tbuckley/cabot-search huggingface dataset:
Advancing the Learning Health System
Authors: J. Michael McGinnis, Harvey V. Fineberg, Victor J. Dzau
Journal: New England Journal of Medicine (2021)

Interview with Dr. J. Michael McGinnis on supporting the evolution of a learning health system. (19:56)Download Recognizing that technological and methodologic advances could improve on the pace, generalizability, and costs of innovation in health and medicine, the National Academy of Medicine has helped steward the evolution of a continuously learning health system.
Resisting the “righting reflex” in conversations about covid vaccine hesitancy
Authors: Graham P Easton
Journal: BMJ (2021)

<h3>Abstract</h3> <h3>Background</h3> During the first wave of COVID-19, hospital and intensive care unit beds got overwhelmed in Italy leading to an increased death burden. Based on data from Italian regions, we disentangled the impact of various factors contributing to the bottleneck situation of health care facilities, not well addressed in classical SEIR-like models. A particular emphasis was set on the dark figure, on the dynamically changing hospital capacity, and on different testing, contact tracing, quarantine strategies. <h3>Methods</h3> We first estimated the dark figure for different Italian regions. Using parameter estimates from literature and, alternatively, with parameters derived from a fit to the initial phase of COVID-19 spread, the model was optimized to fit data (infected, hospitalized, ICU, dead) published by the Italian Civil Protection. <h3>Results</h3> We showed that testing influenced the infection dynamics by isolation of newly detected cases and subsequent interruption of infection chains. The time-varying reproduction number (<i>R</i><sub>t</sub>) in high testing regions decreased to <i>&lt;</i> 1 earlier compared to the low testing regions. While an early test and isolate (TI) scenario resulted in up to ∼ 32% peak reduction of hospital occupancy, the late TI scenario resulted in an overwhelmed health care system. <h3>Conclusions</h3> An early TI strategy would have decreased the overall hospital accessibility drastically and, hence, death toll (∼ 45% reduction in Lombardia) and could have mitigated the lack of health care facilities in the course of the pandemic, but it would not have kept the hospitalization amount within the pre-pandemic hospital limit. We showed that contact tracing and quarantine without testing would have a similar effect and might be an efficient strategy when sufficient test capacities are not available.
Imaging Early Response to Checkpoint Inhibition
Authors: Quinlan Cullen, Kayvan R. Keshari
Journal: Cancer Research (2021)

Abstract Immune checkpoint blockade therapy has achieved remarkable clinical success, but these promising results have been limited to a minority of patients. Thus far, efforts to establish a predictive biomarker or accurately assess early response to treatment have been fruitless. In this issue of Cancer Research, Saida and colleagues utilized advanced molecular imaging modalities to assess changes in the tumor microenvironment that correlate with tumor response to immune checkpoint blockade therapy in vivo. This study suggests a combination of imaging biomarkers with potential for delineating clinical response to immunotherapy. See related article by Saida et al., p. 3693
Neuropathy severity at the time of oxaliplatin treatment alteration in patients with colon cancer (Alliance A151912).
Authors: Daniel Louis Hertz, Travis Dockter, Daniel V. Satele, Charles L. Loprinzi, Jennifer Le-Rademacher
Journal: Journal of Clinical Oncology (2021)

12090 Background: Clinical guidelines recommend altering chemotherapy treatment by decreasing, delaying, or discontinuing dosing in patients (pts) experiencing chemotherapy-induced peripheral neuropathy (CIPN). There are few data available on clinical use of treatment alteration including the severity of CIPN at the time of alteration. Our objective was to investigate the incidence of oxaliplatin treatment alterations and CIPN severity at that time. Methods: This was a retrospective analysis of pts with colon cancer scheduled to receive oxaliplatin-containing combination chemotherapy on the N08CB trial of intravenous calcium and magnesium for prevention of CIPN. Dose alterations were not mandated by the N08CB protocol. Clinicians assessed CIPN using NCI-CTCAE V.4.0; pts used the sensory subscale of the EORTC-QLQ Chemotherapy-Induced Peripheral Neuropathy 20 (CIPN8). Pts were classified as 1) completed oxaliplatin treatment without alteration, 2) dose reduction or delay due to CIPN, 3) discontinuation due to CIPN, 4) discontinuation due to other AE, or 5) discontinuation for another reason. Comparisons focused primarily on pts with alteration due to CIPN (groups 2 and/or 3) compared with pts completing treatment without alteration (group 1) using chi-squared and Kruskal-Wallis tests. Results: In this analysis of 350 N08CB pts, 135 (39%) completed oxaliplatin without treatment alteration, 70 (20%) had a dose reduction (n=66) or delay (n=4) due to CIPN and 35 (10%) discontinued early due to CIPN. Pts who experienced alterations due to CIPN were younger (p=0.0249) and more likely to be female (p=0.008). Clinician-assessed CIPN severity was greater in pts at the time of dose reduction or delay compared with CIPN severity at the end of treatment in pts with no alteration (p&lt;0.0001). Pt-assessed CIPN severity was not different in pts who completed treatment without alteration compared to pts who had a dose reduction or delay (p=0.88) or a discontinuation (p=0.37). CIPN8 scores at cycle 4 were higher (worse) in pts who eventually had any alteration (i.e., reduction, delay, or discontinuation) compared to pts who completed treatment without any alteration (median CIPN8 11.5 vs. 7.7, p=0.023). Conclusions: Treatment alterations due to CIPN are relatively common in pts receiving adjuvant oxaliplatin for colon cancer and are associated with clinician-assessed but not pt-reported CIPN severity. Rapid CIPN8 increases early in treatment are indicative of increased likelihood of a future oxaliplatin treatment alteration, indicating a potential use of early monitoring and intervention. Support: UG1CA189823; https://acknowledgments.alliancefound.org. Clinical trial information: NCT01099449 (NCCTG N08CB).
Identification and Validation of T-cell Receptors Targeting <i>RAS</i> Hotspot Mutations in Human Cancers for Use in Cell-based Immunotherapy
Authors: Noam Levin, Biman C. Paria, Nolan R. Vale, Rami Yossef, Frank J. Lowery, Maria R. Parkhurst, Zhiya Yu, Maria Florentin, Gal Cafri, Jared J. Gartner, Mackenzie L. Shindorf, Lien T. Ngo, Satyajit Ray, Sanghyun P. Kim, Amy R. Copeland, Paul F. Robbins, Steven A. Rosenberg
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Immunotherapies mediate the regression of human tumors through recognition of tumor antigens by immune cells that trigger an immune response. Mutations in the RAS oncogenes occur in about 30% of all patients with cancer. These mutations play an important role in both tumor establishment and survival and are commonly found in hotspots. Discovering T-cell receptors (TCR) that recognize shared mutated RAS antigens presented on MHC class I and class II molecules are thus promising reagents for “off-the-shelf” adoptive cell therapies (ACT) following insertion of the TCRs into lymphocytes. Experimental Design: In this ongoing work, we screened for RAS antigen recognition in tumor-infiltrating lymphocytes (TIL) or by in vitro stimulation of peripheral blood lymphocytes (PBL). TCRs recognizing mutated RAS were identified from the reactive T cells. The TCRs were then reconstructed and virally transduced into PBLs and tested. Results: Here, we detect and report multiple novel TCR sequences that recognize nonsynonymous mutant RAS hotspot mutations with high avidity and specificity and identify the specific class-I and -II MHC restriction elements involved in the recognition of mutant RAS. Conclusions: The TCR library directed against RAS hotspot mutations described here recognize RAS mutations found in about 45% of the Caucasian population and about 60% of the Asian population and represent promising reagents for “off-the-shelf” ACTs.
Favorable outcome of NUTM1-rearranged infant and pediatric B cell precursor acute lymphoblastic leukemia in a collaborative international study
Authors: Judith M. Boer, Maria Grazia Valsecchi, Femke M. Hormann, Željko Antić, Marketa Zaliova, Claire Schwab, Giovanni Cazzaniga, Chloé Arfeuille, Hélène Cavé, Andishe Attarbaschi, Sabine Strehl, Gabriele Escherich, Toshihiko Imamura, Kentaro Ohki, Tanja A. Grüber, Rosemary Sutton, Agata Pastorczak, Tim Lammens, Frédéric Lambert, Chi Kong Li, Enrique Carrillo de Santa Pau, Steve Hoffmann, Anja Möricke, Christine J. Harrison, Monique L. Den Boer, Paola De Lorenzo, Ronald W. Stam, Anke K. Bergmann, Rob Pieters
Journal: Leukemia (2021)
Abstract 16468: Sodium Channel Blockers Normalize Cardiac Repolarization in Rett Syndrome
Authors: Hoang H Nguyen, John Somberg, Wilkie Mary, Jessica Jacobson, Colleen Buhrfiend, Peter Heydemann
Journal: Circulation (2019)

Introduction: Rett syndrome (RTT) is an X-linked disorder caused by mutations in the MECP2 gene. Up to 25% of deaths in RTT are sudden. Prolonged corrected QT (QTc) has also been reported and thoug...
Phase <scp>IIa</scp> Global Study Evaluating Rituximab for the Treatment of Pediatric Patients With Granulomatosis With Polyangiitis or Microscopic Polyangiitis
Authors: Paul Brogan, Rae S. M. Yeung, Gavin Cleary, Satyapal Rangaraj, Ozgur Kasapcopur, Aimee O. Hersh, Suzanne Li, Dusan Paripovic, Kenneth Schikler, Andrew Zeft, Claudia Bracaglia, Despina Eleftheriou, Pooneh Pordeli, Simone Melega, Candice Jamois, Jacques Gaudreault, Margaret Michalska, Paul Brunetta, Jennifer C. Cooper, Patricia B. Lehane
Journal: Arthritis & Rheumatology (2021)

To assess the safety, tolerability, pharmacokinetics, and efficacy of rituximab (RTX) in pediatric patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA).The Pediatric Polyangiitis Rituximab Study was a phase IIa, international, open-label, single-arm study. During the initial 6-month remission-induction phase, patients received intravenous infusions of RTX (375 mg/m2 body surface area) and glucocorticoids once per week for 4 weeks. During the follow-up period, patients could receive further treatment, including RTX, for GPA or MPA. The safety, pharmacokinetics, pharmacodynamics, and exploratory efficacy outcomes with RTX were evaluated.Twenty-five pediatric patients with new-onset or relapsing disease were enrolled at 11 centers (19 with GPA [76%] and 6 with MPA [24%]). The median age was 14 years (range 6-17 years). All patients completed the remission-induction phase. During the overall study period (≤4.5 years), patients received between 4 and 28 infusions of RTX. All patients experienced ≥1 adverse event (AE), mostly grade 1 or grade 2 primarily infusion-related reactions. Seven patients experienced 10 serious AEs, and 17 patients experienced 31 infection-related AEs. No deaths were reported. RTX clearance correlated with body surface area. The body surface area-adjusted RTX dosing regimen resulted in similar exposure in both pediatric and adult patients with GPA or MPA. Remission, according to the Pediatric Vasculitis Activity Score, was achieved in 56%, 92%, and 100% of patients by months 6, 12, and 18, respectively.In pediatric patients with GPA or MPA, RTX is well tolerated and effective, with an overall safety profile comparable to that observed in adult patients with GPA or MPA who receive treatment with RTX. RTX is associated with a positive risk/benefit profile in pediatric patients with active GPA or MPA.
Threats to the effectiveness of insecticide-treated bednets for malaria control: thinking beyond insecticide resistance
Authors: Steve W Lindsay, Matthew B Thomas, Immo Kleinschmidt
Journal: The Lancet Global Health (2021)

From 2004 to 2019, insecticide-treated bednets (ITNs) have been the most effective tool for reducing malaria morbidity and mortality in sub-Saharan Africa. Recently, however, the decline in malaria cases and deaths has stalled. Some suggest that this inertia is due to increasing resistance in malaria vectors to the pyrethroid insecticides used for treating ITNs. However, there is presently little evidence to reach this conclusion and we therefore recommend that a broader perspective to evaluate ITN effectiveness in terms of access to nets, use of nets, bioefficacy, and durability should be taken. We argue that a single focus on insecticide resistance misses the bigger picture. To improve the effects of ITNs, net coverage should increase by increasing funding for programmes, adopting improved strategies for increasing ITN uptake, and enhancing the longevity of the active ingredients and the physical integrity of nets, while simultaneously accelerating the development and evaluation of novel vector control tools.
Multi-Walled Carbon Nano-Tubes (MWCNTs) Accelerate Leukaemia Development in Mice: Implications for Drug Development in Humans
Authors: Bin Yin, Xiaofeng Han, Huikai Miao, Min Zhang, Yanwen Zheng, Huiquan Tao, Guangsong Su, Zhengwei Mao, Haiyan Xu, Hongchao Yin, Jiang Hu, Robert Peter Gale, Fanqing Chen
Journal: Blood (2017)
Weekly Insulin Becoming a Reality
Authors: Jay S. Skyler
Journal: Diabetes Care (2021)

Insulin was first isolated in 1921 and developed as a therapeutic agent in the 1920s. The initial crude preparations were injected multiple times daily because of their short duration of action. Consequently, there were many attempts to develop insulin preparations with prolonged biological availability in the hope that less frequent once-daily administration would be feasible (1). A host of such preparations were introduced, including protamine insulin, protamine zinc insulin, surfen insulin, globin insulin, iso-insulin, isophane insulin (NPH), and insulin zinc suspensions (lente insulins) (1) (Fig. 1). The goal was mainly to reduce the number of injections and thus the patient burden. Yet, with the development of a radioimmunoassay for insulin (2), it became apparent that physiologic insulin secretion involved two components: meal-related insulin secretion with postprandial spikes and basal insulin secretion that remains relatively constant with some minor pulsatility (3). Subsequently, as modern insulin therapy evolved, facilitated by patient self-monitoring of blood glucose (4,5), it became apparent that the inherent peaks in basal insulin preparations, such as with the nonsoluble NPH or lente insulins, created risk of hypoglycemia, especially if the insulin vials were not correctly rolled to create a proper suspension. Moreover, these insulins did not have sufficiently long duration of action to be used once daily. Consequently, in addition to making them soluble, two of the goals in development of basal insulin analogs, such as insulin glargine and insulin detemir, were to eliminate insulin peaks and to prolong the action to approach 24 h (6,7). Second-generation basal insulin analogs, such as insulin degludec and insulin glargine U300, came with …
Time for precision medicine in systemic sclerosis-associated pulmonary arterial hypertension
Authors: David Launay, Sébastien Sanges, Vincent Sobanski
Journal: European Respiratory Journal (2021)

<b>Integration of omics with clinical data through machine learning is the future of personalised and precision medicine in systemic sclerosis-associated pulmonary arterial hypertension</b>https://bit.ly/3jsyBoV
The International Collaboration for Research methods Development in Oncology (CReDO) workshops: shaping the future of global oncology research
Authors: Priya Ranganathan, Girish Chinnaswamy, Manju Sengar, Durga Gadgil, Shivakumar Thiagarajan, Balram Bhargava, Christopher M Booth, Marc Buyse, Sanjiv Chopra, Chris Frampton, Satish Gopal, Nick Grant, Mark Krailo, Ruth Langley, Prashant Mathur, Xavier Paoletti, Mahesh Parmar, Arnie Purushotham, Douglas Pyle, Preetha Rajaraman, Martin R Stockler, Richard Sullivan, Soumya Swaminathan, Ian Tannock, Edward Trimble, Rajendra A Badwe, C S Pramesh
Journal: The Lancet Oncology (2021)
Abstract 15357: Population-based Resequencing of APOA1 in 10,330 Individuals: Spectrum of Genetic Variation, Phenotype, and Comparison with Extreme Phenotype Approach
Authors: Christiane L Haase, Ruth Frikke-Schmidt, Børge G Nordestgaard, Anne Tybjærg-Hansen
Journal: Circulation (2012)

INTRODUCTION: Rare genetic variants, identified by in-detail resequencing of loci, may contribute to complex traits. OBJECTIVE: To use population-based resequencing of the apolipoprotein A-I gene (...
Ten Practical Recommendations for Improving Blinding Integrity and Reporting in Psychotherapy Trials
Authors: David Mataix-Cols, Erik Andersson
Journal: JAMA Psychiatry (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 Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Journals 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
Abstract 412: Chance of Survival Decreases Within 10 Minutes of Transport in Trauma Patients Receiving Preospital Cardiopulmonary Resuscitation
Authors: Hiromichi Naito, Tetsuya Yumoto, Takashi Yorifuji, Tsuyoshi Nojima, Atsunori Nakao
Journal: Circulation (2019)

Introduction: Patients with traumatic cardiac arrest (TCA) are known to have poor prognoses. The joint committee of the National Association of EMS Physicians and the American College of Surgeons Committee on Trauma proposes stopping cardiopulmonary resuscitation (CPR) more than 15 minutes after TCA. However, with advances in resuscitation strategies, recent published data show improved outcomes. Data supporting TCA’s critical time limit is lacking. Hypothesis: We studied whether longer transport time is associated with poor outcomes in TCA. Methods: Retrospective review from the Japan Trauma Data Bank (2004-2017). Inclusion criteria were patients age ≥ 16 with at least one Abbreviated Injury Scale score (AIS) ≥ 3 trauma and CPR performed during the transport. Exclusion criteria were patients with burns, AIS score = 6 in any region, and missing survival data. Primary outcome was the association between transport time and survival in patients with no vital signs at arrival. For secondary outcomes, survival between penetrating injury/blunt injury and no vital signs (Revised Trauma Score [RTS] = 0)/any vital sign (RTS &gt; 0) were compared. For the primary outcome, probability of survival was drawn with risk ratio (reference 15 min) according to transport time. Fisher’s exact test was used to compare secondary outcomes. Results: 5,334 patients were included. Patient characteristics were age (53 ± 21 years), sex (67% male), Injury Severity Score (31 ± 13), blunt trauma (95%), and transportation time (16 ± 15 min). Overall survival rate was 4.5%, survival rate in patients without vital sign at arrival was 1.2%. Survival rate decreased within 10 min ( Figure ). Penetrating trauma increased the chance of survival compared with blunt trauma (7.7% vs. 4.1%, OR 1.9, p = 0.006). Chance of survival increased when the patient had any vital sign at arrival (28% vs. 1.2%, OR 33, p &lt; 0.001). Conclusions: Longer transport time was associated with worse outcome, supporting the current guideline.
Regenerative medicine for digestive fistulae therapy: Benefits, challenges and promises of stem/stromal cells and emergent perspectives via their extracellular vesicles
Authors: Anna C. Sebbagh, Boris Rosenbaum, Guillaume Péré, Hadrien Alric, Arthur Berger, Claire Wilhelm, Florence Gazeau, Noëlle Mathieu, Gabriel Rahmi, Amanda K.A. Silva
Journal: Advanced Drug Delivery Reviews (2021)
Revisiting Old Friends: Adjunctive Therapies in Acute Respiratory Distress Syndrome
Authors: Catherine A. Gao, Ruben J. Mylvaganam, Taylor A. Poor, James M. Walter
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

"Revisiting Old Friends: Adjunctive Therapies in Acute Respiratory Distress Syndrome." American Journal of Respiratory and Critical Care Medicine, 204(4), pp. 473–475
Is Learning Worth the Trouble? — Improving Health Care System Participation in Embedded Research
Authors: Richard Platt, Gregory E. Simon, Adrian F. Hernandez
Journal: New England Journal of Medicine (2021)

Interview with Dr. J. Michael McGinnis on supporting the evolution of a learning health system. (19:56)Download To help address important health issues, embedded pragmatic clinical trials could generate real-world evidence without the limitations associated with observational studies or the time, expense, and lack of generalizability associated with conventional clinical trials.
The TLR7 agonist vesatolimod induced a modest delay in viral rebound in HIV controllers after cessation of antiretroviral therapy
Authors: Devi SenGupta, Cynthia Brinson, Edwin DeJesus, Anthony Mills, Peter Shalit, Susan Guo, Yanhui Cai, Jeffrey J. Wallin, Liao Zhang, Rita Humeniuk, Rebecca Begley, Romas Geleziunas, John Mellors, Terri Wrin, Norman Jones, Jeffrey Milush, April L. Ferre, Barbara L. Shacklett, Greg M. Laird, Brian Moldt, Elena Vendrame, Diana M. Brainard, Moti Ramgopal, Steven G. Deeks
Journal: Science Translational Medicine (2021)

Toll-like receptor 7 (TLR7) agonists, in combination with other therapies, can induce sustained control of simian-human immunodeficiency virus (SHIV) or simian immunodeficiency virus (SIV) in nonhuman primates. Here, we report the results of a randomized, double-blind, placebo-controlled phase 1b clinical trial of an oral TLR7 agonist, vesatolimod, in HIV-1-infected controllers on antiretroviral therapy (ART). We randomized participants 2:1 to receive vesatolimod (n = 17) or placebo (n = 8) once every other week for a total of 10 doses while continuing on ART. ART was then interrupted, and the time to viral rebound was analyzed using the Kaplan-Meier method. Vesatolimod was associated with induction of immune cell activation, decreases in intact proviral DNA during ART, and a modest increase in time to rebound after ART was interrupted. The delayed viral rebound was predicted by the lower intact proviral DNA at the end of vesatolimod treatment (13 days after the final dose). Inferred pathway analysis suggested increased dendritic cell and natural killer cell cross-talk and an increase in cytotoxicity potential after vesatolimod dosing. Larger clinical studies will be necessary to assess the efficacy of vesatolimod-based combination therapies aimed at long-term control of HIV infection.