tbuckley/cabot-search huggingface dataset:
Care of adults in the last days of life: summary of NICE guidance
Authors: Joshua Ruegger, Sarah Hodgkinson, Antonia Field-Smith, Sam H Ahmedzai
Journal: BMJ (2015)

#### What you need to know

In 2013, the UK Department of Health called for the abolition of the Liverpool care pathway, which was designed to bring a standard of care for the dying from the hospice sector into other settings. This move was provoked by an independent review,1 which showed that the pathway had been misused and misinterpreted as a tick box exercise. It called for individualised care plans and better staff training in all aspects of end of life care.1 Care of dying people should be based on evidence and must be tailored to individual needs and wishes, rather than being protocol driven. This article summarises the most recent recommendations from the National Institute for Health and Care Excellence (NICE). 2

#### What’s new in this guidance?

NICE recommendations are based on systematic reviews of best available evidence and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on the committee’s experience and opinion of what constitutes good practice. …
First-line simplified GEMOX (D1-D1) versus classical GEMOX (D1-D2) in metastatic pancreatic adenocarcinoma (MPA). A GERCOR randomized phase II study
Authors: T. Andre, P. Afchain, G. Lledo, S. Nguyen, J. Paitel, L. Mineur, P. Artru, F. Selle, A. de Gramont, C. Louvet
Journal: Journal of Clinical Oncology (2007)

4592 Background: GEMOX was defined as a D1-D2 schedule, based on preclinical data. In order to improve convenience for patients, we evaluated a simplified D1-D1GEMOX regimen (S-GEMOX) in MPA. Methods: Patients (pts) with MPA were 2:1 randomly assigned for first-line treatment to S-GEMOX (arm A : gemcitabine 1,000mg/m 2 , 100 min infusion D1 immediately followed by oxaliplatin 100 mg/m 2 , 120 min infusion) or to GEMOX (arm B : gem D1 and ox D2). Treatment was repeated in each arm every 2 weeks until disease progression. Stratification was performed on centre and PS. Results: Fifty-seven pts were enrolled, A = 37 (PS 2 : 22%), B = 20 (PS 2 : 20%). Populations were well balanced for age (64.9 yrs vs 66.6), gender (57% male vs 65), location of primary tumor (pancreas head 49% vs 50), and metastasic sites (liver 76% vs 85; peritoneum 24% vs 20; lung 16% vs 10; lymph nodes 14% vs 15; other 5% vs 5). Tumor differentiation significantly differed among the 2 groups (A : 8% poorly differentiated vs B : 36%). Response rate was 27% (95% CI : 12–42) in arm A and 10% (95% CI : 0 - 23) in arm B. Median PFS was 4.0 and 2.5 months in arm A and B, respectively. Median OS was 7.6 and 3.2 months in arm A and B, respectively. S-GEMOX was more toxic than GEMOX for gr 3–4 neutropenia (20% vs 0%) and thrombocytopenia (16% vs 10%). Other toxicities were comparable. However, since more cycles were administered in arm A (8.5 (1–29) vs 5.8 (2–12)), gr 3 oxaliplatin- induced neuropathy was higher in arm A (21.6% vs 0%). Conclusions: S-GEMOX is active in MPA. This activity is in the same range as compared to our previous experiences of GEMOX. The very bad outcome of pts randomized in arm B could be in part explained by the high rate of poorly differentiated tumors. This study emphazises one more time the limit of studies with small sample size of pts in MPA. No significant financial relationships to disclose.
Incorporation of bevacizumab in the treatment of recurrent and metastatic cervical cancer: A phase III randomized trial of the Gynecologic Oncology Group.
Authors: Krishnansu Sujata Tewari, Michael Sill, Harry J. Long, Lois M. Ramondetta, Lisa Michelle Landrum, Ana Oaknin, Thomas J Reid, Mario M. Leitao, Helen E Michael, Bradley J. Monk
Journal: Journal of Clinical Oncology (2013)

3 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Sunday, June, 2, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Sunday edition of ASCO Daily News.
THE PHYSICIAN'S RESPONSIBILITY FOR THE NOSTRUM EVIL.
Authors: RICHARD C. CABOT
Journal: JAMA (1906)

As physicians we are largely responsible for the sale of secret remedies. We help to create the demand. We feed it. We feed it because it is shown that 44 per cent. of the prescriptions filled at one of the best of our Back Bay drug stores in Boston call for nostrums—secret remedies of whose constituents we are ignorant. The conditions are the same or worse elsewhere. The manufacturers and those whose living depends on the sale of these nostrums, have done their best to obscure the issue by vilifying the leaders of the present vigorous crusade against secret nostrums; I mean Dr. Simmons and Dr. Billings. The nostrum makers and a group of medical journals which are their organs, try to deceive us into believing that the great crusade for honest, open, intelligent prescribing and against fraud and ignorance in therapeutics, is all the work of those splendid leaders,
Review of<i>Rosenberg’s Molecular and Genetic Basis of Neurological and Psychiatric Disease, 5th ed</i>
Authors: Cyrus P. Zabetian
Journal: JAMA Neurology (2015)

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 Neurology 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 Neurology journal
Abstract 11678: Mitochondrial Reactive Oxygen Species Mediate Lysophosphatidylcholine-Induced Endothelial Cell Activation
Authors: Xinyuan Li, Pu Fang, Ya-Feng Li, Yin-Ming Kuo, Andrew J Andrews, Walter J Koch, Hong Wang, Xiao-Feng Yang
Journal: Circulation (2014)

Background: Lysophosphatidylcholines (LPCs) are a class of pro-inflammatory lipids that play important roles in atherogenesis. LPC activates endothelial cells (ECs) to upregulate adhesion molecules and chemokines, which is the initiation step of atherogenesis. However, the mechanisms underlying LPC-triggered EC activation are not fully understood. Previously considered as the toxic by-products of cellular metabolism, mitochondrial ROS (mtROS) are recently found to directly contribute to both the innate and adaptive immune responses. Here we tested a novel hypothesis that mtROS serve as signaling mediators for LPC-induced EC activation. Methods and Results: Using electron spin resonance and flow cytometry with fluorescence probe MitoSOX, we found that several LPC species including LPC 16:0, 18:0, and 18:1 induced mtROS in human primary aortic ECs (HAECs). Mechanistically, our analysis using mitochondrial calcium inhibitor and Seahorse XF96 mitochondrial function analyzer showed that LPC induced mtROS via increasing mitochondrial calcium entry which resulted in mitochondrial proton leakage. In addition, we found that mtROS scavenger MitoTEMPO abolished LPC-induced EC activation by downregulating Intercellular adhesion molecule 1 (ICAM-1) and Vascular cell adhesion protein 1 (VCAM-1) in HAECs. Moreover, our analysis with transcription factor profiling screening showed that MitoTEMPO acts by blocking LPC-induced nuclear translocation of pro-inflammatory transcription factor activator protein-1 (AP-1). Conclusions: Our results indicate that mtROS are responsible for LPC-induced EC activation and that mtROS may serve as a novel therapeutic target for vascular inflammation.
Emerging Themes in Image Informatics and Molecular Analysis for Digital Pathology
Authors: Rohit Bhargava, Anant Madabhushi
Journal: Annual Review of Biomedical Engineering (2016)

Pathology is essential for research in disease and development, as well as for clinical decision making. For more than 100 years, pathology practice has involved analyzing images of stained, thin tissue sections by a trained human using an optical microscope. Technological advances are now driving major changes in this paradigm toward digital pathology (DP). The digital transformation of pathology goes beyond recording, archiving, and retrieving images, providing new computational tools to inform better decision making for precision medicine. First, we discuss some emerging innovations in both computational image analytics and imaging instrumentation in DP. Second, we discuss molecular contrast in pathology. Molecular DP has traditionally been an extension of pathology with molecularly specific dyes. Label-free, spectroscopic images are rapidly emerging as another important information source, and we describe the benefits and potential of this evolution. Third, we describe multimodal DP, which is enabled by computational algorithms and combines the best characteristics of structural and molecular pathology. Finally, we provide examples of application areas in telepathology, education, and precision medicine. We conclude by discussing challenges and emerging opportunities in this area.
A phase II study of cediranib (AZD2171) in recurrent or persistent ovarian, peritoneal or fallopian tube cancer: Final results of a PMH, Chicago and California consortia trial
Authors: H. W. Hirte, L. Vidal, G. F. Fleming, A. K. Sugimoto, R. J. Morgan, J. J. Biagi, L. Wang, S. McGill, S. P. Ivy, A. M. Oza
Journal: Journal of Clinical Oncology (2008)

5521 Background: VEGF is over-expressed in human ovarian tumours and this is associated with a poor prognosis. Cediranib (AZD2171) is a novel, orally-administered, highly potent inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFRβ and c-kit. A two-stage, multicentre phase 2 clinical trial was initiated to evaluate the activity of cediranib in patients (pts) with recurrent ovarian, peritoneal or fallopian tube cancer. Methods: Pts with ECOG ≤ 2 and adequate organ function were eligible. Prior chemotherapy up to one line was permitted. The initial starting dose of cediranib was reduced from 45 mg orally daily (od) to 30 mg od continuously because of toxicity. The primary endpoint was objective response rate and rate of progression-free survival (PFS) at 16 weeks, with response evaluated every 8 weeks. This study was stratified into two separate arms: platinum-sensitive (pl-s) and platinum-resistant (pl-r) pts. 60 pts were enrolled; follow up is available for 154 cycles of treatment given to 46 pts. Results: 49 pts had ovarian, 8 peritoneal, and 3 fallopian tube cancer. 26 pts were pl-s and 34 pts were pl-r. Median age: 58 years (range 31–87), ECOG 0/1/2:30/25/5 pts. Median number of months of treatment: 3 (range 1–9). The most frequent adverse events (AEs) were fatigue (85%), diarrhea (80%), hypertension (72%), anorexia (57%). Hypertension (33%) and fatigue (20%) were the most frequent grade 3+ AEs. 16 pts required dose reduction to 30 mg (8) and 20 mg (8). Reasons for stopping study treatment were (pl-s/pl-r): PD (12/9), AEs (3/6), investigator decision (1/0) and patient withdrawal (1/2). Excluding patients who are too early for tumor assessment (9 pl-s/10 pl-r), response and prolonged SD rate was 41%/29% for pl- s and pl-r pts respectively. In the pl-s group, there have been 2 confirmed PRs and 1 unconfirmed PR while one unconfirmed PR was observed in the pl-r arm. The median time to progression (TTP) and median survival time for all pts was 4.1 months (95% CI 3.4–7.6) and 11.9 months (95% CI: 9.9-not reached) respectively with no significant differences between groups. Conclusions: Cediranib is well tolerated at 30 mg od and shows significant activity in recurrent ovarian cancer. No significant financial relationships to disclose.
Are Racial/Ethnic Gaps in the Use of Cardiac Resynchronization Therapy Narrowing?
Authors: Zubin J. Eapen, Sana Al-Khatib, Renato D. Lopes, Yongfei Wang, Haikun Bao, Jeptha Curtis, Paul A. Heidenreich, Adrian F. Hernandez, Eric D. Peterson, Stephen C. Hammill
Journal: Journal of the American College of Cardiology (2012)
Age, dementia, dyskinesias, and lithium response
Authors: J M Himmelhoch, J F Neil, S J May, C Z Fuchs, S M Licata
Journal: American Journal of Psychiatry (1980)

Nineteenth-century neuropsychiatrists felt that the aged bipolar patient usually developed chronic mania, which eventually turned into dementia. The authors' elderly patients seemed to experience few such denouements, so they evaluated the course and treatment response of 81 bipolar patients over the age of 55. Fifty-six responded well to lithium. Advanced age had no effect on course or outcome. However, with increased clinical evidence of neurological illness there was an increased incidence of chronic mania, a poorer response to lithium, and more frequent and severe neurotoxicity. Extrapyramidal syndromes were particularly devastating.
Open Access Exercise Electrocardiography: A Service to Improve Management of Ischaemic Heart Disease by General Practitioners
Authors: A N Sulke, V E Paul, C J Taylor, R H Roberts, ADC Norris
Journal: Journal of the Royal Society of Medicine (1991)

An initial study of the use of open access exercise electrocardiography by general practitioners (GPs) in South East Kent showed that patient selection and interpretation of test results was frequently incorrect. After issuing guidelines, modifying the request form and instituting registrar review of all requests, significant improvements in both referral pattern, result interpretation and patient management have resulted. Forty-nine GPs requested 110 exercise tests during 1988/89. Twelve per cent were not undertaken after discussion with the referring practitioner. Eighty-four per cent of those tested would have been referred to the district general hospital cardiology outpatient department in the absence of open access exercise electrocardiography service. Six per cent of patients were referred directly for invasive investigation. Thirty-five per cent were referred to the district general hospital cardiology outpatient department, whilst 42% were spared hospital referral based on the result of the investigation. Better use of the modified service was suggested by: referral of fewer patients with non-cardiac chest pains (P = 0.002); more patients with a moderate pre-test probability of ischaemic heart disease (P less than 0.05); fewer inappropriate requests (P less than 0.01); and fewer inappropriately undertaken tests (P less than 0.001) than in the previous study. All patients with strongly positive test results were appropriately managed. Open access exercise electrocardiography in the format investigated is potentially a cost-effective and useful tool to improve diagnosis and management of heart disease by GPs.
First-Step Mutations during Adaptation Restore the Expression of Hundreds of Genes
Authors: Alejandra Rodríguez-Verdugo, Olivier Tenaillon, Brandon S. Gaut
Journal: Molecular Biology and Evolution (2015)

The temporal change of phenotypes during the adaptive process remains largely unexplored, as do the genetic changes that affect these phenotypic changes. Here we focused on three mutations that rose to high frequency in the early stages of adaptation within 12 Escherichia coli populations subjected to thermal stress (42 °C). All the mutations were in the rpoB gene, which encodes the RNA polymerase beta subunit. For each mutation, we measured the growth curves and gene expression (mRNAseq) of clones at 42 °C. We also compared growth and gene expression with their ancestor under unstressed (37 °C) and stressed conditions (42 °C). Each of the three mutations changed the expression of hundreds of genes and conferred large fitness advantages, apparently through the restoration of global gene expression from the stressed toward the prestressed state. These three mutations had a similar effect on gene expression as another single mutation in a distinct domain of the rpoB protein. Finally, we compared the phenotypic characteristics of one mutant, I572L, with two high-temperature adapted clones that have this mutation plus additional background mutations. The background mutations increased fitness, but they did not substantially change gene expression. We conclude that early mutations in a global transcriptional regulator cause extensive changes in gene expression, many of which are likely under positive selection for their effect in restoring the prestress physiology.
Complete Clinical, Histopathologic and Molecular Remission of Primary Myelofibrosis with Long-Term Treatment with the JAK1/2 Inhibitor Ruxolitinib
Authors: Haifa Kathrin Al-Ali, Karolin Hubert, Thoralf Lange, Udo Siebolts, Claudia Wichenhauser, Gopalakrishna Prashanth, Dietger Niederwieser, Astrid Monecke
Journal: Blood (2014)
Guidelines for management of hypertension
Authors: J D Swales
Journal: BMJ (1994)

Editor,--Gene Feder points out what has been clear for some time--that there are important differences between published guidelines for the treatment of hypertension.1 2 Feder also refers to the development of a “guidelines industry.”

I have no objection to the creation of guidelines for minimal acceptable levels of medical care: indeed, I chaired the working party that prepared the British Hypertension Society's first report.3 The reasons for the diversity of …
Abstract 16887: Impact of Variability in Echocardiographic Interpretation on Assessment of Repair Following Congenital Heart Surgery
Authors: Anitha Parthiban, Jami C Levine, Meena Nathan, Jennifer A Marshall, Girish S Shirali, Steve D Simon, Steven D Colan, Jane W Newburger, Geetha Raghuveer
Journal: Circulation (2014)

Background: Technical Performance Score (TPS), a tool based largely on the presence and magnitude of residua on postoperative echocardiograms (echo), has been used for assessing surgical repair and correlates with outcomes. The reproducibility of the echo measures that drive TPS classification has not been tested. We evaluated reader variability for echo components of TPS for tetralogy of Fallot (TOF) repair and arterial switch operation (ASO) in 2 centers and measured its effect on TPS. Hypothesis: Inter-reader echo measurement variability will not substantially impact TPS classification. Methods: Postoperative echos were evaluated in 67 subjects (39 TOF and 28 ASO). Two readers (1 per center) read each echo, blinded to center of origin. To assess intra-reader variability, 25% of echoes were re-reviewed by each reader. Measurements between readers were compared with Intra-class correlation (ICC). TPS Class (1 Optimal no residua , 2 Adequate minor residua , 3 Inadequate major residua ) was assigned for each echo review by an independent investigator. The impact of measurement variability on overall TPS variability was compared using weighted Kappa (K) and % raw agreement. Results: ICC was highest for Doppler velocity data and lower for measurements of small linear structures such as septal defects and vena contracta Figure. Overall TPS demonstrated good agreement (between reader TOF K = 0.82 and ASO K = 0.81). The 2 readers were concordant for TPS Class for 53 subjects (79%) and discordant for Classes 2 vs. 3 in 6 (9%); no readings were discordant between Classes 1 and 3 Table . Conclusions: Although overall TPS demonstrated good agreement, inter-reader variation for echo measurements had a small, but important effect on TPS for ASO and TOF, particularly for the distinction between minor and major residua. Future studies of generalizability and reproducibility of TPS across centers and lesions are needed before TPS could be adopted as a national quality measure.
Response to: ‘Mutation in MMP2 gene may result in scleroderma-like skin thickening’ by Bader-Meunieret al
Authors: Siddharth Banka, William G Newman
Journal: Annals of the Rheumatic Diseases (2015)

Response to: 'Mutation in MMP2 gene may result in scleroderma-like skin thickening' by Bader-Meunier et al MMP2 related disease (Multicentric osteolysis, nodulosis and arthropathy-MONA syndrome-OMIM #259600) consists of a continuous clinical spectrum in terms of severity. 1Even in the same affected individual, different features may present with varying severity (eg, nodulosis may be absent even with severe osteolysis).Till date less than 15 families with MMP2 mutations have been reported 2 3 and, therefore, it is likely that the full phenotypical spectrum of MMP2-associated conditions has not yet been realised.In this context, this report from Bader-Meunier et al 4 of a patient with biallelic MMP2 mutation and scleroderma-like skin thickening in addition to the other known features of MONA syndrome is instructive.Notably, most previous reports of individuals with MMP2 mutations are of young children and skin thickening can be a progressive feature.In future it will be interesting to learn about evolution of the phenotype in previously reported cases or the adult phenotype of this group of conditions.We reported two families with 8q22.1 duplications and Leri's pleonostoesis (LP) and provided evidence that LP could also be considered as a transforming growth factor (TGF)-betapathy. 5 Interestingly, skin thickening was seen in one of our families with LP but was absent in all the members of the other family.Our previous work and the report of Bader-Meunier et al provides further support that presence of skin thickening can be a clue towards monogenic TGF-betapathies.However, skin thickening may be a more variable feature of those TGF-betapathies where it is not part of the core phenotype (cf Stiff skin syndrome-OMIM #184900). 6ecognising additional monogenic causes of scleroderma due to alterations in the TGF-beta pathway strengthens the possibility that rare variants in genes encoding members of this pathway as being causally linked with more common forms of scleroderma.
Efficacy of adoptive transfer of expanded fetal liver-derived precursor syngeneic and allogeneic murine NK cells against solid tumors
Authors: Xiaoyan Liang, Wenqian Wang, Guanqiao Li, Xiaokui Zhang, Vladimir Jankovic, Uri Herzberg, Wolfgang Hofgartner, Michael T Lotze
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Clinical studies have demonstrated that adoptive transfer of allogeneic Natural Killer (NK) cells can play a therapeutic role in hematological malignancies and potentially solid tumors. We established and characterized ex vivo methods to obtain murine NK1.1+ cells from mouse fetal