tbuckley/cabot-search huggingface dataset:
NHS gets £5.9bn funding boost in autumn budget to tackle waiting lists in England
Authors: Elisabeth Mahase
Journal: BMJ (2021)

The NHS in England will get a £5.9bn (€7bn; $8.1bn) funding boost in the autumn budget to tackle record high waiting lists, the government has announced.1

The 2021 budget states that £2.3bn will be used to increase diagnostic capacity, including 100 community diagnostic centres, while £2.1bn will support the “innovative use of digital technology.”

The NHS will not only be expected to clear the backlog but will also provide around 30% more elective activity by 2024-25 than before the pandemic, the document said. This is despite the Health Foundation estimating that it would cost as much as £16.8bn from now to 2024-25 just to enable the NHS to clear the backlog of people waiting for routine elective care, return to the 18 week waiting time target, and treat millions of patients who had been expected to receive care during the pandemic but did not.2

The number of patients waiting for routine operations and treatments, such as hip replacements and eye cataract surgery, is set to exceed 13 …
The Art and Science of Medicine … and Standardized Test Scores
Authors: Susan E. Quaggin, Luisa Safar-Boueri
Journal: Journal of the American Society of Nephrology (2021)

For the past decade, there has been much discussion about declining interest in nephrology careers.[1][1] The special article from Berns et al. [2][2] about nephrology board scores opens with a comment about this trend and discusses it as a potential reason for declining scores. However, over the
TCT-107 Impact of Baseline Tricuspid Regurgitation Severity on Clinical Outcomes After Transcatheter Edge-to-Edge Repair of the Mitral Valve With the MitraClip System
Authors: Nikhil Agrawal, Lucas Battel, Arjun Jogimahanti, Deepa Raghunathan, Ayush Arora, Jawad Chohan, Yelin Zhao, Enrique Garcia-Sayan, Richard Smalling, Abhjeet Dhoble
Journal: Journal of the American College of Cardiology (2021)
TCT-117 Performance and Safety of the Resorbable Magnesium Scaffold, Magmaris, in a Real-World Setting: Primary and Secondary Endpoint Analysis of the Full Cohort (2,066 Subjects) of the BIOSOLVE-IV Registry
Authors: Johan Bennett, Adrian Wlodarczak, Jan Torzewski, Gregory Starmer, Thomas Buck, Michael Haude, Marco Moccetti, Michael Kang-Yin Lee, Stefan Verheye
Journal: Journal of the American College of Cardiology (2021)
Systematic Review and Meta-analysis of Acute Treatments for Episodic Migraine in Adults
Authors: Xavier Moisset, Geneviève Demarquay, Anne Ducros
Journal: JAMA (2021)

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
A Phase 0 Trial of Ceritinib in Patients with Brain Metastases and Recurrent Glioblastoma
Authors: Shwetal Mehta, Roberto Fiorelli, Xun Bao, Chelsea Pennington-Krygier, Alanna Derogatis, Seongho Kim, Wonsuk Yoo, Jing Li, Nader Sanai
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Ceritinib is an orally bioavailable, small-molecule inhibitor of anaplastic lympoma kinase (ALK), insulin-like growth factor 1 receptor (IGFR1), and focal adhesion kinase (FAK), which are highly expressed in glioblastoma and many brain metastases. Preclinical and clinical studies indicate that ceritinib has antitumor activity in central nervous system (CNS) malignancies. This phase 0 trial measured the tumor pharmacokinetics (PK) and pharmacodynamics (PD) of ceritinib in patients with brain metastasis or recurrent glioblastoma. Patients and Methods: Preoperative patients with brain tumors demonstrating high expression of pSTAT5b/pFAK/pIGFR1 were administered ceritinib for 10 days prior to tumor resection. Plasma, tumor, and cerebrospinal fluid (CSF) samples were collected at predefined timepoints following the final dose. Total and unbound drug concentrations were determined using LC-MS/MS. In treated tumor and matched archival tissues, tumor PD was quantified through IHC analysis of pALK, pSTAT5b, pFAK, pIGFR1, and pIRS1. Results: Ten patients (3 brain metastasis, 7 glioblastoma) were enrolled and no dose-limiting toxicities were observed. Ceritinib was highly bound to human plasma protein [median fraction unbound (Fu), 1.4%] and to brain tumor tissue (median Fu, 0.051% and 0.045% in gadolinium-enhancing and -nonenhancing regions respectively). Median unbound concentrations in enhancing and nonenhancing tumor were 0.048 and 0.006 μmol/L, respectively. Median unbound tumor-to-plasma ratios were 2.86 and 0.33 in enhancing and nonenhancing tumor, respectively. No changes in PD biomarkers were observed in the treated tumor samples as compared to matched archival tumor tissue. Conclusions: Ceritinib is highly bound to plasma proteins and tumor tissues. Unbound drug concentrations achieved in brain metastases and patients with recurrent glioblastoma were insufficient for target modulation.
Plasmacytoid dendritic cell activation is dependent on coordinated expression of distinct amino acid transporters
Authors: Katarzyna M. Grzes, David E. Sanin, Agnieszka M. Kabat, Michal A. Stanczak, Joy Edwards-Hicks, Mai Matsushita, Alexandra Hackl, Fabian Hässler, Kristin Knoke, Sophie Zahalka, Matteo Villa, David M. Kofler, Reinhard E. Voll, Paola Zigrino, Mario Fabri, Erika L. Pearce, Edward J. Pearce
Journal: Immunity (2021)
Communication of Intent to Do Harm Preceding Mass Public Shootings in the United States, 1966 to 2019
Authors: Jillian Peterson, Gina Erickson, Kyle Knapp, James Densley
Journal: JAMA Network Open (2021)

Understanding the motivation of a mass shooter's intent to do harm can help practitioners and policy makers develop more effective intervention strategies.To examine the prevalence of communication of intent to do harm, known as leakage, in a sample of 170 mass public shooters from 1966 to 2019; the characteristics of perpetrators who do and do not leak their plans; and whether leakage is a form of fame-seeking behavior or a cry for help among individuals who are in crisis or suicidal.This cross-sectional study included perpetrators who killed 4 or more people in a public space from 1996 to 2019 and were included in a comprehensive database of US mass shootings. That database was built from August 2017 to December 2019, and analysis took place from January to May 2021.Leakage was identified and coded using publicly available records. Any communication to a third party of an intent to do harm prior to the shooting was coded as leakage. Logistic regression models were used to examine the risk factors associated with leakage. Models estimating leakage were examined to assess the 2 hypothesized pathways to leakage (the cry-for-help model and the fame-seeking model).The 170 participants in this sample included 166 (97.7%) male perpetrators and 3 (2.3%) female perpetrators, with a mean (SD) age of 34 (12) years. Overall, 161 participants had known race and ethnicity: 11 (6.8%) Asian individuals, 35 (21.7%) Black individuals, 14 (8.7%) Latinx individuals, 7 (4.4%) Middle Eastern individuals, 3 (1.9%) Native American individuals, 89 (55.3%) White individuals, and 2 (1.2%) individuals with other race and ethnicity. Overall, 79 mass shooters (46.5%) leaked their plans. Of perpetrators who leaked their plans, 35 (44.3%) leaked specific plans about a mass shooting, and 44 (55.1%) leaked nonspecific plans about generalized violence. The study findings indicate that leakage was associated with receiving counseling (odds ratio, 7.0; 95% CI, 2.0-24.8) and suicidality (odds ratio, 3.7; 95% CI, 1.0-13.6), suggesting that leakage may best be characterized as a cry for help from perpetrators prior to their act.In this study, nearly half of the perpetrators of mass shootings leaked their plans. Leakage was associated with receiving counseling and suicidality. Leakage is a critical moment for mental health intervention to prevent gun violence. Opportunities to report threats of violence need to be increased. Traditional threat assessment models focused on specific threats of violence may miss critical opportunities for intervention.
Health and financial costs of adverse childhood experiences in 28 European countries: a systematic review and meta-analysis
Authors: Karen Hughes, Kat Ford, Mark A Bellis, Freya Glendinning, Emma Harrison, Jonathon Passmore
Journal: The Lancet Public Health (2021)

Adverse childhood experiences (ACEs) are associated with increased health risks across the life course. We aimed to estimate the annual health and financial burden of ACEs for 28 European countries.
Afghanistan’s doctors urge world to put politics and prejudice aside to save its healthcare
Authors: Geetanjali Krishna, Sally Howard
Journal: BMJ (2021)

Afghanistan was already struggling to respond to the needs of its population before the Taliban takeover. Now the healthcare system is on the brink of collapse, and medics say the world must work with the Taliban if it is to help, write <b>Geetanjali Krishna</b> and <b>Sally Howard</b>
Di(Thioether Sulfonate)‐Substituted Quinolinedione as a Rapidly Dissoluble and Stable Electron Mediator and Its Application in Sensitive Biosensors
Authors: Ponnusamy Nandhakumar, Woohyeong Lee, Sangwook Nam, Aman Bhatia, Jia Seo, Gyeongho Kim, Nam‐Sihk Lee, Young Ho Yoon, Jung Min Joo, Haesik Yang
Journal: Advanced Healthcare Materials (2021)

The commonly required properties of diffusive electron mediators for point-of-care testing are rapid dissolubility, high stability, and moderate formal potential in aqueous solutions. Inspired by nature, various quinone-containing electron mediators have been developed; however, satisfying all these requirements remains a challenge. Herein, a strategic design toward quinones incorporating sulfonated thioether and nitrogen-containing heteroarene moieties as solubilizing, stabilizing, and formal potential-modulating groups is reported. A systematic investigation reveals that di(thioether sulfonate)-substituted quinoline-1,4-dione (QLS) and quinoxaline-1,4-dione (QXS) display water solubilities of ≈1 m and are rapidly dissoluble. By finely balancing the electron-donating effect of the thioethers and the electron-withdrawing effect of the nitrogen atom, formal potentials suitable for electrochemical biosensors are achieved with QLS and QXS (-0.15 and -0.09 V vs Ag/AgCl, respectively, at pH 7.4). QLS is stable for >1 d in PBS (pH 7.4) and for 1 h in tris buffer (pH 9.0), which is sufficient for point-of-care testing. Furthermore, QLS, with its high electron mediation ability, is successfully used in biosensors for sensitive detection of glucose and parathyroid hormone, demonstrating detection limits of ≈0.3 × 10-3 m and ≈2 pg mL-1 , respectively. This strategy produces organic electron mediators exhibiting rapid dissolution and high stability, and will find broad application beyond quinone-based biosensors.
TCT-293 Bleeding Complications of Transcatheter Edge-To-Edge Repair: Analysis From the COAPT Trial
Authors: Flavien Vincent, Ioanna Kosmidou, Bjorn Redfors, Ditian Li, Saibal Kar, Scott Lim, Jacob Mishell, Brian Whisenant, JoAnn Lindenfeld, William Abraham, Michael Mack, Gregg Stone
Journal: Journal of the American College of Cardiology (2021)
TCT-186 Effect of Triple Antiplatelet Therapy on Diabetic Patients Who Underwent Endovascular Treatment for Peripheral Artery Disease
Authors: Jung-Joon Cha, Su Bin Lim, Joo Hee Jeong, Hyung Joon Joo, Jae Hyoung Park, Soon Jun Hong, Cheol Woong Yu
Journal: Journal of the American College of Cardiology (2021)
Ultrasound Еxamination of the Еxtrahepatic Bile Ducts in Children (Literature Review with our own Clinical Observations)
Authors: A. A. Yusufov, M. I. Medvedeva, A. A. Plyukhin
Journal: Radiology - Practice (2021)

To study the normal sonographic anatomy of extrahepatic bile ducts, a polypositional ultrasound examination of 120 children aged 0 to 17 years was conducted. The technique of hepatoduodenal ligament ultrasound examination is described. The main sonographic visual indicators for studying the anatomical and topographic structure of extrahepatic bile ducts in children are denoted. The normative parameters of the common bile and common hepatic ducts in children of different age groups are presented.
Global burden of NAFLD and chronic liver disease among adolescents and young adults
Authors: James M. Paik, Khaled Kabbara, Katherine E. Eberly, Youssef Younossi, Linda Henry, Zobair M. Younossi
Journal: Hepatology (2021)

The causes of chronic liver disease (CLD) among adults have changed. Data are lacking on trends among youth. We determined the trends and changes in the global burden of CLD among adolescents and young adults using Global Burden of Disease (GBD) data (2009-2019).The GBD study estimation methods were used to assess CLD prevalence, incidence, and deaths (21 GBD regions). Annual percent change (APC) calculation by joinpoint regression modeling. Age groups were 15-19, 20-24, and 25-29 years old. Globally in 2019, the 15-29 group accounted for 17.2% (0.29 billion) of CLD prevalent cases, 11.2% (n = 232,072) CLD incident cases, and 3.8% (n = 55,515) CLD deaths. Between 2009 and 2019, CLD prevalence rate increased annually among 25-29 (APC = +0.41%, p < 0.001); remained stable among 20-24 (APC = +0.02%, p = 0.582); and decreased among 15-19 (APC = -2.13%, p < 0.001). CLD prevalence increases were driven by the proportion with NAFLD (15-19: 40.8% to 52.9%, p < 0.001); 20-24: 57.6% to 62.7%, p < 0.001); and 25-29: 66.9% to 70.1%, p < 0.001); the proportion with HBV decreased across all age groups. NAFLD prevalence worsening trend (APC ≥ 0%) was global. Overall CLD death rate decreased annually in all age groups, driven by the decrease in the proportion with HBV [aged 15-19 (from 5.90% to 5.20%, p < 0.001); aged 20-24 (from 18.62% to 16.37%, p < 0.001); and aged 25-29 (from 28.69% to 25.28%, p < 0.001)]; from 2015 to 2019, CLD death rate for HCV (APC = +1.46%) and NAFLD (APC = +2.26%) increased.Over the past decade, the causes of CLD among 15-29-year-olds have shifted: viral hepatitis remains the most common cause of CLD deaths, but the global burden of HBV incidence is decreasing, whereas NAFLD is the main driver for increased CLD incidence.
ESKD Immunoglobulin Response at 3 Months Post COVID-19 Vaccination
Authors: Devasmita Choudhury, Lampros S. Karageorge, Alia Hasan
Journal: Journal of the American Society of Nephrology (2021)

Background: End stage kidney disease (ESKD) patients (pts) remain at high risk for COVID 19 infection. Inadequate post infection antibody response is reported in 10-11% of pts1. Current data is limited on ESKD post vaccination (vac)2 We report 3-month (mo) post vac response of ESKD pts receiving 2 doses of either Moderna or Pfizer vaccines. Methods: Twenty-six of 42 stable ESKD pts completed 2 doses of either Moderna or Pfizer vaccination at Salem VAMC or at their nursing home facility during mo 01/02-2021. 17/42 were not vaccinated (7 declined, 2 with COVID 19 infection, 6 acutely hospitalized) during that time. Antibody immune response testing using ADVIA Centaur COV2G automated 2-step sandwich immunoassay using indirect chemiluminescent technology and designed to detect the SARS-CoV-2 surface spike protein receptor binding domain (S1RBD) was completed in 05/2021. Measures obtained included reactivity to total SARS CoV-ab (IgM+ IgG) and IgG separately. Results: Please see table 1 for results Conclusions: ESKD vaccine response to COVID 19 after 3months was 96% for total immunoglobulin response (IgM and IgG) and 87.5% for total IgG antibody response compared to no reactivity in those nonvaccinated patients. Age and presence of diabetes did not significantly affect immune response. Approximately 12.5 % of patients had nonreactivity to IgG antibody after 3 months. Patients not developing an IgG response by 3 mo were found to have underlying immunosuppressive disease. ESKD with COVID 19 infection maintained IgG reactive response 3 months after active disease. Nonreactivity was seen in those neither infected nor vaccinated, suggesting that these patients have likely not been exposed to COVID 19 viral infection.
TCT-33 Complete Versus Culprit-Only Strategy in Older Patients With MI and Multivessel Disease: Results From a Cohort Study Based on 4 International Registries
Authors: Simone Biscaglia, Matteo Serenelli, Albert Ariza Solé, Juan Sanchis Fores, Francesco Giannini, Francesco Gallo, Antonella Scala, Matteo Tebaldi, Gianluca Campo
Journal: Journal of the American College of Cardiology (2021)
A Mutation–Selection Model of Protein Evolution under Persistent Positive Selection
Authors: Asif U Tamuri, Mario dos Reis
Journal: Molecular Biology and Evolution (2021)

We use first principles of population genetics to model the evolution of proteins under persistent positive selection (PPS). PPS may occur when organisms are subjected to persistent environmental change, during adaptive radiations, or in host-pathogen interactions. Our mutation-selection model indicates protein evolution under PPS is an irreversible Markov process, and thus proteins under PPS show a strongly asymmetrical distribution of selection coefficients among amino acid substitutions. Our model shows the criteria ω>1 (where ω is the ratio of nonsynonymous over synonymous codon substitution rates) to detect positive selection is conservative and indeed arbitrary, because in real proteins many mutations are highly deleterious and are removed by selection even at positively selected sites. We use a penalized-likelihood implementation of the PPS model to successfully detect PPS in plant RuBisCO and influenza HA proteins. By directly estimating selection coefficients at protein sites, our inference procedure bypasses the need for using ω as a surrogate measure of selection and improves our ability to detect molecular adaptation in proteins.
The Effects of Osteoporotic and Non-osteoporotic Medications on Fracture Risk and Bone Mineral Density
Authors: Anna C. van der Burgh, Catherine E. de Keyser, M. Carola Zillikens, Bruno H. Stricker
Journal: Drugs (2021)

Osteoporosis is a highly prevalent bone disease affecting more than 37.5 million individuals in the European Union (EU) and the United States of America (USA). It is characterized by low bone mineral density (BMD), impaired bone quality, and loss of structural and biomechanical properties, resulting in reduced bone strength. An increase in morbidity and mortality is seen in patients with osteoporosis, caused by the approximately 3.5 million new osteoporotic fractures occurring every year in the EU. Currently, different medications are available for the treatment of osteoporosis, including anti-resorptive and osteoanabolic medications. Bisphosphonates, which belong to the anti-resorptive medications, are the standard treatment for osteoporosis based on their positive effects on bone, long-term experience, and low costs. However, not only medications used for the treatment of osteoporosis can affect bone: several other medications are suggested to have an effect on bone as well, especially on fracture risk and BMD. Knowledge about the positive and negative effects of different medications on both fracture risk and BMD is important, as it can contribute to an improvement in osteoporosis prevention and treatment in general, and, even more importantly, to the individual's health. In this review, we therefore discuss the effects of both osteoporotic and non-osteoporotic medications on fracture risk and BMD. In addition, we discuss the underlying mechanisms of action.
Real-World Persistence and Time to Next Treatment with Ibrutinib Treatment in Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Including Patients at High Risk for Atrial Fibrillation or Stroke
Authors: Anna Narezkina, Xiaoxiao Lu, Bruno Emond, Aurélie Côté-Sergent, Annalise Hilts, Stephanie Liu, Marie-Hélène Lafeuille, Patrick Lefebvre, Qing Huang
Journal: Blood (2021)
Clinical Characteristics and Short-Term Outcomes of Severe AKI in COVID-19 in Bronx, New York
Authors: Milagros Yunes, Emad Alahiri, Ryan Mocerino, Kalyan Prudhvi, Ladan Golestaneh, Molly Fisher
Journal: Journal of the American Society of Nephrology (2020)

Background: After the first reported case of COVID-19 in the U S , New York City quickly became the epicenter of the pandemic  AKI has been reported in patients with severe COVID-19  The Bronx consists of a predominantly minority population with a high burden of comorbidities that may be at increased risk for AKI in the setting of COVID-19  We aimed to characterize risk factors and short term outcomes in patients hospitalized with COVID-19 and severe AKI  Methods: We performed a retrospective study of 113 adults hospitalized with COVID-19 in a large healthcare system in the Bronx who required nephrology consultation for AKI from March 11-March 30, 2020  We extracted data on demographics, comorbidities, admission vital signs and labs, need for mechanical ventilation, renal replacement therapy (RRT), in-hospital death and discharge  AKI was defined by KDIGO criteria  Chi-square analyses and Wilcoxon tests were used  Data was censored on April 12, 2020  All patients had ≥ 14 days of follow up  Results: Mean age was 63 (SD 12) years old;69% were men and 33% were Black and 23% were Hispanic  Forty-five patients (39 8%) had chronic kidney disease, 58(51%) had diabetes mellitus and 87(77%) had hypertension  The majority presented with AKI within 24 hours of admission and 75% had Stage 3 AKI  Ninety-two (81%) patients had proteinuria and 53(47%) had hematuria  Intensive care unit (ICU) was required in 62(55%), 64(57%) required mechanical ventilation, 56(49 5%) required RRT and 18(16%) were not candidates for RRT  In-hospital death occurred in 68(60%) and 22% were discharged  Of those who required RRT, in-hospital death occurred in 35(62 5%) and only 6 patients were discharged, 5 of whom remained RRT dependent  Heavy proteinuria (3-4+ on urinalysis) and initial C-reactive protein (CRP) were higher in those with AKI who died [21 1 (IQR 14 3-29 6) versus 6 6 (3 2-16 3), p<0 001]  Conclusions: Severe AKI in the setting of COVID-19 is associated with increased utilization of ICU, mechanical ventilation, and RRT  Outcomes are poor in those with Stage 3 AKI, underscoring the need for palliative care involvement and early goals of care discussions  Elevated initial CRP and heavy proteinuria may be useful to risk stratify patients with COVID-19 and severe AKI at increased risk for mortality