tbuckley/cabot-search huggingface dataset:
Postmarket studies required by the US Food and Drug Administration for new drugs and biologics approved between 2009 and 2012: cross sectional analysis
Authors: Joshua D Wallach, Alexander C Egilman, Sanket S Dhruva, Margaret E McCarthy, Jennifer E Miller, Steven Woloshin, Lisa M Schwartz, Joseph S Ross
Journal: BMJ (2018)

<h3>Abstract</h3> <h3>Objectives</h3> To characterize postmarketing requirements for new drugs and biologics approved by the US Food and Drug Administration (FDA), and to examine rates and timeliness of registration, results reporting, and publication of required prospective cohort studies, registries, and clinical trials. <h3>Design</h3> Cross sectional analysis. <h3>Setting</h3> Postmarketing requirements for all new drugs and biologics approved by the FDA between 1 January 2009 and 31 December 2012, with follow-up up to 15 November 2017. <h3>Main outcome measures</h3> Postmarketing requirements and their characteristics known at the time of FDA approval, including FDA authority, study design, and study characteristics. Rates and timeliness of registration and results reporting on ClinicalTrials.gov and publication in peer reviewed journals of required prospective cohort studies, registries, and clinical trials. <h3>Results</h3> Between 2009 and 12, the FDA approved 97 new drugs and biologics for 106 indications with at least one postmarketing requirement at the time of first approval, for a total of 437 postmarketing requirements. Postmarket study descriptions were short (median word count 44 (interquartile range 29-71)) and often lacked information to determine an up to date progress (131 (30%)). 220 (50.3%) postmarketing requirements were for new animal or other studies (including pharmacokinetic studies); 134 (30.7%) were for prospective cohort studies, registries, and clinical trials; and 83 (19.0%) were for secondary analyses or follow-up studies. Of 110 clinical trials, 38 (34.5%), 44 (40.0%), 62 (56.4%), 66 (60.0%), and 98 (89.1%) did not report enough information to establish use of randomization, comparator type, allocation, outcome, and number of patients to be enrolled, respectively. Of 134 required prospective cohort studies, registries, and clinical trials, 102 (76.1%) were registered on ClinicalTrials.gov; of 50 registered and completed studies, 36 (72.0%) had reported results on ClinicalTrials.gov. Among 65 completed studies, 47 (72.3%) had either reported results or were published a median of 47 months (interquartile range 32-67) after FDA approval. 32 (68.1%) of these 47 studies did not report results publicly by the time of their original FDA report submission deadline. <h3>Conclusions</h3> Postmarketing requirements for new drugs and biologics were often briefly described and did not contain enough information to characterize study designs. Approximately three quarters of postmarketing requirements for prospective cohort studies, registries, and clinical trials were registered on ClinicalTrials.gov, and nearly three quarters of completed studies reported results or were published, suggesting that at least a quarter of these required studies are not being publicly disseminated.
Surgical Procedures for Patients With Severe Obesity—Reply
Authors: David Arterburn, Anirban Gupta
Journal: JAMA (2018)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Abstract A27: Exploring the role of glycosylation in pancreatic disease
Authors: Dannielle Engle, Hervé Tiriac, Arnaud Pommier, Christina Schoepfer, Brandon Da Silva, Melissa Yao, Youngkyu Park, Michael A. Hollingsworth, David Tuveson
Journal: Cancer Research (2018)

Abstract Pancreatic ductal adenocarcinoma (PDA) is almost uniformly lethal and surgical intervention is the only cure. Unfortunately, most patients are ineligible for resection because of the advanced stage of disease by the time of diagnosis. This is due in part to the lack of diagnostic tools, especially for families with elevated risk. The PDA biomarker, CA19-9, is measured in the blood to follow tumor burden longitudinally, but is neither sensitive nor specific enough to be used for diagnosis. The use of CA19-9 in PDA diagnosis is problematic given the elevation of CA19-9 in benign pancreatic disease, such as pancreatitis. While CA19-9 has been traditionally used as a diagnostic, retrospective studies reported that PDA patients who maintain a CA19-9 negative/low status have a significantly longer survival relative to those with higher CA19-9 levels in multivariate analyses. The functional significance of CA19-9 to PDA initiation, maintenance, and progression remains unclear due in part to the absence of this carbohydrate modification in mice. We found that expression of CA19-9 in the mouse pancreas is sufficient to induce pancreatitis, a benign proliferative condition that often confounds the diagnosis of PDA. Specifically, CA19-9 elevation resulted in rapid elevation of pancreatic enzymes in the blood, pancreatic infiltration of immune cells, acinar-to-ductal metaplasia and atrophy, as well as increased proliferation. Furthermore, we explored the utility of CA19-9 as a therapeutic target for both acute and chronic pancreatitis. This avenue of treatment strategy exhibits potential given that a pilot study demonstrated that turning off CA19-9 expression results in the normalization of pancreatic enzyme levels within four days following an acute episode of pancreatitis. Future work will focus on how elevation of this glycosylation modification mediates the development of pancreatitis by identifying the signaling pathways that are altered upon CA19-9 expression. In addition, we will explore the efficacy of therapeutically targeting CA19-9 in both pancreatitis and PDA with a larger goal of delineating the role of CA19-9 in pancreatic disease. Citation Format: Dannielle Engle, Hervé Tiriac, Arnaud Pommier, Christina Schoepfer, Brandon Da Silva, Melissa Yao, Youngkyu Park, Michael A. Hollingsworth, David Tuveson. Exploring the role of glycosylation in pancreatic disease [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr A27.
The Immunobiology of Receptor Activator for Nuclear Factor Kappa B Ligand and Myeloid‐Derived Suppressor Cell Activation in Immunoglobulin G4–Related Sclerosing Cholangitis
Authors: Min Lian, Qixia Wang, Xiang Jiang, Jun Zhang, Yiran Wei, Yanmei Li, Bo Li, Weihua Chen, Haiyan Zhang, Qi Miao, Yanshen Peng, Xiao Xiao, Li Sheng, Weici Zhang, Jingyuan Fang, Ruqi Tang, M. Eric Gershwin, Xiong Ma
Journal: Hepatology (2018)

The primary function of myeloid‐derived suppressor cells (MDSCs) is reflected in their immune modulatory role in several immune‐mediated diseases. In immunoglobulin G4 (IgG4)–related disease (IgG4‐RD), it has been hypothesized that there are selective regulatory defects that lead to a T helper 2 (Th2) bias immune response. Herein we have taken advantage of a large cohort of patients with IgG4‐related sclerosing cholangitis (IgG4‐SC), the most common extrapancreatic involvement of IgG4‐RD, as well as controls consisting of primary sclerosing cholangitis, autoimmune hepatitis, and healthy volunteers, to study MDSCs. We report dramatically increased levels of receptor activator for nuclear factor kappa B ligand (RANKL) expression in serum and liver from patients with IgG4‐SC compared to both liver‐disease and healthy controls. Moreover, in IgG4‐SC liver, RANKL‐secreting cells specifically colocalized with cluster of differentiation 38–positive plasma cells and MDSCs, particularly monocytic MDSCs, and express the RANKL receptor in liver. Similarly, the frequency and number of peripheral blood MDSCs were significantly increased. Importantly, serum expression levels of RANKL were inversely correlated with the serum level of gamma‐glutamyltransferase but significantly positively correlated with the frequency of MDSCs. Moreover, we confirmed that RANKL induced the expansion and activation of MDSCs through the RANKL/RANK/nuclear factor kappa B signal pathway. Of note, RANKL‐treated MDSCs suppressed T‐cell proliferation and induced Th2 differentiation. Conclusion: Our data suggest that plasma cell–derived RANKL induces the expansion and activation of MDSCs, which suppress T‐cell proliferation and contribute to the Th2‐type response characteristic of IgG4‐SC.
Genome-wide analyses identify 68 new loci associated with intraocular pressure and improve risk prediction for primary open-angle glaucoma
Authors: Anthony P. Khawaja, Jessica N. Cooke Bailey, Nicholas J. Wareham, Robert A. Scott, Mark Simcoe, Robert P. Igo, Yeunjoo E. Song, Robert Wojciechowski, Ching-Yu Cheng, Peng T. Khaw, Louis R. Pasquale, Jonathan L. Haines, Paul J. Foster, Janey L. Wiggs, Chris J. Hammond, Pirro G. Hysi
Journal: Nature Genetics (2018)
Sources of Funding for Research in Evidence Reviews That Inform Recommendations of the US Preventive Services Task Force
Authors: Jennifer Villani, Quyen Ngo-Metzger, Isaah S. Vincent, Carrie N. Klabunde
Journal: JAMA (2018)

The US Preventive Services Task Force (USPSTF) is an independent panel of national experts in disease prevention and evidencebased medicine that develops recommendations for the delivery of clinical preventive services including screening tests, preventive medications, and behavioral counseling. 1 To develop recommendations, the USPSTF evaluates the quantity, quality, and strength of evidence from systematic reviews of published studies. 2 It is important that high-quality research studies on prevention and screening compose the evidence base for the USPSTF, and that funders of these studies are unbiased.However, little is known about the funders of these studies.This study characterizes the sources of funding for the scientific evidence base used by the USPSTF.
Air Pollution and Mortality in the Medicare Population
Authors: S. Stanley Young
Journal: JAMA (2018)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Asthma in low-income and middle-income countries: an urgent call to action
Authors: J Mark FitzGerald, Khalid Al Efraij
Journal: Thorax (2018)

The global burden of asthma is significant.1 Although mortality rates have improved, recent data have suggested that even in developed economies, asthma deaths are at unacceptable levels and in many cases are associated with avoidable factors.2 3 Traditionally, asthma has been seen as a disease primarily impacting developed economies while communicable diseases were considered to be the major priority in low-income and middle-income countries. It is now recognised that chronic non-communicable diseases exert a greater impact than communicable diseases in these regions of the world.4 Despite awareness of this change in epidemiology, we currently lack robust epidemiological and health outcomes asthma data in these countries. The study by Kirenga and colleagues from Uganda fills such a gap and also highlights the importance of evaluating health outcomes in these settings.5 

In this study, a cohort of 449 patients with asthma were identified and followed for 2 years documenting rates of exacerbations …
IOC consensus statement on relative energy deficiency in sport (RED-S): 2018 update
Authors: Margo Mountjoy, Jorunn Kaiander Sundgot-Borgen, Louise M Burke, Kathryn E Ackerman, Cheri Blauwet, Naama Constantini, Constance Lebrun, Bronwen Lundy, Anna Katarina Melin, Nanna L Meyer, Roberta T Sherman, Adam S Tenforde, Monica Klungland Torstveit, Richard Budgett
Journal: British Journal of Sports Medicine (2018)

In 2014, the IOC published a consensus statement entitled 'Beyond the Female Athlete Triad: Relative Energy Deficiency in Sport (RED-S)'. The syndrome of RED-S refers to 'impaired physiological functioning caused by relative energy deficiency and includes, but is not limited to, impairments of metabolic rate, menstrual function, bone health, immunity, protein synthesis and cardiovascular health'. The aetiological factor of this syndrome is low energy availability (LEA).1 The publication of the RED-S consensus statement stimulated activity in the field of Female Athlete Triad science, including some initial controversy2 3 followed by numerous scientific publications addressing: 1. The health parameters identified in the RED-S conceptual model (figure 1).1 4 2. Relative energy deficiency in male athletes. 3. The measurement of LEA. 4. The performance parameters identified in the RED-S conceptual model (figure 2).1 4 The IOC RED-S consensus authors have reconvened to provide an update summary of the interim scientific progress in the field of relative energy deficiency with the ultimate goal of stimulating advances in RED-S awareness, clinical application and scientific research to address current gaps in knowledge. Figure 1 Health consequences of Relative Energy Deficiency in Sport (RED-S) showing an expanded concept of the Female Athlete Triad to acknowledge a wider range of outcomes and the application to male athletes (*Psychological consequences can either precede RED-S or be the result of RED-S).1 4 Figure 2 Potential Performance consequences of Relative Energy Deficiency in Sport (*Aerobic and anerobic performance).1 4 ### Low energy availability LEA, which underpins the concept of RED-S, is a mismatch between an athlete's energy intake (diet) and the energy expended in exercise, leaving inadequate energy to support the functions required by the body to maintain optimal health and performance. Operationally, energy availability (EA) is defined as: ![Formula][1]</img> where exercise energy expenditure (EEE) is calculated as the additional energy expended above that of … [1]: /embed/mml-math-1.gif
A Role for Hypocretin/Orexin in Metabolic and Sleep Abnormalities in a Mouse Model of Non-metastatic Breast Cancer
Authors: Jeremy C. Borniger, William H. Walker II, None Surbhi, Kathryn M. Emmer, Ning Zhang, Abigail A. Zalenski, Stevie L. Muscarella, Julie A. Fitzgerald, Alexandra N. Smith, Cornelius J. Braam, Tial TinKai, Ulysses J. Magalang, Maryam B. Lustberg, Randy J. Nelson, A. Courtney DeVries
Journal: Cell Metabolism (2018)
Abstract B01: A genetically engineered mouse model of de novo bone metastasis
Authors: Juan Martin Arriaga, Cory Abate-Shen
Journal: Cancer Research (2018)

Abstract The primary metastatic site of prostate cancer is the bone, which is associated with high morbidity and mortality. Despite this fact, very few genetically engineered mouse models recapitulate this phenotype, hindering our ability to model and understand the molecular drivers of bone metastasis. Our laboratory has generated a highly metastatic mouse model of castration-resistant prostate cancer based on the monoallelic loss of function of Nkx3.1, biallelic deletion of Pten, and oncogenic mutation of Kras in the prostate, termed the NPK model. By tracking these tumors with a bright fluorescent reporter, we now show that these tumors metastasize to bone with a penetrance of ~45% and display a bone distribution similar to that of human cancer. This model has thus allowed us to comprehensively profile the molecular alterations of bone metastatic lesions compared to the primary tumor and other metastatic sites. We found that differential gene expression profiles comparing bone metastases with primary tumors differ from those comparing lung metastases with primary tumors, suggesting that different biologic principles underlie metastasis to these two organ sites. Furthermore, gene-expression profiling demonstrated significant overlap with human bone metastases at the gene, master regulator, and pathway levels. Even though expression of the androgen receptor (AR) is maintained in the primary tumor and most lung metastases, bone lesions are AR-, without evidence of neuroendocrine (NE) differentiation, pointing to an AR-, NE- prostate cancer subtype, which is increasingly frequent in human prostate cancer. These results lay the groundwork for understanding the molecular drivers and pathways that are important for bone metastatic spread and may hopefully aid in selecting appropriate molecular targets to combat the metastatic disease. Citation Format: Juan Martin Arriaga, Cory Abate-Shen. A genetically engineered mouse model of de novo bone metastasis [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr B01.
Partitioning of pulmonary vascular resistances in group 2 pulmonary hypertension: insightful suggestions for bridging haemodynamics to underlying mechanisms
Authors: Marco Guazzi
Journal: European Respiratory Journal (2018)

<b>The relevance of partitioning pulmonary vascular resistance in the different determinants in group 2 PH represent a step forward in the diagnosis and definition of left-sided PH</b>http://ow.ly/gx6330jTzwu
Human milk oligosaccharide profiles and food sensitization among infants in the <scp>CHILD</scp> Study
Authors: K. Miliku, B. Robertson, A. K. Sharma, P. Subbarao, A. B. Becker, P. J. Mandhane, S. E. Turvey, D. L. Lefebvre, M. R. Sears, L. Bode, M. B. Azad
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.
Five-Year Risk of Stroke after TIA or Minor Ischemic Stroke
Authors: Pierre Amarenco, Philippa C. Lavallée, Linsay Monteiro Tavares, Julien Labreuche, Gregory W. Albers, Halim Abboud, Sabrina Anticoli, Heinrich Audebert, Natan M. Bornstein, Louis R. Caplan, Manuel Correia, Geoffrey A. Donnan, José M. Ferro, Fernando Gongora-Rivera, Wolfgang Heide, Michael G. Hennerici, Peter J. Kelly, Michal Král, Hsiu-Fen Lin, Carlos Molina, Jong Moo Park, Francisco Purroy, Peter M. Rothwell, Tomas Segura, David Školoudík, P. Gabriel Steg, Pierre-Jean Touboul, Shinichiro Uchiyama, Éric Vicaut, Yongjun Wang, Lawrence K.S. Wong
Journal: New England Journal of Medicine (2018)

After a transient ischemic attack (TIA) or minor stroke, the long-term risk of stroke and other vascular events is not well known. In this follow-up to a report on 1-year outcomes from a registry of TIA clinics in 21 countries that enrolled 4789 patients with a TIA or minor ischemic stroke from 2009 through 2011, we examined the 5-year risk of stroke and vascular events.
Cognitive impairment in metabolically-obese, normal-weight rats: identification of early biomarkers in peripheral blood mononuclear cells
Authors: Margalida Cifre, Andreu Palou, Paula Oliver
Journal: Molecular Neurodegeneration (2018)

Metabolically-obese, normal-weight (MONW) individuals are not obese in terms of weight and height but have a number of obesity-related features (e.g. greater visceral adiposity, insulin resistance, and increased risk of cardiovascular disease). The MONW phenotype is related to the intake of unbalanced diets, such as those rich in fat. Increasing evidence shows a relationship between high-fat diet consumption and mild cognitive impairment and dementia. Thus, MONW individuals could be at a greater risk of cognitive dysfunction. We aimed to evaluate whether MONW-like animals present gene expression alterations in the hippocampus associated with an increased risk of cognitive impairment, and to identify early biomarkers of cognitive dysfunction in peripheral blood mononuclear cells (PBMC). Wistar rats were chronically fed with a 60% (HF60) or a 45% (HF45) high-fat diet administered isocalorically to control animals to mimic MONW features. Expression analysis of cognitive decline-related genes was performed using RT-qPCR, and working memory was assessed using a T-maze. High-fat diet consumption altered the pattern of gene expression in the hippocampus, clearly pointing to cognitive decline, which was accompanied by a worse performance in the T-maze in HF60 animals. Remarkably, Syn1 and Sorl1 mRNA showed the same expression pattern in both the hippocampus and the PBMC obtained at different time-points in the HF60 group, even before other pathological signs were observed. Our results demonstrate that long-term intake of high-fat diets, even in the absence of obesity, leads to cognitive disruption that is reflected in PBMC transcriptome. Therefore, PBMC are revealed as a plausible, minimally-invasive source of early biomarkers of cognitive impairment associated with increased fat intake.
Doughnuts and Discounts — Changes to Medicare Part D under the Bipartisan Budget Act of 2018
Authors: Julie M. Donohue, Haiden A. Huskamp
Journal: New England Journal of Medicine (2018)

Interview with Dr. Julie Donohue on changes to Medicare Part D's benefit design under the Bipartisan Budget Act. (07:43)Download The Bipartisan Budget Act of 2018 accelerates changes to Medicare Part D that were begun by the Affordable Care Act. But though the changes reduce beneficiaries' out-of-pocket burden in the short run, their effects on drug prices in the long run are less clear.