tbuckley/cabot-search huggingface dataset:
Pattern of utilization of pegfilgrastim in patients with chemotherapy-induced neutropenia: A retrospective analysis of administrative claims data
Authors: A. T. Skarin, F. Vekeman, F. Laliberté, O. Afonja, M. Lafeuille, V. Barghout, M. S. Duh
Journal: Journal of Clinical Oncology (2009)

9624 Background: Pegfilgrastim is a long-acting granulocyte colony-stimulating factor (G-CSF) used to prevent or treat febrile neutropenia associated with myelosuppressive anticancer therapies. According to the prescribing information, pegfilgrastim should not be administered within 14 days before or 24 hours after cytotoxic chemotherapy because of the potential for myeloid toxicity. This study examined use patterns of pegfilgrastim in real-life practice. Methods: Analysis of health insurance claims data in 2000- 2007 from &gt; 35 large health plans across the US was conducted. Patients who had a cancer diagnosis and chemotherapy within 120 days of their first pegfilgrastim injection were identified. The proportion of pegfilgrastim injections that were followed by administration of chemotherapy within 11 and 9 days was calculated. Analysis was also stratified by cancer type [Non-Hodgkin's lymphoma (NHL), lung, breast]. Results: A total of 13,526 cancer patients received 57,118 pegfilgrastim injections. NHL, lung, and breast cohorts comprised 2,722, 2,772, and 4,955 patients, respectively. Mean age (SD) was 55.0 (11.6) and women represented 65.9% of study population. Among all cancer types, 19.2% of pegfilgrastim injections had a chemotherapy claim within the following 11 days. This pattern of use was the highest in NHL (18.9%), followed by lung (17.1%), and breast (16.2%). Similar results were observed in the 9-day sensitivity analysis (see Table ). Conclusions: Based on the retrospective analysis of this administrative claims database, the use of pegfilgrastim within 11 days of an administration of chemotherapy was observed in 15–20% of cases which is inconsistent with the recommended guidelines. Pegfilgrastim use in these situations may have the potential to increase sensitivity of rapidly dividing myeloid cells to cytotoxic chemotherapy. Further research is being conducted to assess the related clinical and economic impact of this pattern of usage. [Table: see text] [Table: see text]
Returning to School in the Era of COVID-19
Authors: Danielle G. Dooley, Joelle N. Simpson, Nathaniel S. Beers
Journal: JAMA Pediatrics (2020)

Emily Kroshus, ScD, MPH; Matt Hawrilenko, PhD; Pooja S. Tandon, MD, MPH; Dimitri A. Christakis, MD, MPH
A new approach to an old problem: Overview of the East African Community’s Medicines Regulatory Harmonization initiative
Authors: Margareth Ndomondo-Sigonda, Gugu Mahlangu, Margaret Agama-Anyetei, Emer Cooke
Journal: PLoS Medicine (2020)

Substandard and/or falsified medical products may result in treatment failure and/or death.• The capacity to regulate medical products is key for ensuring the quality, safety, and efficacy of medical products circulating in a market.
Maternal High-Dose Vitamin D Supplementation and Offspring Bone Mineralization Until Age 6 Years—Reply
Authors: Nicklas Brustad, Hans Bisgaard, Bo L. Chawes
Journal: JAMA Pediatrics (2020)

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 Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Pediatrics journal
Consent, capacity and compliance in concussion management: cave ergo medicus (let the doctor beware)
Authors: Michael Turner, David Maddocks, Majid Hassan, Adrian Anderson, Paul McCrory
Journal: British Journal of Sports Medicine (2020)

While the acute effects of concussion and mild traumatic brain injury (TBI) are well understood, the certainty in the medical literature regarding the long-term outcomes of sports-related concussion is limited. Long-term deficits that may result from single, repeated concussions, and possibly subconcussive impacts, include cognitive dysfunction, depression and executive dysfunction. Perhaps most troublingly, repetitive head impacts have been linked to neurodegenerative diseases, including chronic traumatic encephalopathy (CTE), although the precise risk of long-term consequences remains unknown. CTE represents a distinct tauopathy with an unknown incidence in athletic populations; however, a cause and effect relationship has not yet been demonstrated between CTE and concussions or between CTE and exposure to contact sports, as no prospective longitudinal studies have been performed to address that question. Studies of high-school sports exposure and long-term outcomes have not demonstrated consistent findings. Medical advice regarding return to play and the risk of acute and/or long-term consequences is therefore problematic. It is important that the individual’s right to make their own choices regarding their health is respected. Team, coach, parental, peer or financial pressures should not influence this decision. The choice to return to play after a concussion or mild TBI injury is the athlete’s decision once they have (1) recovered from their injury and have the legal capacity to make an informed decision; (2) been medically assessed and (3) been informed of any possible long-term risks in a language that they can understand. Given the current lack of certainty in relation to long-term outcomes from concussion, is it possible to provide a framework to inform players of current evidence, as part of a consent process, even if the information upon which the decision to return to sport is based remains uncertain and evolving?
Association Between Number of In-Person Health Care Visits and SARS-CoV-2 Infection in Obstetrical Patients
Authors: Sharon C. Reale, Kara G. Fields, Mario I. Lumbreras-Marquez, Chih H. King, Stacey L. Burns, Krista F. Huybrechts, Brian T. Bateman
Journal: JAMA (2020)

This case-control study estimates the risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among pregnant women making antenatal visits to 4 Boston, Massachusetts, area hospitals during April-June 2020 vs uninfected controls matched on gestational age.
Identification of Undetected Monogenic Cardiovascular Disorders
Authors: Jawan W. Abdulrahim, Lydia Coulter Kwee, Fawaz Alenezi, Albert Y. Sun, Aris Baras, Teminioluwa A. Ajayi, Ricardo Henao, Christopher L. Holley, Robert W. McGarrah, James P. Daubert, Lauren K. Truby, Sreekanth Vemulapalli, Andrew Wang, Michel G. Khouri, Svati H. Shah
Journal: Journal of the American College of Cardiology (2020)
Overseas doctors stranded by cancelled exams can stay in UK without extra visa costs
Authors: Abi Rimmer
Journal: BMJ (2020)

The Home Office will allow doctors left stranded in the UK by postponed exams to stay in the country long enough to take the rescheduled tests at no extra cost.

In June the BMA wrote to the home secretary, Priti Patel, about the more than 3000 doctors who were waiting to take their second Professional and Linguistic Assessments Board (PLAB 2) test, the final assessment needed before overseas doctors are granted a licence to practise …
Association of Recent Stressful Life Events With Mental and Physical Health in the Context of Genomic and Exposomic Liability for Schizophrenia
Authors: Lotta-Katrin Pries, Jim van Os, Margreet ten Have, Ron de Graaf, Saskia van Dorsselaer, Maarten Bak, Bochao D. Lin, Kristel R. van Eijk, Gunter Kenis, Alexander Richards, Michael C. O’Donovan, Jurjen J. Luykx, Bart P. F. Rutten, Sinan Guloksuz
Journal: JAMA Psychiatry (2020)

Both adulthood stressful life events (SLEs) and liability for schizophrenia have been associated with poor mental and physical health in the general population, but their interaction remains to be elucidated to improve population-based health outcomes.
Annals Graphic Medicine - The Palliative Path
Authors: Frank Deng
Journal: Annals of Internal Medicine (2020)

Web Exclusives18 August 2020Annals Graphic Medicine - The Palliative PathFREEFrank DengFrank DengBrown University, Providence, Rhode Island (F.D.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G19-0067 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Brown University, Providence, Rhode Island (F.D.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G19-0067.Author/Illustrator Information: Frank Deng (e-mail, [email protected]edu).This article was published at Annals.org on 11 August 2020. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 18 August 2020Volume 173, Issue 4Page: W67-W68KeywordsConflicts of interestDisclosureHealth care ePublished: 11 August 2020 Issue Published: 18 August 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
PTH-086 Biological therapy in elderly onset ibd: sense,science and sensibility
Authors: B Miller, B Crooks, W Garr, A Sorrentino, J Scott, U Nosegbe, J Limdi
Journal: Gut (2017)

Introduction  The role of biological therapies in the decisive induction and maintenance of remission of moderate-severe inflammatory bowel disease (IBD) is established through pivotal trials. There is a lack of data on their use in older patients. The primary aims of our study were to assess the efficacy and safety of biological therapies in older IBD patients at our institution.  Method  We conducted a retrospective study of patients aged 60 and above with IBD treated with a biological agent at our institution. Data was collected using electronic case records and included demographics, disease characteristics (Montreal classification), treatment and adverse events.  Results  Of 56 patients over the age of 60 who were treated with a biologic, 30 were diagnosed with IBD age 60 or over (range 60–84, median 66 years), 16 of whom were male. 15 patients had Crohn’s disease (CD), 13 had a diagnosis of Ulcerative colitis (UC) and 2 had IBD unspecified. Median time to first biologic was 19 months (range 0–188). Median duration on biological therapy was 16 months (range 0.5–72 months). 50% of the patients were on concomitant immunomodulator therapy: 2 patients on methotrexate and 13 patients on azathioprine.  Initial biological therapy was with infliximab (25 patients) or adalimumab (5 patients). Clinical response was noted in 25, partial response in 1 and 2 were primary non-responders. Data was not available for 2 patients. At 6 month follow-up, 21 patients showed continued clinical response to therapy, 1 showed a partial response and 1 patient had loss of response. 7 patients had loss of response at a later date (range 10–56 months).  9 patients required a switch in biological therapy to adalimumab (8) or vedolizumab (1). 6 patients demonstrated clinical response at 10 weeks, 2 patients had a partial response and 1 patient had no documented follow-up.  5 patients had major adverse events from biological therapy: 1 patient died due to cryptococcal meningitis, 3 patients required admission due to opportunistic infection and 1 patient required surgery for non-response to medical therapy. 10 patients suffered from minor adverse events due to biological therapy: infection not requiring hospital admission (4), infusion reaction to infliximab (2), basal cell carcinoma requiring excision (1), intolerance (1), arthralgia (1), transient neutropenia (1).  Conclusion  Anti-TNF therapy may be effective in well-selected patients with elderly-onset IBD but may be associated with significant adverse effects. Real world safety and efficacy data are urgently needed to enable clinicians to make personalised but evidence-based decisions for considered and optimal management of older patients with IBD.  Disclosure of Interest  None Declared
Hedgehog Pathway Inhibitors: A New Therapeutic Class for the Treatment of Acute Myeloid Leukemia
Authors: Catriona Jamieson, Giovanni Martinelli, Cristina Papayannidis, Jorge E. Cortes
Journal: Blood Cancer Discovery (2020)

Abstract Targeting Hedgehog (Hh) pathway components, such as Smoothened (SMO), is a developing strategy for the treatment of acute myeloid leukemia (AML) and for overcoming relapsed/refractory forms of this disease. Several SMO inhibitors are in clinical development for the treatment of various tumor types and the results from some clinical trials in AML have been reported. This review will discuss the role of Hh signaling in AML pathogenesis, describe the preclinical and clinical development of Hh pathway inhibitors for the treatment of AML, and examine the current evidence on Hh pathway inhibitor resistance and the implications for treatment selection in AML. Significance: In acute myeloid leukemia (AML), components of the Hedgehog (Hh) signaling pathway, such as Smoothened (SMO), have been implicated in the development, maintenance, and expansion of leukemic stem cells (LSC), as well as sensitization to chemotherapy and the development of drug resistance in AML. Observations in preclinical studies of AML, as well as from samples of patients with AML, demonstrate that Hh pathway inhibitors act primarily on the stem cell pathway as differentiation agents. The current data for hematologic malignancies indicate the potential for a synergistic effect when a Hh pathway inhibitor is administered in combination with chemotherapy or investigational agents. It is thought that Hh pathway inhibitors act as agents that reduce LSC dormancy and promote LSC differentiation, thus the newly dividing LSCs can then be targeted by other chemotherapeutic drugs.
Preservation of alveolar ridge height through mechanical memory: A novel dental implant design
Authors: Shi Yin, Wenjie Zhang, Yanmei Tang, Guangzheng Yang, Xiaolin Wu, Sihan Lin, Xuanyong Liu, Huiliang Cao, Xinquan Jiang
Journal: Bioactive Materials (2020)

Irreversible marginal bone loss can hinder recovery around dental implants. Insufficient alveolar osteogenesis and stress concentration during chewing contribute to marginal bone resorption and can result in implant failure. A biomaterial with a micropore-channel structure was developed using 3D printing technology. This design facilitated bony ingrowth and provided similar mechanical stimulation at the implant neck during mastication to a natural tooth. The micropore channels provided a guiding structure for bone mesenchymal stem cell proliferation and differentiation without the need for growth factors. Specifically, this was achieved through mechanical transduction by F-actin remodeling and the activation of Yes-associated protein (YAP). The implants were verified in a canine dental implant surgery model, which demonstrated the promising use of biomaterial-based dental implants in future clinical applications.
Abstract 12739: A Reduction in Novel Long Noncoding RNA lncX Exacerbates Heart Failure Accompanied CKD
Authors: Takuya Kumazawa, Hitoshi Nakagawa, Yasuki Nakada, Tomoya Nakano, Kenji Onoue, Yoshihiko Saito
Journal: Circulation (2018)

Background: Patients with chronic kidney disease (CKD) are highly prone to cardiovascular diseases, including heart failure, cardiac hypertrophy, and atherosclerosis, named as the cardio-renal synd...
Abstract 12099: Exercise Training of Different Intensities in Heart Failure With Ischemic and Non-Ischemic Etiology - Results From the SMARTEX Trial
Authors: Martin Halle, Eva Prescott, Axel Linke, Oyvind Ellingsen
Journal: Circulation (2018)

Introduction: Exercise training of moderate intensity is recommended for patients with Heart Failure with reduced Ejection Fraction (HFrEF). Hypothesis: It is unknown, whether the etiology of HFrEF...
Contrasting contributions of TNF from distinct cellular sources in arthritis
Authors: Andrey Kruglov, Marina Drutskaya, Dirk Schlienz, Ekaterina Gorshkova, Katharina Kurz, Lars Morawietz, Sergei Nedospasov
Journal: Annals of the Rheumatic Diseases (2020)

Objectives Neutralisation of tumour necrosis factor (TNF) is widely used as a therapy for rheumatoid arthritis (RA). However, this therapy is only effective in less than a half of patients and is associated with several side effects. We hypothesised that TNF may possess non-redundant protective and immunomodulatory functions in vivo that cannot be blocked without a cost. The present work aimed to identify cellular sources of protective and pathogenic TNF, and its molecular forms during autoimmune arthritis. Methods Mice lacking TNF expression by distinct cell types, such as myeloid cells and T or B lymphocytes, were subjected to collagen-induced arthritis (CIA) and collagen antibody-induced arthritis. Mice lacking soluble TNF production were also employed. The severity and incidence of the disease, as well as humoral and cellular responses were assessed. Results Myeloid cell-derived TNF contributes to both induction and pathogenesis of autoimmune arthritis. Conversely, T cell-derived TNF is protective during the induction phase of arthritis via limiting of interleukin-12 production by dendritic cells and by subsequent control of autoreactive memory T cell development, but is dispensable during the effector phase of arthritis. B cell-derived TNF mediates severity of CIA via control of pathogenic autoantibody production. Conclusions Distinct TNF-producing cell types may modulate disease development through different mechanisms, suggesting that in arthritis TNF ablation from restricted cellular sources, such as myeloid cells, while preserving protective TNF functions from other cell types may be superior to pan-anti-TNF therapy.
Targeted Intraoperative Radiotherapy for Early Breast Cancer—Reply
Authors: Jayant Sharad Vaidya, Max Bulsara, Michael Baum
Journal: JAMA Oncology (2020)

In Reply We thank Shah et al, Bentzen et al, and Fastner et al for their comments on our randomized clinical trial of delayed second-procedure targeted intraoperative radiotherapy (TARGIT-IORT).1 We address their points here.
P21-Activated Kinase 1: Emerging biological functions and potential therapeutic targets in Cancer
Authors: Dahong Yao, Chenyang Li, Muhammad Shahid Riaz Rajoka, Zhendan He, Jian Huang, Jinhui Wang, Jin Zhang
Journal: Theranostics (2020)

The p21-Activated kinase 1 (PAK1), a member of serine-threonine kinases family, was initially identified as an interactor of the Rho GTPases RAC1 and CDC42, which affect a wide range of processes associated with cell motility, survival, metabolism, cell cycle, proliferation, transformation, stress, inflammation, and gene expression. Recently, the PAK1 has emerged as a potential therapeutic target in cancer due to its role in many oncogenic signaling pathways. Many PAK1 inhibitors have been developed as potential preclinical agents for cancer therapy. Here, we provide an overview of essential roles that PAK1 plays in cancer, including its structure and autoactivation mechanism, its crucial function from onset to progression to metastasis, metabolism, immune escape and even drug resistance in cancer; endogenous regulators; and cancer-related pathways. We also summarize the reported PAK1 small-molecule inhibitors based on their structure types and their potential application in cancer. In addition, we provide overviews on current progress and future challenges of PAK1 in cancer, hoping to provide new ideas for the diagnosis and treatment of cancer.
An <i>In Vivo Kras</i> Allelic Series Reveals Distinct Phenotypes of Common Oncogenic Variants
Authors: Maria Paz Zafra, Marie J. Parsons, Jangkyung Kim, Direna Alonso-Curbelo, Sukanya Goswami, Emma M. Schatoff, Teng Han, Alyna Katti, Maria Teresa Calvo Fernandez, John E. Wilkinson, Elena Piskounova, Lukas E. Dow
Journal: Cancer Discovery (2020)

Abstract KRAS is the most frequently mutated oncogene in cancer, yet there is little understanding of how specific KRAS amino acid changes affect tumor initiation, progression, or therapy response. Using high-fidelity CRISPR-based engineering, we created an allelic series of new LSL-Kras mutant mice, reflecting codon 12 and 13 mutations that are highly prevalent in lung (KRASG12C), pancreas (KRASG12R), and colon (KRASG13D) cancers. Induction of each allele in either the murine colon or pancreas revealed striking quantitative and qualitative differences between KRAS mutants in driving the early stages of transformation. Furthermore, using pancreatic organoid models, we show that KRASG13D mutants are sensitive to EGFR inhibition, whereas KRASG12C-mutant organoids are selectively responsive to covalent G12C inhibitors only when EGFR is suppressed. Together, these new mouse strains provide an ideal platform for investigating KRAS biology in vivo and for developing preclinical precision oncology models of KRAS-mutant pancreas, colon, and lung cancers. Significance: KRAS is the most frequently mutated oncogene. Here, we describe new preclinical models that mimic tissue-selective KRAS mutations and show that each mutation has distinct cellular consequences in vivo and carries differential sensitivity to targeted therapeutic agents. See related commentary by Kostyrko and Sweet-Cordero, p. 1626. This article is highlighted in the In This Issue feature, p. 1611
3rd Party CMV-Specific T Cells Provide Long Term Protection Against Episodes of Recurrent CMV after Allogeneic Stem Cell Transplant Despite Lack of Persistence in Peripheral Blood
Authors: Emily Blyth, Barbara Withers, Leighton Edward Clancy, Agnes S. M. Yong, Christopher Fraser, Jane Burgess, Renee Simms, Gloria Castellano Gonzalez, David Kliman, Ming-Celine Dubosq, David Bishop, Gaurav Sutrave, Chun Kei Kris Ma, Peter J. Shaw, Kenneth P. Micklethwaite, David Gottlieb
Journal: Blood (2017)