tbuckley/cabot-search huggingface dataset:
Changes in the use of eythropoetin-stimulating agents (ESAs) in cancer patients: Before and after FDA safety advisories.
Authors: Dana Stafkey-Mailey, Mike Dickson, LeAnn B. Norris, Charles L. Bennett
Journal: Journal of Clinical Oncology (2012)

9143 Background: Benefits of ESAs in the treatment of cancer-induced anemia have been well documented, most importantly reducing the likelihood of patients needing red blood cell transfusions. However, in early 2007, the FDA issued a series of cautions and Black Box Warning (BBW), that ESAs may enhance tumor progression, increase likelihood of a VTE and decrease patient survival. The objective of this study is to elucidate population patterns and trends in ESA use for cancer patients pre- and post- the BBW and examine their associated outcomes. Methods: Data for this analysis was derived from South Carolina Medicaid claims. Patients with a diagnosis of Lung Cancer (162.x), Breast Cancer (174.x) or Non-Hodgkin's Lymphoma (200.x or 202.x) receiving chemotherapy between January 1, 1994 and December 31, 2010 were eligible for inclusion. The main outcome measures were ESA utilization, blood transfusion, and venous thromboembolism. The percentage of patients experiencing these outcomes were plotted over time to allow for visual examination of changes due to the BBW. In addition, we used multivariable logistic regression models to analyze each of the associated outcomes with clinical and demographic variables. Results: Among the 9,280 patients with one of the study cancers, an average of 25.4% received an ESA. The proportion of patients receiving an ESA increased from 6.2% in 1994 to a high of 47.1% in 2005 at which time utilization began to decline. In 2010, only 7.8% of these patients received an ESA. Use was associated with older age, female sex, and receipt of radiation therapy. The rate of blood transfusion varied sporadically throughout the study period from 5.2% (2008) to 11.7% (1994) (p&lt;0.0001). Venous thromboembolisms developed in 12.3% and 8.5% of patients receiving and not receiving an ESA, respectively (OR= 1.31;p&lt;0.001). Conclusions: As the FDA advisory cautioned, we find an increased risk of venous thromboembolisms associated with ESA use. In contrast to our a priori beliefs initial decline in utilization of ESAs began, in 2005, prior to the BBW and was likely due to changes in reimbursement rates. However, the BBW resulted in the largest decline in ESA use, 19.1 percentage points, between 2007 and 2008.
Prenatal Exposure to Phthalates and Newborn Telomere Length: A Birth Cohort Study in Wuhan, China
Authors: Lulu Song, Bingqing Liu, Mingyang Wu, Lina Zhang, Lulin Wang, Bin Zhang, Chao Xiong, Yuanyuan Li, Zhongqiang Cao, Youjie Wang, Shunqing Xu
Journal: Environmental Health Perspectives (2019)

Background: Telomere length (TL) is a marker of biological aging and is inversely related to aging-related diseases. The setting of TL at birth may have important implications for lifelong telomere dynamics; however, its determinants remain poorly understood. Objectives: The purpose of our study was to explore the relationships between prenatal exposure to phthalates and umbilical cord blood TL. Methods: A total of 762 mother–newborn pairs were recruited from a birth cohort study performed between November 2013 and March 2015 in Wuhan, China. Relative cord blood TL was measured using quantitative real-time polymerase chain reaction. Six phthalate metabolites were measured in urine samples acquired from pregnant women during the three trimesters. Multiple informant models were applied to estimate the associations between prenatal exposure to phthalates and cord blood TL and to evaluate potential windows of vulnerability. Results: Exposure to mono-ethyl phthalate (MEP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-butyl phthalate (MBP), and di(2-ethylhexyl) phthalate (ΣDEHP) during the first trimester were inversely related to cord blood TL. In addition, we observed a female-specific association between maternal exposure to MEP during the first trimester and cord blood TL (psex‐int=0.03). The associations between maternal exposure to MECPP, MEHHP, MEOHP, and ΣDEHP during the first trimester and cord blood TL were consistent between males and females (all psex‐int>0.10). Conclusion: This prospective study demonstrated that prenatal exposure to some phthalate metabolites were associated with shorter cord blood TL. Our results, if confirmed in other populations, may provide more evidence of adverse health outcomes of phthalate exposure and support the hypothesis that the intrauterine environment may be one of the major determinants for newborn TL. https://doi.org/10.1289/EHP4492
Psychiatry’s Obligation to Treat and Mitigate the Rising Burden of Age-Related Mental Disorders
Authors: Warren D. Taylor, Charles F. Reynolds
Journal: JAMA Psychiatry (2019)

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 Psychiatry 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 Psychiatry journal
A phase I/II trial of VX15/2503 in children, adolescents, and young adults with relapsed or refractory solid tumors (ADVL1614).
Authors: Emily Gustava Greengard, Robin Lesley Williams, Xiaowei Liu, Olga Militano, Terrence Lee Fisher, Elizabeth E. Evans, Charles G. Minard, Joel M. Reid, Stephan D. Voss, Stacey L. Berg, Elizabeth Fox, Brenda Weigel
Journal: Journal of Clinical Oncology (2019)

e21519 Background: Semaphorins regulate tumor progression, immune responses, and angiogenesis. SEMA4D was identified as a candidate proto-oncogene by a Sleeping Beauty forward genetic screen that induced osteosarcoma in mice. SEMA4D is expressed on tumors, including osteosarcoma, and in the tumor microenvironment. VX15/2503, a humanized IgG4 monoclonal antibody, binds SEMA4D, blocks receptor interaction and enhances the anti-tumor immune response in preclinical studies. This trial aimed to determine the tolerability and recommended dose of VX15/2503 in patients with relapsed/refractory solid tumors and activity in patients with osteosarcoma. Methods: Part A enrolled patients age≤ 21y with refractory solid tumors to assess the tolerability of VX15/2503 (20 mg/kg) IV every 14 days x 2 doses/cycle. The recommended dose was one that was tolerated and achieved sustained target saturation. Up to 6 additional children were enrolled to assess pharmacokinetics (PK). In part B, a two-stage design was used to assess the activity of VX15/2503 in patients with measurable, relapsed /refractory osteosarcoma. In part B1 patients &gt; 21-30y accrued concurrently with part A; Part B2 (patients £ 21y) was initiated after the pediatric recommended dose was determined. Correlative studies including target saturation by VX15/2503 were required. Results: 18 eligible patients enrolled, 16 evaluable for toxicity. In part A (n = 12) the median (range) age was 12.5 (1-20) y. Diagnoses included osteosarcoma (8), neuroblastoma (2), other (2). No dose limiting toxicities (DLTs) were observed. In Part B1, (n = 6) median (range) age was 22.5 (22-30) y; one patient had cycle 1 DLTs (grade 3 acute kidney injury, creatinine increase, arthralgia and myalgia); a second patient had a later cycle DLT (grade 4 pericardial effusion). Given only 1/18 had a cycle 1 DLT, this did not impact dose selection. T-cell saturation by VX15/2503 was adequate and sustained in all patients. Conclusions: VX15/2503 was well tolerated at 20 mg/kg IV every 2 weeks and is the recommended dose in children, adolescents and young adults. The activity in osteosarcoma is under evaluation. Future trials combining VX15/2503 with novel agents are in development. Clinical trial information: NCT03320330.
Once-daily oral omadacycline versus twice-daily oral linezolid for acute bacterial skin and skin structure infections (OASIS-2): a phase 3, double-blind, multicentre, randomised, controlled, non-inferiority trial
Authors: William O'Riordan, Carrie Cardenas, Elliot Shin, Alissa Sirbu, Lynne Garrity-Ryan, Anita F Das, Paul B Eckburg, Amy Manley, Judith N Steenbergen, Evan Tzanis, Paul C McGovern, Evan Loh
Journal: The Lancet Infectious Diseases (2019)
A phase II, double-blinded, randomized study using a proprietary amino acid mixture as diarrhea prevention in patients undergoing autologous stem cell transplantation (AST) for multiple myeloma (MM) and non-Hodgkin lymphoma (NHL).
Authors: Laura Luque, Robert Soiffer, Brett Glotzbecker, Haesook Kim, Zachariah Michael DeFilipp, Dorothy Mary Kate Keefe
Journal: Journal of Clinical Oncology (2019)

11607 Background: Melphalan, remains the mainstay of conditioning for autologous hematopoietic stem cell transplantation (HSCT) in multiple myeloma (MM) and non-Hodgkin lymphoma (NHL) patients. Gastrointestinal symptoms represent the most significant non-hematologic toxicities following high-dose melphalan conditioning, with approximately 40% of patients experiencing CTCAE grade 2 or higher diarrhea following conditioning regimens containing melphalan. Enterade is a proprietary blend of electrolytes and five amino-acids that can facilitate retention of the absorbing capacity of the small intestine by rebuilding the villi and reduce antigenic translocation by tightening the mucosal barrier. In a study of irradiated mice, enterade improved survival and improved body weight following irradiation. The goal was to investigate the effectiveness of enterade to reduce GI toxicities after high-dose melphalan chemotherapy. Methods: The trial was designed as a Phase 2, multi-center, double-blinded, 2-arm randomized study. 114 MM or NHL patients were enrolled between October 2016 and October 2017. Patients received either two 8oz bottles/day of enterade or placebo starting on the day of admission through Day +14. GI toxicity was scored by the CT-CAE 4.0 system from admission through Day + 14. Compliance was arbitrarily set at consumption of 2 bottles daily for 11+ days. Results: Of the 114 enrolled patients, 99 (61 MM, 38 NHL) attempted to consume at least 1 dose of enterade/placebo. Compliance overall was much lower than anticipated; with no MM patients achieving compliance compared to 34.2% in the NHL group. Compliance in NHL patients was 31.6% in the enterade group versus 36.8% in the placebo group. Analysis of primary endpoint in NHL patients showed a 16% incidence of diarrhea ≥ grade 2 in enterade compliant patients versus 86% in the placebo group (p= 0.02). Conclusions: Eleven days of two 8oz bottles of liquid is a difficult task during ASCT, especially for MM with nausea, altered taste and poor appetite. For those NHL patients, compliant per protocol (who consumed ≥11 days), enterade significantly reduced diarrhea. The use of enterade to prevent diarrhea following high-dose chemotherapy should be explored further in populations capable of reasonable oral intake. Clinical trial information: NCT02919670.
Solid organ transplantation after treatment for childhood cancer: a retrospective cohort analysis from the Childhood Cancer Survivor Study
Authors: Andrew C Dietz, Kristy Seidel, Wendy M Leisenring, Daniel A Mulrooney, Jean M Tersak, Richard D Glick, Cathy A Burnweit, Daniel M Green, Lisa R Diller, Susan A Smith, Rebecca M Howell, Marilyn Stovall, Gregory T Armstrong, Kevin C Oeffinger, Leslie L Robison, Amanda M Termuhlen
Journal: The Lancet Oncology (2019)
A Text-Book on Diseases of the Ear, Nose and Throat.
Journal: JAMA (1901)

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
Interval-compressed vincristine, doxorubicin, cyclophosphamide (VAC), alternating with ifosfamide and etoposide (IE) for adults with Ewing or Ewing-like sarcoma.
Authors: Eric Lu, Christopher W. Ryan, Solange Bassale, Jeong Youn Lim, Lara Emily Davis
Journal: Journal of Clinical Oncology (2019)

11025 Background: In Children’s Oncology Group trial AEWS0031, VAC alternating with IE administered every 2 weeks rather than every 3 weeks resulted in a superior event-free survival (EFS). In the 2-week dosing group, a median interval of 15 days (mean 17.3) was achieved. Only 12% of patients enrolled in the trial were age 18+ and thus the feasibility of interval-compressed VAC/IE in the adult population remains poorly described. We conducted a retrospective analysis of our institutional experience using this regimen. Methods: Pharmacy administration records at Oregon Health and Science University were reviewed to identify patients age 18+ with Ewing and Ewing-like sarcoma who received VAC/IE q2wk, with first dose between January 2011 and March 2018. Results: 24 patients were identified. Median age was 28 (range 18 to 60). At diagnosis, 67% had localized disease. The most common primary sites were extremity (38%) and pelvis (17%); another 25% had extra-osseous primary tumors. Local therapy included surgery in 50% and XRT in 33% of subjects. The median interval between cycles was 16.7 days (mean 17.5). The median number of admissions for toxicity per patient was 2. The median number of dose delays (toxicity prolonging the 2 week interval) per patient was 4. Early treatment discontinuation occurred in 17%. Cumulative doses are outlined in Table. 5-year overall survival was 41%. 5-year EFS was 52% among patients with localized disease and 0% among those with metastatic disease. Conclusions: For adults with Ewing and Ewing-like sarcoma, chemotherapy administered every 2 weeks is a feasible and effective therapy, without significant dose reductions required. Our results are comparable to prior studies involving a primarily pediatric population. [Table: see text]
Outcome of non-small cell lung cancer in females with gefitinib therapy: An experience from eastern India.
Authors: Tanweer Shahid, Soma Mukhopadhyay, Jayasri Basak, Sudeshna Gangopadhyay, Swati Dasgupta, Ashis Mukhopadhyay
Journal: Journal of Clinical Oncology (2012)

e18043 Background: Non-small cell lung carcinoma is usually an incurable disease with average overall survival of 7-9 months. But studies in recent years have shown that adenocarcinoma in nonsmokers with epidermal growth factor receptor (EGFR) positivity has shown disease control for longer duration. Female patients with adenocarcinoma where EGFR is positive show higher response rate with EGFR blocker. In eastern India, lung cancer contributes 21.3% of all cancers and female lung cancer contributes about 20% of them. The aim of our study was to see the age at diagnosis, histological type, EGFR status, smoking status and the response rate with Gefitinib, an EGFR tyrosine kinase inhibitor, for the female patients with carcinoma of lung. Methods: We randomly selected 50 female lung cancer patients, who had not previously received chemotherapy, during the period from November, 2006 to November, 2011. The mean age group at diagnosis was 55 years (range 26-85 years). 48 patients (96%) never had smoking habit, 2 (4%) were active smokers and the rest were passive smokers. Results: Twenty six (52%) patients had histological type of adenocarcinoma, 18 (36%) had squamas cell carcinoma, 4 were poorly differentiated and 2 (4%) had large cell carcinoma. Trucut biopsy showed EGFR positivity in 22 patients. All patients were started with single agent Gefitinib therapy at least for 6 months; after that according to response rate, same dose was continued. If there were progression of the disease, they were switched over to other chemotherapeutic agents. The median follow up was 1.5 years; the progression free survival (PFS) was seen in 19 (38%) patients. Adenocarcinoma patients with EGFR positivity had significantly higher PFS than those with non-adenocarcinoma and EGFR negative status. There was no difference of response rate between smokers and nonsmokers (never-smokers). Older patients showed higher response rates. Conclusions: Our data suggested that older patients with adenocarcinoma and EGFR positivity had long term progression free survival. So in developing countries like ours, where molecular diagnosis is not feasible many a times, this result might help clinicians to select a beneficial subgroup in female lung cancer patients.
Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders
Authors: Simone B. Sartori, Nicolas Singewald
Journal: Pharmacology & Therapeutics (2019)

Current medication for anxiety disorders is suboptimal in terms of efficiency and tolerability, highlighting the need for improved drug treatments. In this review an overview of drugs being studied in different phases of clinical trials for their potential in the treatment of fear-, anxiety- and trauma-related disorders is presented. One strategy followed in drug development is refining and improving compounds interacting with existing anxiolytic drug targets, such as serotonergic and prototypical GABAergic benzodiazepines. A more innovative approach involves the search for compounds with novel mechanisms of anxiolytic action using the growing knowledge base concerning the relevant neurocircuitries and neurobiological mechanisms underlying pathological fear and anxiety. The target systems evaluated in clinical trials include glutamate, endocannabinoid and neuropeptide systems, as well as ion channels and targets derived from phytochemicals. Examples of promising novel candidates currently in clinical development for generalised anxiety disorder, social anxiety disorder, panic disorder, obsessive compulsive disorder or post-traumatic stress disorder include ketamine, riluzole, xenon with one common pharmacological action of modulation of glutamatergic neurotransmission, as well as the neurosteroid aloradine. Finally, compounds such as D-cycloserine, MDMA, L-DOPA and cannabinoids have shown efficacy in enhancing fear-extinction learning in humans. They are thus investigated in clinical trials as an augmentative strategy for speeding up and enhancing the long-term effectiveness of exposure-based psychotherapy, which could render chronic anxiolytic drug treatment dispensable for many patients. These efforts are indicative of a rekindled interest and renewed optimism in the anxiety drug discovery field, after decades of relative stagnation.
Metastatic breast cancer subtypes and central nervous system metastases.
Authors: Caterina Aversa, Elena Geuna, Rossella Martinello, Andrea Milani, Valentina Rossi, Stefania Redana, Giorgio Valabrega, Massimo Aglietta, Filippo Montemurro
Journal: Journal of Clinical Oncology (2013)

e11581 Background: The relapse pattern, survival and response to therapy are known to be different between breast cancer (BC) subtypes defined by combining hormone-receptor (HR) and HER2 status. Our aim was to study incidence and predictors of central nervous system metastases (CNS-M) and the outcome after CNS-M according to tumor subtype. Methods: 488 patients (pts) treated with at least one line of chemotherapy for metastatic BC were retrospectively evaluated. According to the combination of HR and HER2 status, tumors were grouped in: Luminal (Lum): HR+/HER2-, Luminal/HER2+ (Lum/HER2+): HR+/HER2+, pure HER2 positive (pHER2+): HR-/HER2+, and triple negative (TN): HR-/HER2-. All HER2+ patients received treatment with Lapatinib or Trastuzumab in addition to chemotherapy for metastatic disease. Median follow up was 34 months. Results: 133 pts (27%) developed CNS-M, with a median time to CNS progression of 43 months. The rate of CNS-M by subtype was: Lum 18%, Lum/HER2+ 37%, pHER2+ 49%, TN 25% (p &lt;0.001). Multivariate analysis confirmed that, compared with Lum tumors, Lum/HER2+ ( HR 2.556, p&lt;0.001), pHER2+ (HR 4.444, p&lt;0.001) and TN (2.249, p=0.011) subtypes were at higher risk of CNS-M. Median overall survival (OS) CNS-M was 8.8 months in the whole series (IC 95% 6.6-11.0). Median OS in months by subtype was: Lum 9, Lum/HER2+ 18, pHER2+ 7, TN 7 (p&lt;0.001). Multivariate analysis revealed that belonging to the Lum/HER2+ subtype (HR 0.528 compared with the Lum subtype, p&lt;0.001) and having isolated CNS (HR 0.398, compared with CNS-M plus systemic progression, p&lt;0.001) predicted significantly reduced risk of death. Conclusions: Among pts with a known increased risk of brain metastases, the Lum/HER2+ subtype appears associated with the longest OS after CNS-M, probably due to different biology and better extracranial disease control by chemotherapy, hormonal therapy and target agents. These results suggest that these patients may benefit from a more aggressive treatment of CNS-M and, possibly, from the screening for asymptomatic CNS lesions.