tbuckley/cabot-search huggingface dataset:
Awareness of fetal movements and care package to reduce fetal mortality (AFFIRM): a stepped wedge, cluster-randomised trial
Authors: Jane E Norman, Alexander E P Heazell, Aryelly Rodriguez, Christopher J Weir, Sarah J E Stock, Catherine J Calderwood, Sarah Cunningham Burley, J Frederik Frøen, Michael Geary, Fionnuala Breathnach, Alyson Hunter, Fionnuala M McAuliffe, Mary F Higgins, Edile Murdoch, Mary Ross-Davie, Janet Scott, Sonia Whyte
Journal: The Lancet (2018)

2·6 million pregnancies were estimated to have ended in stillbirth in 2015. The aim of the AFFIRM study was to test the hypothesis that introduction of a reduced fetal movement (RFM), care package for pregnant women and clinicians that increased women's awareness of the need for prompt reporting of RFM and that standardised management, including timely delivery, would alter the incidence of stillbirth.This stepped wedge, cluster-randomised trial was done in the UK and Ireland. Participating maternity hospitals were grouped and randomised, using a computer-generated allocation scheme, to one of nine intervention implementation dates (at 3 month intervals). This date was concealed from clusters and the trial team until 3 months before the implementation date. Each participating hospital had three observation periods: a control period from Jan 1, 2014, until randomised date of intervention initiation; a washout period from the implementation date and for 2 months; and the intervention period from the end of the washout period until Dec 31, 2016. Treatment allocation was not concealed from participating women and caregivers. Data were derived from observational maternity data. The primary outcome was incidence of stillbirth. The primary analysis was done according to the intention-to-treat principle, with births analysed according to whether they took place during the control or intervention periods, irrespective of whether the intervention had been implemented as planned. This study is registered with www.ClinicalTrials.gov, number NCT01777022.37 hospitals were enrolled in the study. Four hospitals declined participation, and 33 hospitals were randomly assigned to an intervention implementation date. Between Jan 1, 2014, and Dec, 31, 2016, data were collected from 409 175 pregnancies (157 692 deliveries during the control period, 23 623 deliveries in the washout period, and 227 860 deliveries in the intervention period). The incidence of stillbirth was 4·40 per 1000 births during the control period and 4·06 per 1000 births in the intervention period (adjusted odds ratio [aOR] 0·90, 95% CI 0·75-1·07; p=0·23).The RFM care package did not reduce the risk of stillbirths. The benefits of a policy that promotes awareness of RFM remains unproven.Chief Scientist Office, Scottish Government (CZH/4/882), Tommy's Centre for Maternal and Fetal Health, Sands.
Postnatal Cardiac Gene Editing Using CRISPR/Cas9 With AAV9-Mediated Delivery of Short Guide RNAs Results in Mosaic Gene Disruption
Authors: Anne Katrine Johansen, Bas Molenaar, Danielle Versteeg, Ana Rita Leitoguinho, Charlotte Demkes, Bastiaan Spanjaard, Hesther de Ruiter, Farhad Akbari Moqadam, Lieneke Kooijman, Lorena Zentilin, Mauro Giacca, Eva van Rooij
Journal: Circulation Research (2017)

CRISPR/Cas9 (clustered regularly interspaced palindromic repeats/CRISPR-associated protein 9)-based DNA editing has rapidly evolved as an attractive tool to modify the genome. Although CRISPR/Cas9 has been extensively used to manipulate the germline in zygotes, its application in postnatal gene editing remains incompletely characterized.
Electronic physician ratings and reviews process.
Authors: Diane Denny, DBA, Sarah Hizon, Lauren Caldarello, Scott Hartman, Maurie Markman
Journal: Journal of Clinical Oncology (2018)

209 Background: According to JAMA, Public Awareness, Perception, and Use of Online Physician Rating Sites; 35% of patients selected a physician based on good ratings, and 37% avoided one with bad ratings. Yet, there exists a stark difference between unstructured (i.e. Yelp) online reviews as compared to validated survey-generated data. A national network of hospitals that specializes in treating patients with complex cancer had been collecting patient satisfaction data using a validated tool administered by a 3 rd party for some time. An electronic physician rating and review process was implemented as an adjunct to that survey process, providing a new mechanism for consumers visiting the networks’ website with accurate information about patients’ satisfaction with its oncologists. Methods: Physician ratings are obtained directly from patients who had an encounter using two specific questions regarding confidence and likelihood to recommend. Ratings are posted by physician and maintained on a 12-month rolling basis once a minimum of 30 ratings is achieved. Likert scale survey data are converted to a one-to-five star rating. De-identified verbatim comments are also posted. Criteria are in place to review comments prior to posting with limited exclusions, such as comments containing PHI or slanderous content. Physicians receive an email to review comments 15 days prior to posting, allowing a process for advance notice or appeal. Both positive and negative reviews are published. Results: Physician performance scores were 4.7 stars pre-launch compared to 4.8 stars post-launch. Additional performance statistics are provided below. Conclusions: Sharing information on the talent of physicians is an important component of transparency and arming patients with information to make informed treatment decisions. As a result, physicians have become more engaged with their data and utilizing reviews to identify improvement opportunities. This translates to a culture of accountability and deepened understanding of patients’ perceptions about care.[Table: see text]
The institution of a white cell growth factor appropriate non-use policy for incurable metastatic solid tumors within a community oncology practice.
Authors: J. Russell Hoverman, Brian Turnwald, Jody S. Garey, Jad Hayes, B. Brooke Mann, Bo He, Lalan S. Wilfong
Journal: Journal of Clinical Oncology (2018)

33 Background: Texas Oncology (TO) is a community-based practice. with over 250 physicians (MD) who order chemotherapy. In 2015, pegfilgrastim (pgcsf) was the highest individual drug in billed claims. Concurrently, TO was participating in the United Healthcare (UHC) Episode of Care (EOC) program and anticipating the Oncology Care Model. Patient and program expense dictated understanding pgcsf utilization. Methods: Data were obtained in 9/2015 from EOC claims to identify overall and individual pgcsf use in solid tumor metastatic disease (MDx). Chart review was done for the top prescribers. In 3/16, ASCO pgcsf guidelines and TO education materials were emailed to all physicians. In 3/17 appropriate non-use recommendations were communicated and a real-time internal approval process begun. On 10/1/2017, UHC instituted a pgcsf prior authorization (PA) program. Retrospective data from the iKnowMed EHR system was collected in 3-month intervals from April 2016 through March 2018 and evaluated for number of pgcsf administrations at TO for MDx, as well as, administrations/provider/quarter for TO and The US Oncology Network. MDx was defined by any of the following criteria: stage IV at diagnosis (with certain disease exceptions); TNM M value of “1” or “+”; a metastatic line of therapy; evidence of metastatic disease documented within the EHR. Results: Initial survey of EOC claims indicated 16% of patients received pgcsf for MDx. Rates per MD ranged from 0 to 57%. Review of the top users indicated 90% of uses could have been addressed with dose reduction. In the first measured quarter of April to June 2016 to the last, October to December 2017, pgcsf use dropped by 50%. Changes for some diseases were dramatic: Use in colon cancer fell from 132 uses/quarter to a low of 46, and for non-small lung cancer – 80 to 23 respectively. Conclusions: The deadopting of low value care can be challenging. In the case of pgcsf substantial reductions in use were achieved using data and guidelines for education in the setting of value based contracts. Ultimately, the most change was achieved by an internal real time approval process. This was reinforced by a payer PA requirement.
Abstract 18182: Phosphodiesterase 10A Regulates Vascular Inflammation and Pathogenesis of Abdominal Aortic Aneurysms
Authors: Yujun Cai, Yujun Cai, Chen Yan, Raul J Guzman
Journal: Circulation (2015)

Rationale: Abdominal aortic aneurysms (AAA) are characterized by aortic enlargement and underlying weakness of the vessel wall. Experimental and clinical evidence suggests that vascular inflammation is a central trigger of AAA formation. Phosphodiesterases (PDEs), known regulators of cyclic nucleotide signaling, play a critical role in vascular inflammation. Objective: In this study, we sought to determine the role and function of PDE10A in vascular inflammation and AAA formation. Methods and Results: Extensive evidence suggests that angiotensin II (Ang II) signaling plays an important causative role in AAA formation. Therefore, Real-time PCR array for all 22 known PDE genes was performed in control and Ang II-treated VSMCs. We observed that PDE10A elicited the highest levels of induction by Ang II among all PDEs. Moreover, we found that PDE10A was dramatically upreguated in the Ang II-infused AAA mouse model and in human AAA specimens. PDE10A was primarily expressed in medial VSMCs and infiltrating macrophages in AAA. More importantly, deficiency of PDE10A or PDE10A inhibition significantly attenuated AAA formation in vivo. In cultured VSMCs, knockdown of PDE10A with specific siRNA and inhibition of PDE10A by papaverine markedly suppressed Ang II-induced vascular cell adhesion molecule 1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-1) and MMP2 expression. Deficiency of PDE10A also blocked lipopolysaccharide (LPS)-induced TNF-α, MCP-1, and MMP9 expression in peritoneal macrophages isolated from PDE10A knockout mice. Further mechanistic studies revealed that histone deacetylase 5 (HDAC5) plays an important role in PDE10A-regulated vascular inflammation via cAMP-dependent protein kinase (PKA). Conclusions: These findings demonstrate that PDE10A is an important regulator of vascular inflammation and AAA development. They further provide evidence for PDE10A as a potential therapeutic target for aortic aneurysms and other vascular diseases.
Safety of delivering chemotherapy by community nursing staff supervised by telemedicine in remote New South Wales (NSW).
Authors: Florian Honeyball
Journal: Journal of Clinical Oncology (2018)

82 Background: Outcomes for cancer patients living in rural and remote areas are worse than for their metropolitan peers. Disparity in access to treatment is one of the causes for this difference. Using non-oncology, community based nurses with basic training in safe handling of chemotherapy to administer cancer treatments under the supervision of a medical oncologist and senior oncology nurse via telemedicine has been successful in remote Queensland. This is the pilot study analysing Remote Video Assisted Chemotherapy (RVAC) in NSW. Methods: Demographic data, regimens, and toxicity profiles of patients at the trial site in Coonabarabran was extracted from the electronic medical record. Similar data was extracted from all patients receiving the same treatment regimens in Dubbo, the referral hospital for Western NSW, 160km to the south. Data was analysed using a two-sample proportions z-test. Results: Data was collected in the 7 months after opening the trial site. This is summarised in the table below. There is no evidence to suggest differences in toxicity between the hub site and the trial site. Of those with grade 3 or 4 toxicity, 6 at the main site (40% of those on chemotherapy) and 2 at the trial site (50%) received chemotherapy. A higher proportion of patients receiving chemotherapy at the trial site may explain this difference. Although there was a significantly increased number of delayed doses at the trial site, the majority were due to logistic issues in the first two months. Conclusions: Using this model to deliver chemotherapy is safe. Toxicity numbers are low in this cohort, given the high number of patients receiving low risk anticancer drugs including endocrine and monoclonal antibody therapy.[Table: see text]
Differential Nanoscale Topography and Functional Role of GluN2-NMDA Receptor Subtypes at Glutamatergic Synapses
Authors: Blanka Kellermayer, Joana S. Ferreira, Julien Dupuis, Florian Levet, Dolors Grillo-Bosch, Lucie Bard, Jeanne Linarès-Loyez, Delphine Bouchet, Daniel Choquet, Dmitri A. Rusakov, Pierre Bon, Jean-Baptiste Sibarita, Laurent Cognet, Matthieu Sainlos, Ana Luisa Carvalho, Laurent Groc
Journal: Neuron (2018)
Are Patient Self-Reported Outcome Measures Sensitive Enough to Be Used as End Points in Clinical Trials?
Authors: Lee Jones, David F. Garway-Heath, Augusto Azuara-Blanco, David P. Crabb, David F. Garway-Heath, David P. Crabb, Catey Bunce, Gerassimos Lascaratos, Francesca Amalfitano, Nitin Anand, Augusto Azuara-Blanco, Rupert R. Bourne, David C. Broadway, Ian A. Cunliffe, Jeremy P. Diamond, Scott G. Fraser, Tuan A. Ho, Keith R. Martin, Andrew I. McNaught, Anil Negi, Krishna Patel, Richard A. Russell, Ameet Shah, Paul G. Spry, Katsuyoshi Suzuki, Edward T. White, Richard P. Wormald, Wen Xing, Thierry G. Zeyen
Journal: Ophthalmology (2018)
Three Factors Combined Predict Futility of Emergency Coronary Angiography After Out-of-Hospital Cardiac Arrest
Authors: Liam S. Hirt, Sri Raveen Kandan, Hazim Rahbi, Amardeep Dastidar, Muhammed Zeeshan Khawaja, Abdul Mozid, Stephen Dorman, Thomas W. Johnson, James C. Spratt, Julian W. Strange
Journal: Journal of the American College of Cardiology (2018)
Impact of diabetes and hyperglycemia on health care utilization, infection risk, and survival in patients with cancer receiving glucocorticoids with chemotherapy.
Authors: Dylan M. Zylla, Grace Gilmore, Justin Eklund, Sara Richter, Anders Carlson
Journal: Journal of Clinical Oncology (2018)

19 Background: Glucocorticoid (GC) use is commonly used in chemotherapy regimens and may lead to hyperglycemia and increased infection rates. We assessed the impact of diabetes (DM) and hyperglycemia on rates of health-care utilization, infections and survival among patients with cancer receiving chemotherapy. Methods: We performed a retrospective analysis on 1,781 patients who received intravenous chemotherapy with GC between 2010 and 2015. Demographic, clinical, and health-care utilization (HCU) data was obtained using electronic medical record, billing modules, and the tumor registry; HCU included tallies of emergency room, urgent care, and inpatient visits. Logistic regression models were used to compare survival and new infections between patients with and without DM, after adjusting for demographic and cancer-related variables. Results: In the first 12 months following chemotherapy, patients with DM (n = 330) had higher rates of hospital admissions (70.9% vs 57.4%, p&lt; 0.001), more infection-related admissions (37.0% vs 29.2%, p = 0.007), and increased rates of new infections (61.2% vs 49.2%, p &lt; 0.001) when compared to patients without DM (n = 1,451). One-year survival rate was worse among patients with DM (67.3% vs 78.3%, p &lt; 0.001), as well as patients with at least one glucose reading above 300 mg/dL following chemotherapy (60.8% vs 78.5, p &lt; 0.001). After adjusting for cancer stage, age, and gender, we found DM history increased the odds of dying within one year after diagnosis by 86% (OR 1.86, 95% CI (1.37  2.52), p &lt; 0.001) and of new infections by 68% (OR 1.68, 95% CI (1.26  2.24), p &lt; 0.001). Conclusions: Among patients with cancer receiving intravenous chemotherapy with GC we demonstrate patients with DM have more hospital admissions, increased rates of infections, and worse survival. Prospective studies are urgently needed to elucidate what level of glycemic control is needed to potentially improve outcomes for patients with DM receiving chemotherapy with GC.
Enhanced compliance with appropriate antiemetic prescribing guidelines by utilizing a medically integrated pharmacy antiemetic therapeutic interchange protocol.
Authors: Lalan S. Wilfong, Carla Portnoy, J. Russell Hoverman, Kathryn Wallace, Jim R. Schwartz, Neal Dave, Sabrina Q. Mikan, Debra A. Patt
Journal: Journal of Clinical Oncology (2018)

55 Background: Appropriate antiemetic prescribing remains an unmet need in patients receiving emetogenic chemotherapy. Non-compliance with standard antiemetic guidelines is well reported, and a focus of the American Society of Clinical Oncology Choosing Wisely campaign. Using our medically integrated pharmacies, a community oncology practice sought to maximize compliance with national guidelines by minimizing the use of NK1 inhibitors for low and minimally emetogenic regimens and optimizing medications for highly emetogenic regimens per NCCN guidelines. Methods: A retrospective review of a medically integrated pharmacy antiemetic therapeutic interchange policy. Trained oncology pharmacists imbedded within 2 cancer centers evaluated all new chemotherapy orders to determine the level of emetogenicity per NCCN guidelines. Pharmacists then used a guideline compliant prespecified therapeutic interchange protocol to adjust the antiemetic medications. Patient education to enhance medication compliance was performed by the pharmacists, nurses, and in one on one treatment review sessions with an advance practice provider. Results: Of 271 low to minimally emetogenic regimens, 99% did not receive an NK1 inhibitor on the first cycle. Of 367 highly emetogenic regimens, 97% appropriately received guideline based therapy. Additionally, the use of olanzapine was non-existent in the practice prior to this protocol and increased to 55% of patients with highly emetogenic regimens. Conclusions: We demonstrated that a therapeutic interchange policy with a medically integrated pharmacist shows enhanced compliance with guideline based antiemetic medication usage. This system also allows rapid uptake of changes in supportive care guidelines such as rapid adoption of olanzapine. Efficacy results of this protocol will be reported separately.
Abstract 14358: Determinants of Diffuse Myocardial Fibrosis in Patients With Heart Failure With Preserved Ejection Fraction Compared to Age-Matched Volunteers.
Authors: Clotilde Roy, Alisson Slimani, Christophe de Meester, Mihaela Amzulescu, Agnès Pasquet, David Vancraeynest, Christophe Beauloye, Jean-Louis Vanoverschelde, Bernhard Gerber, Anne-Catherine Pouleur
Journal: Circulation (2016)

Background: Several studies have shown that increased myocardial fibrosis may play a key role in HFpEF pathophysiology. The aim of this study was to evaluate the presence and the determinants of diffuse fibrosis in HFpEF patients compared to age-matched volunteers. Methods: Between January 2015 and May 2016, we prospectively included 102 consecutive patients with HFpEF (78±9 years, 66% women) defined by LVEF≥ 50%, Framingham HF criteria, prior hospitalization for HF or NT-proBNP >350pg/ml. LV and RV functions were assessed by 2D echocardiography and cardiac magnetic resonance (cMR). Diffuse myocardial fibrosis was estimated by extra cellular volume (ECV) quantified by 3 Tesla cMR with the Modified Look-Locker Inversion Recovery sequence. We determined an ECV age-adjusted cutoff value (cutoff = 35%) corresponding to mean + 2 standard deviations in 27 age-matched volunteers (74±7years, 63% women) without previous cardiac history. Results: Fibrosis estimated by ECV was significantly higher in HFpEF patients ...
Expansion of Interleukin‐22– and Granulocyte–Macrophage Colony‐Stimulating Factor–Expressing, but Not Interleukin‐17A–Expressing, Group 3 Innate Lymphoid Cells in the Inflamed Joints of Patients With Spondyloarthritis
Authors: Iris C. J. Blijdorp, Silvia Menegatti, Leonike J. J. van Mens, Marleen G. H. van de Sande, Sijia Chen, Hulda S. Hreggvidsdottir, Troy Noordenbos, Talia E. Latuhihin, Jochem H. Bernink, Hergen Spits, Lars Rogge, Dominique L. P. Baeten, Nataliya G. Yeremenko
Journal: Arthritis & Rheumatology (2018)

Clinical trials of the anti-interleukin-17A (anti-IL-17A) antibody secukinumab have demonstrated a crucial role of the cytokine IL-17A in the pathogenesis of spondyloarthritis (SpA); however, its cellular source in this condition remains a matter of controversy. Group 3 innate lymphoid cells (ILC3s) have been recently identified as potent producers of proinflammatory cytokines, including IL-17A and IL-22, in a number of different tissues. This study was undertaken to characterize the presence and composition of ILCs, and investigate whether these cells are an important source of IL-17A, in the synovial tissue (ST) of patients with SpA.Matched ST, synovial fluid, and peripheral blood (PB) samples were obtained from SpA patients with actively inflamed knee joints. ILC subsets were characterized by flow cytometry. Gene expression analysis at the single-cell level was performed directly ex vivo and after in vitro activation. An IL-17A enzyme-linked immunospot assay was used to detect IL-17A-secreting cells.ILCs, and particularly NKp44+ ILC3s, were expanded in inflamed arthritic joints. Single-cell expression analysis demonstrated that ST ILCs were clearly distinguishable from ST T cells and from their PB counterparts. Expression of the Th17 signature transcripts RORC, AHR, and IL23R was detected in a large proportion of ST ILC3s. These cells were capable of inducing expression of IL22 and CSF2, but not IL17A, in response to in vitro restimulation.Our findings demonstrate that absolute and relative numbers of ILC3s are enriched in the synovial joints of patients with SpA. However, these cells are not a significant source of IL-17A in this disease.
Beneficial effects on vision in patients undergoing retinal gene therapy for choroideremia
Authors: Kanmin Xue, Jasleen K Jolly, Alun R. Barnard, Anna Rudenko, Anna P. Salvetti, Maria I. Patrício, Thomas L. Edwards, Markus Groppe, Harry O. Orlans, Tanya Tolmachova, Graeme C. Black, Andrew R. Webster, Andrew J. Lotery, Graham E. Holder, Susan M. Downes, Miguel C. Seabra, Robert E. MacLaren
Journal: Nature Medicine (2018)