tbuckley/cabot-search huggingface dataset:
Comparison of Costs of Care for Medicare Patients Hospitalized in Teaching and Nonteaching Hospitals
Authors: Laura G. Burke, Dhruv Khullar, Jie Zheng, Austin B. Frakt, E. John Orav, Ashish K. Jha
Journal: JAMA Network Open (2019)

Little empirical work has been performed on whether teaching hospitals are more expensive when considering total costs of care for an acute care episode.To compare total standardized costs at 30 days by hospital teaching status for common conditions.This cross-sectional study assessed the costs of hospitalizations among US Medicare beneficiaries 65 years and older at major, minor, and nonteaching hospitals from January 1, 2014, to November 30, 2015, for 15 medical conditions and 6 surgical procedures. Data analysis was performed from February 26, 2019, to April 16, 2019.Hospital teaching status (major, minor, and nonteaching hospitals).The primary outcome was 30-day total standardized costs to Medicare for hospitalizations for all 21 conditions in aggregate as well as stratified by medical and surgical condition categories. Secondary outcomes included 30-day spending for individual components of care (index hospitalization, physician services, readmission, and outpatient and post-acute care services) as well as total standardized costs at 90 days.The sample consisted of 1 249 006 hospitalizations at 3064 hospitals (232 [7.6%] major teaching, 837 [27.3%] minor teaching, and 1995 [65.1%] nonteaching hospitals). Treatment at a major teaching hospital was associated with lower total 30-day adjusted standardized costs ($18 605 vs $18 793 at minor teaching hospitals and $18 873 at nonteaching hospitals; difference between major and nonteaching hospitals: -$268; 95% CI, -$456 to -$80; P = .005). Treatment at a major teaching hospital was associated with higher spending for the index hospitalization ($8529 vs $8370 at minor teaching hospitals and $8180 at nonteaching hospitals; difference between major and nonteaching hospitals: $349; 95% CI, $308-$390; P < .001) but lower physician costs ($677 vs $725 at minor teaching hospitals and $728 at nonteaching hospitals; difference: -$50; 95% CI, -$60 to -$41; P < .001). Furthermore, post-acute care costs at 30 days were lowest at major teaching hospitals ($6015 vs $6239 for minor teaching hospitals and $6260 for nonteaching hospitals; difference: -$245; 95% CI, -$375 to -$115; P < .001). Thirty-day total costs were lower at major teaching hospitals compared with nonteaching hospitals for 12 of the 21 individual conditions examined. There was no difference in costs by teaching status at 90 days ($24 982 at major teaching hospitals vs $24 959 at minor teaching hospitals vs $25 044 at nonteaching hospitals; difference: -$61; 95% CI, -$310 to $188; P = .63).Medicare patients treated at major teaching hospitals had lower Medicare spending at 30 days and similar costs at 90 days compared with Medicare patients at nonteaching hospitals. These findings appear to raise doubts that care at teaching hospitals is necessarily more expensive than care at nonteaching hospitals.
“Not Shared” Need Not Mean “Not Patient Centered”: Deciding That a Patient Is Not a Candidate
Authors: Jacob A. Blythe, Jason N. Batten, David C. Magnus
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
Mifepristone abrogates repopulation of ovarian cancer cells in between courses of cisplatin treatment
Authors: Elizabeth Freeburg, Alicia Goyeneche, Carlos Telleria
Journal: Cancer Research (2008)

1210  Abstract 1210 has been selected for inclusion in the AACR’s Annual Meeting press program and is therefore embargoed until date and time of press briefing or scientific presentation, whichever comes first. The abstract is scheduled for scientific presentation and will be posted to this site at or after the following date and time: 4/13/2008 1:00 PM.
How an Expanded Vision of Managed Care Organizations Could Tackle Inequities
Authors: Stuart M. Butler
Journal: JAMA (2019)

Wright said he and his coauthors were surprised to see that in the weeknight sleep-restricted group, men slept more on the weekend than women.While both men and women slept longer on Friday night than they had at baseline, only men did on Saturday night."What we do know as a general rule is that women are at a higher risk for insomnia than men," he said.
High-Resolution Bisulfite-Sequencing of Peripheral Blood DNA Methylation in Early-Onset and Familial Risk Breast Cancer Patients
Authors: Justin Chen, Maria K. Haanpää, Joshua J. Gruber, Natalie Jäger, James M. Ford, Michael P. Snyder
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Understanding and explaining hereditary predisposition to cancer has focused on the genetic etiology of the disease. However, mutations in known genes associated with breast cancer, such as BRCA1 and BRCA2, account for less than 25% of familial cases of breast cancer. Recently, specific epigenetic modifications at BRCA1 have been shown to promote hereditary breast cancer, but the broader potential for epigenetic contribution to hereditary breast cancer is not yet well understood. Experimental Design: We examined DNA methylation through deep bisulfite sequencing of CpG islands and known promoter or regulatory regions in peripheral blood DNA from 99 patients with familial or early-onset breast or ovarian cancer, 6 unaffected BRCA mutation carriers, and 49 unaffected controls. Results: In 9% of patients, we observed altered methylation in the promoter regions of genes known to be involved in cancer, including hypermethylation at the tumor suppressor PTEN and hypomethylation at the proto-oncogene TEX14. These alterations occur in the form of allelic methylation that span up to hundreds of base pairs in length. Conclusions: Our observations suggest a broader role for DNA methylation in early-onset, familial risk breast cancer. Further studies are warranted to clarify these mechanisms and the benefits of DNA methylation screening for early risk prediction of familial cancers.
Potential Benefit of Nonsurgical Management to Periappendicular Abscess
Authors: Chris Li, Dean Owyang
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
Prediction of Low and Very Low Bone Mineral Density Among Adult Survivors of Childhood Cancer
Authors: Jenneke E. van Atteveld, Saskia M.F. Pluijm, Kirsten K. Ness, Melissa M. Hudson, Wassim Chemaitilly, Sue C. Kaste, Leslie L. Robison, Sebastian J.C.M.M. Neggers, Yutaka Yasui, Marry M. van den Heuvel-Eibrink, Carmen L. Wilson
Journal: Journal of Clinical Oncology (2019)

PURPOSE To develop and validate prediction models for low and very low bone mineral density (BMD) on the basis of clinical and treatment characteristics that identify adult survivors of childhood cancer who require screening by dual-energy x-ray absorptiometry. PATIENTS AND METHODS White survivors of childhood cancer (n = 2,032; median attained age, 29.3 years [range, 18.1 to 40.9 years]) enrolled in the St Jude Lifetime Cohort (SJLIFE; development) and survivors treated at the Erasmus Medical Center (validation) in the Netherlands (n = 403; median age, 24.2 years [range, 18.0 to 40.9 years]) were evaluated with dual-energy x-ray absorptiometry to determine lumbar spine BMD and total-body BMD. Low and very low BMD were defined as lumbar spine BMD and/or total-body BMD z scores of −1 or lower or −2 or lower, respectively. Multivariable logistic regression was used to build prediction models; performance was assessed using receiver operating characteristic curves. Diagnostic values were calculated at different probabilities. RESULTS Low BMD was present in 51% and 45% of SJLIFE and Dutch participants, respectively, and very low BMD was present in 20% and 10%, respectively. The model for low BMD included male sex (odds ratio [OR], 3.07), height (OR, 0.95), weight (OR, 0.98), attained age (OR, 0.97), current smoking status (OR, 1.48), and cranial irradiation (OR, 2.11). Areas under the curve were 0.72 (95% CI, 0.70 to 0.75) in the SJLIFE cohort and 0.69 (95% CI, 0.64 to 0.75) in the Dutch cohort. The sum of the sensitivity (69.0%) and specificity (64.0%) was maximal at the predicted probability of 50%. The model for very low BMD included male sex (OR, 3.28), height (OR, 0.95), weight (OR, 0.97), attained age (OR, 0.98), cranial irradiation (OR, 2.07), and abdominal irradiation (OR, 1.61), yielding areas under the curve of 0.76 (95% CI, 0.73 to 0.78; SJLIFE cohort) and 0.75 (95% CI, 0.67 to 0.83; Dutch cohort). CONCLUSION Validated prediction models for low and very low BMD, using easily measured patient and treatment characteristics, correctly identified BMD status in most white adult survivors through age 40 years.
Pembrolizumab with or without chemotherapy versus chemotherapy for advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma: The phase III KEYNOTE-062 study.
Authors: Josep Tabernero, Eric Van Cutsem, Yung-Jue Bang, Charles S. Fuchs, Lucjan Wyrwicz, Keun Wook Lee, Iveta Kudaba, Marcelo Garrido, Hyun Cheol Chung, Hugo Raul Castro Salguero, Wasat Mansoor, Maria Ignez Freitas Melro Braghiroli, Eray Goekkurt, Joseph Chao, Zev A. Wainberg, Uma Kher, Sukrut Shah, SoonMo Peter Kang, Kohei Shitara
Journal: Journal of Clinical Oncology (2019)

LBA4007 Background: KEYNOTE062 (NCT02494583) was a randomized, active controlled study of 1L P or P+C vs C in pts with PD-L1 combined positive score ≥1 (CPS ≥1), HER2-negative, advanced GC. Methods: Eligible pts were randomized 1:1:1 to P 200 mg Q3W for up to 2 y, P+C (cisplatin 80 mg/m 2 + 5-FU 800 mg/m 2 /d on d1-d5 Q3W [or capecitabine 1000 mg/m 2 BID on d1-d14 Q3W per local guideline]) or placebo Q3W + C. Randomization was stratified by region, disease status, and fluoropyrimidine treatment. Primary endpoints were OS in CPS ≥1 and CPS ≥10 for P+C vs C and P vs C and PFS (RECIST v1.1; central review) in CPS ≥1 for P+C vs C. ORR (RECIST v1.1; central review) in CPS ≥1 for P+C vs C was the secondary endpoint. Final analysis cutoff date was 26 Mar 2019. Results: 763 pts (281 with CPS ≥10) were randomized to P+C (257), P (256), or C (250) (Table). Median follow-up was 11.3 mo. P was noninferior to C for OS in CPS ≥1 per prespecified margins. P vs C prolonged OS in CPS ≥10 (median 17.4 vs 10.8 mo; HR 0.69; 95% CI 0.49-0.97) but wasn’t tested per analysis plan. P+C vs C was not superior for OS in CPS ≥1 or CPS ≥10, with a favorable trend for P+C. P+C did not significantly prolong PFS in CPS ≥1. ORR was higher for P+C vs C. Grade 3-5 drug-related AE rates were 17% (P), 73% (P+C), and 69% (C). Conclusions: As 1L therapy for advanced GC, P was noninferior to C for OS in CPS ≥1 with clinically meaningful improvement for OS in CPS ≥10. P+C did not show superior OS and PFS in CPS ≥1 and OS in CPS ≥10. The safety profile was more favorable for P vs C. Clinical trial information: NCT02494583. [Table: see text]
Insys and Mallinckrodt settle allegations of paying doctors to prescribe drugs
Authors: Owen Dyer
Journal: BMJ (2019)

Two companies that have drawn heavy criticism from legislators investigating some of the drug industry’s worst practices have paid the US government to settle allegations of kickbacks to doctors to prescribe their drugs.

Insys Therapeutics paid $225m (£180m; €200m) to settle allegations of paying kickbacks to off-label prescribers of its fentanyl sublingual spray Subsys, leading to addictions and deaths.

UK based Mallinckrodt paid $15.4m to settle allegations of paying doctors to prescribe an infant epilepsy drug whose price had risen by 97 000%. But within hours of Mallinckrodt settling that case, the government announced another one relating to the marketing of the same drug, Acthar (corticotropin).

Insys will enter into a five year deferred prosecution agreement with the US Justice Department, and its operating subsidiary will plead guilty to five counts of mail fraud.

The founder of Insys, John Kapoor, and …
18F-PSMA 1007 Brain PET/CT Imaging in Glioma Recurrence
Authors: Fahad Marafi, Arun Sasikumar, Wael Fathallah, Abdulredh Esmail
Journal: Clinical Nuclear Medicine (2019)

A 64-year-old man with a known case of right parietal lobe glioblastoma multiforme operated on in August 2018 was referred for F-FDG PET/CT with a clinical suspicion of recurrence. He underwent F-FDG and F-PSMA 1007 scans. Both the scans showed intense tracer uptake in right parietal lobe lesion, which concurred with MRI findings of recurrent disease and was later proven on histopathologic examination as recurrence. Our case highlights the feasibility of F-PSMA 1007 PET/CT imaging of suspected glioblastoma recurrence. Considering its similarity to PSMA-617, it may be used as a surrogate imaging tracer for potential theranostic application using alpha or beta emitters.
Inflammasome Regulates Hematopoiesis through Cleavage of the Master Erythroid Transcription Factor GATA1
Authors: Sylwia D. Tyrkalska, Ana B. Pérez-Oliva, Lola Rodríguez-Ruiz, Francisco J. Martínez-Morcillo, Francisca Alcaraz-Pérez, Francisco J. Martínez-Navarro, Christophe Lachaud, Nouraiz Ahmed, Timm Schroeder, Irene Pardo-Sánchez, Sergio Candel, Azucena López-Muñoz, Avik Choudhuri, Marlies P. Rossmann, Leonard I. Zon, María L. Cayuela, Diana García-Moreno, Victoriano Mulero
Journal: Immunity (2019)
Should measles vaccination be compulsory?
Authors: Eleanor Draeger, Helen E Bedford, David A C Elliman
Journal: BMJ (2019)

Making MMR vaccination mandatory would still allow parents to choose not to vaccinate their children while protecting those attending schools or nurseries, says <b>Eleanor Draeger</b>. But <b>Helen Bedford</b> and <b>David Elliman</b> worry that such a step might lead to unintended consequences and recommend exploring potential obstacles to vaccine uptake first
A Model System for Studying the DNMT3A Hotspot Mutation (DNMT3AR882) Demonstrates a Causal Relationship between Its Dominant-Negative Effect and Leukemogenesis
Authors: Rui Lu, Jun Wang, Zhihong Ren, Jiekai Yin, Yinsheng Wang, Ling Cai, Gang Greg Wang
Journal: Cancer Research (2019)

Abstract Mutation of DNA methyltransferase 3A at arginine 882 (DNMT3AR882mut) is prevalent in hematologic cancers and disorders. Recently, DNMT3AR882mut has been shown to have hypomorphic, dominant-negative, and/or gain-of-function effects on DNA methylation under different biological contexts. However, the causal role for such a multifaceted effect of DNMT3AR882mut in leukemogenesis remains undetermined. Here, we report TF-1 leukemia cells as a robust system useful for modeling the DNMT3AR882mut-dependent transformation and for dissecting the cause–effect relationship between multifaceted activities of DNMT3AR882mut and leukemic transformation. Ectopic expression of DNMT3AR882mut and not wild-type DNMT3A promoted TF-1 cell transformation characterized by cytokine-independent growth, and induces CpG hypomethylation predominantly at enhancers. This effect was dose dependent, acted synergistically with the isocitrate dehydrogenase 1 (IDH1) mutation, and resembled what was seen in human leukemia patients carrying DNMT3AR882mut. The transformation- and hypomethylation-inducing capacities of DNMT3AR882mut relied on a motif involved in heterodimerization, whereas its various chromatin-binding domains were dispensable. Mutation of the heterodimerization motif that interferes with DNMT3AR882mut binding to endogenous wild-type DNMT proteins partially reversed the CpG hypomethylation phenotype caused by DNMT3AR882mut, thus supporting a dominant-negative mechanism in cells. In mice, bromodomain inhibition repressed gene-activation events downstream of DNMT3AR882mut-induced CpG hypomethylation, thereby suppressing leukemogenesis mediated by DNMT3AR882mut. Collectively, this study reports a model system useful for studying DNMT3AR882mut, shows a requirement of the dominant-negative effect by DNMT3AR882mut for leukemogenesis, and describes an attractive strategy for the treatment of leukemias carrying DNMT3AR882mut. Significance: These findings highlight a model system to study the functional impact of a hotspot mutation of DNMT3A at R882 in leukemia.
WHO reports “concerning lack of progress” in stopping STI spread
Authors: Elisabeth Mahase
Journal: BMJ (2019)

There are more than one million new cases of curable sexually transmitted infections (STIs) among people aged 15 to 49 years every day worldwide, according to the latest figures from the World Health Organization.1

Approximately 1 in 25 people globally have at least one STI, with some experiencing multiple infections at the same time, and four key infections—chlamydia, gonorrhoea, trichomoniasis, and syphilis—account for over 376 million new cases annually, the report showed.

WHO said these findings are a “wake up call” for the international community, …
Substrate Reduction Therapy for Sandhoff Disease through Inhibition of Glucosylceramide Synthase Activity
Authors: John Marshall, Jennifer B. Nietupski, Hyejung Park, James Cao, Dinesh S. Bangari, Cristina Silvescu, Terry Wilper, Kristen Randall, Drew Tietz, Bing Wang, Xiaoyou Ying, John P. Leonard, Seng H. Cheng
Journal: Molecular Therapy (2019)

Neuronopathic glycosphingolipidoses are a sub-group of lysosomal storage disorders for which there are presently no effective therapies. Here, we evaluated the potential of substrate reduction therapy (SRT) using an inhibitor of glucosylceramide synthase (GCS) to decrease the synthesis of glucosylceramide (GL1) and related glycosphingolipids. The substrates that accumulate in Sandhoff disease (e.g., ganglioside GM2 and its nonacylated derivative, lyso-GM2) are distal to the drug target, GCS. Treatment of Sandhoff mice with a GCS inhibitor that has demonstrated CNS access (Genz-682452) reduced the accumulation of GL1 and GM2, as well as a variety of disease-associated substrates in the liver and brain. Concomitant with these effects was a significant decrease in the expression of CD68 and glycoprotein non-metastatic melanoma B protein (Gpnmb) in the brain, indicating a reduction in microgliosis in the treated mice. Moreover, using in vivo imaging, we showed that the monocytic biomarker translocator protein (TSPO), which was elevated in Sandhoff mice, was normalized following Genz-682452 treatment. These positive effects translated in turn into a delay (∼28 days) in loss of motor function and coordination, as measured by rotarod latency, and a significant increase in longevity (∼17.5%). Together, these results support the development of SRT for the treatment of gangliosidoses, particularly in patients with residual enzyme activity.
The Case for Selective Withdrawal of Antidepressants in Patients with Advanced Kidney Disease
Authors: Joseph Chilcot, Ken Farrington
Journal: Journal of the American Society of Nephrology (2019)

We read with interest “Comparative cardiac safety of selective serotonin reuptake inhibitors among individuals receiving maintenance hemodialysis” by Assimon et al.1 This large retrospective analysis found that patients on hemodialysis who initiated selective serotonin reuptake inhibitors (SSRIs) with higher QT-prolonging potential (citalopram and escitalopram) had a significantly increased risk of sudden cardiac death (adjusted hazard ratio, 1.18; 95% confidence interval, 1.05 to 1.31) compared with patients who initiated SSRIs with lower QT-prolonging potential (fluoxetine, fluvoxamine, paroxetine, and sertraline). Given the lack of evidence regarding the efficacy of SSRIs for major depressive disorder in patients with advanced kidney disease and the prevalence of premature cardiovascular mortality in this setting, the findings of Assimon et al.1 raise important questions about the use of these agents in this context. Depression is a common comorbidity among patients with advanced kidney disease,2 although diagnosis is complicated by the overlap of clinical features of these two conditions. Notwithstanding this, depression in this setting is associated with adverse clinical outcomes, including increased mortality risk.3 It is far from clear, however, whether the association is independent of antidepressant use. Three randomized, placebo-controlled trials of SSRIs in individuals with kidney disease4–6 have failed to provide evidence of benefit while signposting increased risks of adverse events (reviewed in ref. 7). A recent randomized trial comparing sertraline with cognitive behavioral therapy in patients on dialysis showed a modest difference in favor of sertraline,8 although there was no control group. We appreciate that additional randomized, controlled trials are needed in this area and that the study of Assimon et al.1 is not able to provide evidence for the absolute mortality risk associated with antidepressant use. However, we feel that there is a real possibility that, in some patients at least, these agents may be doing more harm than good. Hence, it may be appropriate to consider whether withdrawing antidepressants in suitable patients may be the appropriate strategy. Withdrawal could mean withdrawing one agent and switching to another, withdrawing and switching to a psychological treatment, or stopping all together. Antidepressant withdrawal requires careful risk assessment, patient education and counseling, and a considered tapering regimen to mitigate symptoms of withdrawal.9 We believe that there is a strong case for empirical studies of antidepressant withdrawal in suitable patients with advanced kidney disease. Disclosures None.