tbuckley/cabot-search huggingface dataset:
The Cost-Effectiveness of Cognitive Behavioral Therapy Versus Second-Generation Antidepressants for Initial Treatment of Major Depressive Disorder in the United States
Authors: Eric L. Ross, Sandeep Vijan, Erin M. Miller, Marcia Valenstein, Kara Zivin
Journal: Annals of Internal Medicine (2019)

Background: Most guidelines for major depressive disorder recommend initial treatment with either a second-generation antidepressant (SGA) or cognitive behavioral therapy (CBT). Although most trials suggest that these treatments have similar efficacy, their health economic implications are uncertain. Objective: To quantify the cost-effectiveness of CBT versus SGA for initial treatment of depression. Design: Decision analytic model. Data Sources: Relative effectiveness data from a meta-analysis of randomized controlled trials; additional clinical and economic data from other publications. Target Population: Adults with newly diagnosed major depressive disorder in the United States. Time Horizon: 1 to 5 years. Perspectives: Health care sector and societal. Intervention: Initial treatment with either an SGA or group and individual CBT. Outcome Measures: Costs in 2014 U.S. dollars, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. Results of Base-Case Analysis: In model projections, CBT produced higher QALYs (3 days more at 1 year and 20 days more at 5 years) with higher costs at 1 year (health care sector, $900; societal, $1500) but lower costs at 5 years (health care sector, −$1800; societal, −$2500). Results of Sensitivity Analysis: In probabilistic sensitivity analyses, SGA had a 64% to 77% likelihood of having an incremental cost-effectiveness ratio of $100 000 or less per QALY at 1 year; CBT had a 73% to 77% likelihood at 5 years. Uncertainty in the relative risk for relapse of depression contributed the most to overall uncertainty in the optimal treatment. Limitation: Long-term trials comparing CBT and SGA are lacking. Conclusion: Neither SGAs nor CBT provides consistently superior cost-effectiveness relative to the other. Given many patients' preference for psychotherapy over pharmacotherapy, increasing patient access to CBT may be warranted. Primary Funding Source: Department of Veterans Affairs, National Institute of Mental Health
Cyclic RGD-Functionalized and Disulfide-Crosslinked Iodine-Rich Polymersomes as a Robust and Smart Theranostic Agent for Targeted CT Imaging and Chemotherapy of Tumor
Authors: Yan Zou, Yaohua Wei, Yinping Sun, Jie Bao, Feirong Yao, Zekun Li, Fenghua Meng, Chunhong Hu, Gert Storm, Zhiyuan Zhong
Journal: Theranostics (2019)

There is tremendous interest in integrating CT imaging with chemotherapy; however, reported iodine-based nanosystems such as nanogels and nano-emulsions display typically reduced contrast coefficient, low drug loading and stability, and poor targetability.Here, cRGD-functionalized disulfide-crosslinked iodine-rich polymersomes (cRGD-XIPs) were designed as a novel, robust and smart theranostic agent and investigated for targeted CT imaging and chemotherapy of malignant tumors.Methods: cRGD-XIPs were prepared from co-self-assembly of poly(ethylene glycol)-b-poly(dithiolane trimethylene carbonate-co-iodinated trimethylene carbonate) (PEG-P(DTC-IC)) and cRGD-PEG-P(DTC-IC) block copolymers.In vitro and in vivo CT contrast effect of cRGD-XIPs was studied using αvβ3-overexpressing B16 melanoma as a tumor model in comparison with clinical agent iohexol.The therapeutic efficacy of doxorubicin-loaded cRGD-XIPs (cRGD-XIPs-Dox) to B16 melanoma was investigated and compared with XIPs-Dox (non-targeted), cRGD-IPs-Dox (non-crosslinked) and free Dox.Results: cRGD-XIPs were formed with 55.5 wt.% iodine and ca.90 nm in diameter.cRGD-XIPs-Dox with a Dox loading of 15.3 wt.% bared superior colloidal stability and reduction-responsive drug release.Notably, blank cRGD-XIPs showed a maximum-tolerated dose (MTD) > 400 mg iodine equiv./kgwhile cRGD-XIPs-Dox had an MTD > 150 mg Dox equiv./kg,ca.15-fold improvement over free Dox.cRGD-XIPs revealed superior CT contrast effect and achieved 46.5-and 24.0-fold better enhancement of CT imaging of B16 melanoma than iohexol at 4 h following intratumoral and intravenous injection, respectively.cRGD-XIPs-Dox displayed an elimination half-life of 6.5 h and an elevated accumulation of 6.68% ID/g in the tumors.Furthermore, cRGD-XIPs-Dox was significantly more effective than XIPs-Dox and cRGD-XPs-Dox in inhibiting growth of B16 melanoma model. Conclusion:This proof-of-concept study demonstrates that cRGD-XIPs are a robust, non-toxic and smart polymeric theranostic agent that can not only significantly enhance CT imaging of tumors but also mediate efficient tumor-targeted chemotherapy.XIPs offer a unique and safe platform for theranostic polymersomes that pre-select patients using CT imaging prior to targeted chemotherapy with the same system.
Revenues and Profits From Medicare Patients in Hospitals Participating in the 340B Drug Discount Program, 2013-2016
Authors: Rena M. Conti, Sayeh S. Nikpay, Melinda B. Buntin
Journal: JAMA Network Open (2019)

<h3>Importance</h3> The federal 340B program lowers the acquisition cost of prescription drugs and places no limits on what hospitals charge payers. Congress established the program to allow 340B profits (the difference between payments and acquisition costs) to subsidize other safety-net services. Little is known about the magnitude of revenues and profits from the 340B program among participating hospitals. <h3>Objective</h3> To report revenues and estimated profits from the 340B program that hospitals collect from Medicare and Medicare beneficiaries for outpatient clinic administration of prescription drugs covered under Medicare Part B. <h3>Design, Setting, and Participants</h3> This cross-sectional descriptive study used 100% Medicare outpatient Part B claims from January 1, 2013, to December 31, 2016, from fee-for-service Medicare beneficiaries administered separately payable drugs at general acute care nonprofit or public hospitals without special payment designations. Claims data (N = 11 298 860) were aggregated to the hospital-year level (N = 6000) and linked to hospital finances and 340B participation from Medicare cost reports and the 340B covered entity list. <h3>Main Outcomes and Measures</h3> Outcomes studied were revenue and estimated profits, assuming a 50% discount from 340B-discounted drug administrations to Medicare patients, as well as Medicare 340B profits relative to hospital net operating revenue, uncompensated care, and disproportionate share hospital payments. <h3>Results</h3> During the study period, hospitals received approximately $2.1 billion in 340B revenue from Medicare in 2013, increasing to $3.7 billion in 2016. Estimated 340B profits from Medicare in 2016 totaled $1.9 billion, and per-hospital estimated 340B profits were $2.5 million but exhibited variability (median, $0.8 million; interquartile range, $0.1 million-$2.8 million). In 2016, median estimated 340B profits from Medicare were 0.3% (interquartile range, 0.1%-0.7%; mean, 0.4%) of hospital operating budgets and 9.4% (interquartile range, 1.8%-26.5%; mean, 16.6%) of hospital uncompensated care costs. <h3>Conclusions and Relevance</h3> Estimated profits that hospitals derived from administering 340B-discounted drugs to Medicare patients are small compared with operating budgets yet substantial compared with uncompensated care costs for many hospitals. Revenue and profit estimates from 340B-discounted drugs represent a lower bound because data on revenue from the sale of outpatient retail dispensed drugs by hospital contract pharmacies and commercial insurer claims are not available.
EGFL7 Antagonizes NOTCH Signaling and Represents a Novel Therapeutic Target in Acute Myeloid Leukemia
Authors: Marius Bill, Aparna Pathmanathan, Malith Karunasiri, Changxian Shen, Matthew H. Burke, Parvathi Ranganathan, Dimitrios Papaioannou, Nina C. Zitzer, Katiri Snyder, Allison LaRocco, Allison E. Walker, Zachary J. Brannan, Ansel P. Nalin, Aharon G. Freud, Mikhail M. Dikov, Xiaoli Zhang, Clara D. Bloomfield, Ramiro Garzon, Adrienne M. Dorrance
Journal: Clinical Cancer Research (2019)

EGF-like domain 7 (EGFL7) is a secreted protein and recently has been shown to play an important role in acute myeloid leukemia (AML); however, the underlying mechanism by which EGFL7 promotes leukemogenesis is largely unknown.
Isotretinoin, Patient Safety, and Patient-Centered Care—Time to Reform iPLEDGE
Authors: John S. Barbieri, Ilona J. Frieden, Arielle R. Nagler
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal
Eric Robert Beck: cofounder of the Doctors Award Redistribution Scheme and major contributor to medical education
Authors: Barry Hoffbrand
Journal: BMJ (2019)

In 1983, after a pay award to doctors that was far greater than that for non-medical NHS workers, Eric Beck was the senior author of a letter in the Times decrying the award as divisive. The letter went on to say that the signatories would donate the difference, some 4.1% of the rise, to a fund to be called the Doctors Award Redistribution Scheme (DARE) that would be used to fund projects not covered by the NHS and for an annual lecture at the Faculty of Public Health Medicine. The latter continues to this day as the DARE lecture. 

One project the fund financed was a telephone helpline in Salford for the mothers of newborn babies who would not stop screaming. One could not have a better example of putting your money where your mouth is.

Eric was passionate about social justice and equality and the principles of the NHS, attitudes to which his refugee background probably contributed. His German speaking father, Adolph Beck, was born in Austro-Hungarian Prague. He qualified in medicine in Frankfurt, …
Protecting the Sanctity of the Patient-Physician Relationship
Authors: Stephanie Harman, Abraham Verghese
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 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
Turabali M H Chakera
Authors: Kishore Shah
Journal: BMJ (2019)

Turabali M H Chakera (“Turab”) was born in Dar Es Salaam, Tanganyika (now Tanzania, Africa), the middle child in a family of five children. After initial education in east Africa, Turab, at the age of 15 years, was sent to the UK to study for A levels and then read medicine at the University of Birmingham Medical School. After completing house jobs in Birmingham, he held senior house officer posts in Plymouth and then a registrar position in Southampton, obtaining his membership of the Royal College of Physicians in 1970. He returned to Africa to work with the Zambian Flying Doctor Service, where he met Margaret, and they were …
On-demand PEGylation and dePEGylation of PLA-based nanocarriers <i>via</i> amphiphilic mPEG-<i>TK</i>-Ce6 for nanoenabled cancer chemotherapy
Authors: Yueqiang Zhu, Chao Chen, Ziyang Cao, Song Shen, Laisheng Li, Dongdong Li, Junxia Wang, Xianzhu Yang
Journal: Theranostics (2019)

Rationale: PEGylation of nanocarriers could extend blood circulation time and enhance tumor accumulation via the enhanced permeability and retention (EPR) effect.Unfortunately, the PEG moiety suppresses tumor cell internalization of nanocarriers, resulting in limited therapeutic efficiency (known as the PEG dilemma).Designing stimuli-responsive shell-detachable nanocarriers, which could detach the PEG corona from the nanocarriers in desired tumor tissues in response to the local environment, is an appealing approach to overcome the PEG dilemma, but nanocarrier applications are also limited by a lack of universal stimuli for PEG detachment.Methods: In this study, we synthesized red light-responsive, amphiphilic mPEG bridged to the photosensitizer Ce6 via a thioketal (TK) bond (mPEG-TK-Ce6), which was then used to achieve the PEGylation of polylactide (PLA)-based nanoparticles encapsulating the Pt(IV) prodrug.The therapeutic efficacy of the prepared nanoparticles was evaluated in vitro and in vivo.Results: We demonstrated that the amphiphilic mPEG-TK-Ce6 can realize the PEGylation of Pt(IV) prodrug-loaded PLA nanoparticles and consequently enhanced nanoparticle accumulation in tumor tissues.When the tumor tissues were subjected to 660 nm irradiation, reactive oxygen species (ROS) generated by Ce6 induced the rapid degradation of the adjacent TK bond, resulting in PEG detachment and enhanced tumor cell internalization.Therefore, mPEG-TK-Ce6 facilely achieved PEGylation and light-responsive dePEGylation of the nanocarrier for enhanced antitumor efficacy in nanomedicine.Conclusion: Such red light-responsive amphiphilic mPEG-TK-Ce6 facilely achieved PEGylation and dePEGylation of the nanocarrier, providing a facile strategy to overcome PEG dilemma.
Elizabeth Donald Hibbard
Authors: Bryan Hibbard
Journal: BMJ (2019)

Elizabeth Donald Hibbard started her professional life in Aberdeen, caring for sick children. She then turned to obstetrics and moved to London, where she met her future husband. They developed a symbiotic relationship in work and play, and their first joint publication won the BMA Katharine Bishop Harman Prize.

They moved to Liverpool in 1955. They soon decided that a lifestyle based on two mainstream obstetricians was …
Phosphorylation of RAB7 by TBK1/IKKϵ Regulates Innate Immune Signaling in Triple-Negative Breast Cancer
Authors: Jessica L. Ritter, Zehua Zhu, Tran C. Thai, Navin R. Mahadevan, Philipp Mertins, Erik H. Knelson, Brandon P. Piel, Saemi Han, Jacob D. Jaffe, Steven A. Carr, David A. Barbie, Thanh U. Barbie
Journal: Cancer Research (2019)

Abstract Triple-negative breast cancer (TNBC) is a heterogeneous disease enriched for mutations in PTEN and dysregulation of innate immune signaling. Here, we demonstrate that Rab7, a recently identified substrate of PTEN phosphatase activity, is also a substrate of the innate immune signaling kinases TANK-binding kinase 1 (TBK1)/IκB kinase ϵ (IKKϵ) on the same serine-72 (S72) site. An unbiased search for novel TBK1/IKKϵ substrates using stable isotope labeling with amino acids in cell culture phosphoproteomic analysis identified Rab7-S72 as a top hit. PTEN-null TNBC cells expressing a phosphomimetic version of Rab7-S72 exhibited diffuse cytosolic Rab7 localization and enhanced innate immune signaling, in contrast to a kinase-resistant version, which localized to active puncta that promote lysosomal-mediated stimulator of interferon genes (STING) degradation. Thus, convergence of PTEN loss and TBK1/IKKϵ activation on Rab7-S72 phosphorylation limited STING turnover and increased downstream production of IRF3 targets including CXCL10, CCL5, and IFNβ. Consistent with this data, PTEN-null TNBC tumors expressed higher levels of STING, and PTEN-null TNBC cell lines were hyperresponsive to STING agonists. Together, these findings begin to uncover how innate immune signaling is dysregulated downstream of TBK1/IKKϵ in a subset of TNBCs and reveals previously unrecognized cross-talk with STING recycling that may have implications for STING agonism in the clinic. Significance: These findings identify Rab7 as a substrate for TBK1 for regulation of innate immune signaling, thereby providing important insight for strategies aimed at manipulating the immune response to enhance therapeutic efficacy in TNBC.
Comparison of tenofovir and entecavir on the risk of hepatocellular carcinoma and mortality in treatment-naïve patients with chronic hepatitis B in Korea: a large-scale, propensity score analysis
Authors: Sung Won Lee, Jung Hyun Kwon, Hae Lim Lee, Sun Hong Yoo, Hee Chul Nam, Pil Soo Sung, Soon Woo Nam, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon, Nam Ik Han, Jeong Won Jang
Journal: Gut (2019)

Objective The use of tenofovir (TDF) and entecavir (ETV) in patients with chronic hepatitis B (CHB) has led to a decrease in the incidence of hepatocellular carcinoma (HCC) and liver-related events. However, whether there is a difference between the two agents in the extent of improving such outcomes has not been clarified thus far. Therefore, we aimed to compare TDF and ETV on the risk of HCC and mortality. Design A total of 7015 consecutive patients with CHB who were treated with TDF or ETV between February 2007 and January 2018 at the liver units of the Catholic University of Korea were screened for study eligibility and 3022 patients were finally analysed. Study end points were HCC and all-cause mortality or liver transplantation (LT) within 5 years after the initiation of antiviral therapy. Propensity score matching (PSM) and inverse probability of treatment weighting methods were used. Results No difference was observed between TDF and ETV in the incidence rates of HCC in the entire cohort (HR 1.030; 95% CI 0.703 to 1.509, PSM model, p=0.880) and subgroups of patients with chronic hepatitis and cirrhosis. Also, no difference was observed between TDF and ETV in the incidence rates of all-cause mortality or LT in the entire cohort (HR 1.090; 95% CI 0.622 to 1.911, PSM model, p=0.763), and patients with chronic hepatitis and cirrhosis. Conclusion This study has demonstrated the clinical outcomes in patients with CHB who received TDF or ETV treatment. There was no difference in the intermediate-term risk of HCC and mortality or LT between the two drugs.
Ticagrelor Alone Versus Dual Antiplatelet Therapy From 1 Month After Drug-Eluting Coronary Stenting
Authors: Anna Franzone, Eugène McFadden, Sergio Leonardi, Raffaele Piccolo, Pascal Vranckx, Patrick W. Serruys, Edouard Benit, Christoph Liebetrau, Luc Janssens, Maurizio Ferrario, Aleksander Zurakowski, Roberto Diletti, Marcello Dominici, Kurt Huber, Ton Slagboom, Paweł Buszman, Leonardo Bolognese, Carlo Tumscitz, Krzysztof Bryniarski, Adel Aminian, Mathias Vrolix, Ivo Petrov, Scot Garg, Christoph Naber, Janusz Prokopczuk, Christian Hamm, Philippe Gabriel Steg, Dik Heg, Peter Jüni, Stephan Windecker, Marco Valgimigli
Journal: Journal of the American College of Cardiology (2019)
Diabetes Prevalence and Incidence Among Medicare Beneficiaries — United States, 2001–2015
Authors: Linda J. Andes, Yanfeng Li, Meera Srinivasan, Stephen R. Benoit, Edward Gregg, Deborah B. Rolka
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

Diabetes affects approximately 12% of the U.S. adult population and approximately 25% of adults aged ≥65 years. From 2009 to 2017, there was no significant change in diabetes prevalence overall or among persons aged 65-79 years (1). However, these estimates were based on survey data with <5,000 older adults. Medicare administrative data sets, which contain claims for millions of older adults, afford an opportunity to explore both trends over time and heterogeneity within an older population. Previous studies have shown that claims data can be used to identify persons with diagnosed diabetes (2). This study estimated annual prevalence and incidence of diabetes during 2001-2015 using Medicare claims data for beneficiaries aged ≥68 years and found that prevalence plateaued after 2012 and incidence decreased after 2006. In 2015 (the most recent year estimated) prevalence was 31.6%, and incidence was 3.0%. Medicare claims can serve as an important source of data for diabetes surveillance for the older population, which can inform prevention and treatment strategies.
SIV-specific CD8+ T cells are clonotypically distinct across lymphoid and mucosal tissues
Authors: Carly E. Starke, Carol L. Vinton, Kristin Ladell, James E. McLaren, Alexandra M. Ortiz, Joseph C. Mudd, Jacob K. Flynn, Stephen H. Lai, Fan Wu, Vanessa M. Hirsch, Samuel Darko, Daniel C. Douek, David A. Price, Jason M. Brenchley
Journal: Journal of Clinical Investigation (2019)

CD8+ T cell responses are necessary for immune control of simian immunodeficiency virus (SIV). However, the key parameters that dictate antiviral potency remain elusive, conceivably because most studies to date have been restricted to analyses of circulating CD8+ T cells. We conducted a detailed clonotypic, functional, and phenotypic survey of SIV-specific CD8+ T cells across multiple anatomical sites in chronically infected rhesus macaques with high (>10,000 copies/mL plasma) or low burdens of viral RNA (<10,000 copies/mL plasma). No significant differences in response magnitude were identified across anatomical compartments. Rhesus macaques with low viral loads (VLs) harbored higher frequencies of polyfunctional CXCR5+ SIV-specific CD8+ T cells in various lymphoid tissues and higher proportions of unique Gag-specific CD8+ T cell clonotypes in the mesenteric lymph nodes relative to rhesus macaques with high VLs. In addition, public Gag-specific CD8+ T cell clonotypes were more commonly shared across distinct anatomical sites than the corresponding private clonotypes, which tended to form tissue-specific repertoires, especially in the peripheral blood and the gastrointestinal tract. Collectively, these data suggest that functionality and tissue localization are important determinants of CD8+ T cell–mediated efficacy against SIV.