tbuckley/cabot-search huggingface dataset:
NHS was overcharged for thyroid drug after company raised price by 6000%
Authors: Nigel Hawkes
Journal: BMJ (2017)

The UK competition authority has provisionally found that a drug company abused its dominant position by overcharging for a drug used to treat hypothyroidism, costing the NHS tens of millions of pounds a year.

Last year the NHS spent £34m (€38.4m: $45m) on liothyronine, compared with only £600 000 in 2006. The price increase of almost 6000% was imposed by Concordia, a Canadian drug company that was the monopoly supplier of the drug until early this year, and by two other companies that had owned it previously.

An investigation was opened in October 2016 by the Competition and …
Pitfalls in the determination of mutant alleles of the thiopurine methyltransferase (TPMT) gene: does TPMT*3B exist?
Authors: C Brouwer, RA De Abreu, JJ Keizer-Garritsen, Pgjh ter Riet, Lhj Lambooy, Jfm Trijbels, ER van Wering, Jpm Bokkerink
Journal: Leukemia (2001)
Management of Suspected Opioid Overdose With Naloxone in Out-of-Hospital Settings
Authors: Roger Chou, P. Todd Korthuis, Dennis McCarty, Phillip O. Coffin, Jessica C. Griffin, Cynthia Davis-O'Reilly, Sara Grusing, Mohamud Daya
Journal: Annals of Internal Medicine (2017)

Naloxone is effective for reversing opioid overdose, but optimal strategies for out-of-hospital use are uncertain.To synthesize evidence on 1) the effects of naloxone route of administration and dosing for suspected opioid overdose in out-of-hospital settings on mortality, reversal of overdose, and harms, and 2) the need for transport to a health care facility after reversal of overdose with naloxone.Ovid MEDLINE (1946 through September 2017), PsycINFO, Cochrane Central Register of Controlled Trials, CINAHL, U.S. Food and Drug Administration (FDA) materials, and reference lists.English-language cohort studies and randomized trials that compared different doses of naloxone, administration routes, or transport versus nontransport after reversal of overdose with naloxone. Main outcomes were mortality, reversal of overdose, recurrence of overdose, and harms.Dual extraction and quality assessment of individual studies; consensus assessment of overall strength of evidence (SOE).Of 13 eligible studies, 3 randomized controlled trials and 4 cohort studies compared different administration routes. At the same dose (2 mg), 1 trial found similar efficacy between higher-concentration intranasal naloxone (2 mg/mL) and intramuscular naloxone, and 1 trial found that lower-concentration intranasal naloxone (2 mg/5 mL) was less effective than intramuscular naloxone but was associated with decreased risk for agitation (low SOE). Evidence was insufficient to evaluate other comparisons of route of administration. Six uncontrolled studies reported low rates of death and serious adverse events (0% to 1.25%) in nontransported patients after successful naloxone treatment.There were few studies, all had methodological limitations, and none evaluated FDA-approved autoinjectors or highly concentrated intranasal formulations.Higher-concentration intranasal naloxone (2 mg/mL) seems to have efficacy similar to that of intramuscular naloxone for reversal of opioid overdose, with no difference in adverse events. Nontransport after reversal of overdose with naloxone seems to be associated with a low rate of serious harms, but no study evaluated risks of transport versus nontransport.Agency for Healthcare Research and Quality. (PROSPERO: CRD42016053891).
Using a framework for resource stratification to adapt palliative care guidelines to Sub-Saharan Africa.
Authors: Maria Cristina Dans, Kunuz Abdella, Dinah Baah-Odoom, Rinty Kintu, Israel Kolawole, Sebastien Manirakiza, Esther Munyoro, Megan Obrien, Robert W. Carlson
Journal: Journal of Clinical Oncology (2017)

145 Background: The National Comprehensive Cancer Network (NCCN) is a not-for-profit alliance of 27 leading cancer centers in the United States (US), but the NCCN’s mission to improve cancer care extends world-wide. Nearly half of the registered users of the NCCN Guidelines are based outside the US, and the NCCN has developed a process for adapting its Guidelines to lower-resourced settings. The cancer burden in Sub-Saharan Africa (SSA) is significant – by 2030, annual cancer deaths in the region are projected to reach 1,000,000 people – and most cancers diagnosed in SSA are late-stage. Methods: The NCCN Framework outlines a rational approach for constructing cancer management systems to provide the highest achievable care. Each of the 4 NCCN Framework levels builds on the one before it, so care can evolve as resources grow: “Basic Resources” are essential for care; “Core Resources” add services improving disease outcomes; and “Enhanced Resources” include more cost-prohibitive services. The Guidelines themselves are the final level: evidence-based, consensus-driven recommendations from each NCCN Panel. Resource-stratification begins with modification of the Guidelines by a NCCN Framework Committee within each Panel. Results: In the case of SSA, organizers from the NCCN, American Cancer Society, Clinton Health Access Initiative, and IBM arranged 3 consensus meetings in which resource-stratified drafts of the Guidelines for Palliative Care and Cancer Pain will be refined by a committee of NCCN representatives, oncologists, and palliative care providers from Burundi, Ethiopia, Ghana, Kenya, Nigeria, Uganda, and the US. Important themes emerging from the first meeting included early screening for palliative care needs, even before tissue diagnosis, in areas with limited availability of anti-cancer therapy. In addition, cultural differences on the topic of “Physician-Aid-in-Dying” led to its replacement with guidance on caring for patients expressing a wish to die. Conclusions: Collaboration with colleagues in SSA, and other areas around the globe, to resource-stratify NCCN Guidelines will allow more systematic use of the guidelines and improve the quality, effectiveness, and efficiency of cancer care.
Lessons from bereaved families: Insights about how the care of patients impacts bereavement.
Authors: Sue Ellen Morris, Susan Block
Journal: Journal of Clinical Oncology (2017)

87 Background: Feedback from bereaved families, including surveys of family members’ experiences during the patient’s illness and final days, can provide important insights into ways to improve the care of patients with advanced illness and their families. Methods: A convenience sample of 140 bereaved family members from Dana-Farber Cancer Institute (DFCI) completed a survey developed by the authors about their bereavement experiences. Families were asked to describe ways in which the clinical team was helpful in dealing with their loss; what they wished the clinical team had done prior to the death that would have helped in dealing with their loss; and actions taken by the team that were unhelpful or difficult for them in dealing with their loss. The Institutional Review Board at DFCI approved the study. Results: 67% of participants were female and 81% had lost a spouse or partner. The most common responses about ways in which the team was helpful in dealing with their loss included: showing compassion, sending condolence letters or making calls, and offering honest facts and information. Prior to the death of the patient, the most common response about what they wish the team had done was providing more realistic information about prognosis. When asked about actions that were unhelpful or difficult, only 24 responses were given with 50% of participants omitting this question and the remaining stating that there was nothing that the team did that was unhelpful. Of the 24 responses, the most common concerned a lack of contact or contact that was impersonal after the death. Conclusions: This survey demonstrated that families could provide input about ways clinicians can have a positive impact on the bereavement experience of families in caring for the patient before death. Compassion, accurate information, especially about prognosis, and contact with the clinician during early bereavement were highly valued by respondents. The most common unhelpful behavior identified was lack of personal contact following the death of the patient. Improved communication by the clinician, both before and after the patient’s death, has potential to improve the bereavement experience of family members.
Granulocyte-Monocyte Progenitors and Monocyte-Dendritic Cell Progenitors Independently Produce Functionally Distinct Monocytes
Authors: Alberto Yáñez, Simon G. Coetzee, Andre Olsson, David E. Muench, Benjamin P. Berman, Dennis J. Hazelett, Nathan Salomonis, H. Leighton Grimes, Helen S. Goodridge
Journal: Immunity (2017)
Embracing nonfiction: How to extend the Distancing-Embracing model
Authors: Deena Skolnick Weisberg, Stacie Friend
Journal: Behavioral and Brain Sciences (2017)

Abstract The Distancing factor of Menninghaus et al.'s model includes schemas that remind consumers that the representation is fictional. Although they claim that these schemas are crucial to the functioning of the Embracing factor of the model, we argue that consumers can have similar responses to nonfictional representations. We urge the authors to expand their model to include such cases.
Association between duration of hydroxyurea administration before matinib mesylate to the achievement of major molecular response (MMR) in chronic phase of chronic myelocytic leukemia: A review on P-glycoprotein
Authors: I. Rinaldi, A.H. Reksodiputro, S.W.A. Jusman, A. Harahap, R. Setiabudy, S.I. Wanandi, K. Tambunan, C. Suharti
Journal: Annals of Oncology (2017)
Introduction: Working Party on Less Harmful Ways of Smoking
Authors: C. M. Fletcher, C.B.E., M.D., F.R.C.P.
Journal: JNCI Journal of the National Cancer Institute (1972)

Journal Article Introduction: Working Party on Less Harmful Ways of Smoking Get access C. M. Fletcher, C.B.E., M.D., F.R.C.P. C. M. Fletcher, C.B.E., M.D., F.R.C.P. Vice-Chairman Health Education Council, Middlesex House, Wembley HAO 1HH Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 48, Issue 6, June 1972, Pages 1743–1744, https://doi.org/10.1093/jnci/48.6.1743 Published: 01 June 1972
Avatar therapy reduces auditory hallucinations in schizophrenia, trial finds
Authors: Susan Mayor
Journal: BMJ (2017)

An experimental form of therapy involving a conversation between a patient with schizophrenia and a computer generated avatar representing the patient’s auditory hallucinations reduces symptoms more effectively than standard counselling, a trial has shown.1

Auditory hallucinations are common in schizophrenia, as 60-70% of patients “hear voices” that are typically derogatory, and around a quarter of patients continue to experience them despite treatment. Cognitive behavioural therapy for psychosis is helpful, but this generally takes time to be effective and achieves only limited benefit in some patients.

“A large proportion of people with schizophrenia continue to experience distressing voices despite lengthy treatment, so it is important that we look at newer, effective and shorter forms …
Diallyl trisulfide inhibits phorbol ester-induced COX-2 expression in mouse skin by blocking activation of AP-1: Akt and JNK as potential upstream targets
Authors: Sangeeta Shrotriya, Joydeb Kundu, Hye Na, Young Surh
Journal: Cancer Research (2008)

3817   Multiple lines of evidence suggest an inverse association between the garlic consumption and the cancer risk. Some volatile organosulfur compounds present in processed garlic oil have been reported to inhibit chemically-induced carcinogenesis and exert antiproliferative activities in many cancerous cells .  Recently much attention has been focused on intracellular signaling cascades as common molecular targets of numerous chemopreventive phytochemicals with structural diversity. As abnormally elevated expression of cyclooxygenase-2 (COX-2) is frequently observed in the majority of malignancies, we have investigated the effects of garlic-derived organsulfur compounds on 12- O -tetradecanoylphorbol-13-acetate (TPA)-induced COX-2 expression in female ICR mouse skin  in vivo.  Of the three organosulfur compounds tested, i.e., diallyl trisulfide (DATS), diallyl disulfide (DADS) and diallyl sulfide (DAS), DATS was found to have the most potent inhibitory effects on COX-2 expression when topically applied to mouse skin 30 min prior to TPA (10 nmol) treatment. DATS failed to inhibit TPA-induced DNA binding as well as translocation to the nucleus of nuclear factor kappaB (NF-κB), but suppressed TPA-mediated DNA binding activity of activator protein-1 (AP-1), another key transcription factor involved in COX-2 induction, and also down-regulated c-Jun and c-Fos expression. To elucidate the molecular mechanism underlying inhibition of AP-1 inactivation as well as COX-2 induction by DATS, we examined its effect on TPA-induced activation of some representative upstream kinases including Akt and JNK. We found that that TPA treatment led to rapid activation of Akt and JNK in mouse skin, which was abrogated by DATS as well as the Akt-specific inhibitor (LY29002) or the JNK-specific inhibitor (SP600125). LY29002 and SP600125 also blunted TPA-induced epidermal COX-2 expression and DNA binding of AP-1. In the present study, DATS was also tested for its antitumor promoting effects on two stage mouse skin carcinogenesis. DATS effectively delayed the onset of tumorogenesis as well as reduced the cumulative number of tumors and the average number of tumors per mouse. Taken together, DATS inhibits TPA-mediated COX-2 expression in mouse skin  in vivo  by blocking activation of AP-1, via Akt and JNK signaling. .
Abstract 20959: Inhibition of Shp2 Ameliorates Systemic Lupus Erythematosus-Associated Cardiac Pathogenesis
Authors: Jianxun Wang, Li-Fan Zeng, Zhong-Yin Zhang, Maria Kontaridis
Journal: Circulation (2017)

Introduction: Systemic lupus erythematous (SLE) is a devastating autoimmune disorder affecting multiple tissues, including heart. However, the molecular mechanisms that cause cardiac effects in SLE remain unclear. PTPN11 , the gene encoding the SH2 domain-containing protein tyrosine phosphatase SHP2, is critical for development and is the first tyrosine phosphatase known to have a functional role in the adult heart. Moreover, gain-of-function mutations in SHP2 have been associated with onset of SLE. Here, sought to identify the mechanistic role for SHP2 in the cardiac pathogenesis of SLE. Methods and Results: We analyzed hearts from 18-week old female MRL/lpr (SLE-prone) and MRL/MpJ (control) mice. As compared to controls, MRL/lpr hearts showed substantial interstitial fibrosis and had elevated numbers of infiltrated CD11b + leukocytes. Moreover, MRL/lpr hearts displayed decreased fractional shortening and enlarged chamber dimensions, as measured by echocardiography. MRL/lpr heart lysates revealed significantly elevated SHP2 phosphatase activity, as compared to controls. Immunoprecipitation of SHP2 from MRL/lpr hearts revealed Focal Adhesion Kinase (FAK) in complex with SHP2. FAK is required to maintain cardiac function under conditions of stress. Significantly, SHP2 is a negative regulator of FAK, suggesting SHP2 may be involved in cardiac pathogenesis through dephosphorylation of FAK. Here, MRL/lpr heart lysates had decreased pY397-FAK activity, in conjunction with decreased p-ERK levels, suggesting that SHP2 may play a role in cardiac pathogenesis of SLE through aberrant FAK -mediated regulation of ERK. To test whether higher SHP2 activity contributes to the cardiac pathogenesis in lupus, we utilized a potent SHP2 inhibitor, 11a-1, to treat MRL/lpr mice for 6 weeks starting at 12 weeks of age. Hearts from these mice displayed improved cardiac structure and function, with reduced chamber dimensions, had decreased numbers of CD11b + leukocytes and lessened cardiac fibrosis. Moreover, pY397-FAK and p-ERK activities were both nearly normalized in response to treatment with the SHP2 inhibitor. Conclusion: These data suggest that SHP2 affects cardiac pathogenesis in SLE hearts through regulation of FAK and ERK signaling.
Interim Analysis of A Single-Arm Phase 2 Clinical Trial of Regorafenib in Patients with Epithelial Ovarian Cancer
Authors: T. Tan, W.S. Ong, S. Chan, J. Chan, W.Y. Chay, E. Lim, S.L. Lim, L.T. Soh, D.S. Tan, J. Chia
Journal: Annals of Oncology (2017)
The European Society for Medical Oncology (ESMO) Precision Medicine Glossary
Authors: L.R. Yates, J. Seoane, C. Le Tourneau, L.L. Siu, R. Marais, S. Michiels, J.C. Soria, P. Campbell, N. Normanno, A. Scarpa, J.S. Reis-Filho, J. Rodon, C. Swanton, F. Andre
Journal: Annals of Oncology (2017)
Combating the Spread of Ineffective Medical Procedures
Authors: Ari J. Green, Hooman Kamel, S. Andrew Josephson
Journal: JAMA Neurology (2017)

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
Treatment of Acute Hepatitis C With Ledipasvir and Sofosbuvir in Patients With Hematological Malignancies Allows Early Re-start of Chemotherapy
Authors: Giuseppina Brancaccio, Maria Chiara Sorbo, Ferdinando Frigeri, Viviana Rizzo, Marco Cantone, Francesco Genderini, Lavinia Fabeni, Antonio Pinto, Carlo Federico Perno, Francesca Ceccherini-Silberstein, Giovanni Battista Gaeta
Journal: Clinical Gastroenterology and Hepatology (2017)
Art and fiction are signals with indeterminate truth values
Authors: Nathaniel Rabb
Journal: Behavioral and Brain Sciences (2017)

Abstract Menninghaus et al. distinguish art from fiction, but no current arguments or data suggest that the concept of art can be meaningfully circumscribed. This is a problem for aesthetic psychology. I sketch a solution by rejecting the distinction: Unlike most animal communication, in which signals are either true or false, art and fiction consist of signals without determinate truth values.
Mesoporous Carbon Nanospheres as a Multifunctional Carrier for Cancer Theranostics
Authors: Libo Zhou, Ying Jing, Yubin Liu, Zhihe Liu, Duyang Gao, Haobin Chen, Weiye Song, Tao Wang, Xiaofeng Fang, Weiping Qin, Zhen Yuan, Sheng Dai, Zhen-An Qiao, Changfeng Wu
Journal: Theranostics (2017)

Optical nanomaterials with intense absorption in near-infrared (NIR) region hold great promise for biomedical applications such as photothermal therapy (PTT) and photoacoustic imaging (PAI). In this work, we report mesoporous carbon nanospheres (Meso-CNs) with broadband and intense absorption in the UV-Vis-NIR region (300-1400 nm) and explore their potential as a multifunctional platform for photoacoustic imaging and chemo-photothermal therapy.
NR4A1 inhibition synergizes with ibrutinib in killing mantle cell lymphoma cells
Authors: Yangguang Li, Fangyu Wang, Li Lu, Fen Zhu, Shengjian Huang, Krystle Nomie, Liang Zhang, David T. Yang, Wei Huang, Brad S. Kahl, Stephen Safe, Michael Wang, Lixin Rui
Journal: Blood Cancer Journal (2017)
Use of hospice services among Medicare beneficiaries with acute and chronic leukemias.
Authors: Thomas William LeBlanc, Adam J. Olszewski
Journal: Journal of Clinical Oncology (2017)

68 Background: Studies show lower rates of hospice use among patients (pts) with hematologic malignancies. Our objective was to describe trends in hospice use and in quality measures for end-of-life (EOL) care among Medicare beneficiaries with leukemias. Methods: From the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database, we selected pts with acute (myeloid or lymphoblastic) or chronic (lymphocytic, myeloid, or myelomonocytic) leukemias diagnosed in 1996-2011 who died in 2001-2011. We identified hospice enrollment at death, duration of hospice enrollment, inpatient deaths, intensive care unit (ICU) admissions within 30 days of death, and chemotherapy use in the last 14 days of life. We summarized linearized trends by year of death using log-binomial regression, reporting average annual percent change (APC). Results: Among 38,038 leukemia pts (41% acute, median age 78 years) 81% died, after median 2.8 months from diagnosis (95%CI, 2.7-2.9) for acute and 49.1 months (95%CI, 47.9-50.1) for chronic leukemias. Among pts who died in 2001-2011 ( N= 23,941), 42% were enrolled in hospice at the time of death. This proportion significantly increased between 2001 and 2011, from 33% to 48% (APC +4.1%, P&lt; .001), both for acute and chronic leukemias ( P interaction = .25). Median time on hospice was 8 days, and the proportion of pts with &lt; 3 days on hospice increased from 20% to 24% between 2001 and 2001 (APC +1.2%, P= .05). Inpatient deaths significantly decreased from 54% to 39%, respectively (APC -3.2%, P&lt; .001), but ICU use at EOL increased from 34% to 41% (APC +2.4%, P&lt; .001). Chemotherapy use at EOL was more frequent in acute (17%) than chronic (6%) leukemia, and decreased for both (overall from 15% to 10%, APC -3.2%, P&lt; .001). Conclusions: The use of hospice services among older pts with leukemia has increased, suggesting its wider acceptance over time. However, the increasing proportion of brief, terminal hospice admissions, and increasing rate of ICU use at EOL reflect persistent barriers to early enrollment in this population. Some measures of aggressiveness of care (inpatient deaths, chemotherapy at EOL) are lower in the community than previously reported from academic centers (El-Jawahri, Cancer 2015).
PKC-zeta associates and phosphorylates IKK-α/β in breast cancer cells
Authors: Diondra Hill, Hla Win, Mildred Acevedo-Duncan
Journal: Cancer Research (2008)

LB-30  Breast cancers are highly lethal tumors and are one of the leading causes of death among women. The objective of this study was to focus on the role of protein kinase C-zeta (PKC-ζ) in breast cancer cell survival through the NF-κB pathway. It has been previously demonstrated that Tumor Necrosis Factor alpha (TNF-α) induces the NF-κB pathway and plays a critical role in the survival and apoptotic pathways. In the present study, we determined whether PKC-ζ associates with the inhibitor of nuclear factor kappa-B kinase-α /β (IKK-α /β) in breast cancer cells. Estrogen independent MDA-MB 468 breast cancer cells were treated with PKC-ζ short interfering RNAs (siRNA) for 24, 48, and 72 hours. The cells were than treated with TNF-α for 20 minutes. Western blots of PKC-ζ in IKK-α /β immunoprecipitates depicted an association of IKK-α /β with PKC-ζ. Additionally, Western blots probing for phosphorylated IKK-α /β demonstrated that cells treated with PKC-ζ siRNA and immunoprecipitated for IKK-α /β had significantly reduced phosphorylated IKK-α /β compared to the control siRNA-A. These results suggest that treatment of MDA-MB-468 breast cancer cells with TNF-α promotes the association of PKC-ζ with IKK-α /β leading to phosporylation and activation of IKK-α /β.