tbuckley/cabot-search huggingface dataset:
Correction: The Effect of Raltegravir Intensification on Low-level Residual Viremia in HIV-Infected Patients on Antiretroviral Therapy: A Randomized Controlled Trial
Authors: Rajesh T. Gandhi, Lu Zheng, Ronald J. Bosch, Ellen S. Chan, David M. Margolis, Sarah Read, Beatrice Kallungal, Sarah Palmer, Kathy Medvik, Michael M. Lederman, Nadia Alatrakchi, Jeffrey M. Jacobson, Ann Wiegand, Mary Kearney, John M. Coffin, John W. Mellors, Joseph J. Eron
Journal: PLoS Medicine (2011)

Background: Most HIV-1-infected patients on effective antiretroviral therapy (ART) with plasma HIV-1 RNA levels below the detection limits of commercial assays have residual viremia measurable by more sensitive methods.We assessed whether adding raltegravir lowered the level of residual viremia in such patients.Methods and Findings: Patients receiving ART who had plasma HIV-1 RNA levels below 50 copies/mL but detectable viremia by single copy assay (SCA) were randomized to add either raltegravir or placebo to their ART regimen for 12 weeks; patients then crossed-over to the other therapy for an additional 12 weeks while continuing pre-study ART.The primary endpoint was the plasma HIV-1 RNA by SCA averaged between weeks 10 and 12 (10/12) compared between treatment groups.Fifty-three patients were enrolled.The median screening HIV-1 RNA was 1.7 copies/mL.The HIV-1 RNA level at weeks 10/12 did not differ significantly between the raltegravir-intensified (n = 25) and the placebo (n = 24) groups (median 1.2 versus 1.7 copies/mL, p = 0.55, Wilcoxon rank sum test), nor did the change in HIV-1 RNA level from baseline to week 10/12 (median 20.2 and 20.1 copies/mL, p = 0.71, Wilcoxon rank sum test).There was also no significant change in HIV-1 RNA level from weeks 10/12 to weeks 22/24 after patients crossed-over.There was a greater CD4 cell count increase from baseline to week 12 in the raltegravir-intensified group compared with the placebo group (+42 versus 244 cells/mm 3 , p = 0.082, Wilcoxon rank sum test), which reversed after the cross-over.This CD4 cell count change was not associated with an effect of raltegravir intensification on markers of CD4 or CD8 cell activation in blood. Conclusion:In this randomized, double-blind cross-over study, 12 weeks of raltegravir intensification did not demonstrably reduce low-level plasma viremia in patients on currently recommended ART.This finding suggests that residual viremia does not arise from ongoing cycles of HIV-1 replication and infection of new cells.New therapeutic strategies to eliminate reservoirs that produce residual viremia will be required to eradicate HIV-1 infection.
Other Books
Journal: JAMA (1966)

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Report of the Special Committee Appointed by the Local Authority at Their Meeting of the 30th April, 1927 (p. 80, item 2) on the Question of the Establishment of a Standard of Purity for the Port-of-Spain Water Supply.
Journal: JAMA (1930)

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CSF Data Errors in Text and Table
Authors: Robert Miller
Journal: JAMA (2014)

The NORDIC Idiopathic Intracranial Hypertension Study Group Writing Committee; Michael Wall, MD; Michael P. McDermott, PhD; Karl D. Kieburtz, MD, MPH; James J. Corbett, MD; Steven E. Feldon, MD; Deborah I. Friedman, MD, MPH; David M. Katz, MD; John L. Keltner, MD; Eleanor B. Schron, PhD; Mark J. Kupersmith, MD
THE ST. PAUL MEETING.
Journal: JAMA (1901)

<h3>HISTORICAL.</h3> The Republic of the United States was already more than sixty years old when the first settlement was made upon the site of the present city of St. Paul, the capital of the State of Minnesota. This event, which happened in the month of September, 1838, occurred some eighteen years later than the first settlement in that part of the country, the military post now Fort Snelling having been established in 1820. The first settler of St. Paul built his cabin some four miles below and on the opposite bank of the river from the fort, and history, truthful but not poetic, records that the spot was selected not on account of the romantic beauties of the situation but because it was the most convenient place outside of military jurisdiction from which to sell whisky to the soldiers and Indians. The fact that it was at the head of
Thrombolytic Therapy for Elderly Patients With Myocardial Infarction-Reply
Authors: Jerry H. Gurwitz
Journal: JAMA (1997)

<h3>To the Editor.</h3> —Previous work has clearly demonstrated that severe comorbidity has a negative impact on the receipt of thrombolytic therapy in patients with acute myocardial infaction who are eligible for treatment. In a study of 37 Minnesota hospitals from October 1992 to July 1993, McLaughlin et al<sup>1</sup>observed that, after controlling for other factors reported to influence use of thrombolysis, the odds of receipt of thrombolytic therapy among patients with severe comorbidity were 0.49 (95% confidence interval, 0.27-0.88), when compared with individuals without this characteristic. These findings have implications for the measurement of physician adherence to evidence-based treatment guidelines. Apparent noncompliance with guidelines is commonly interpreted as reflecting gaps in knowledge or lack of acceptance of guideline recommendations. However, nonuse of an indicated treatment may reflect a conscious decision to withhold a therapy, based on other clinical considerations. Functional status is another important patient characteristic to consider in regard to decisions
ACTR-09. A PHASE 0 PHARMACODYNAMIC AND PHARMACOKINETIC STUDY OF EVEROLIMUS IN VESTIBULAR SCHWANNOMA (VS) AND MENINGIOMA PATIENTS
Authors: Matthias Karajannis, Judith Goldberg, J Thomas Roland, Chandranath Sen, Dimitris Placantonakis, John Golfinos, Jeffrey Allen, Erin Dunbar, Scott Plotkin, Srivandana Akshintala, Robert Schneider, Jingjing Deng, Thomas A Neubert, Filippo Giancotti, David Zagzag, Jaishri O Blakeley
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Inhibition of mTORC1 signaling has been shown to diminish growth of NF2 deficient tumors in preclinical studies, and clinical data suggest that everolimus, an orally administered mTORC1 inhibitor, may slow tumor progression in a subset of adult and pediatric NF2 patients with VS. To assess the pharmacokinetics, pharmacodynamics and potential mechanisms of treatment resistance, we performed a pre-surgical (“phase 0”) clinical trial of everolimus in patients undergoing surgery for VS or meningiomas. METHODS Eligible patients with meningioma or VS requiring tumor resection received everolimus 10 mg daily for 10 days immediately prior to surgery. Everolimus blood levels were determined immediately prior to and after surgery. Tumor samples were collected intraoperatively. RESULTS Ten patients completed protocol therapy, including 5 patients with NF2-related meningioma, 3 patients with sporadic meningioma, and 2 patients with NF2-related VS. Median pre- and post-operative plasma levels of everolimus were found to be in a high therapeutic range (17.4 ng/ml and 9.4 ng/ml, respectively). Median tumor tissue drug concentration determined by mass spectrometry was 24.3 ng/g (range 9.2–169.2), and median tumor tissue to post-operative plasma drug concentration ratio was 0.39. We observed only partial inhibition of phospho-S6 in the treated tumors, indicating incomplete target inhibition compared to matched control tissues from untreated patients (p = 0.005). Consistent with prior observations that inhibition of mTORC1 may lead to MAPK pathway activation through a PI3K-dependent feedback loop, we observed a statistically significant increase of phospho-ERK (p &lt; 0.03) versus untreated controls. CONCLUSIONS In patients with meningioma or VS, treatment with everolimus leads to incomplete inhibition of mTORC1 signaling and upregulation phospho-ERK. These data may explain the limited anti-tumor effect of everolimus observed in clinical studies for NF2 patients and identify upregulation of phospho-ERK as a likely resistance mechanism that could be addressed with combination therapies.
Phase II pharmacodynamic trial of erlotinib in advanced non-small cell lung cancer (NSCLC) patients previously treated with platinum-based chemotherapy: preliminary results
Authors: E. Felip, F. Rojo, A. Heller, D. Foernzler, C. Valverde, B. Klughammer, J. Ramos, H. Maacke, U. Brennscheidt, J. Baselga
Journal: Journal of Clinical Oncology (2005)

7100 Background: Erlotinib is a potent epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor that significantly prolongs survival in 2nd and 3rd-line NSCLC treatment. This ongoing trial aims to identify predictive markers of clinical benefit, to study the effects of erlotinib on EGFR and downstream signaling components, and to estimate response rates to erlotinib, in NSCLC patients who progressed after platinum-based chemotherapy. Methods: All patients underwent tumor biopsy at study entry, and then started treatment with erlotinib 150mg/d p.o. In a subgroup of patients a further biopsy was performed after 6 weeks of erlotinib treatment. Results: As of October 2004, characteristics of the 54 patients included were: median age 56 (range 35–78); sex: male 71%, female 29%; histology: adenocarcinoma 49%, large cell 33%, squamous cell 18%. Of 49 evaluable patients, 5 (10%) achieved partial response (PR), 19 (39%) had stable disease (SD) and 25 (51%) had progression (PD). PRs were observed in 3 females/2 males; in 2 adenocarcinomas/2 large cell/1 squamous cell; and in 2 current/2 former/1 never-smoker. Erlotinib was well tolerated, 70% of patients had grade 1–3 rash and no unexpected toxicities were seen. On analyzing tumor samples from diagnosis, EGFR mutations were found in 2 patients with PR. No mutations were seen in 1 patient with SD or in 5 with PD. The effects of 6 weeks of erlotinib on EGFR pathway were analyzed in 12 patients for whom tumor samples were available both at study entry and after 6 weeks of treatment. After erlotinib treatment, EGFR expression remained unchanged whereas there was a decrease in phosphorylated (p) MAPK (p=0.002) and Ki-67 expression (p=0.033). Additionally, in those patients with clinical benefit there was a decrease in pAKT expression (p=0.08) after 6-weeks of erlotinib treatment. Conclusions: Erlotinib achieves significant clinical benefit in previously-treated NSCLC patients. EGFR mutations are seen in some erlotinib responders. In serial tumor biopsies, erlotinib was shown to decrease levels of pMAPK and Ki-67. Accrual is ongoing to 80 patients and affymetrix analyses are to be performed. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Hoffmann-La Roche Ltd., Roche, Roche Diagnostics GmbH Hoffmann-La Roche Ltd.
Journal of Clinical Investigation, Boston
Journal: JAMA (1965)

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Prevention and treatment of hepatitis C in injection drug users
Authors: Brian R. Edlin
Journal: Hepatology (2002)

Injection drug users constitute the largest group of persons infected with the hepatitis C virus (HCV) in the United States, and most new infections occur in drug users. Controlling hepatitis C in the U.S. population, therefore, will require developing, testing, and implementing effective prevention and treatment strategies for persons who inject drugs. Fortunately, a substantial body of research and clinical experience exists on the prevention and management of chronic viral diseases among injection drug users. The need to implement interventions to stop the spread of HCV among drug users is critical. The capacity of substance-use treatment programs need to be expanded to accommodate all who want and need treatment. Physicians and pharmacists should be educated in how to provide access to sterile syringes and to teach safe injection techniques, both of which are lifesaving interventions. The treatment of hepatitis C in drug users requires an interdisciplinary approach that brings together expertise in treating hepatitis and caring for drug users. Treatment decisions should be made individually by patients with their physicians, based on a balanced assessment of risks and benefits and the patient’s personal values. Physicians should carefully assess, monitor, and support adherence and mental health in all patients, regardless of whether drug use is known or suspected. Research is needed to better understand how best to prevent and treat hepatitis C in substance users. In the meantime, substantial progress can be made if existing knowledge and resources are brought to bear. (Hepatology 2002;36:S210-S219).
Drug Regulation and AMA Department of Drugs
Journal: JAMA (1973)

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Medicolegal.
Journal: JAMA (1904)

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Errors in Figures.
Journal: JAMA (1992)

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THE CONVULSIVE DISORDERS OF CHILDHOOD
Journal: JAMA (1922)

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Editorial Board
Authors: Bruce Thiers, Dirk Elston, Detra Davis, Anna Krueger, Kenneth Katz, Jack Lesher, Mary Spellman, Jeffrey Weinberg, Dermatologic Surgery, Clifford Perlis, Julie Prendiville, Frcpc Dermatopathology, John Maize, Social Media, Emily Altman, Robert Dellavalle, J Smith, Editors Emeritus, Richard Dobson, Jeffrey Bernhard, Calvin Mccall, Brett Sloan, James Solomon, Stephen Tyring, George Hruza, Pediatric Dermatology, Kelly Cordoro, Dermatopathology Carlson, Tammie Ferringer, Cyberdermatology Consultant, Daniel Siegel, Clara Kim, Bryan Anderson, Salvador Arias-Santiago, Trisha Beute, John Binhlam, Diana Bolotin, Markus Braun-Falco, Nooshin Brinster, Patrick Carrington, Zoe Draelos, Nananamibia Duffy, Laura Ferris, David Fivenson, Joel Gelfand, Camille Introcaso, Nathaniel Jellinek, Jonathan Kantor, Matthew Kanzler, Kevin Kia, Nikki Levin, J Am, Acad Dermatol
Journal: Journal of the American Academy of Dermatology (2015)
International Congress of Gynaecology and Obstetrics
Journal: BMJ (1899)

International Congress of Gynecology and Obstetrics, has written a letter to the secretary of the British Gynecological Society thanking it for its efforts in regard to the pro- posal to hold the next session of the Congress in London in the year 1902, and expressing a hope that at some future time the Congress may meet here.By postponing the meeting for some years it is to be hoped that when it does take place the Congress will receive a hearty welcome, not from one or other society or group of practitioners but from the gynaecologists of England.
Alzheimer Aubade
Authors: Marjorie Maddox
Journal: JAMA (2020)

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