tbuckley/cabot-search huggingface dataset:
Optimizing design of research to evaluate antibiotic stewardship interventions: consensus recommendations of a multinational working group
Authors: V.A. Schweitzer, C.H. van Werkhoven, J. Rodríguez Baño, J. Bielicki, S. Harbarth, M. Hulscher, B. Huttner, J. Islam, P. Little, C. Pulcini, A. Savoldi, E. Tacconelli, J.-F. Timsit, M. van Smeden, M. Wolkewitz, M.J.M. Bonten, A.S. Walker, M.J. Llewelyn
Journal: Clinical Microbiology and Infection (2019)

<h2>Abstract</h2><h3>Background</h3> Antimicrobial stewardship interventions and programmes aim to ensure effective treatment while minimizing antimicrobial-associated harms including resistance. Practice in this vital area is undermined by the poor quality of research addressing both what specific antimicrobial use interventions are effective and how antimicrobial use improvement strategies can be implemented into practice. In 2016 we established a working party to identify the key design features that limit translation of existing research into practice and then to make recommendations for how future studies in this field should be optimally designed. The first part of this work has been published as a systematic review. Here we present the working group's final recommendations. <h3>Methods</h3> An international working group for design of antimicrobial stewardship intervention evaluations was convened in response to the fourth call for leading expert network proposals by the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR). The group comprised clinical and academic specialists in antimicrobial stewardship and clinical trial design from six European countries. Group members completed a structured questionnaire to establish the scope of work and key issues to develop ahead of a first face-to-face meeting that (a) identified the need for a comprehensive systematic review of study designs in the literature and (b) prioritized key areas where research design considerations restrict translation of findings into practice. The working group's initial outputs were reviewed by independent advisors and additional expertise was sought in specific clinical areas. At a second face-to-face meeting the working group developed a theoretical framework and specific recommendations to support optimal study design. These were finalized by the working group co-ordinators and agreed by all working group members. <h3>Results</h3> We propose a theoretical framework in which consideration of the intervention rationale the intervention setting, intervention features and the intervention aims inform selection and prioritization of outcome measures, whether the research sets out to determine superiority or non-inferiority of the intervention measured by its primary outcome(s), the most appropriate study design (e.g. experimental or quasi- experimental) and the detailed design features. We make 18 specific recommendation in three domains: outcomes, objectives and study design. <h3>Conclusions</h3> Researchers, funders and practitioners will be able to draw on our recommendations to most efficiently evaluate antimicrobial stewardship interventions.
Association of Sodium-Glucose Cotransporter 2 Inhibitor Treatment With Risk of Hospitalization for Fournier Gangrene Among Men
Authors: Chintan V. Dave, Sebastian Schneeweiss, Elisabetta Patorno
Journal: JAMA Internal Medicine (2019)

Noam Tau, MD; Tzippy Shochat, MSc; Anat Gafter-Gvili, MD; Ariadna Tibau, MD, PhD; Eitan Amir, MD, PhD; Daniel Shepshelovich, MD
Optimizing supportive measures for the safe administration of FOLFIRINOX as first-line treatment in advanced, inoperable pancreatic cancer (aPDAC) patients (pts) in routine clinical practice.
Authors: Vanja Vaccaro, Emilio Bria, Isabella Sperduti, Maria Simona Pino, Francesco Massari, Alain Gelibter, Alessandra Auriemma, Angela Torsello, Davide Melisi, Carmen Nuzzo, Melissa Frizziero, Sabrina Vari, Eleonora Lucchini, Carlo Garufi, Silvia Cottini, Massimo Zeuli, Virginia Ferraresi, Francesco Cognetti, Giampaolo Tortora, Michele Milella
Journal: Journal of Clinical Oncology (2012)

e14661 Background: FOLFIRINOX is an important addition to our therapeutic armamentarium for the treatment of aPDAC; however, safety and tolerability issues (hematologic toxicity, increased risk of AE in pts carrying biliary stents) may limit its use in routine clinical practice. Methods: We reviewed the clinical charts of 36 aPDAC pts receiving first-line FOLFIRINOX at two different institutions and analyzed toxicity and outcomes according to the presence or absence of a biliary stent and whether they received (n=21) or not (n=15) primary prophylactic G-CSF (d 7-9-11). Results: 36 pts (M/F: 22/14; median age: 57 yrs, range: 37-70; stage III/IV: 10/26; ECOG PS 0/1: 33/3) and 241 cycles were analyzed. Toxicity was mild with G3/4 adverse events (AE) in &lt;1% of cycles, except for G3/4 neutropenia (16.6% of pts, 3.7% of cycles); dose was reduced to 75% in 48/205 cycles (23%); 3 pts discontinued treatment after 1 cycle (G3 gastro-intestinal toxicity in 1 pt and early progressive disease, PD in 2 pts). Overall and G3/4 toxicities were not significantly different in 7 pts carrying a biliary stent. G3/4 neutropenia was observed in 5/155 (3.2%) and 4/86 (4.6%) cycles among pts receiving or not G-CSF prophylaxis (p=n.s.); anemia and thrombocytopenia (any grade) were more common among pts receiving G-CSF (p&lt;0.001 and p=0.009, respectively). Palonosetron/aprepitant/dexamethasone achieved complete control of nausea/vomiting at cycle 1 in 72% (95% CI: 58-87%) and 86% (95% CI: 75-97%) of pts. Partial response (PR) occurred in 25% and stable disease (SD) in 43% of 28 evaluable pts (disease control rate, DCR: 68%, 95% CI: 51-85%). A &gt;50% reduction in CA19.9 occurred in 61% of pts. Median PFS was 8 mos (95% CI: 6-9 mos). Conclusions: FOLFIRINOX is well tolerated and easily manageable on an outpatient basis in young (&lt;70 yrs) and fit (PS 0-1) aPDAC pts and can be safely used in pts carrying biliary stents. Routine G-CSF prophylaxis is not currently recommended, but may be useful to carefully extend FOLFIRINOX use to older/less fit/comorbid pts with aPDAC.
Diabetes mellitus in ankylosing spondylitis
Authors: Kuan-Fu Liao, Yu-Hung Kuo, Shih-Wei Lai
Journal: Annals of the Rheumatic Diseases (2019)

Ankylosing spondylitis is a systemic inflammatory disease which always influences the spine joints. The association between ankylosing spondylitis and multiple systemic comorbidities has been well assessed.1 2 Recently, one meta-analysis conducted by Mathieu et al published in Annals of the Rheumatic Diseases reported that persons with ankylosing spondylitis were significantly associated with increased risks of myocardial infarction and stroke when compared with controls (risk ratio=1.44 for myocardial infarction, and risk ratio=1.37 for stroke).3 Mathieu et al ’s research is well performed and informative to the readers.

Diabetes mellitus is a well-established risk factor for myocardial infarction and stroke. One cross-sectional study reported that 13.64% of persons with ankylosing spondylitis had diabetes mellitus.4 We make a rational hypothesis that diabetes mellitus could be involved in the association between ankylosing …
Epigenetic Control of Fatty-Acid Metabolism Sustains Glioma Stem Cells
Authors: Hayley C. Affronti, Kathryn E. Wellen
Journal: Cancer Discovery (2019)

Abstract Summary: In this issue of Cancer Discovery, Gimple and colleagues examine superenhancers in glioblastoma and glioma stem cells (GSC), identifying one which promotes expression of ELOVL2, an enzyme in polyunsaturated fatty acid (PUFA) synthesis. They find that ELOVL2 products help maintain cell membrane organization and EGFR signaling in GSCs, and that targeting PUFA metabolism along with EGFR offers a potential novel therapeutic strategy for glioblastoma. See related article by Gimple et al., p. 1248.
P14.62 Safety and adverse event profile post-market surveillance analysis of Tumor Treating Fields (TTFields) in EMEA
Authors: T Schmidt, S Kebir, L Lazaridis, A Stoppek, M Glas
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Tumor Treating Fields (TTFields) are established as modality in glioblastoma (GBM) therapy. GBM is the most aggressive brain tumor in adults, constituting approximately 15 % of all primary brain tumors. At diagnosis, a considerable subgroup of GBM patients is ≥65 years of age. The phase 3 EF-14 trial demonstrated a significant improvement of progression free, overall and longterm survival in newly diagnosed GBM (ndGBM) patients by the addition of TTFields compared temozolomide therapy. No treatment limiting systemic adverse events in the EF-14 trial for ndGBM or in the EF-11 trial for recurrent GBM (rGBM) were observable. Here, we present post-market surveillance data from patients in the EMEA region including elderly patients (≥ 65 years) treated with TTFields. METHODS Based on the MedDRA body system (system organ class) and preferred terms surveillance data of patients in the EMEA region were assessed. Additionally, surveillance data of patients &lt; 65 as well as ≥ 65 years of age in this region were separately analyzed. RESULTS A total of 11,048 patients were treated with TTFields (ndGBM 53.3 %, rGBM 39.5 %, other diagnoses 7.2 %) of whom 2,252 (20.4 %) patients were treated in the EMEA region. 19.6 % of patients treated in this region were ≥65 years of age at the time of TTFields therapy initiation. One or more adverse events were reported by 64 % of EMEA patients &lt; 65 and in 67 % of elderly EMEA patients. The most prevalent adverse event in both age groups was skin reactions, occurring in 30 % of patients &lt; 65 years of age and 33 % elderly patients. Likewise, further adverse events in elderly patients in the EMEA region were comparable to patients younger than 65 years of age, e.g. heat sensation (&lt; 65; ≥ 65: 4 %; 4 %) and general physical health deterioration (14 %; 18 %). CONCLUSION These real-life data demonstrate a good safety profile of TTFields in elderly patients as well as in patients &lt; 65. The most frequent registered adverse event was skin reaction, which is in line with the results of the phase 3 EF-11 trial for rGBM and the EF-14 trial for ndGBM patients. In summary, these results from post-marketing surveillance emphasize the safety of TTFields in GBM treatment, particularly in the elderly population.
Lymphangiogenesis in a mouse model of renal transplant rejection extends life span of the recipients
Authors: Mads S. Pedersen, Mathias Müller, Thomas Rülicke, Nicole Leitner, Renate Kain, Heinz Regele, Shijun Wang, Hermann-Josef Gröne, Song Rong, Hermann Haller, Faikah Gueler, Andrew J. Rees, Dontscho Kerjaschki
Journal: Kidney International (2019)
OS5.4 Characteristics of adult diffuse H3K27M-mutant gliomas at recurrence
Authors: K Hodroj, D Meyronet, M Barritault, V Bourg, E Cohen-Moyal, S Cartalat, R Ameli, M Berhouma, J Honnorat, F Ducray
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Adult diffuse H3K27M-mutant gliomas are rare and associated with a poor prognosis but could benefit in the next future from specific therapeutic strategies. In this context, the aim of the present study was to describe the characteristics of these tumors at recurrence. MATERIAL AND METHODS We retrospectively analyzed the characteristics of a series of 27 adult diffuse H3K27M-mutant gliomas at recurrence RESULTS Median age at diagnosis was 37 years. Initial treatment consisted of temozolomide radiochemotherapy (n=17, 62%), radiotherapy alone (n=1, 4%), chemotherapy alone (n=4, 15%), wait and see (n=1, 4%) and palliative care (n=4, 15%). Median PFS and median OS were 11 and 22 months in the whole series and 15 and 29 months in the patients who were treated with temozolomide radiochemotherapy. The pattern of recurrence could be analyzed in 19 patients. Ten patients (50%) demonstrated a local recurrence, five patients a local and distant recurrence (25%), two patients only a distant recurrence (10%) and two patients a leptomeningeal progression (10%). At recurrence, 15 patients received an oncological treatment that consisted of an alkylating chemotherapy (n=5), a bevacizumab based chemotherapy regimen (n=9) and of radiotherapy (n=1). Median PFS and OS after first recurrence in these patients were 6 and 14 months, respectively. An activating FGFR1 mutation was identified in 4 out of the 9 patients in whom it was assessed. CONCLUSION At recurrence, adult diffuse H3K27M-mutant gliomas are associated with a high rate of distant locations. A subset of patients harbor targetable FGFR1 activating mutations.
Manual of Practical Obstetrics.
Journal: JAMA (1894)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Yin Yang 1 Suppresses Dilated Cardiomyopathy and Cardiac Fibrosis Through Regulation of <i>Bmp7</i> and <i>Ctgf</i>
Authors: Chia Yee Tan, Jing Xuan Wong, Pui Shi Chan, Hansen Tan, Dan Liao, Weiming Chen, Lek Wen Tan, Matthew Ackers-Johnson, Hiroko Wakimoto, Jonathan G. Seidman, Christine E. Seidman, Ida Gjervold Lunde, Feng Zhu, Qidong Hu, Jinsong Bian, Jiong-Wei Wang, Roger S. Foo, Jianming Jiang
Journal: Circulation Research (2019)

Pathogenic variations in the lamin gene (LMNA) cause familial dilated cardiomyopathy (DCM). LMNA insufficiency caused by LMNA pathogenic variants is believed to be the basic mechanism underpinning LMNA-related DCM.To assess whether silencing of cardiac Lmna causes DCM and investigate the role of Yin Yang 1 (Yy1) in suppressing Lmna DCM.We developed a Lmna DCM mouse model induced by cardiac-specific Lmna short hairpin RNA. Silencing of cardiac Lmna induced DCM with associated cardiac fibrosis and inflammation. We demonstrated that upregulation of Yy1 suppressed Lmna DCM and cardiac fibrosis by inducing Bmp7 expression and preventing upregulation of Ctgf. Knockdown of upregulated Bmp7 attenuated the suppressive effect of Yy1 on DCM and cardiac fibrosis. However, upregulation of Bmp7 alone was not sufficient to suppress DCM and cardiac fibrosis. Importantly, upregulation of Bmp7 together with Ctgf silencing significantly suppressed DCM and cardiac fibrosis. Mechanistically, upregulation of Yy1 regulated Bmp7 and Ctgf reporter activities and modulated Bmp7 and Ctgf gene expression in cardiomyocytes. Downregulation of Ctgf inhibited TGF-β (transforming growth factor-β)/Smad signaling in DCM hearts. Regulation of both Bmp7 and Ctgf further suppressed TGFβ/Smad signaling. In addition, co-modulation of Bmp7 and Ctgf reduced CD3+ T cell numbers in DCM hearts.Our findings demonstrate that upregulation of Yy1 or co-modulation of Bmp7 and Ctgf offer novel therapeutic strategies for the treatment of DCM caused by LMNA insufficiency.
Regulatory T cells in skin are uniquely poised to suppress profibrotic immune responses
Authors: Lokesh A. Kalekar, Jarish N. Cohen, Nicolas Prevel, Priscila Muñoz Sandoval, Anubhav N. Mathur, Joshua M. Moreau, Margaret M. Lowe, Audrey Nosbaum, Paul J. Wolters, Anna Haemel, Francesco Boin, Michael D. Rosenblum
Journal: Science Immunology (2019)

Skin T regs depend on GATA3 to attenuate immune cell–stimulated cutaneous fibrosis. See the related Focus by Bal and Stadhouders .
Annals Story Slam - Orange You Glad I Am Not Your Kid: When the Research Hits Close to Home
Authors: Rosemary Frasso
Journal: Annals of Internal Medicine (2019)

Web Exclusives3 September 2019Annals Story Slam - Orange You Glad I Am Not Your Kid: When the Research Hits Close to HomeFREERosemary Frasso, PhD, CPHRosemary Frasso, PhD, CPHSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W19-0016 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - Orange You Glad I Am Not Your Kid: When the Research Hits Close to Home "Orange You Glad I Am Not Your Kid: When the Research Hits Close to Home," by Rosemary Frasso, PhD, CPH (Duration 5:05)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 3 September 2019Volume 171, Issue 5Page: SS1 ePublished: 3 September 2019 Issue Published: 3 September 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.Loading ...
P14.29 Prediction of overall survival in patients with malignant glioma using dynamic O-(2-[18F]-fluoroethyl)-L-tyrosine PET
Authors: E K Bauer, G Stoffels, T Blau, G Reifenberger, J M Werner, P Lohmann, M Rapp, G R Fink, K Langen, N Galldiks
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Characterization of gliomas according to the revised World Health Organization (WHO) classification of 2016 has gained major importance regarding prognostication. The present study aimed at exploring the prognostic value of dynamic O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET in newly diagnosed and molecularly defined astrocytic high-grade glioma (HGG) of the WHO grades III or IV. MATERIAL AND METHODS Before initiation of treatment, dynamic FET PET imaging was performed in patients with newly diagnosed glioblastoma (GBM) and anaplastic astrocytoma (AA). Static FET PET parameters such as maximum and mean tumor/brain ratios (TBRmax/mean), as well as the dynamic FET PET parameters time-to-peak (TTP) and slope, were obtained. The predictive ability of FET PET parameters was evaluated with regard to the overall survival (OS). Using ROC analyses, threshold values for FET PET parameters were obtained. Subsequently, univariate Kaplan-Meier and multivariate Cox regression survival analyses were performed to assess their predictive power for OS. RESULTS Sixty patients (45 GBM, 15 AA) of two university centers were retrospectively identified. Patients with a methylated MGMT promoter as well as with an IDH mutation had a significantly longer OS (both P&lt;0.001). Furthermore, ROC analysis revealed in IDH-wildtype HGG (n=45) that a TTP&gt;25 minutes (AUC, 0.90; sensitivity, 90%; specificity, 87%; P&lt;0.001) was highly prognostic for a longer OS (29 vs. 12 months; P&lt;0.001). Besides a complete resection and a methylated MGMT promoter, TTP remained significant in the multivariate survival analysis (P=0.002, P=0.016, and P=0.003, respectively), indicating an independent predictor for OS. In contrast, both TBRmax and TBRmean were not prognostic (AUC, 0.37 and 0.32, respectively). CONCLUSION Data suggest that within the subgroup of patients with newly diagnosed and untreated IDH-wildtype GBM and AA, dynamic FET PET additionally allows the identification of patients with an improved OS.
NHS to step up efforts to tackle “health emergency” of climate change
Authors: Gareth Iacobucci
Journal: BMJ (2019)

The NHS will accelerate its efforts to tackle climate change with a series of coordinated measures to reduce its carbon output, the chief executive of NHS England has said.

The health service should also embolden staff to lead discussions with the public about the wider measures needed to tackle climate change, said Simon Stevens.

The comments came during a panel at the Health and Care Innovation Expo in Manchester, at which participants discussed how the NHS should work with local government and other partners to lead the agenda on climate change.

“The climate emergency is a health emergency,” Stevens said. “We, the NHS, as the …
Abstract P053: Diabetes Risk Prediction and Sickle Cell Trait in African Americans From CARDIA and the Jackson Heart Study
Authors: Mary E Lacy, Gregory A Wellenius, Adolfo Correa, Mercedes R Carnethon, Robert I Leim, Xi Luo, James G Wilson, Annie Gjelsvik, April P Carson, David R Jacobs, Charles B Eaton, Wen-Chih Wu
Journal: Circulation (2017)

Introduction: Existing models to predict incident diabetes mellitus (DM) perform better in Whites than African Americans. In models that incorporate hemoglobin A1c (A1C) as a predictor of DM, the difference in model performance by race is more pronounced. In a recent study, we found that A1C was systematically underestimating glycemia in African Americans with sickle cell trait (SCT). Hypothesis: Given the poorer performance of DM prediction models in African Americans than Whites and the impact of SCT on the A1C-glycemia association, we hypothesized that incorporating sickle cell trait into DM prediction models would improve the ability of the model to predict future risk of DM. Methods: We pooled data collected from 2000-2012 on 3,122 African Americans (8.6% with SCT) from the Jackson Heart Study (JHS; n=2,065; mean age=54.71 years) and CARDIA (n=1,057; mean age=44.53). Over 5 years of follow-up in CARDIA and 10 years of follow-up in JHS, 85 CARDIA participants (8.1%) and 342 JHS participants (16.6%) developed DM. Using generalized estimating equations to account for correlation of repeated measures, we compared the discriminative ability and net reclassification improvement (NRI) resulting from the addition of SCT for a series of prediction models. Results: Overall, the addition of SCT to prediction models did not result in significant improvement in the discriminative ability. However, by the NRI index, the addition of SCT to measures of glycemia and to a fuller risk prediction model did improve prediction of DM. In the full model, adding SCT*A1C as a predictor resulted in 2% of events being reclassified as higher risk and 45% of non-events being reclassified as lower risk. Conclusion: Our results suggest that incorporating SCT into DM prediction for African Americans may result in modest improvement in model performance.