tbuckley/cabot-search huggingface dataset:
A survey on antimicrobial stewardship in 116 tertiary hospitals in China
Authors: J. Zhou, X. Ma
Journal: Clinical Microbiology and Infection (2018)

We aimed to assess the status and possible problems of antimicrobial stewardship (AMS) in Grade-A tertiary hospitals in China.A questionnaire was designed according to the United States Centers for Disease Control and Prevention 'Core Elements of Hospital Antibiotic Stewardship Programs'. We extracted 10-15% from Grade A tertiary hospitals in every province of mainland China; 165 hospitals in total were selected. Electronic questionnaires were forwarded to these hospitals.Of the hospitals surveyed, 116 (70.3%) responded. Participating hospitals accounted for 8.9% (116/1308) of all the Grade A tertiary hospitals in mainland China, covering all provinces and municipalities. Our study revealed that an AMS team was set up for an antimicrobial stewardship programme (ASP) in 110 hospitals (94.8%). Thirty hospitals lacked a formal department of infectious diseases (DID). A formal DID can positively promote an ASP. More hospitals with a formal DID developed their internal guidelines (54.7% versus 33.3%, p 0.044) and technical documents (83.7% versus 63.3%, p 0.019) on antimicrobial use than hospitals without a formal DID. All the 116 hospitals strengthened appropriate use of antimicrobials by some administration-dominated measures, among which the most frequent measures were classification management of antimicrobial agents (114 hospitals, 98.3%) and post-prescription review with feedback (106 hospitals, 91.4%). Prescription preauthorization and pre-prescription review with feedback were implemented in nearly 50% of the hospitals. More hospitals with a DID conducted pre-prescription review with feedback (53.5% versus 26.7%, p 0.027). The most frequent indicator to assess the impact of AMS was the defined daily dose (DDD) (103 hospitals, 96.3%).The survey showed significant achievements in China in AMS, mainly including the antibiotic consumption index; there is still a lot of work to be done, such as how to evaluate patient safety and infection outcome after strict restriction of antibiotic use.
Development and validation of a simple tool for the assessment of home noninvasive ventilation: the S<sup>3</sup>-NIV questionnaire
Authors: Elise Dupuis-Lozeron, Grégoire Gex, Patrick Pasquina, Pierre-Olivier Bridevaux, Jean-Christian Borel, Paola M. Soccal, Wolfram Windisch, Jean-Louis Pépin, Jean-Paul Janssens, Dan Adler
Journal: European Respiratory Journal (2018)

Patient-centred outcomes are significantly modified by long-term home noninvasive ventilation (NIV), but a short, self-administered, specific tool for routine clinical assessment is lacking. The aim of this study was to develop and validate the S 3 -NIV questionnaire, a short questionnaire to measure respiratory s ymptoms, s leep quality and NIV-related s ide effects. Patients with stable disease who were under long-term home NIV were recruited from three outpatient NIV services. Questionnaire development consisted of a selection of core items for analysis, followed by item reduction, validation and test–retest reliability. 338 patients completed a 22-item questionnaire. 11 items were removed because of non-scalability (n=2), redundancy (n=8) and lack of fit (n=1). The final version of the S 3 -NIV questionnaire consisted of 11 items covering two dimensions: “respiratory symptoms” (Cronbach's α=0.84) and “sleep &amp; NIV-related side effects” (Cronbach's α=0.77). Convergent validity was high between the “respiratory symptoms” subscale of the S 3 -NIV questionnaire and the St George's Respiratory Questionnaire (rho= −0.76, p&lt;0.001), and between the “sleep &amp; NIV-related side effects” subscale and the Quebec Sleep Questionnaire (rho=0.51, p&lt;0.001). The S 3 -NIV questionnaire had good test­–retest reliability after 4 weeks (intraclass correlation coefficient=0.72). The S 3 -NIV questionnaire is a short, valid and repeatable self-completed tool for the routine clinical assessment of patients undergoing home NIV.
Expansion of high-quality specialized services: The gynecologic oncology experience in Ontario hospitals.
Authors: Julie Gilbert, Sarah Wheeler, Junell D'Souza, Jonathan Crawford Irish, Elaine Meertens, Vicky Simanovski, Garth Matheson
Journal: Journal of Clinical Oncology (2018)

39 Background: In Ontario’s publicly funded cancer system, patient access to Gynecological Oncology (GyneOnc) care is threatened by growing demand, waiting times and need for lengthy patient travel. Cancer Care Ontario has published organizational standards that lay out the minimum clinical elements and infrastructure needed for a high quality program. Capacity planning and readiness assessments were used to guide GyneOnc expansion into non-academic regional cancer centres to alleviate system pressure. We evaluated early expansion activities to learn about critical factors and generate recommendations for future growth of this specialized oncology service. Methods: Capacity planning for new centres factored health human resources (HHR), patient volume and travel distances, ensuring that existing programs maintain critical mass. Evaluation included review of documents and readiness assessments related to the expansion projects undertaken to date. Interviews were done with GyneOncologists and administrators working at local and provincial levels to discover areas of risk, key factors for success, and recommended strategies for future expansion. Results: Gyne Onc programs need adequate resourcing (minimum 3 GyneOncs) to meet patient demand, support on-call and offer resilience to parental/medical leaves. Programs need engagement from other surgical and medical subspecialties, and clinical services (e.g. pathology, diagnostic imaging) for integrated, multidisciplinary care. Academic appointments, residencies, fellowships, and support for research provide links with universities, important for credibility. Endorsement by senior leadership - both management and clinical - is crucial. Organizational standards need specificity around the infrastructure and multidisciplinary environment needed for program success. Conclusions: HHR planning and readiness assessment are critical enablers in the expansion of specialized services like GyneOnc beyond academic centres. New programs need to consider the adequacy and appropriateness of staffing models, broad engagement of the clinical team, and linkages to academia, in order to ensure program sustainability and acceptability.
Peripheral group 2 innate lymphoid cells are decreased following nasal allergen challenge in allergic rhinitis
Authors: Mark W. Tenn, Jenny Thiele, Lisa M. Steacy, Daniel E. Adams, Anne K. Ellis
Journal: Allergy (2018)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Renal compartment–specific genetic variation analyses identify new pathways in chronic kidney disease
Authors: Chengxiang Qiu, Shizheng Huang, Jihwan Park, YoSon Park, Yi-An Ko, Matthew J. Seasock, Joshua S. Bryer, Xiang-Xi Xu, Wen-Chao Song, Matthew Palmer, Jon Hill, Paolo Guarnieri, Julie Hawkins, Carine M. Boustany-Kari, Steven S. Pullen, Christopher D. Brown, Katalin Susztak
Journal: Nature Medicine (2018)
Landscape of Acquired Resistance to Osimertinib in <i>EGFR</i>-Mutant NSCLC and Clinical Validation of Combined EGFR and RET Inhibition with Osimertinib and BLU-667 for Acquired <i>RET</i> Fusion
Authors: Zofia Piotrowska, Hideko Isozaki, Jochen K. Lennerz, Justin F. Gainor, Inga T. Lennes, Viola W. Zhu, Nicolas Marcoux, Mandeep K. Banwait, Subba R. Digumarthy, Wenjia Su, Satoshi Yoda, Amanda K. Riley, Varuna Nangia, Jessica J. Lin, Rebecca J. Nagy, Richard B. Lanman, Dora Dias-Santagata, Mari Mino-Kenudson, A. John Iafrate, Rebecca S. Heist, Alice T. Shaw, Erica K. Evans, Corinne Clifford, Sai-Hong I. Ou, Beni Wolf, Aaron N. Hata, Lecia V. Sequist
Journal: Cancer Discovery (2018)

We present a cohort of 41 patients with osimertinib resistance biopsies, including 2 with an acquired CCDC6-RET fusion. Although RET fusions have been identified in resistant EGFR-mutant non-small cell lung cancer (NSCLC), their role in acquired resistance to EGFR inhibitors is not well described. To assess the biological implications of RET fusions in an EGFR-mutant cancer, we expressed CCDC6-RET in PC9 (EGFR del19) and MGH134 (EGFR L858R/T790M) cells and found that CCDC6-RET was sufficient to confer resistance to EGFR tyrosine kinase inhibitors (TKI). The selective RET inhibitors BLU-667 and cabozantinib resensitized CCDC6-RET-expressing cells to EGFR inhibition. Finally, we treated 2 patients with EGFR-mutant NSCLC and RET-mediated resistance with osimertinib and BLU-667. The combination was well tolerated and led to rapid radiographic response in both patients. This study provides proof of concept that RET fusions can mediate acquired resistance to EGFR TKIs and that combined EGFR and RET inhibition with osimertinib/BLU-667 may be a well-tolerated and effective treatment strategy for such patients. SIGNIFICANCE: The role of RET fusions in resistant EGFR-mutant cancers is unknown. We report that RET fusions mediate resistance to EGFR inhibitors and demonstrate that this bypass track can be effectively targeted with a selective RET inhibitor (BLU-667) in the clinic.This article is highlighted in the In This Issue feature, p. 1494.
Triple-negative breast cancer treatment pattern and factors associated with its treatment in the United States: A population study using Central Cancer Registry data, 2013-2015.
Authors: Manxia Wu
Journal: Journal of Clinical Oncology (2018)

24 Background: Large population-based studies on TNBC epidemiology and treatment pattern in the US were generally limited due to lack of routinely data collection on these biomarkers until recent years. This study examined and documented general treatment status and factors associated with the treatments among TNBC patients in the US. Methods: We used the latest released NPCR and SEER combined cancer registry data, which covers 100% of the US population. All women in the US with a primary invasive TNBC breast cancer diagnosed between 2013 and 2015 were included. First course treatment patterns by AJCC staging on TNBC were examined based on corresponding year’s NCCN guideline recommendations. Regression analysis were performed to identify factors associated with treatments. Results: There were 74,952 TNBC women included in the study. Ninety three percent of women with early stage of TNBC had surgery, and 35% women with mastectomy chose to undergo contralateral prophylactic mastectomy. Among stage I-III patients, those aged &lt; 35, Non-Hispanic Asian Pacific Islander, living in other regions than northeast or metropolitan were more likely to have mastectomy compared to BCS. Radiation therapy were only received for 65% women with breast conserving surgery (BCS), which were less likely to be performed in non-Hispanic Black, Hispanic, and among those aged &lt; 35 or &gt; 70+. Chemotherapy were received for 75% of TNBC women, ranged from 63% (stage I) to 86% (stage III). Treatment variations among different demographic and geographic characteristics in chemotherapy were also observed. Conclusions: Overall, current treatment practice for TNBC in the US is generally concordance with the recommended breast cancer care except a relative low radiation therapy among BCS women. However, treatment disparities existed within the limited treatment options, and factors associated with the disparities also varied. More effective treatment options and treatment equality are warranted to improve overall care of this subtype.
Design and implementation of a predictive risk model to improve oncology patient management.
Authors: Garrett Young, Whitney Church, Ashley Roper, Tiffany Hoy
Journal: Journal of Clinical Oncology (2018)

154 Background: Methods to identify cancer patients that are likely to seek inpatient care for conditions that can be treated in the outpatient setting are not well defined. In light of the rise in value-based care programs, there is increased pressure on oncology providers to decrease costs of care while continuing to achieve high-quality outcomes. One way this can be achieved is by decreasing avoidable, high-cost utilization through population management. We sought to investigate the feasibility of creating a model to predict which patients were more likely to utilize emergency department (ED) and inpatient hospital (IP) services as well as the impact such a model may have on patient management. Methods: For a sample of 1093 patients, historical information was gathered across four domains: Cancer-specific Attributes, Comorbidity Burden, Social Factors, and Utilization History. This data set was then used to design a predictive model which assigned a numerical “acuity” score to each patient. Patients were ranked by numerical score, and their subsequent ED and IP utilization was measured. The developed model was then tested on an independent set of 591 patients to assess broader validity. After development, the predictive model was built into a tool for use in patient management by a team of nurse care managers. Results: Of the 100 highest-ranking patients in the training sample, 29% had at least one future hospitalization and 33% had at least one future ED visit, compared to 13% and 19% in the entire sample, respectively. In the validation sample, 11% of the 100 highest-ranking patients had at least one future hospitalization and 20% had at least one future ED visit, compared to 5% and 13% in the entire sample, respectively. Before model deployment, an average of 39 follow-up touchpoints were completed for high-risk patients per month. In the 6 months after deployment, the average rose to 171 touchpoints per month, an increase of 335%. Conclusions: Models can be developed to proactively identify cancer patients at higher risk of utilizing ED and inpatient hospital services. Implementation of such a model can also increase targeted outreach and communication with patients at greater risk of utilizing high-cost services.
Abstract 15389: Prognostic Impact of Family History on Mortality in Dilated Cardiomyopathy
Authors: Kyohei Marume, Emi Tateishi, Seiji Takashio, Tsukasa Kamakura, Kengo f Kusano, Satoshi Yasuda, Kenichi Tsujita, Teruo Noguchi
Journal: Circulation (2017)

Background: Depending on diagnostic methods, familial dilated cardiomyopathy (FDCM) is estimated to have a prevalence of 2-50%. Anecdotal data suggested that some patients with familial disease fol...
Washington State Community Cancer Care Report: Implications for value-based purchasing.
Authors: Laura Elizabeth Panattoni, Qin Sun, Catherine R. Fedorenko, Karma L. Kreizenbeck, Scott David Ramsey
Journal: Journal of Clinical Oncology (2018)

104 Background: As quality reports are released for regions and individual clinics, an important question is whether those reports can be used for value based purchasing, particularly for community oncology clinics. We evaluated the reliability of select quality measures and estimated the likelihood that a clinic’s performance would be incorrectly categorized (misclassified) in the top quartile. Methods: We linked 2014-2016 cancer registry records for patients with enrollment and claims from Medicare and two major commercial insurers in Washington State. We calculated risk standardized rates (RSRs) for ED and hospital use during treatment and 3 quality measures for end of life care. Reliability (0-1 scale: 0-unreliabile, &gt; 0.7 good reliability, 1 perfectly reliable) was calculated as signal/(signal + statistical noise) from hierarchical logistic regression modeling for each metric. Misclassification was characterized as the probability of false negative and false positive assignment of clinics to the top quartile of performers in the region. We generated results for 3 and 1 year performance periods. Results: Over the 3 year period, the hospitalization metrics included 7,373 patients, 25 clinics; end of life metrics included 8,165 patients; 24 clinics. Conclusions: Although these metrics had fairly high levels of reliability, approximately one-third of clinics could be incorrectly identified as a top quartile performer. Use of these metrics in value based purchasing should account for potential misclassification to minimize unintended consequences.[Table: see text]
Abstract B30: Three-dimensional organoid model for acquired drug resistance in non-small cell lung cancer
Authors: Navika D. Shukla, Ameen A. Salahudeen, Sukhmani K. Padda, Joel W. Neal, Heather A. Wakelee, Calvin J. Kuo
Journal: Clinical Cancer Research (2018)

Abstract Background: Targeted therapies against specific driver mutations of cancer progression have been used to improve survival of lung adenocarcinoma patients. In KRAS mutant NSCLC specifically, however, after some initial improvement in lung cancer patients, targeted therapies often fail due to acquired drug resistance. To uncover mechanisms of resistance and to discover new drivers, genome-scale sequencing of lung cancers has identified candidate genes, but these data have not rapidly translated in preclinical validation. A major obstacle in lung cancer research has been the deficiencies of standard in vitro models. Methods: To address the deficiencies within standard models we have developed an in vitro 3-dimensional, KRAS-mutated “organoid” model of lung adenocarcinoma that surpasses both in vitro and in vivo models by possessing the tractability of cell lines and the 3-dimensional architecture and morphology of animal models. We have engineered a p53 knockout and KRAS mutation on top of normal wild-type lung epithelium to achieve oncogenicity. Result: Through an optimized growth period in the presence of drug, an organoid model of resistance has been developed through which de novo genetic events underlying acquired resistance can be studied. Conclusion: The highly defined genetic background of the KRAS-mutated 3-D organoid model serves as a tabula rasa upon which stochastic secondary genetic and epigenetic changes can be identified and mechanistically studied by forward and reverse genetics approaches in order to rapidly identify mechanisms of acquired drug resistance and validate therapeutic options. Citation Format: Navika D. Shukla, Ameen A. Salahudeen, Sukhmani K. Padda, Joel W. Neal, Heather A. Wakelee, Calvin J. Kuo. Three-dimensional organoid model for acquired drug resistance in non-small cell lung cancer [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr B30.
Abstract 19925: Predictors of Quality-of-Life Benefit After Cardiac Resynchronization Therapy
Authors: Michael Nassif, William T Abraham, John G Cleland, Philip G Jones, Dan Schaber, Lou Sherfesee, Yuanyuan Tang, James B Young, John A Spertus
Journal: Circulation (2016)

Background: While clinical trials have clearly established the average benefit of cardiac resynchronization therapy (CRT), estimating the benefits for an individual patient remains difficult due to the heterogeneity of treatment response. To better inform patient selection for CRT, based upon effects on quality of life (QoL), we created a multivariable risk prediction model of benefit in QoL at 3 months after CRT implantation. Methods: Patient-level data from 5 randomized controlled trials comparing CRT with control groups were used to create prediction models of QoL response based on the Minnesota living with Heart Failure questionnaire (MLHFQ). A partial proportional odds model for the categories of worse QoL, no change, small, moderate, large improvement were created. The c-statistics for each threshold were calculated. Results: Of 3716 patients available for analysis most were in NYHA class II (49%) or III (45%). Across the 5 studies, the mean difference in MLHFQ scores was 3.5 points (-13.7 with CRT ...
Changes in lung cancer screening knowledge, beliefs, and practices among health care providers.
Authors: Louise Henderson, Caitlin Bearden, Dan Reuland, Alison Tytell Brenner, Adam Goldstein, Susan Maygarden, M. Patricia Rivera
Journal: Journal of Clinical Oncology (2018)

117 Background: In 2013, the U.S. Preventative Task Force began recommending lung cancer screening (LCS) annually for patients ages 55-80 years who are current or former (quit within the last 15 years) smokers with a 30 pack-year history. Since then, the proportion of eligible patients undergoing LCS has been reported to be low, ranging from 3-5%. We sought to compare LCS practices and beliefs among health care providers at a large academic medical center from 2015 to 2018. Methods: In 2015 and 2018, we surveyed physicians and residents in pulmonology, family, and internal medicine using a 23-item Qualtrics survey developed with the Tailored Design Method. To evaluate potential workforce issues in LCS we compared responses regarding provider’s opinions, referral patterns, and barriers to LCS from 2015 to 2018 using chi-squared tests. Results: Response rates were 39% in 2015 and 26% in 2018. From 2015 to 2018 there was an increase in the proportion of providers who reported LCS as beneficial (44.6% vs 75.7%, p &lt; 0.0001), cost effective (20.0% vs 38.6%, p = 0.002), and as having enough knowledge to explain the risks and benefits of LCS (53.6% vs 75.7%, p = 0.001). In both years, the majority of providers reported time restrictions during a patient’s clinic visit meant that other problems had higher priority than LCS (65.1% vs 71.4%, p = 0.85). Over the 3-year period the proportion of providers who reported ordering a LCS exam more than doubled (32.2% to 74.6%, p &lt; 0.00001) and the percentage who initiated discussion about the risks and benefits increased from 45.9% to 87.3%. The proportion of providers who reported that a patient asked about LCS increased (22.8% to 37.7%, p = 0.001). While some reported barriers did not change from 2015 to 2018 (concern regarding false negatives, false positives, cost to system/patients, or potential for physical/emotional harm), more providers reported low patient acceptance or adherence (7.4% vs 13.0%, p = 0.01). Conclusions: From 2015 to 2018 healthcare providers reported a more favorable opinion of LCS and a higher proportion of providers reported ordering a LCS exam. Time constraints during the patient visit remained an issue and a higher proportion reported low patient acceptance/adherence as a barrier.