tbuckley/cabot-search huggingface dataset:
Characteristics and Price Increases Among Sole-Source, Off-Patent Drugs in the United States, 2008 to 2018
Authors: Jonathan D. Alpern, Arman A. Shahriar, Min Xi, Sunita Thapa, Amy J. Kodet, William M. Stauffer, Gabriela Vazquez Benitez, Pamala A. Pawloski, Steven P. Dehmer
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Some sole-source, off-patent drugs in the United States have undergone substantial price hikes in recent years. Despite increased attention by lawmakers, there are limited data to guide policy. <h3>Objectives</h3> To describe key attributes of sole-source, off-patent, off-exclusivity drugs; to characterize the prevalence of price increases; and to identify attributes associated with price increases. <h3>Design, Setting, and Participants</h3> In this cross-sectional study, 300 sole-source, off-patent, off-exclusivity drug products met inclusion criteria and were selected for analysis from January 1, 2008, to December 31, 2018. Attributes were identified from multiple sources, and yearly wholesale acquisition cost prices were determined from First Databank. <h3>Main Outcomes and Measures</h3> The association of drug attributes with the following 2 price change thresholds was measured after adjusting for inflation: 25% or more price increase in a calendar year (wholesale acquisition cost) and 50% or more price increase in a calendar year. The rate of annual price increase over time was also measured. <h3>Results</h3> Of the 300 drug products and 2242 observations analyzed, the overall inflation-adjusted mean increase in drug prices was 8.8% (95% CI, 7.8%-9.8%) per year. Ninety-five drugs (31.7%) increased by 25% or more during any calendar year, and 66 drugs (22.0%) increased by 50% or more during any calendar year. An initial price of less than $2 per unit (adjusted odds ratio [aOR], 2.36; 95% CI, 1.69-3.29), antineoplastic and immunomodulatory class (aOR, 2.72; 95% CI, 1.31-5.65), dermatologic class (aOR, 2.95; 95% CI, 1.80-4.84), oral route (aOR, 2.01; 95% CI, 1.45-2.79), and US Food and Drug Administration (FDA) approval before 1990 (aOR, 1.52; 95% CI, 1.14-2.03) were attributes of drugs that were more likely to be associated with a 25% or more price increase in a calendar year after adjusting for by initial price. Similarly, an initial price of less than $2 per unit (aOR, 2.68; 95% CI, 1.76-4.09), antineoplastic and immunomodulatory class (aOR, 3.07; 95% CI, 1.54-6.12), oral route of administration (aOR, 1.70; 95% CI, 1.11-2.60), and FDA approval before 1990 (aOR, 2.02; 95% CI, 1.40-2.94) were attributes of drugs that were more likely to be associated with a 50% or more price increase in a calendar year after adjusting for by initial price. Price increases of 25% or more were most common in 2014, and price increases of 50% or more were most common in 2013. <h3>Conclusions and Relevance</h3> Price increases among sole-source, off-patent drugs are common, and policy interest in this practice is warranted. These findings should inform state drug pricing legislation.
Lost Dopaminergic Bindings in the Caudate of a Patient With Frontotemporal Lobar Degeneration–Motor Neuron Disease
Authors: Feng-Tao Liu, Jian Wang, Yan Chen
Journal: JAMA Neurology (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 Neurology 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 Neurology journal
SAT0393 DISCREPANCY IN THE CARDIOVASCULAR RISK SEVERITY CALCULATED USING DIFFERENT RATING SCALES IN PATIENTS WITH AXIAL SPONDYLOARTHRITIS
Authors: E. Vasilenko, V. Mazurov, R. Samigullina, A. Dadalova, I. Gaydukova
Journal: Annals of the Rheumatic Diseases (2020)

Background: Cardiovascular risk (CVR) in patients (pts) with axial spondyloarthritis (axSpA) exceed the populational level. However, it remains unclear, which of the cardiovascular risk assessment systems is the most accurate in cases of chronic inflammation.. Objectives: of the current study were to assess the CVR in pts with axSpA and to compare different cardiovascular risk scales in these pts. Methods: The study included 118 patients at the age of 25-65 years with diagnosis of axSpA fulfilling ASAS criteria (2009) from St. Petersburg’ axSpA register. Three indices of cardiovascular risk evaluation (Systematic COronary Risk Evaluation (SCORE) with increasing coefficient 1.5 for inflammatory diseases, Reynolds Risk Score (RRS), and the third modification of QRESEARCH Cardiovascular Risk Algorithm (QRISK3) were calculated. For the pts below 40 years old only QRISK3 was calculated. Results: Mean age of the pts was 44.3±11.1 years; 91(77.1%) pts were males, HLA-B27 positive – 83 (70.3%) of the pts; mean disease duration 13.0±8.3 years. Mean value of SCORE was 2.78±1.89%, of RRS – 5.28±3.31%, of QRISK3 – 7.91±3.8% (figure 1). Cronbach’s alpha for the scales was 0.873. Figure 1. Cardiovascular risk evaluation indices in patients with axial spondyloarthritis, n=118 for QRISK3, n=72 for SCORE and RRS. High CVR (≥5 %) was found in 14 (11,7%) of the pts according to the SCORE, in 65 (55,1%) of the pts according to the RRS, and in 81 (69%) of the pts according to the QRISK3. Ranking of CVR severity did not match in SCORE and QRISK3 indices in 83.72% of cases, in SCORE and RRS – in 51.16% of cases, and in QRISK3 and RRS in 8% of cases. The SCORE index showed the lower values of the expected risk as compared to the QRISK3 and RRS (figure1). In axSpA pts at age 25-40 years old (n=46, mean age 32.6±4.0 years, males 36 (78.3%)), mean value of QRISK3 was 1.16±0.99 %; in 14 from 46 (30.4%) of those pts increased CVR was registered (figure 2). Figure 2. QRISK3 index in axSpA patients 25-40 years old, n=46 Conclusion: There was a discrepancy in the severity of CVR calculated using different rating scales in axSpA patients. The SCORE index showed lower values of CVR as compared to the QRISK3 and RRS, which hypothetically could be the consequence of CVR underestimation. QRISK3 demonstrated the highest CVR and was the only index useful in pts below 40 years old. To exclude hyper- or underestimation of CVR calculation more data about CVR calculations and frequency of CV events, occurring in axSpA patients are needed. Disclosure of Interests: Elizaveta Vasilenko: None declared, V Mazurov: None declared, Ruzana Samigullina: None declared, Anna Dadalova: None declared, Inna Gaydukova Grant/research support from: JSC BIOCAD, Speakers bureau: Pfizer, Novartis, AbbVie, JSC BIOCAD, Сelgene, MSD, Sanofi
The rush to create a covid-19 vaccine may do more harm than good
Authors: Els Torreele
Journal: BMJ (2020)

The rush to create a covid-19 vaccine may do more harm than goodThe focus on speed risks damaging public confidence in vaccines Els Torreele researcher and advocateThe global race for a covid-19 vaccine seems under way to break all speed records.But this focus on rapid development, fuelled by unprecedented political, financial, and populist pressures, risks missing the target of global access to effective vaccines that can curb the pandemic, while irreparably damaging public confidence.
Extensive peritumoral edema and brain-to-tumor interface MRI features enable prediction of brain invasion in meningioma: development and validation
Authors: Leehi Joo, Ji Eun Park, Seo Young Park, Soo Jung Nam, Young-Hoon Kim, Jeong Hoon Kim, Ho Sung Kim
Journal: Neuro-Oncology (2020)

Abstract Background Brain invasion by meningioma is a stand-alone criterion for tumor atypia in the 2016 World Health Organization classification, but no imaging parameter has yet been shown to be sufficient for predicting it. The aim of this study was to develop and validate an MRI-based radiomics model from the brain-to-tumor interface to predict brain invasion by meningioma. Methods Preoperative T2-weighted and contrast-enhanced T1-weighted imaging data were obtained from 454 patients (88 patients with brain invasion) between 2012 and 2017. Feature selection was performed from 3222 radiomics features obtained in the 1 cm thickness tumor-to-brain interface region using least absolute shrinkage and selection operator. Peritumoral edema volume, age, sex, and selected radiomics features were used to construct a random forest classifier–based diagnostic model. The performance was evaluated using the areas under the curves (AUCs) of the receiver operating characteristic in an independent cohort of 150 patients (29 patients with brain invasion) between 2018 and 2019. Results Volume of peritumoral edema was an independent predictor of brain invasion (P &amp;lt; 0.001). The top 6 interface radiomics features plus the volume of peritumoral edema were selected for model construction. The combined model showed the highest performance for prediction of brain invasion in the training (AUC 0.97; 95% CI: 0.95–0.98) and validation sets (AUC 0.91; 95% CI: 0.84–0.98), and improved diagnostic performance over volume of peritumoral edema only (AUC 0.76; 95% CI: 0.66–0.86). Conclusion An imaging-based model combining interface radiomics and peritumoral edema can help to predict brain invasion by meningioma and improve the diagnostic performance of known clinical and imaging parameters.
SAT0246 Characterising the effects of anakinra therapy on functional status of patients with rheumatoid arthritis using methotrexate
Authors: SB Cohen, JM Woolley, WW Chan
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To characterise the effects of anakinra on the functional status of subjects with rheumatoid arthritis using methotrexate. <h3>Methods</h3> In a large multidose placebo controlled study of anakinra in subjects with rheumatoid arthritis (RA), functional status was evaluated at baseline and after 24 weeks of therapy using the Health Assessment Questionnaire (HAQ). The HAQ includes questions designed to assess functional status as related to dressing and grooming (D&amp;G), arising (ARI), eating (EAT), walking (WLK), hygiene (HYG), reach (RCH), grip (GRP), and activities (ACT). Comparisons between Methotrexate (MTX) alone (n = 74), and anakinra + MTX (n = 131), based on the combined data for the two highest doses (1 mg/kg and 2 mg/kg), were analysed using change in scores from baseline through 24 weeks. <h3>Results</h3> Change scores for all eight of the HAQ scales (Table 1) were positive, and six were statistically significant. The biggest effects were seen in reach, hygiene, and eating, while walking showed the smallest effect. Furthermore, by the end of the study a greater percentage of subjects on anakinra + MTX reported functionality without any difficulty, as compared to those on MTX alone (data not shown). <h3>Conclusion</h3> Subjects receiving at least 1 mg/kg of anakinra showed statistically significant improvements in functional status as measured by the HAQ. Improvements were evident in almost all of the HAQ scales. Anakinra improves functional status across a wide range of domains in subjects with rheumatoid arthritis.
Identifying essential components of surgical care delivery through quality improvement: An updated surgical assessment tool
Authors: Yihan Lin, Nakul P. Raykar, Saurabh Saluja, Swagoto Mukhopadhyay, Sristi Sharma, Brigitte Frett, Sam Enumah, Katherine R. Iverson, Walter Johnson, John G. Meara, Mark G. Shrime
Journal: International Journal of Surgery (2020)
Heterogeneity of lower airway inflammation in patients with NSAID-exacerbated respiratory disease
Authors: Bogdan Jakiela, Jerzy Soja, Krzysztof Sladek, Marek Przybyszowski, Hanna Plutecka, Anna Gielicz, Ana Rebane, Grazyna Bochenek
Journal: Journal of Allergy and Clinical Immunology (2020)
A 3D-Bioprinted dual growth factor-releasing intervertebral disc scaffold induces nucleus pulposus and annulus fibrosus reconstruction
Authors: Binbin Sun, Meifei Lian, Yu Han, Xiumei Mo, Wenbo Jiang, Zhiguang Qiao, Kerong Dai
Journal: Bioactive Materials (2020)

Regeneration of Intervertebral disc (IVD) is a scientific challenge because of the complex structure and composition of tissue, as well as the difficulty in achieving bionic function. Here, an anatomically correct IVD scaffold composed of biomaterials, cells, and growth factors were fabricated via three-dimensional (3D) bioprinting technology. Connective tissue growth factor (CTGF) and transforming growth factor-β3 (TGF-β3) were loaded onto polydopamine nanoparticles, which were mixed with bone marrow mesenchymal stem cells (BMSCs) for regenerating and simulating the structure and function of the nucleus pulposus and annular fibrosus. In vitro experiments confirmed that CTGF and TGF-β3 could be released from the IVD scaffold in a spatially controlled manner, and induced the corresponding BMSCs to differentiate into nucleus pulposus like cells and annulus fibrosus like cells. Next, the fabricated IVD scaffold was implanted into the dorsum subcutaneous of nude mice. The reconstructed IVD exhibited a zone-specific matrix that displayed the corresponding histological and immunological phenotypes: primarily type II collagen and glycosaminoglycan in the core zone, and type I collagen in the surrounding zone. The testing results demonstrated that it exhibited good biomechanical function of the reconstructed IVD. The results presented herein reveal the clinical application potential of the dual growth factors-releasing IVD scaffold fabricated via 3D bioprinting. However, the evaluation in large mammal animal models needs to be further studied.
Cosmetic surgeon who practised without insurance is struck off
Authors: Clare Dyer
Journal: BMJ (2020)

A cosmetic surgeon whose patients went uncompensated for unsatisfactory surgery because he lacked insurance has been struck off the UK medical register.

Arnaldo Paganelli, an Italian surgeon who worked privately as an independent contractor for The Hospital Group (THG) in Birmingham, was found to have “deliberately frustrated the purpose of the professional insurance which he is bound to hold” in the cases of four female patients.

A medical practitioners tribunal found that, in the only one of those four cases for which Paganelli had valid insurance, he failed to provide the documentation required by his insurer after the patient, Natasha Stewart, secured a UK court judgment in 2012 for £27 384 damages and over £39 000 costs.

The tribunal found that two factors had informed Paganelli’s state …
CircRNAs in anticancer drug resistance: recent advances and future potential
Authors: Tianwei Xu, Mengwei Wang, Lihua Jiang, Li Ma, Li Wan, Qinnan Chen, Chenchen Wei, Zhaoxia Wang
Journal: Molecular Cancer (2020)

Abstract CircRNAs are a novel class of RNA molecules with a unique closed continuous loop structure. CircRNAs are abundant in eukaryotic cells, have unique stability and tissue specificity, and can play a biological regulatory role at various levels, such as transcriptional and posttranscriptional levels. Numerous studies have indicated that circRNAs serve a crucial purpose in cancer biology. CircRNAs regulate tumor behavioral phenotypes such as proliferation and migration through various molecular mechanisms, such as miRNA sponging, transcriptional regulation, and protein interaction. Recently, several reports have demonstrated that they are also deeply involved in resistance to anticancer drugs, from traditional chemotherapeutic drugs to targeted and immunotherapeutic drugs. This review is the first to summarize the latest research on circRNAs in anticancer drug resistance based on drug classification and to discuss their potential clinical applications.
Assessment of SARS-CoV-2 Transmission on an International Flight and Among a Tourist Group
Authors: Sebastian Hoehl, Onur Karaca, Niko Kohmer, Sandra Westhaus, Jürgen Graf, Udo Goetsch, Sandra Ciesek
Journal: JAMA Network Open (2020)

It has previously been observed for SARS and influenza that transmission may also occur among passengers seated beyond the 2-row perimeter, 2,3 indicating possible airborne transmission.Our findings do not rule out airborne transmission of SARS-CoV-2 in an airplane cabin.This study had several limitations.We did not obtain information on the crew of the airplane and were not able to contact all passengers.We also did not obtain antibody tests from all passengers.Additional transmissions may have occurred and remained undetected.
Abstract 4217: Synergy of tyrosine kinase inhibitor HQP1351 and MDM2-P53 antagonist, APG-115, in preclinical models of <i>FLT3</i> mutant and <i>TP53</i> wild-type acute myeloid leukemia
Authors: Douglas D. Fang, Qiuqiong Tang, Qixin Wang, Na Li, Xu Fang, Jiaxing Gu, Yanhui Kong, Tao Rong, Guangfeng Wang, Dajun Yang, Yifan Zhai
Journal: Cancer Research (2020)

Abstract HQP1351 is a novel, orally bioavailable multi-kinase inhibitor targeting BCR-ABL, KIT, and FLT3. Currently, HQP1351 is in phase II clinical trials in relapsed and refractory chronic myeloid leukemia (CML) patients by targeting BCR-ABL. Besides, HQP1351 inhibits both wild-type and mutant FLT3 in kinase binding assay. APG-115 is another clinical stage, small molecule MDM2 antagonist. In the present study, we explored the antitumor effect of the combination of HQP1351 and APG-115, and the molecular mechanism in FLT3-ITD and TP53 wild-type acute myeloid leukemia (AML) in the preclinical setting. First, the effect of HQP1351 as single agent on cell viability in FLT3-ITD mutant and TP53 wild-type human AML cell lines, including MV-4-11 and MOLM-13. Second, antitumor activity of the combination was investigated in systemic and subcutaneous xenograft models in NOD/SCID mice derived from these cells. The results showed that HQP1351 alone exhibited potent antiproliferative activity in both cell lines in vitro, with nanomolar IC50 values. The activity was enhanced in the combination treatment with APG-115. In vivo, HQP1351 single agent demonstrated significant antitumor activity evidenced by a markedly reduction of tumor burden (i.e., CD45+ human tumor cells) in systemic MOLM-13 xenograft model. Treatment with HQP1351 at 3, 10 and 30 mg/kg significantly prolonged mice survival with median survival of 20.5 days, 26.0 days and 35 days, respectively, compared with 18 days in the control group. In subcutaneous MV-4-11 xenograft model, treatment with HQP1351 or APG-115 single agents achieved T/C values of 28.6% and 59.6%, respectively. The combination achieved synergistic antitumor activity with a T/C value of 13.4%. The benefit of the combination was also demonstrated in systemic MOLM-13 xenograft model. Mechanistically, the combined treatment synergistically downregulated p-FLT3, p-ERK, p-STAT5 and anti-apoptotic protein MCL-1, and thus enhanced antitumor effect. Taken together, our data provide scientific rationale for clinical development of the combination of HQP1351 and APG-115 in FLT3-ITD mutant and TP53 wild-type AML patients. Citation Format: Douglas D. Fang, Qiuqiong Tang, Qixin Wang, Na Li, Xu Fang, Jiaxing Gu, Yanhui Kong, Tao Rong, Guangfeng Wang, Dajun Yang, Yifan Zhai. Synergy of tyrosine kinase inhibitor HQP1351 and MDM2-P53 antagonist, APG-115, in preclinical models of FLT3 mutant and TP53 wild-type acute myeloid leukemia [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4217.
Shared P53 gene mutation and gene expression in concurrent small cell and acinar adenocarcinoma of the prostate.
Authors: Donna E. Hansel, Masashi Nakayama, Jun Luo, Charles Bieberich, Jonathan I. Epstein, Jasek Mostwin, Angelo M. De Marzo
Journal: Cancer Research (2006)

5288  Background: Prostate cancer is a leading cause of morbidity and mortality among men in the United States. Adenocarcinoma comprises the majority of prostate cancers, although other unusual subtypes exist. Small cell carcinoma of the prostate, which often occurs in the context of late-stage acinar adenocarcinoma, has been proposed to arise either from a common stem cell or from a clonal evolution of pre-existent carcinoma, although molecular evidence is lacking. Methods: A highly unusual case of prostate cancer containing adjacent elements of acinar adenocarcinoma, neuroendocrine carcinoma, and small cell carcinoma was examined at our institution. Acinar adenocarcinoma and small cell carcinoma elements were separated via Laser Capture Microdissection. Each component was examined for P53 gene sequence mutations and gene expression profiles. Confirmation of gene expression analysis was performed by immunolabeling analysis. Results: Sequencing of the P53 gene revealed a shared missense mutation of a hotspot within the DNA binding domain, indicating a common clonal origin for both small cell carcinoma and acinar adenocarcinoma in this case. To examine the shared nature of gene expression within these two clonally-related populations, gene expression analysis was performed, which revealed markedly different gene expression profiles. The small cell carcinoma component demonstrated an upregulation of 57 genes in comparison to the acinar adenocarcinoma. Upregulation of the neuroendocrine markers chromogranin-C (SCG2) and chromogranin-A (CHGA) was present in the small cell component, which serves, therefore, as an internal validation of our gene analysis. Additional upregulated genes included secreted growth factors (BMP7, FGF12, DLL3), intracellular signaling molecules and transcription factors (MYC, RAB6A), inflammatory mediators (IL1RL1LG, NOS2A), and treatment-resistance molecules (SCG2, ALDH1A1). Downregulation of 42 gene tags in the small cell carcinoma component was identified, including cell adhesion molecules (L1CAM, MMP7, CLDN10), drug-treatment related molecules (CYP1B1, MGST1, CASP10), and growth factors (OPN, sFRP4, FGF18). Conclusions: To the best of our knowledge, this is the first report of shared P53 mutations between different subtypes of prostate cancer, suggesting a clonal evolution between acinar adenocarcioma and small cell carcinoma in this organ. The extent of divergent gene expression obtained in this study may reflect underlying genetic and/or epigenetic alterations in the progression of a carcinoma to a more highly malignant phenotype. Further validation of these findings in a larger collection of prostate cancer specimens is necessary to determine the utility of these differential genetic changes in the progression of prostate cancer and the development of the neuroendocrine phenotype.
Hyperprogressive disease during PD-1 blockade in patients with advanced hepatocellular carcinoma
Authors: Chang Gon Kim, Chan Kim, Sang Eun Yoon, Kyung Hwan Kim, Seong Jin Choi, Beodeul Kang, Hye Ryun Kim, Su-Hyung Park, Eui-Cheol Shin, Yeun-Yoon Kim, Dae Jung Kim, Hyun Cheol Chung, Hong Jae Chon, Hye Jin Choi, Ho Yeong Lim
Journal: Journal of Hepatology (2020)