bluuebunny/crossref_metadata_2025 huggingface dataset:
Primary Tr1 cells from metastatic melanoma eliminate tumor-promoting macrophages through granzyme B- and perforin-dependent mechanisms
Authors: Yan Hongxia , Zhang Ping , Kong Xue , Hou Xianglian , Zhao Li , Li Tianhang , Yuan Xiaozhou , Fu Hongjun
Published: April 2017

In malignant melanoma, tumor-associated macrophages play multiple roles in promoting tumor growth, such as inducing the transformation of melanocytes under ultraviolet irradiation, increasing angiogenesis in melanomas, and suppressing antitumor immunity. Because granzyme B- and perforin-expressing Tr1 cells could specifically eliminate antigen-presenting cells of myeloid origin, we examined whether Tr1 cells in melanoma could eliminate tumor-promoting macrophages and how the interaction between Tr1 cells and macrophages could affect the growth of melanoma cells. Tr1 cells were characterized by high interleukin 10 secretion and low Foxp3 expression and were enriched in the CD4+CD49b+LAG-3+ T-cell fraction. Macrophages derived from peripheral blood monocytes in the presence of modified melanoma-conditioned media demonstrated tumor-promoting capacity, exemplified by improving the proliferation of cocultured A375 malignant melanoma cells. But when primary Tr1 cells were present in the macrophage-A375 coculture, the growth of A375 cells was abrogated. The conventional CD25+ Treg cells, however, were unable to inhibit macrophage-mediated increase in tumor cell growth. Further analyses showed that Tr1 cells did not directly eliminate A375 cells, but mediated the killing of tumor-promoting macrophages through the secretion of granzyme B and perforin. The tumor-infiltrating interleukin 10+Foxp3−CD4+ T cells expressed very low levels of granzyme B and perforin, possibly suggested the downregulation of Tr1 cytotoxic capacity in melanoma tumors. Together, these data demonstrated an antitumor function of Tr1 cells through the elimination of tumor-promoting macrophages, which was not shared by conventional Tregs.
The CJEU likes to blame loudly and to applaud quietly: the co-respondent mechanism in the light of opinion 2/13
Authors: Korenica Fisnik , Doli Dren
Published: April 2017

The Draft Accession Agreement (DAA) for the EU’s accession to the ECHR has been found to be incompatible with the EU Treaties by the Court of Justice of the European Union (CJEU). One of the grounds on which the CJEU condemned the Agreement was the design of the co-respondent mechanism. The issue of attributing responsibility to the EU and its Member States for joint violations of the ECHR has been central to the legal debate over the EU’s accession to the ECHR. To this end, this article examines the co-respondent mechanism in light of the findings in Opinion 2/13, considering each of its claims regarding the modes for triggering the co-respondent procedure, the concerns on the joint-responsibility model and the assumed loopholes on the possibility that one of the (co-)respondent(s) withdraw from the procedure before the European Court of Human Rights. The article also presents an analysis to the question of whether the CJEU was right to reject the core provisions of the co-respondent mechanism established by the DAA.
“Stories Take Your Role Away From You”: Understanding the Impact on Health Care Professionals of Viewing Digital Stories of Pediatric and Adolescent/Young Adult Oncology Patients
Authors: Laing Catherine M. , Moules Nancy J. , Estefan Andrew , Lang Mike
Published: April 2017

The purpose of this philosophical hermeneutic study was to understand the effects on health care providers (HCPs) of watching digital stories made by (past and present) pediatric and adolescent/young adult (AYA) oncology patients. Twelve HCPs participated in a focus group where they watched digital stories made by pediatric/AYA oncology patients and participated in a discussion related to the impact the stories had on them personally and professionally. Findings from this research revealed that HCPs found digital stories to be powerful, therapeutic, and educational tools. Health care providers described uses for digital stories ranging from education of newly diagnosed families to training of new staff. Digital stories, we conclude, can be an efficient and effective way through which to understand the patient experience, implications from which can range from more efficient patient care delivery to decision making. Recommendations for incorporating digital storytelling into healthcare delivery are offered.
Leveraging the accelerated processing units for seismic imaging: A performance and power efficiency comparison against CPUs and GPUs
Authors: Said Issam , Fortin Pierre , Lamotte Jean–Luc , Calandra Henri
Published: April 2017

Oil and gas companies rely on high performance computing to process seismic imaging algorithms such as reverse time migration. Graphics processing units are used to accelerate reverse time migration, but these deployments suffer from limitations such as the lack of high graphics processing unit memory capacity, frequent CPU-GPU communications that may be bottlenecked by the PCI bus transfer rate, and high power consumptions. Recently, AMD has launched the Accelerated Processing Unit (APU): a processor that merges a CPU and a graphics processing unit on the same die featuring a unified CPU-GPU memory. In this paper, we explore how efficiently may the APU be applicable to reverse time migration. Using OpenCL (along with MPI and OpenMP), a CPU/APU/GPU comparative study is conducted on a single node for the 3D acoustic reverse time migration, and then extended on up to 16 nodes. We show the relevance of overlapping the I/O and MPI communications with the computations for the APU and graphics processing unit clusters, that performance results of APUs range between those of CPUs and those of graphics processing units, and that the APU power efficiency is greater than or equal to the graphics processing unit one.
Comparison of two sedation protocols for short electroretinography in cats
Authors: Del Sole María J , Nejamkin Pablo , Cavilla Verónica , Schaiquevich Paula , Moreno Laura
Published: April 2017

Objectives

The objectives were to compare two different sedative combinations, xylazine–ketamine and dexmedetomidine–ketamine, for the short electroretinography (ERG) protocol and their impact on sedative effect, reversal times and physiological variables in cats.

Methods

Six healthy spayed female domestic cats were sedated using one of two ketamine-containing protocols: intramuscular xylazine hydrochloride (1 mg/kg) plus ketamine hydrochloride (3 mg/kg) (XK), and dexmedetomidine hydrochloride (5 µg/kg) plus ketamine hydrochloride (3 mg/kg) (DK). A short ERG protocol was recorded from the left eye of each cat under XK and DK sedation. Thirty minutes later, the effects were reversed with yohimbine or atipamezole for the XK and DK treatment, respectively. The cats were evaluated for time to recumbency, time to head elevation, and time to standing position after reversal treatments. Other variables recorded were: systolic blood pressure, cardiac rhythm, heart rate, pulse oximetry and respiratory rate. Recorded ERG variables included a- and b-wave amplitudes and implicit times under photopic, scotopic and scotopic mixed ERG conditions.

Results

Time to lateral recumbency with XK was shorter than for DK ( P <0.05). After reversal, head elevation and standing position times were significantly longer for the XK than the DK group ( P <0.05). Heart rate increased and systolic blood pressure decreased from baseline in both groups ( P <0.05), but there were no significant differences between treatment groups. The b-wave amplitude recorded in the photopic study of cats treated with XK was lower than in animals treated with DK ( P <0.05). No other significant differences in ERG variables were observed between treatment groups ( P >0.05).

Conclusions and relevance

The present study shows that XK and DK treatments are chemical restraint alternatives for ERG recording in cats, with significant differences only in the photopic b-wave amplitude.
Emotions as mediators of the stereotype–discrimination relationship: A BIAS map replication
Authors: Bye Hege H. , Herrebrøden Henrik
Published: April 2017

A central theoretical assumption in the Behaviors from Intergroup Affect and Stereotypes (BIAS) map framework is that emotions mediate the relationships between stereotypes and intergroup behavior. Despite the BIAS map’s popularity, very few studies have tested the model’s mediation hypotheses and none have tested them by replicating the original study (Cuddy, Fiske, & Glick, 2007, Study 1). We provide a replication in a Norwegian sample ( N = 244). The results supported that stereotype content is related to behavior tendencies, mediated through emotional prejudices. However, for each of the four behavior outcomes the effect of stereotype content was mediated through one emotion rather than two as predicted by the BIAS map. Our findings both converge and diverge from those of Cuddy and colleagues, and provide support for theoretical propositions unsupported by the original study. Overall, the study provides empirical support for the BIAS map framework and its cross-cultural validity.
Weber and Simmel on the sociological form (transcription of a round of ‘Sociology, the game’)
Authors: Thériault Barbara , Dion Rosalie
Published: April 2017

In the following transcription, the reader will witness the progress of a board game invented and played by two sociologists. In the round of ‘Sociology, the game’ described here, the two players chose to play two classical sociologists, Max Weber and Georg Simmel. Upon picking question cards relating to different themes (on concepts, writing and methods, among others), they answer with their authors in mind, translating their approach in contemporary language and trying to address some of today’s issues. As the game moves on, the reader will observe that the players engage in a dialogue and seem increasingly concerned with the sociological form and the place of imagination in doing sociology: moving back and forth between each author’s stance and their own concerns as contemporary sociologists, the game helps them at once to bring two different thinkers closer together, and to gain perspective on current issues in doing and writing sociology. The reader will note that the format of the game provides an interesting laboratory of ideas, while not precluding humour and entertainment.
Theorising love in sociological thought: Classical contributions to a sociology of love
Authors: Rusu Mihai Stelian
Published: April 2017

This article sets out to explore the contributions of classical social thinkers to a sociological understanding of love. It builds on the premise that despite its major relevance and consequential importance in shaping both individual lives and the social world, until recently love was a heavily undertheorised topic in the sociological tradition. Moreover, the body of disparate sociological reflections that have been made on the social nature of love has been largely forgotten in the discipline’s intellectual legacy. The article then proceeds in unearthing the classics’ contributions to a sociology of love. It starts with Max Weber’s view that love promises to be a means of sensual salvation in an increasingly rationalised social world based on impersonal formal relationships. Next, it critically examines Pitirim A. Sorokin’s integral theory of love. It then moves to address Talcott Parsons’ view on love as a binding force whose social function is to integrate the conjugal couple of the modern nuclear family in the absence of the external pressures exerted by the kinship network. The article concludes by showing how these conceptualisations of love were all embedded in wider theoretical constructions set up to account for the modernisation process.
Conducting Nursing Research to Advance and Inform Health Policy
Authors: Ellenbecker Carol Hall , Edward Jean
Published: April 2017

The primary roles of nurse scientists in conducting health policy research are to increase knowledge in the discipline and provide evidence for informing and advancing health policies with the goal of improving the health outcomes of society. Health policy research informs, characterizes, explains, or tests hypotheses by employing a variety of research designs. Health policy research focuses on improving the access to care, the quality and cost of care, and the efficiency with which care is delivered. In this article, we explain how nurses might envision their research in a policy process framework, describe research designs that nurse researchers might use to inform and advance health policies, and provide examples of research conducted by nurse researchers to explicate key concepts in the policy process framework. Health policies are well informed and advanced when nurse researchers have a good understanding of the political process. The policy process framework provides a context for improving the focus and design of research and better explicating the connection between research evidence and policy. Nurses should focus their research on addressing problems of importance that are on the healthcare agenda, work with interdisciplinary teams of researchers, synthesize, and widely disseminate results.
Adaptive control of two-wheeled mobile balance robot capable to adapt different surfaces using a novel artificial neural network–based real-time switching dynamic controller
Authors: Unluturk Ali , Aydogdu Omer
Published: April 2017

In this article, a novel real-time artificial neural network–based adaptable switching dynamic controller is developed and practically implemented. It will be used for real-time control of two-wheeled balance robot which can balance itself upright position on different surfaces. In order to examine the efficiency of the proposed controller, a two-wheeled mobile balance robot is designed and a test platform for experimental setup is made for balance problem on different surfaces. In a developed adaptive controller algorithm which is capable to adapt different surfaces, mean absolute target angle deviation error, mean absolute target displacement deviation error and mean absolute controller output data are employed for surface estimation by using artificial neural network. In a designed two-wheeled mobile balance robot system, robot tilt angle is estimated via Kalman filter from accelerometer and gyroscope sensor signals. Furthermore, a visual robot control interface is developed in C++ software development environment so that robot controller parameters can be changed as desired. In addition, robot balance angle, linear displacement and controller output can be observed online on personal computer. According to the real-time experimental results, the proposed novel type controller gives more effective results than the classic ones.
Maximizing safety margins in task-based design of redundant manipulators for cluttered environments
Authors: Singla E. , Singh S. , Dasgupta B.
Published: April 2017

Kinematically redundant manipulators help in handling environmental constraints with extra degrees of freedom, but a large number of links may also lead to significant cumulative errors at the distal end, increasing the likelihood of collisions. The focus of this paper is to synthesize a robot with maximized tolerance to avoid potential collisions, while maneuvering in the workspace. A maximized-tolerance-based method in the design stage provides a significant margin to be utilized further during architectural planning and/or in error compensation against any joint clearance error. This is the main contribution of this paper. The strategy is applicable with even a large number of degrees of freedom. A measure, named as RoboGin, is defined both for a single configuration and for a set of configurations. Maximizing this metric over the large solution space of all robotic parameters provides an optimized design from the reliability perspective. The other requirements related to robot’s reachability at the specified task space locations (TSLs), kinematic conditioning and path connectivity are framed as constraints in the formulated optimization problem. The global solutions computed through a simulated annealing technique show significant improvements in overall safety margins even in highly cluttered environments and with a large number of links. Implementation of the proposed strategy is demonstrated through realistic cluttered environments of a power plant, for a leakage testing application.
Exposure to advertising and perception, interest, and use of e-cigarettes among adolescents: findings from the US National Youth Tobacco Survey
Authors: Pu Jia , Zhang Xiao
Published: April 2017

Objective:

US adolescents are exposed to high levels of advertisements for electronic cigarettes (e-cigarettes). This study aimed to examine the associations between exposure to e-cigarette advertisements and perception, interest, and use of e-cigarettes among US middle school and high school students.

Methods:

Data from the 2014 cross-sectional National Youth Tobacco Survey were used. Logistic regressions were conducted to model four outcomes, including perception of reduced harmfulness compared to regular cigarettes, perception of reduced addictiveness, intention to use, and current use of e-cigarettes. Main predictors were exposure to e-cigarette advertisements via four sources, including Internet, newspaper/magazines, retail stores, and TV.

Results:

When all the four sources of e-cigarette advertisements exposure were evaluated jointly, exposure via the Internet was associated with elevated likelihood of reporting all four outcomes related to e-cigarettes, while exposure via retail stores was associated with higher likelihood of current e-cigarette use and perception of reduced harmfulness of e-cigarettes compared to regular cigarettes ( p < .05). However, exposure via newspaper/magazines and TV was associated with lower likelihood of perceiving e-cigarettes to be less harmful or addictive ( p < .05).

Conclusion:

Exposure to e-cigarette advertisements via the Internet and retail stores may play a significant role in adolescents’ use and perception of e-cigarettes. The results call for more research on the influence of different sources of advertising exposure on e-cigarette use to help public health programmes curtail the fast growing use of e-cigarette products among youth.
Bacterial infections in acute variceal hemorrhage despite antibiotics—a multicenter study of predictors and clinical impact
Authors: Lee Stephen , Saxinger Lynora , Ma Mang , Prado Verónica , Fernández Joaquin , Kumar Deepali , Gonzalez‐Abraldes Juan , Keough Adam , Bastiampillai Ravin , Carbonneau Michelle , Fernandez Javier , Tandon Puneeta
Published: April 2017

Background and aims

Current guidelines recommend antibiotic prophylaxis in all patients presenting with cirrhosis and acute variceal hemorrhage (AVH). We aimed to evaluate the characteristics and clinical impact of “early” infections (developing within 14 days) of AVH in a real‐world setting.

Methods

We analyzed retrospective data from a cohort of 371 adult patients with cirrhosis and AVH all of whom had received antibiotic prophylaxis (74% men; mean age 56 years), admitted to tertiary care hospitals in Edmonton, Alberta, Canada, and Barcelona, Spain. Sensitivity analyses were presented for culture‐positive (confirmed) infections.

Results

The mean MELD was 16. Fifty‐two percent of patients received quinolones, 45% third‐generation cephalosporins and 3% other antibiotics. Fourteen percent (51/371) developed an infection within 14 days of AVH. Seventy‐five percent of infections were culture positive and occurred at a mean of six days from AVH. When all infections were considered, respiratory infections were the most common (53%) followed by urinary tract infections (17%) and bacteremia (16%). Resistance patterns differed between countries. Outpatient antibiotic prophylaxis (OR 5.4) and intubation (OR 2.6) were independent predictors of bacterial infection. Bacterial infection (OR 2.6) and the MELD (OR 1.2) were independent predictors of six‐week mortality.

Conclusions

Early bacterial infections develop in 14% of cirrhotic patients with AVH despite antibiotic prophylaxis, and have a negative impact on six‐week mortality. Intubation and outpatient antibiotic prophylaxis are associated with increased risk of early bacterial infections. Patients at risk should be followed closely with prompt infection workup and local antibiogram‐based expansion of antibiotic therapy in case of clinical decline.
Impact of Bubble Packaging on Adherence to Long-Term Oral Medications Used to Prevent Cardiovascular Disease
Authors: Shah Surbhi , Galdo John , Cox Elizabeth D. , Moreno Megan A. , Young Henry N.
Published: April 2017

Background: Adherence to long-term pharmacotherapy is problematic in the United States. Bubble packaging of medications has been touted to improve patients’ use of medications. Scant research has assessed bubble packaging’s impact on adherence to multiple medications. Objective: To compare medication adherence between patients receiving medications to address cardiovascular disease risk factors in bubble packages to those receiving medications in pill bottles. Methods: This retrospective cohort study utilized prescription dispensing records from an independent pharmacy. Patients receiving statins, β-blockers, angiotensin-converting enzyme inhibitors, or oral hypoglycemic agents were identified and grouped into those who received medications in bubble packages and those received medications in pill bottles. Adherence was assessed with medication possession ratios. Patients were classified as adherent if their medication possession ratio was 80% or more. Results: Receiving medications in bubble packaging was significantly associated with greater adherence compared to pill bottles ( P < .001). In adjusted models, greater numbers of medications filled ( P = .024) and increasing patient age ( P = .018) were significantly associated with low adherence, while bubble packaging was not ( P = .13). Stratified analyses revealed that bubble packaging was significantly associated with greater adherence when 4 or fewer medications are filled ( P = .012) and for patients between 18 and 44 years of age ( P = .023). Conclusion: Bubble packages can improve medication adherence. However, they may not resolve complex issues contributing to the problem of nonadherence, especially for older patients and those prescribed multiple medications.
Brazilian Society for Food and Nutrition position statement: nutrigenetic tests
Authors: Cominetti Cristiane , Horst Maria Aderuza , Rogero Marcelo Macedo
Published: April 2017

Position statement: The Brazilian Society for Food and Nutrition (SBAN) bases the following position statement on a critical analysis of the literature on nutritional genomics and nutrigenetic tests: (1) Nutrigenetic tests are predictive and not diagnostic, should not replace other evaluations required to treatment, and should only be used as an additional tool to nutritional prescription; (2) Nutritionists/registered dietitians and other health professionals must be able to interpret the nutrigenetic tests and properly guide their patients, as well as build their professional practice on general ethical principles and those established by regulatory authorities; (3) It is extremely important to highlight that the misinterpretation of nutrigenetic tests can cause psychological and health problems to the patient; (4) Currently, there is insufficient scientific evidence for the recommendation of dietary planning and nutritional supplementation based only on nutrigenetic tests. This position statement has been externally reviewed and approved by the board of SBAN and has not gone through the journal’s standard peer review process.
Death Within 1 Month of Diagnosis in Childhood Cancer: An Analysis of Risk Factors and Scope of the Problem
Authors: Green Adam L. , Furutani Elissa , Ribeiro Karina Braga , Rodriguez Galindo Carlos
Published: April 2017

Purpose

Despite advances in childhood cancer care, some patients die soon after diagnosis. This population is not well described and may be under-reported. Better understanding of risk factors for early death and scope of the problem could lead to prevention of these occurrences and thus better survival rates in childhood cancer.

Methods

We retrieved data from SEER 13 registries on 36,337 patients age 0 to 19 years diagnosed with cancer between 1992 and 2011. Early death was defined as death within 1 month of diagnosis. Socioeconomic status data for each individual’s county of residence were derived from Census 2000. Crude and adjusted odds ratios and corresponding 95% CIs were estimated for the association between early death and demographic, clinical, and socioeconomic factors.

Results

Percentage of early death in the period was 1.5% (n = 555). Children with acute myeloid leukemia, infant acute lymphoblastic leukemia, hepatoblastoma, and malignant brain tumors had the highest risk of early death. On multivariable analysis, an age younger than 1 year was a strong predictor of early death in all disease groups examined. Black race and Hispanic ethnicity were both risk factors for early death in multiple disease groups. Residence in counties with lower than median average income was associated with a higher risk of early death in hematologic malignancies. Percentages of early death decreased significantly over time, especially in hematologic malignancies.

Conclusion

Risk factors for early death in childhood cancer include an age younger than 1 year, specific diagnoses, minority race and ethnicity, and disadvantaged socioeconomic status. The population-based disease-specific percentages of early death were uniformly higher than those reported in cooperative clinical trials, suggesting that early death is under-reported in the medical literature. Initiatives to identify those at risk and develop preventive interventions should be prioritized.
Use of Adjuvant Bisphosphonates and Other Bone-Modifying Agents in Breast Cancer: A Cancer Care Ontario and American Society of Clinical Oncology Clinical Practice Guideline
Authors: Dhesy-Thind Sukhbinder , Fletcher Glenn G. , Blanchette Phillip S. , Clemons Mark J. , Dillmon Melissa S. , Frank Elizabeth S. , Gandhi Sonal , Gupta Rasna , Mates Mihaela , Moy Beverly , Vandenberg Ted , Van Poznak Catherine H.
Published: April 2017

Purpose

To make recommendations regarding the use of bisphosphonates and other bone-modifying agents as adjuvant therapy for patients with breast cancer.

Methods

Cancer Care Ontario and ASCO convened a Working Group and Expert Panel to develop evidence-based recommendations informed by a systematic review of the literature.

Results

Adjuvant bisphosphonates were found to reduce bone recurrence and improve survival in postmenopausal patients with nonmetastatic breast cancer. In this guideline, postmenopausal includes patients with natural menopause or that induced by ovarian suppression or ablation. Absolute benefit is greater in patients who are at higher risk of recurrence, and almost all trials were conducted in patients who also received systemic therapy. Most studies evaluated zoledronic acid or clodronate, and data are extremely limited for other bisphosphonates. While denosumab was found to reduce fractures, long-term survival data are still required.

Recommendations

It is recommended that, if available, zoledronic acid (4 mg intravenously every 6 months) or clodronate (1,600 mg/d orally) be considered as adjuvant therapy for postmenopausal patients with breast cancer who are deemed candidates for adjuvant systemic therapy. Further research comparing different bone-modifying agents, doses, dosing intervals, and durations is required. Risk factors for osteonecrosis of the jaw and renal impairment should be assessed, and any pending dental or oral health problems should be dealt with prior to starting treatment. Data for adjuvant denosumab look promising but are currently insufficient to make any recommendation. Use of these agents to reduce fragility fractures in patients with low bone mineral density is beyond the scope of the guideline. Recommendations are not meant to restrict such use of bone-modifying agents in these situations. Additional information at www.asco.org/breast-cancer-adjuvant-bisphosphonates-guideline , www.asco.org/guidelineswiki , https://www.cancercareontario.ca/guidelines-advice/types-of-cancer/breast .
Differences in Treatment Effect Size Between Overall Survival and Progression-Free Survival in Immunotherapy Trials: A Meta-Epidemiologic Study of Trials With Results Posted at ClinicalTrials.gov
Authors: Tan Aidan , Porcher Raphael , Crequit Perrine , Ravaud Philippe , Dechartres Agnes
Published: April 2017

Purpose

We aimed to compare treatment effect sizes between overall survival (OS) and progression-free survival (PFS) in trials of US Food and Drug Administration–approved oncology immunotherapy drugs with results posted at ClinicalTrials.gov .

Methods

We searched ClinicalTrials.gov for phase II to IV cancer trials of Food and Drug Administration–approved immunotherapy drugs and selected those reporting results for both OS and PFS. For each trial, we extracted the hazard ratios (HRs) with 95% CIs for both outcomes and evaluated the differences by a ratio of HRs (rHRs): the HR for PFS to that for OS. We performed a random effects meta-analysis across trials to obtain a summary rHR. We also evaluated surrogacy of PFS for OS by the coefficient of determination and the surrogacy threshold effect, the minimal value of HR for PFS to predict a non-null effect on OS.

Results

We identified 51 trials assessing 14 drugs across 15 conditions. Treatment effect sizes were 17% greater, on average, with PFS than with OS (rHR, 0.83; 95% CI, 0.79 to 0.88; I2 = 34.4%; P = .01; τ2 = 0.0129). Nearly one half of the trials (n = 23, 45%) showed statistically significant benefits for PFS but not for OS. Differences were great for trials of obinutuzumab (rHR, 0.21; 95% CI, 0.08 to 0.54), bevacizumab (rHR, 0.75; 95% CI, 0.67 to 0.84), and rituximab (rHR, 0.79; 95% CI, 0.64 to 0.98). The coefficient of determination was 38% and the surrogacy threshold effect was 0.50.

Conclusion

Treatment effect sizes in trials of immunotherapy drugs were greater for PFS than for OS, with important differences for some drugs, which is consistent with surrogacy metrics. Caution must be taken when interpreting PFS in the absence of OS data.
Can a web-based tracking and feedback tool improve breast cancer care at safety-net hospitals?
Authors: Bickell Nina A. , Castaldi Maria , Shah Ajay , Sickles Alan , Lewis Theophilus , Arora Shalini , Clarke Kevin , Pappas Peter J , Kemeny Margaret , Srinivasan Anitha , Franco Rebeca , Fei Kezhen , Parides Michael , McAlearney Ann Scheck
Published: April 2017

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Background: System failures, a cause of underuse in which doctors order care, patients don’t refuse but care doesn’t ensue, tend to happen more at safety net hospitals (SNH). Tracking & follow-up approaches that close referral loops in SNHs may reduce underuse. In a randomized trial, we tested a Tracking & Feedback (T&F) tool to reduce underuse of adjuvant breast cancer treatment. Methods: We recruited 5 community & 5 municipal SNHs that serve a large proportion of minorities in the NYC metropolitan area. We implemented rapid case ascertainment, a T&F tool and trained point persons at each site to determine if women with newly operated stage 1-3 breast cancer, connected with the oncologist since such connections are associated with getting treated. The tool created a daily “to do” reminder for point persons to ascertain if patients were seen by the oncologist. Point persons then relayed this information to surgeons to follow through as they deemed necessary. Underuse includes: no RT after lumpectomy or mastectomy with > 4 positive nodes; no chemo for HR- and no hormonal therapy for HR+ tumors > 1cm; no trastuzumab for Her2+ tumors. We interviewed key informants about tool usefulness. We conducted intention to treat and pre-post analyses to assess tool and implementation effectiveness, respectively. Results: Pre-intervention, despite randomizing hospitals, intervention (INT) hospitals had fewer whites (4% vs 14%; p = 0.0005), poorer follow-up approaches (0.68 vs 0.80; p = 0.07), less Medicaid & uninsured patients (36% vs 62%; p < .0001) and more underuse (28% vs 15%; p = 0.002) compared to control (CNTL) hospitals; comorbidities and stage were similar. The RCT found no difference in underuse rates (9% at INT & 11% at CNTL hospitals; p = 0.8). Because randomization did not result in equivalent distributions, we modeled pre- (N = 403) and post (N = 191) populations controlling for time period and clustering & found that hospitals with better follow-up (OR = 0.82; 95% CI: 0.71-0.96) had less underuse. In settings with poor follow-up & tracking approaches, key informants found the tool useful. Conclusions: While the RCT findings were negative, they suggest a T&F tool may help reduce underuse in SNHs with poor follow-up capabilities. Clinical trial information: NCT01544374.
Addressing risk of financial toxicity in an ambulatory oncology practice: Our institutional experience with the ASCO Quality Training Program.
Authors: Hensing Thomas A. , Bauer Tyler , Palafox Anna , Whalen Margaret , Carro George W.
Published: April 2017

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Background: Due to escalating cost of cancer care, patients (PTs) with cancer are at increased risk for financial toxicity (FTOX) that can exacerbate disparities in care and lead to clinically relevant adverse PT outcomes; including quality of life; symptom burden; adherence; and survival. A review of our informed consent (IC) process demonstrated that PTs were not routinely informed of financial risks of high-cost (HC) cancer therapies at the time of IC. Methods: A multidisciplinary team was formed to conduct a rapid-cycle quality improvement project with the aim of reducing FTOX through improvement in patient education at the time of IC. Because of HC and increased utilization, the initial pilot focused on treatment with immune checkpoint inhibitors (ICI). A cause and effect diagram identified the potential causes that FTOX was not addressed during the IC process. Diagnostic data were obtained through staff surveys and querying our EMR from June to August, 2016. A Pareto chart identified lack of educational (ED) tools at the time of IC and a poorly understood prior authorization (PA) process as the most common causes for not addressing risk of FTOX during IC. Plan-do-study-act (PDSA) #1 began with development of a PT ED tool to be used during IC. The tool was approved by the Patient Advisory Board. Staff from clinical teams utilizing ICI for approved indication completed training on its use and a pilot study was initiated. PDSA#2 focused on optimizing the PA process and PDSA#3 focused on PT distress and FTOX monitoring through the NCCN distress and a validated patient-reported-outcome tools (COST), respectively. Results: The utilization of the PT ED tool reached the project aim (administer to > 65% of pts during IC) during initial phase of PDSA#1, although accrual is ongoing. A revised PA process (PDSA#2) was developed, staff were educated and the updated PA process was initiated. Work on PDSA#3 is ongoing. Conclusions: This QI project suggests that it is feasible to address FTOX through PT ED during IC for HC cancer therapies. However, the impact of this intervention on PT distress, overall FTOX and treatment disparities will need to be monitored closely.
Faster and better: Improving the diagnostic phase of lung cancer at a system level.
Authors: Kaan Melissa , Holloway Claire , Gilbert Julie , Simanovski Vicky , Matheson Garth
Published: April 2017

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Background: For many patients going through diagnostic testing for cancer, the time from suspicion to diagnosis or rule-out, can be a confusing and anxious time. In 2007, Cancer Care Ontario began investing in the implementation of diagnostic assessment programs (DAPs) across Ontario, Canada to improve the quality of care during the diagnostic phase of lung cancer. DAPs consist of multidisciplinary healthcare teams that manage and coordinate a patient’s diagnostic care from testing to a definitive diagnosis. The objectives of the DAPs are to: 1) decrease time from suspicion to diagnosis or resolution; 2) optimize the patient’s experience during the diagnostic process; 3) optimize satisfaction and experience among primary care providers and specialists; and 4) provide a sustainable solution by offering good value for money. Today over 35,000 patients have been diagnosed in one of the 18 lung DAPs that exist across the province. Methods: The implementation of DAPs featured the introduction of a patient navigator to act as the primary point of contact for patients, improve the patient experience and ensure their patients were progressing through any required diagnostic imaging and consultations in a timely manner. Cancer Care Ontario also engaged with primary care providers to refer patients with findings suspicious for lung cancer to DAPs as early as possible to ensure they benefited from organized assessment. Cancer Care Ontario has collected patient level data to measure wait times and implemented a patient survey to assess patient experience. Results: In the past five years, the median wait time from referral to a lung DAP to diagnosis or rule out has decreased by 19% to 24 days and the 90th %tile has decreased by 28% to 51 days. The large majority of patients have had a positive experience with their DAPs, with 95% of patients scoring their experience in the diagnostic process as “good” or “excellent”. Conclusions: The implementation of DAPs across the province is seen as a valuable component of quality of care by improving the diagnostic phase of cancer. The sustainability of the DAP model is demonstrated by the continued improvements in access and maintained patient experience in spite of growing volumes (91% increase in the past five years).
Trends in survival and costs among U.S. patients with multiple myeloma.
Authors: Maiese Eric , Evans Kristin , Chu Bong-Chul , Irwin Debra E.
Published: April 2017

12

Background: Survival among patients with multiple myeloma (MM)has improved over time, but little is known about concurrent changes in health care costs. This study examined trends in both survival and health care costs over the same time periods in U.S. patients with MM. Methods: The MarketScan Commercial and Medicare claims dataset was used to identify 5199 adult patients diagnosed with MM from Jan. 2006 to Dec. 2014. Patients had no prior evidence of cancer, were continuously enrolled for ≥ 12 months prior to MM diagnosis, and were followed through the earliest event (death, end of enrollment, or end of the study period (9/30/2015)). Multivariate GLM and Cox proportional hazards models estimated health care costs and survival probabilities, respectively, for two time periods during which patients were diagnosed with MM (2006-2010 vs. 2011-2014) while controlling for demographic and clinical characteristics. The recycled prediction method was used to calculate the incremental cost estimates between the time periods. Results: Patients diagnosed in 2011-2014 had a 35% lower risk of death compared to those diagnosed in 2006-2010 (HR [95% CI] = 0.65 [0.57-0.74]). Patients diagnosed in 2011-2014 had 18% (95% CI: 6-31%) higher all cause and 26% (95% CI: 6-50%) higher MM-related per patient per month costs compared to those diagnosed in 2006-2010 (see table). Conclusions: Among patients with MM, survival has improved at a greater rate than the increase in health care costs. In addition to improvements in MM treatment, changes in overall disease management may have contributed to both the increased expenditures and survival improvements observed in this study.[Table: see text]
Right patient, right appointment, right provider at the right time.
Authors: Roy Megan , Fanslau Katie , Malloy Maria , Sweeney Suzanne , Miller Eleanor , Rummel Margaret
Published: April 2017

125

Background: Patients with a suspicious scan or confirmed cancer diagnosis are anxious to be seen by an oncology provider. It’s important that patients are scheduled to see the most appropriate providers in the right order and timing for their clinical needs. At one large academic medical center, where patient volumes are high, the system is complex, and patients often travel. It was identified that patients were being scheduled out of order, had incomplete information, or could have been scheduled with improved timing and with additional support. This occurred in multiple disease sites. Methods: Based on this assessment, a process has been initiated to where the intake forms completed on each new patient scheduled are routed to the oncology nurse navigators via the electronic medical record. The nurse navigators then reach out to the patient prior to their appointment to further triage their needs, identify barriers and provide education and additional resources. Results: This intervention, while in early stages, has improved nurse navigator involvement with the new oncology patients to ensure they are set up appropriately, with accurate information, and has decreased providers scrambling to add patients on the same day. Outcomes from the navigator’s assessment can include any of the following: leave the appointment as is, reschedule it with the same or different provider, coordinate with another provider, or add additional information to the chart as the patient’s story evolves. Regardless, the patient receives an introduction to the nurse navigator, education, and support prior to being seen. Conclusions: By identifying an area where nurse navigators can improve patient care processes, patients are now able to get personalized assessment and appropriate appointments, no matter how they present to the cancer center. Not only are patients able to be seen by the most appropriate provider at correct timing, but the assessment for clinical needs and barriers to care can be addressed proactively. This wouldn’t be possible without the collaboration of staff and providers, willing and eager to improve the process for patient care.
ONCOPRE: A new chemotherapy benefit prediction model to assist treatment decision making.
Authors: Yusuf Dimas , Ho Maria Yi , Cheung Winson Y.
Published: April 2017

126

Background: Clinical decision support tools (CDSTs) can help physicians make complex treatment decisions and inform care. For colon cancer, CDSTs such as Adjuvant! Online and Numeracy were widely used to estimate the effects of adjuvant treatment and guide conversations with patients. Existing CDSTs, however, do not consider more contemporary predictive and prognostic factors, such as microsatellite instability (MSI), BRAF mutational status, or the presence of additional high risk clinical or pathological features (HRFs), in their assessment of outcomes. Current CDSTs are also not optimized for handheld devices. Methods: We developed ONCOPRE, which is an adjuvant chemotherapy benefit calculator for colon cancer that addresses the limitations of current CDSTs. Based on a comprehensive review of epidemiological data and results of landmark trials, ONCOPRE was devised to predict 5 year colon cancer recurrence and death. To validate ONCOPRE, we compared its predictions with those generated by existing CDSTs as well as real-world data from 7 tertiary cancer centers across Canada. Results: ONCOPRE is able to predict 5-year DFS and OS of patients with colon cancer based on age, sex, TNM status, and contemporary risk factors such as MSI status, BRAF mutations, and other HRFs. ONCOPRE’s predictions compare favorably with real-world data and predictions from other CDSTs. ONCOPRE’s predictions are typically more optimistic than historical outcomes, and this likely reflects the fact that current day colon cancer patients experience better prognosis with the use of modern therapy and improved supportive care. These attributes make ONCOPRE a potentially new benchmark among CDSTs that can reliably predict colon cancer outcomes. Conclusions: ONCOPRE ( http://www.oncopre.com/ ) represents a new CDST that can assist in adjuvant treatment decision-making and patient counseling. We make the case that the next generation of CDSTs in oncology must take into account more contemporary clinical, biochemical, and genetic risk factors since these elements significantly affect outcomes. The ONCOPRE platform serves as a potential model on which to develop prediction tools for other forms of cancers.
Use of a comparative database to identify excessive hematology/medical oncology hospital days and readmissions.
Authors: Halbert Brian , Zerillo Jessica A.
Published: April 2017

131

Background: Reducing length of stay and readmissions are important goals to improve healthcare quality and decrease costs. We identified diagnostic categories accounting for excessive hospital days and readmissions on our hematology/medical oncology (HO) service. Methods: We used a third-party comparative clinical database (Vizient Inc, Clinical Data Base/Resource Manager) to identify discharges from our HO service in 2015. Cases were categorized by All Patients Refined Diagnosis Related Groups (APR DRG), and we calculated excess hospital days attributed to each using the number of cases and their observed/expected length of stay. We also collected 30-day readmission rates for each APR DRG on our HO service and hospital wide. Readmission rates were compared using Fisher exact tests. Results: We identified 1,361 discharges from our HO service with 134 APR DRG codes and 880.5 excess hospital days. Fourteen APR DRGs accounted for over 80% of the excess hospital days. Readmission rates ranged from 0% to 66.7%, and were generally higher than rates hospital wide. Readmissions for septicemia and major operating room (OR) procedures for lymphatic neoplasms were significantly higher on the HO service. Conclusions: Relatively few APR DRGs accounted for the majority of our excess hospital days, and also had high readmission rates. We will conduct additional review of these APR DRGs to identify opportunities to improve quality and reduce cost. [Table: see text]
An EPIC electronic decision support tool to identify percentage of patients with stage IV thoracic or gastrointestinal malignancy who would benefit from concurrent palliative care but do not currently receive it.
Authors: Adelson Kerin B. , Trant Amelia Anne , Framski Kim , Swidler Mark , Kashyap Nitu
Published: April 2017

133

Background: In 2016 ASCO updated its guideline for early integration of palliative care (PC) into standard oncologic care for all “inpatients and outpatients with advanced cancer.” PC has been shown to improve quality of life, align care at the end of life with patient preferences, and reduce health-care utilization. In preparation for the expansion of our palliative care service into ambulatory disease-based practices at Smilow Cancer Hospital at Yale-New Haven, we sought to create a decision support tool (DST) in the EPIC Electronic Health Record (EHR) that would identify patients for PC referral. Methods: This DST identifies patients with a GI or thoracic malignancy who have had an ICD-10 diagnosis of metastatic or stage IV disease, have not had a palliative care visit in the last 6 months, and are not enrolled in hospice. If the patient meets criteria, the DST will remind providers that “this patient meets ASCO and IOM criteria for concurrent palliative care with oncologic care ” and offers a one-click option to place the referral. To understand the volume of patients this DST would refer, we ran it silently in the EHR background from 7/15/16 through 9/1/16. We tracked how many patients were seen in the clinics, how many were eligible, and how many were referred to PC. Results: See table. Conclusions: Our silent BPA indicated that only 5% of patients eligible for a palliative care consult received it at baseline; this matches national data, which suggests that most patients who would benefit from PC do not receive it. This DST has the potential to dramatically improve PC referral rates and increase adherence with ASCO and IOM guidelines. We plan to move the DST into the live clinical EHR in 2017 after the integrated PC clinics are open. We anticipate that once our BPA is activated, we will see a dramatic increase in the number of eligible patients referred to palliative care. [Table: see text]