonstrated that circulating Dectin-1+CD14++CD16- and Dectin-1+CD14++CD16+ monocyte levels were significantly higher in patients with ST-segment-elevation myocardial infarction than in controls and positively correlated with the severity of cardiac dysfunction. Our results reveal a crucial role of Dectin-1 in the process of mouse myocardial IR injury and provide a new, clinically significant therapeutic target.
Patient-centered cancer care (PCCC) as a roadmap to success in Alternate Payment Model (APM): A case study-based learning.
Authors: Kashyap B. Patel, Natasha Clinton
Journal: Journal of Clinical Oncology (2018)

318 Background: Cancer care is among the fastest-growing segments of the US healthcare system. In the US, total spending on cancer care has increased to $124 billion in 2010. Total costs of cancer care for the US population are predicted to increase across all phases of care. One possible way to reduce overall cost, improve patient experience, and improve outcomes is to shift care away from volume and towards value. Patient-centered cancer care (PCCC) holds the promise of addressing these issues. The Oncology Care Model (OCM), developed by CMS’s Center for Medicare &amp; Medicaid Innovation (CMMI), is a pilot designed to assess the efficacy of PCCC for Medicare beneficiaries over the next 5 years. Our practice participates in the OCM model. We share our practice transformation into PCCC reducing cost, reduce ER visit and improve patient experience. Methods: At CBCCA, we transitioned to PCCC center for accreditation as a Patient Centered Specialty Practice (PCSP) through the National Center for Quality Assurance (NCQA). Our path for PCSP primed us for the OCM with expanded access (including same-day appointments and weekend access), reduced ER visits and hospitalizations. We predicted that transition to PCCC would lower expenses, improve the patient experience, and likely improve outcomes. Based on our projected savings with the delivery of PCCC, we expected CMMI to save about a million dollars. Upon receiving reconciliation reports from CMMI, we were pleased to see that our projections were well within the actual outcomes of savings. Results: Pursuant to our transition to PCCC we were able to reduce ED visits by 40%, hospital stay by 20%, Observation unit stay by 45%, stay in long term care unit by 40% and home health visits by 24%, resulting in overall savings to over $500,000 savings to CMS. Our patient satisfaction survey was in 75% across major parameters. Conclusions: PCCC transition is a viable option for physicians to reduce overall cost, maintain or improve outcomes and patient experience. OCM is the first major initiative that will likely validate journey towards value-based care. Close to 25% of all practices have achieved target savings.
Sleep quality in hematopoietic stem cell transplant recipients and caregivers.
Authors: Priscila Badia Alonso, Victoria Hickey, Laura Flesch, Megan Byerly, Chelsea Sensibaugh, Katherine Potts, Celia Michel, Alisha Drozd, Christopher Eugene Dandoy
Journal: Journal of Clinical Oncology (2018)

165 Background: Sleep is an essential biological function vital for physiological rest, healing and emotional well-being. Sleep disruption, defined as alterations to the normal sleeping patterns, is commonly seen in patients and caregivers with lengthy hospital stays. Sleep disruption in caregivers can lead to increased stress and fatigue, decrease quality of life and ultimately affect the caregiver ability to support their loved one. Methods: We studied through a longitudinal observational cohort study, the quality and quantity of sleep in pediatric patients undergoing hematopoietic stem cell transplant (HSCT) and their caregivers; we identified a high level of sleep disturbance utilizing actigraphy and recounted poor sleep through qualitative assessments. We then performed a cross sectional focus group analysis of patients/caregivers and medical staff to identify the factors associated with poor sleep. The global aim of our quality improvement initiative was to improve sleep quality in HSCT patients and caregivers through a reduction of the nighttime noise (9pm-7am) in the bone marrow transplant unit, from 46 decibels (dB) (mean baseline data) to 38dB (WHO recommends night outside noise of less than 40dB) in a 6 month period. Results: We identified the factors associated with sleep disruption; noisy room entries, overnight trash pulls, loud hallway noise and hospital staff. A simplified failure mode analysis identified four main key drivers; reliable nighttime awareness system, quiet nighttime nursing system, unobtrusive nighttime cleaning process and awareness maintenance system. Several PDSA (plan, do, study, and act) interventions took place and were adopted. After four months the overnight mean dB have decreased to 42dB (9% reduction). Overnight noise spikes above 60dB have decreased from a mean of 271 spikes to a mean of 151 spikes (44% reduction). By September 2018 we expect further decrease in spikes and overnight dB and follow up quantitative and qualitative sleep assessments. Conclusions: With a quality improvement initiative, we identified factors that negatively impact sleep and performed interventions that successfully mitigate these factors, leading to improve quality of sleep in HSCT patients and caregivers.
Letter by Woodard et al Regarding Article, “Exposure to Low-Dose Ionizing Radiation From Cardiac Procedures and Malignancy Risk in Adults With Congenital Heart Disease”
Authors: Pamela K. Woodard, Kathryn J. Lindley, Henry D. Royal
Journal: Circulation (2018)

We read with interest the article by Cohen et al, 1 and we agree that as low as reasonably achievable imaging in all patients, including those with congenital heart disease, is critical to good patient care.However, some flaws with the presented analysis should be considered.First, although the incidence of congenital heart disease surgery in the patients with cancer was less than in the patients without cancer, we do not know what percentage of the surgeries in each arm were Fontan repairs, which over time are associated with a significant increase in cirrhosis and development of hepatocellular carcinomas at a rate of 1.5% to 5.0% per year after Fontan. 2 The authors also do not consider the incidence of transplant procedures in each arm.Patients receiving a transplant have a disproportionately high number of cancers, and differences in the number of patients receiving a transplant in the arms of the study could skew the results. 3The analysis should be corrected for increased incidence of hepatocellular carcinomas in patients undergoing a Fontan procedure and cancers in patients who have had transplant procedures.Moreover, this study does not meet any of the basic requirements for a valid radiation causation study.Basic requirements for a radiation causation study include organ dose assessment (the authors used effective dose), cancer incidence in exposed organs (authors assessed total cancer in each patient), and demonstration of a dose-response curve using organ doses.Thus, it is possible that this article overestimates the risk of cancer caused by imaging in this patient population, which clearly benefits from imaging in terms of surgical planning and follow-up.Moreover, the risk from suboptimal imaging, which may be caused by aggressive radiation-dose management decreasing the quality of the presurgical imaging road map, may indeed be greater than the risk of increased incidence of cancer in these patients.Indeed, thoughtful imaging in this patient population is needed, and the increased use of echocardiography and MRI, which do not expose the patient to ionizing radiation, should be considered.MRI maintains its own risks in repeated gadolinium-based contrast administration 4 and in the sedation of young patients.Overall, keeping in mind that as low as reasonably achievable radiation exposure is critical, patients should receive the quality imaging they need to manage their patient care effectively.
HIV Testing and Risk Behaviors Among Gay, Bisexual, and Other Men Who Have Sex with Men — United States
Authors: Gabriela Paz-Bailey, H. Irene Hall, Richard J. Wolitski, Joseph Prejean, Michelle M. Van Handel, Binh Le, Michael LaFlam, Linda J. Koenig, Maria Corazon Bueno Mendoza, Charles Rose, Linda A. Valleroy
Journal: MMWR Morbidity and Mortality Weekly Report (2013)
Abstract 11585: Long-term Therapy With a Chymase-1 Inhibitor (BAY 1142524) Improves Left Ventricular Systolic Function and Prevents Progressive Chamber Remodeling in Dogs With Heart Failure
Authors: Hani N Sabbah, Ramesh C Gupta, Hanna Tinel
Journal: Circulation (2017)

Introduction: Chymase-1 (CMA1) is a serine protease found in secretary granules of mast cells. When stimulated to de-granulate by an enhanced inflammatory state, as in heart failure (HF), mast cell...
Reducing infusion wait time: Redesigning medication order verification workflow at a comprehensive cancer center.
Authors: Michael D Kearney, Rachel A Wolfberg, Mark Sudol, Shital Shukla, Barbara Fine, Michael S. Rabin, Ursula A. Matulonis, Jing Jing Wang Yakowec, Nancy Hilton, Andrew J. Wagner, Sylvia Bartel, Hakim Lakhani
Journal: Journal of Clinical Oncology (2018)

129 Background: Many factors contribute to long wait times for cancer patients on the day of their infusion. At Dana-Farber Cancer Institute (DFCI), a contributing factor is patient flow between exam and infusion. Order verification affects patient flow and begins when the following two criteria are met: provider signed an order and the patient’s scheduled infusion appointment arrives. Patients often check-in to infusion before their scheduled infusion appointment. Order verification has three sequential steps: nurse verification, pharmacist 1 verify (V1), and pharmacist 2 verify (V2). Methods: A team of pharmacists, nurses, providers, and process improvement leads designed a pilot in which V1 moved before nurse verification, concurrent with patient check-in to infusion. Further, V1 began as soon as an order was signed; the pharmacist did not wait for a patient’s scheduled infusion appointment. Nurse verification and V2 occurred in sequence after V1. Timestamp data were extracted from Epic and analyzed via Tableau to assess reduction in verification throughput, defined as time between infusion check-in and V2. Fourteen providers and one pharmacist joined a 6-week pilot to adopt the redesigned workflow beginning 4/23/18. Results: At baseline, time between check-in and V2 was consistent for pilot and non-pilot orders. During the pilot, time between check-in and V2 was shorter for pilot orders, showing a sustained decrease of approximately 10 minutes. The table below provides time in minutes between infusion check-in and V2 for pilot and non-pilot orders at baseline (3/12/18-4/20/18) and following workflow redesign (4/23/18-6/1/18). Conclusions: Implementing the pilot workflow reduced order verification throughput time and enabled drug preparation to begin sooner. Expanding this workflow to all medication orders can decrease infusion wait time at DFCI.[Table: see text]
Harnessing the electronic health record to optimize oral anticancer therapy monitoring and follow-up.
Authors: Kate Jeffers, Amy Walde
Journal: Journal of Clinical Oncology (2018)

305 Background: UCHealth pursued and became certified as a Quality Oncology Program from the Quality Oncology Practice Initiative (QOPI) through the American Society of Clinical Oncology (ASCO) in 2015. During our gap analysis to prepare for certification, we identified a deficit in our education, monitoring, and follow up relating to oral anti-cancer therapies. Although we used QOPI as a benchmark, we sought to improve patient care and safety in the realm of oral anti-cancer therapies. Methods: UCHealth has implemented policies surrounding oral chemotherapy to include patient education, consent, use of the EHR for ordering, and patient monitoring of adherence and toxicity through development of a flowsheet. This includes the use of Best Practice Alerts (BPA) to trigger staff to evaluate adherence and compliance, smart texts to pull data into progress notes, silent BPAs to remind staff to call patients within 10 days of starting oral chemotherapy, and weekly reporting of staff compliance with assessing patient adherence. Results: EHR changes were implemented in May, 2015 with reporting of staff compliance beginning in September. At that time, UCHealth was only monitoring adherence and toxicity in 24% of patients on an oral anti-cancer therapy. Through continued quality improvement projects, staff education, and optimization of clinical decision support tools, UCHealth consistently monitors adherence and toxicity in over 85% of patients on an oral anti-cancer therapy. Results have been monitored for over two years with continued improvements seen. Conclusions: Using the reporting data, we are able to identify quality improvement projects to include discrete data such as individual staff member compliance. Continuous refinements of the BPA and report have occurred as a result of discrete data analysis by a multi-disciplinary committee.
Treatment patterns, toxicity, and outcomes of elderly patients with advanced pancreatic cancer receiving first-line chemotherapy.
Authors: Robert Kudlovich, Hanbo Zhang, Christina Kim, David Dawe
Journal: Journal of Clinical Oncology (2018)

71 Background: Advanced pancreatic cancer (APC) has a poor prognosis despite treatment with palliative chemotherapy. Randomized trials have demonstrated improved overall survival (OS) with combination chemotherapy including 5-fluorouracil, irinotecan, leucovorin, and oxaliplatin (FOLFIRINOX) or nab-plaxictaxel and Gemcitabine (NG) compared to Gemcitabine (GEM) alone, however, combination therapy is associated with higher rates of toxicity. There is limited data regarding the efficacy and toxicity of FOLFIRINOX, NG, and GEM in elderly patients with APC. Objective: Describe the treatment patterns, toxicity, and outcomes of patients ≥ 65 years of age treated with first-line palliative FOLFIRINOX, NG, or GEM. Methods: Patients ≥ 65 diagnosed with APC from 2012-2016 and treated with palliative chemotherapy in Manitoba were identified from the Manitoba Cancer Registry. Retrospective review identified patients who received first line FOLFIRINOX, NG, or GEM. Patient and treatment characteristics including hematologic and non-hematologic toxicities, dose reductions or delays, tumour response and survival were recorded. Results: 87 patients aged ≥ 65 received palliative chemotherapy: 52 (60%) FOLFIRINOX, 21 (24%) NG, and 14 (16%) GEM, with median ages of 69 (65-84), 75 (65-88), and 73 (67-82), respectively. More patients treated with FOLFIRINOX had an ECOG 0-1 compared to other treatments (p = &lt; 0.001). There was no difference in hematologic toxicity according to treatment group (p = 0.807). There was more non-hematologic toxicity with FOLFIRINOX (p = &lt; 0.001), particularly neuropathy (p = 0.008), fatigue (p = &lt; 0.001), and nausea/vomiting (p = 0.008). Tumour response was highest with FOLFIRINOX (p = 0.005), with a trend towards improved survival compared to NG and GEM (median OS 267 vs 232 and 126 days, respectively, p = 0.057). Conclusions: Many older patients with APC received FOLFIRINOX, with more toxicity, but also greater tumour response and a trend toward improved survival. This suggests that selected elderly patients can tolerate first-line FOLFIRINOX. This may be also due to effective patient evaluation and appropriate assignment to different treatments.
Barriers to Receipt of Prenatal Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis Vaccine Among Mothers of Infants Aged &lt;4 Months with Pertussis — California, 2016
Authors: Sarah New, Kathleen Winter, Rebeca Boyte, Kathleen Harriman, Anya Gutman, Amber Christiansen, Sarah Royce
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Vaccination with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine is recommended for all pregnant women to protect infants who are too young for vaccination from severe pertussis-related outcomes (1-3). However, Tdap vaccine coverage among pregnant women remains suboptimal in California (4). California mothers whose infants developed pertussis in 2016 and their prenatal care providers were interviewed to ascertain possible reasons for low Tdap vaccine coverage. Mothers who were offered Tdap vaccination on-site during a routine prenatal visit were more likely to be vaccinated than were mothers who were referred off-site for vaccination. Mothers insured by Medicaid were less likely to receive Tdap vaccine than were mothers with private insurance, even when the vaccine was stocked on-site. Nearly all vaccinated mothers received Tdap vaccine in their prenatal clinic. Incorporating Tdap vaccination into routine prenatal care visits is an effective means to increase prenatal Tdap vaccination coverage.
Electronic monitoring of patient-reported adherence and symptoms on oral chemotherapy at an academic and a community site.
Authors: Jim Doolin, Daniel Aaron Roberts, Christina Cibotti, Scott M Devlin, Holly Dowling, Virginia Seery, Noah Xavier Tocci, Kelsey Trillo, Danielle Wright, Mary Yenulevich, Jessica A. Zerillo, Meghan Shea
Journal: Journal of Clinical Oncology (2018)

283 Background: Monitoring of toxicity and adherence is often lacking for patients recently started on oral chemotherapy. National guidelines recommend active outreach to patients within a week after treatment start. We developed an online tool to actively reach out to patients newly started on oral chemotherapy at one academic medical center and community practice. Methods: A multi-disciplinary team, including patients, developed an online oral chemotherapy adherence, symptom, and financial toxicity assessment tool within REDCap. We implemented this tool for new oral chemotherapy prescriptions in May 2018 in the gastrointestinal oncology group of an academic medical center and a general community practice. To quantify the impact of this tool on symptom management, we completed a retrospective analysis of patients receiving new oral chemotherapy prescriptions at these same sites, in the 13 months immediately preceding clinical implementation of the online tool, May 2017 to May 2018. Results: In the pre-intervention historical cohort (n = 58) the median time to first symptom assessment by a clinician was 7 days (range 1 – 41 days, SD 7 days), median time to identifying a new or worsening symptom was 10 days (range 1-55 days, SD 10 days), and median time to clinical action regarding a new or worsening symptom was 10 days (range 1-104, SD 20 days). Our first intervention patient used the online tool in May 2018 to report symptoms of “nausea and fatigue,” 4 days after starting oral chemotherapy. This resulted in an oncology clinical nurse calling the patient to review symptom management by phone. Conclusions: The median time to first symptom assessment in our historical control cohort is 7 days, with standard deviation of 7 days, suggesting potential room for improvement. Thus far, the online tool has been completed by one patient. Further data will be reported regarding the uptake of this tool, the tool’s impact on quality measures, and patient reported symptoms, adherence, and financial toxicity.
Prevalence of Variant Reclassification Following Hereditary Cancer Genetic Testing
Authors: Jacqueline Mersch, Nichole Brown, Sara Pirzadeh-Miller, Erin Mundt, Hannah C. Cox, Krystal Brown, Melissa Aston, Lisa Esterling, Susan Manley, Theodora Ross
Journal: JAMA (2018)

<h3>Importance</h3> Variant reclassification is an important component of hereditary cancer genetic testing; however, there are few published data quantifying the prevalence of reclassification. <h3>Objective</h3> Retrospective cohort study of individuals who had genetic testing from 2006 through 2016 at a single commercial laboratory. <h3>Design, Setting, and Participants</h3> A retrospective cohort of individuals who had genetic testing between 2006 and 2016 at a single commercial laboratory was assessed. Variants were classified as benign, likely benign, variant of uncertain significance, likely pathogenic, or pathogenic. Retrospective chart reviews were conducted for patients from the University of Texas Southwestern (UTSW) Medical Center. <h3>Exposures</h3> Hereditary cancer genetic testing. <h3>Main Outcomes and Measures</h3> Frequency of and time to amended reports; frequency and types of variant reclassification. <h3>Results</h3> From 2006 through 2018, 1.45 million individuals (median [interquartile range] age at testing, 49 years [40.69-58.31 years], 95.6% women) had genetic testing, and 56.6% (n = 821 724) had a personal history of cancer. A total of 1.67 million initial tests were reported and 59 955 amended reports were issued due to variant reclassification. Overall, 6.4% (2868 of 44 777) of unique variants were reclassified. Reclassification to a different clinical category was rare among unique variants initially classified as pathogenic or likely pathogenic (0.7%, 61 of 9112) or benign or likely benign (0.2%, 15 of 8995). However, 7.7% (2048 of 26 670) of unique variants of uncertain significance were reclassified: 91.2% (1867 of 2048) were downgraded to benign or likely benign (median time to amended report, 1.17 years), 8.7% (178 of 2048) were upgraded to pathogenic or likely pathogenic variants (median time to amended report, 1.86 years). Because most variants were observed in more than 1 individual, 24.9% (46 890 of 184 327) of all reported variants of uncertain significance were reclassified. <h3>Conclusions and Relevance</h3> Following hereditary cancer genetic testing at a single commercial laboratory, 24.9% of variants of uncertain significance were reclassified, which included both downgrades and upgrades. Further research is needed to assess generalizability of the findings for other laboratories, as well as the clinical consequences of the reclassification as a component of a genetic testing program.