tbuckley/cabot-search huggingface dataset:
Smartphone-Based Detection of Middle Ear Fluid
Authors: Jennifer Abbasi
Journal: JAMA (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 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
Industry payments to doctors drive surge in gabapentinoid prescribing, study finds
Authors: Owen Dyer
Journal: BMJ (2019)

Drug makers’ payments to doctors have helped to drive the growing use of gabapentinoids, says a research letter in JAMA Internal Medicine .1

The frequent off-label prescribing of this class of drugs has attracted criticism on both sides of the Atlantic this year because of the paucity of evidence.

Researchers from Yale University and the University of Connecticut compared Medicare and Medicaid prescribing data from 2014 to 2016 with the Open Payments database, in which drug companies are legally required to record all gifts and payments to doctors. They looked at the original gabapentinoid, gabapentin, approved as Pfizer’s Neurontin in 1993, which now has several generic competitors. They also measured prescribing of two branded slow-release versions of gabapentin, Gralise and Horizant, and of the other drug …
Considering the Source of Information in the Evaluation of Maltreatment Experiences
Authors: Janik Goltermann, Nils Opel, Udo Dannlowski
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
Phenotypic Manifestations of Arrhythmogenic Cardiomyopathy in Children and Adolescents
Authors: Elizabeth S. DeWitt, Stephanie F. Chandler, Robyn J. Hylind, Virginie Beausejour Ladouceur, Elizabeth D. Blume, Christina VanderPluym, Andrew J. Powell, Francis Fynn-Thompson, Amy E. Roberts, Stephen P. Sanders, Vassilios Bezzerides, Neal K. Lakdawala, Calum A. MacRae, Dominic J. Abrams
Journal: Journal of the American College of Cardiology (2019)
Association of Lifestyle and Genetic Risk With Incidence of Dementia
Authors: Ilianna Lourida, Eilis Hannon, Thomas J. Littlejohns, Kenneth M. Langa, Elina Hyppönen, Elzbieta Kuzma, David J. Llewellyn
Journal: JAMA (2019)

Genetic factors increase risk of dementia, but the extent to which this can be offset by lifestyle factors is unknown.To investigate whether a healthy lifestyle is associated with lower risk of dementia regardless of genetic risk.A retrospective cohort study that included adults of European ancestry aged at least 60 years without cognitive impairment or dementia at baseline. Participants joined the UK Biobank study from 2006 to 2010 and were followed up until 2016 or 2017.A polygenic risk score for dementia with low (lowest quintile), intermediate (quintiles 2 to 4), and high (highest quintile) risk categories and a weighted healthy lifestyle score, including no current smoking, regular physical activity, healthy diet, and moderate alcohol consumption, categorized into favorable, intermediate, and unfavorable lifestyles.Incident all-cause dementia, ascertained through hospital inpatient and death records.A total of 196 383 individuals (mean [SD] age, 64.1 [2.9] years; 52.7% were women) were followed up for 1 545 433 person-years (median [interquartile range] follow-up, 8.0 [7.4-8.6] years). Overall, 68.1% of participants followed a favorable lifestyle, 23.6% followed an intermediate lifestyle, and 8.2% followed an unfavorable lifestyle. Twenty percent had high polygenic risk scores, 60% had intermediate risk scores, and 20% had low risk scores. Of the participants with high genetic risk, 1.23% (95% CI, 1.13%-1.35%) developed dementia compared with 0.63% (95% CI, 0.56%-0.71%) of the participants with low genetic risk (adjusted hazard ratio, 1.91 [95% CI, 1.64-2.23]). Of the participants with a high genetic risk and unfavorable lifestyle, 1.78% (95% CI, 1.38%-2.28%) developed dementia compared with 0.56% (95% CI, 0.48%-0.66%) of participants with low genetic risk and favorable lifestyle (hazard ratio, 2.83 [95% CI, 2.09-3.83]). There was no significant interaction between genetic risk and lifestyle factors (P = .99). Among participants with high genetic risk, 1.13% (95% CI, 1.01%-1.26%) of those with a favorable lifestyle developed dementia compared with 1.78% (95% CI, 1.38%-2.28%) with an unfavorable lifestyle (hazard ratio, 0.68 [95% CI, 0.51-0.90]).Among older adults without cognitive impairment or dementia, both an unfavorable lifestyle and high genetic risk were significantly associated with higher dementia risk. A favorable lifestyle was associated with a lower dementia risk among participants with high genetic risk.
Phase II study of perioperative chemotherapy with cisplatin (C) and pemetrexed (P) in non-small cell lung cancer (NSCLC).
Authors: Aamer Farooq, Grace K. Dy, Todd L. Demmy, Paul Bogner, Cynthia Nowadly, Wei Tan, Hongbin Chen, Saikrishna S. Yendamuri, Chukwumere E. Nwogu, Peter Walter Bushunow, Alex A. Adjei, Nithya Ramnath
Journal: Journal of Clinical Oncology (2012)

e17535 Background: Pathological complete response (pCR) with neoadjuvant chemotherapy is associated with improved survival in many solid tumors. We evaluated efficacy and tolerability of neoadjuvant plus adjuvant C+P in this phase II trial. Methods: We recruited patients (pts) with clinical stage IB-IIIA (TNM 7th ed) NSCLC, ECOG performance status (PS) 0-1 in this single-arm phase II trial using two-stage design with 90% power to detect pCR rate of &gt;10% (vs null hypothesis of &lt;2%). Pre-treatment mediastinal biopsy was required. Protocol was amended in 2009 to exclude squamous histology. Pts received 3 cycles of C 75mg/m 2 + P 500mg/m 2 (day 1 every 21 days) followed by surgical resection. Two cycles were delivered adjuvantly within 60-80 days after surgery. The primary end point was pCR. Secondary endpoints were objective response rate (ORR), overall survival (OS), disease-free survival (DFS), and adverse events (AEs). Results: 38 pts were enrolled with median age of 62 yrs, 19 males: 19 females. 74% (N=28) had ECOG PS 0. Preoperatively, 26% (N=10) had squamous histology, 29% (N=11) had biopsy-proven N2 involvement. Median of 4 cycles were administered. ORR was 29% (11 pts with PR). 4 pts did not undergo surgery (3 had disease progression; one became hypoxic during intubation in the OR). Resection status was R2 in 9% (3 of 34 pts), remaining pts had R0 resection. 6 pts had documented N2 clearance; median DFS (mDFS) and OS (mOS) of these pts have not reached (NR) vs 15 and 24 months respectively, in pts with persistent N2 disease. CTC grade 3+ nonhematologic AEs (&lt;10%) include arterial thrombosis, bronchopleural fistula, empyema, hyperglycemia, fatigue and tinnitus. There was no pCR seen and thus accrual to 2nd stage was not pursued. There was no correlation between DFS or OS with ORR or pre-operative stage. There was statistically signification association between DFS with histology (favoring squamous, p=0.03) and post-op stage (p=0.024). The table shows mDFS and mOS in months according to pre-op stage. Conclusions: While the primary endpoint was not met, this regimen is active and well-tolerated perioperatively in NSCLC pts. [Table: see text]
Mesenchymal Stem Cell–Mediated Delivery of an Oncolytic Adenovirus Enhances Antitumor Efficacy in Hepatocellular Carcinoma
Authors: A-Rum Yoon, JinWoo Hong, Yan Li, Ha Chul Shin, Hyunah Lee, Hyun Soo Kim, Chae-Ok Yun
Journal: Cancer Research (2019)

Abstract Oncolytic virotherapy is a promising alternative to conventional treatment, yet systemic delivery of these viruses to tumors remains a major challenge. In this regard, mesenchymal stem cells (MSC) with well-established tumor-homing property could serve as a promising systemic delivery tool. We showed that MSCs could be effectively infected by hepatocellular carcinoma (HCC)-targeted oncolytic adenovirus (HCC-oAd) through modification of the virus' fiber domain and that the virus replicated efficiently in the cell carrier. HCC-targeting oAd loaded in MSCs (HCC-oAd/MSC) effectively lysed HCC cells in vitro under both normoxic and hypoxic conditions as a result of the hypoxia responsiveness of HCC-oAd. Importantly, systemically administered HCC-oAd/MSC, which were initially infected with a low viral dose, homed to HCC tumors and resulted in a high level of virion accumulation in the tumors, ultimately leading to potent tumor growth inhibition. Furthermore, viral dose reduction and tumor localization of HCC-oAd/MSC prevented the induction of hepatotoxicity by attenuating HCC-oAd hepatic accumulation. Taken together, these results demonstrate that MSC-mediated systemic delivery of oAd is a promising strategy for achieving synergistic antitumor efficacy with improved safety profiles. Significance: Mesenchymal stem cells enable delivery of an oncolytic adenovirus specifically to the tumor without posing any risk associated with systemic administration of naked virions to the host.
HIV-1 Epidemic Control — Insights from Test-and-Treat Trials
Authors: Salim S Abdool Karim
Journal: New England Journal of Medicine (2019)

Debate ensued when mathematical models1 predicted that universal testing and treatment could achieve epidemic control within a few years in a high-burden setting. However, the idea rapidly gained new credence when antiretroviral therapy (ART)–induced viral suppression was shown to be highly effective in preventing transmission of human immunodeficiency virus type 1 (HIV-1) in a clinical trial.2 Four large, cluster-randomized, controlled trials, each with a different approach to maximizing viral suppression, set out to assess the effect of universal testing and treatment on community HIV incidence. In 2018, the Treatment as Prevention (TasP) trial3 involving 28,419 persons in 22 communities showed . . .
Managing combination immunotherapy trials from a contract research organization's (CRO's) perspective.
Authors: Jai Balkissoon, Binh Nguyen, Austin J. Combest, Konstantin Yordanov Stoitchkov, Nikolay Stoyanov, Judy Hsu, Dirk J. Reitsma
Journal: Journal of Clinical Oncology (2019)

19 Background: With the increased clinical activity that we are seeing with combination IO therapies, more sponsors are searching for contract research organizations (CROs) that have experience managing combination IO clinical trials which are often large, complex, multi-national, resource-intensive, competitive and highly specialized. Pharmaceutical Product Development (PPD), a contract research organization (CRO) has worked with sponsors in managing combination IO clinical trials. This includes early and late phase trials with many different classes of agents in multiple tumor types. We sought to review PPDs experience in combination immunotherapy trials and highlight key challenges, efficiencies, innovative modern trial designs, endpoints and enrollment strategies in a competitive market. Methods: We reviewed IO trials managed by PPD over the past 5 years, information from PPDs Immuno-Oncology Center of Excellence (IOCOE) and Immuno-Oncology Working Group (IOWG) and the current pace of development of IO therapies. Results: PPD has collaborated with multiple sponsors to manage innovative, complex IO trials that push the boundaries of clinical development. Comprehensive planning and risk management strategies steeped in a deep understanding of the trial environment are essential for successful IO protocols. Protocol and trial optimization have been useful to make trials more efficient and less expensive. Conclusions: IO approvals are increasing at a rapid pace and both sponsors and CROs will need to work together to continue to develop innovative trial designs, biomarkers and endpoints that will determine efficacy and tolerability of combination IO therapies. PPDs innovative tools, technology and resources have been useful to help sponsors with enrollment strategies to prevent increasing study timelines and delays in study results. The IO space is pushing the limitations of scientific, technological and operational advances, and we are happy to continue to share our learnings in this ever-evolving landscape.
Dexmedetomidine reduces norepinephrine requirements and preserves renal oxygenation and function in ovine septic acute kidney injury
Authors: Yugeesh R. Lankadeva, Shuai Ma, Naoya Iguchi, Roger G. Evans, Sally G. Hood, David G.S. Farmer, Simon R. Bailey, Rinaldo Bellomo, Clive N. May
Journal: Kidney International (2019)
PBPK modeling-based optimization of site-specific chemo-photodynamic therapy with far-red light-activatable paclitaxel prodrug
Authors: Mengjie Li, Luong Nguyen, Bharathiraja Subramaniyan, Moses Bio, Cody J. Peer, Jessica Kindrick, William D. Figg, Sukyung Woo, Youngjae You
Journal: Journal of Controlled Release (2019)
Early ultrasound for diagnosis and treatment of vascular adverse events with hyaluronic acid fillers
Authors: Leonie W. Schelke, Peter Velthuis, Jonathan Kadouch, Arthur Swift
Journal: Journal of the American Academy of Dermatology (2019)

Hyaluronic acid fillers are known for a reliable safety profile, but complications do occur, even serious vascular adverse events.To improve the treatment outcome after a vascular adverse event with use of hyaluronic acid filler treatments.Duplex ultrasonography is used to detect the hyaluronic acid filler causing the intra-arterial obstruction.If treated in time, 1 single treatment of ultrasonographically guided injections of hyaluronidase into the filler deposit will prevent skin necrosis.Because the use of duplex ultrasonography adds extra essential information, its use may become an integral part of the prevention and treatment of injection adverse events.
Spending on World Health Organization essential medicines in Medicare Part D, 2011-15: retrospective cost analysis
Authors: David G Li, Mehdi Najafzadeh, Aaron S Kesselheim, Arash Mostaghimi
Journal: BMJ (2019)

Abstract Objectives To characterize the trends, drivers, and potential modifiers of increased spending by US Medicare beneficiaries on medicines deemed essential by the World Health Organization. Design Retrospective cost analysis of Medicare Part D Prescriber Public Use File, detailing annual generic and brand name drug prescribing and spending from 2011 through 2015 by Medicare Part D participants who filled prescriptions for WHO essential medicines. Setting US Medicare System. Main outcome measures Total and per beneficiary Medicare spending, total and per beneficiary out-of-pocket patient spending, cumulative beneficiary count, claim count, and per unit drug cost. All spending measures were adjusted for inflation and reported in 2015 US dollars. Results Medicare Part D expenditures on 265 WHO essential medicines between 2011 and 2015 was $87.2bn (£68.4bn; €76.5bn), with annual spending increasing from $11.9bn in 2011 to $25.8bn in 2015 (116%). Patients’ out-of-pocket spending for essential medicines over the same period was $12.1bn. Total annual out-of-pocket spending increased from $2.0bn to $2.9bn (47%), and annual per beneficiary out-of-pocket spending on these drugs increased from $20.42 to $21.17 (4%). Total prescription count increased from 376.1m to 498.9m (33%), and cumulative beneficiary count grew from 95.9m to 135.8m (42%). Of the essential medicines included in the study, the per unit cost of 133 (50%) agents increased faster than the average inflation rate during this period. Overall, approximately 58% of the increase in total spending during this period can be attributed to the introduction of novel agents. Conclusions Spending associated with essential medicines grew substantially from 2011 to 2015, driven largely by the increased use of two expensive novel drugs used in treating hepatitis C. Approximately 22% of increased total spending during this period can be attributed to increases in per unit cost of existing drugs. These trends may limit patients’ access to essential drugs while also increasing healthcare system costs.
Mutations in the KEAP1-NFE2L2 Pathway Define a Molecular Subset of Rapidly Progressing Lung Adenocarcinoma
Authors: Frauke Goeman, Francesca De Nicola, Stefano Scalera, Francesca Sperati, Enzo Gallo, Ludovica Ciuffreda, Matteo Pallocca, Laura Pizzuti, Eriseld Krasniqi, Giacomo Barchiesi, Patrizia Vici, Maddalena Barba, Simonetta Buglioni, Beatrice Casini, Paolo Visca, Edoardo Pescarmona, Marco Mazzotta, Ruggero De Maria, Maurizio Fanciulli, Gennaro Ciliberto, Marcello Maugeri-Saccà
Journal: Journal of Thoracic Oncology (2019)
Mutations in KIRREL1, a slit diaphragm component, cause steroid-resistant nephrotic syndrome
Authors: Ashish K. Solanki, Eugen Widmeier, Ehtesham Arif, Shailza Sharma, Ankana Daga, Pankaj Srivastava, Sang-Ho Kwon, Hannah Hugo, Makiko Nakayama, Nina Mann, Amar J. Majmundar, Wei Tan, Heon Yung Gee, Caroline E. Sadowski, Choni Rinat, Rachel Becker-Cohen, Carsten Bergmann, Seymour Rosen, Michael Somers, Shirlee Shril, Tobias B. Huber, Shrikant Mane, Friedhelm Hildebrandt, Deepak Nihalani
Journal: Kidney International (2019)

Steroid-resistant nephrotic syndrome is a frequent cause of chronic kidney disease almost inevitably progressing to end-stage renal disease. More than 58 monogenic causes of SRNS have been discovered and majority of known steroid-resistant nephrotic syndrome causing genes are predominantly expressed in glomerular podocytes, placing them at the center of disease pathogenesis. Herein, we describe two unrelated families with steroid-resistant nephrotic syndrome with homozygous mutations in the KIRREL1 gene. One mutation showed high frequency in the European population (minor allele frequency 0.0011) and this patient achieved complete remission following treatment, but later progressed to chronic kidney disease. We found that mutant KIRREL1 proteins failed to localize to the podocyte cell membrane, indicating defective trafficking and impaired podocytes function. Thus, the KIRREL1 gene product has an important role in modulating the integrity of the slit diaphragm and maintaining glomerular filtration function.Graphical abstract
ERβ mRNA expression in ERα-negative and triple-negative breast cancers.
Authors: Young Choi, Hadong Kim, Tae-Hoon Kim
Journal: Journal of Clinical Oncology (2012)

574 Background: ERα is the main prognostic and therapeutic marker in breast cancer (BC). About 30% of BC cases are negative for ER (ERα-) and do not benefit from antiestrogen therapy (TAM). We aim to study ER-beta (ERβ) expression in ERα- and triple negative (TN) cancers to explore alternate pathway of treatment in this cohort. Methods: We studied 67 ERα- BC cases including 44 TN together with 74 ERα +BC cases obtained from patients aged 29 to 97 years old between 2003 and 2010. The histology included 110 intraductal, 12 medullary and 19 other types. 78 cases were grade 3, 52 were grade 2, and 11 were grade 1. RNA was extracted from FFPE and mRNA levels of ERβ isoform and ERα were determined by real-time quantitative reverse transcription PCR. IHC stains were done on TMA the sections for ERα, PR, Her-2, Ki-67, CK5/6 and Cyclin D1. Results: ERβ isoforms were highly expressed in ERα-, TN, basal-like and HER2 type BC cases. ERβ2 was the major ERβ variant expressed. Ki-67 proliferating cells (&gt;20% nuclear staining) were mostly in ERα- rather than ERα+ cases (69.0% vs. 31.0%) as were cyclin D1- cells (82.2% vs. 17.8%). On the other hand, in ERα+ BC, ERα mRNA expression was consistently high and upregulated, and ERβ, low and down regulated, and the ratio of ERα+ to ERβ+ ranged from 3 to 100. ERβ1, 2 and 5 were co-expressed with ERα in 56%, 63%, and 30% of cases, respectively. Overall, ERβ mRNA levels did not show any significant correlation with age, tumor size, lymph node status and histological grades. Conclusions: ERβ-dependent proliferating tumor cells may render them more sensitive to TAM, and increase the effectiveness of TAM and its metabolites in ERα- and TN cases. Increased overall survival after adjuvant TAM ERα-BC may be directly related to ERβ over-expression. ERβ isoform is potential selective therapeutic target in a sub-cohort of ERα- BC. Additionally, when ERβ and ERα are co-expressed, ERβ appears to play a distinct role from its action in ERα- BC. [Table: see text]
Magnetically Actuated Degradable Microrobots for Actively Controlled Drug Release and Hyperthermia Therapy
Authors: Jongeon Park, Chaewon Jin, Seungmin Lee, Jin‐Young Kim, Hongsoo Choi
Journal: Advanced Healthcare Materials (2019)

Abstract Microrobots facilitate targeted therapy due to their small size, minimal invasiveness, and precise wireless control. A degradable hyperthermia microrobot (DHM) with a 3D helical structure is developed, enabling actively controlled drug delivery, release, and hyperthermia therapy. The microrobot is made of poly(ethylene glycol) diacrylate (PEGDA) and pentaerythritol triacrylate (PETA) and contains magnetic Fe 3 O 4 nanoparticles (MNPs) and 5‐fluorouracil (5‐FU). Its locomotion is remotely and precisely controlled by a rotating magnetic field (RMF) generated by an electromagnetic actuation system. Drug‐free DHMs reduce the viability of cancer cells by elevating the temperature under an alternating magnetic field (AMF), a hyperthermic effect. 5‐FU is released from the proposed DHMs in normal‐, high‐burst‐, and constant‐release modes, controlled by the AMF. Finally, actively controlled drug release from the DHMs in normal‐ and high‐burst‐release mode results in a reduction in cell viability. The reduction in cell viability is of greater magnitude in high‐burst‐ than in normal‐release mode. In summary, biodegradable DHMs have potential for actively controlled drug release and hyperthermia therapy.