tbuckley/cabot-search huggingface dataset:
Ethical, Legal, and Social Implications of Genomic Medicine
Authors: Ellen Wright Clayton
Journal: New England Journal of Medicine (2003)

s detailed in other articles in the Genomic Medicine series , genomics has contributed greatly to our understanding of the molecular basis of disease and, to a lesser but growing extent, to the development of effective interventions.Clinicians and society at large, however, are concerned about the effect genetic knowledge will have on the well-being of individual persons and groups.Much effort is being devoted to trying to anticipate, understand, and address the ethical, legal, social, and political implications of genetics and genomics.The inquiry is complex.Understanding the social effects of genomics requires an analysis of the ways in which genetic information and a genetic approach to disease affect people individually, within their families and communities, and in their social and working lives.Genomics presents particular challenges with respect to clinicians' ethical and professional responsibilities, including the appropriate use of genomic information in the health care setting.In this article, I examine public concerns about genetic information and discuss a few recent cases in some depth to highlight a few of the dilemmas presented by genomics and emerging solutions.a what genetic information is and what people are worried about
New DTCA Guidance — Enough to Empower Consumers?
Authors: Christopher T. Robertson
Journal: New England Journal of Medicine (2015)

Interview with Dr. Christopher Robertson on the FDA’s new draft guidelines on direct-to-consumer pharmaceutical advertising. (07:33)Download In new draft guidance, the FDA recommends using evidence-based formats for conveying risk information about drugs in direct-to-consumer advertising but gives companies more discretion about which risks to disclose and how. But is disclosure an effective regulatory tool?
Woman who was granted right to refuse kidney dialysis dies
Authors: Clare Dyer
Journal: BMJ (2015)

A 50 year old woman who was judged to have the mental capacity to decide her own treatment and to be entitled to refuse the kidney dialysis keeping her alive has died.

In a judgment delivered two weeks ago but published only this week the High Court ruled that the woman, referred to as “C,” was entitled to make her own decision, even though that decision would “alarm and possibly horrify many.” The Court of Protection in London heard that “C” had been married four times and had a number of affairs, spending freely and moving on when the money …
Mediastinoscopy after negative endoscopic mediastinal nodal staging: can it be omitted?
Authors: Wilson W.L. Li, Erik F.M. van der Heijden, Ad F.T.M. Verhagen
Journal: European Respiratory Journal (2015)

We read with great interest the study by Vilmann et al. [1], proposing new guidelines for diagnosis and staging of lung cancer, particularly discussing the role of combined endobronchial ultrasound (EBUS) and endoscopic oesophageal ultrasound (EUS) in mediastinal nodal staging. We have several comments on this paper. Mediastinoscopy should not be omitted after negative EBUS/EUS <http://ow.ly/T4Qap>
Survival Impact of Increasing Time to Treatment Initiation for Patients With Head and Neck Cancer in the United States
Authors: Colin T. Murphy, Thomas J. Galloway, Elizabeth A. Handorf, Brian L. Egleston, Lora S. Wang, Ranee Mehra, Douglas B. Flieder, John A. Ridge
Journal: Journal of Clinical Oncology (2015)

Purpose To estimate the overall survival (OS) impact from increasing time to treatment initiation (TTI) for patients with head and neck squamous cell carcinoma (HNSCC). Methods Using the National Cancer Data Base (NCDB), we examined patients who received curative therapy for the following sites: oral tongue, oropharynx, larynx, and hypopharynx. TTI was the number of days from diagnosis to initiation of curative treatment. The effect of TTI on OS was determined by using Cox regression models (MVA). Recursive partitioning analysis (RPA) identified TTI thresholds via conditional inference trees to estimate the greatest differences in OS on the basis of randomly selected training and validation sets, and repeated this 1,000 times to ensure robustness of TTI thresholds. Results A total of 51,655 patients were included. On MVA, TTI of 61 to 90 days versus less than 30 days (hazard ratio [HR], 1.13; 95% CI, 1.08 to 1.19) independently increased mortality risk. TTI of 67 days appeared as the optimal threshold on the training RPA, statistical significance was confirmed in the validation set (P &lt; .001), and the 67-day TTI was the optimal threshold in 54% of repeated simulations. Overall, 96% of simulations validated two optimal TTI thresholds, with ranges of 46 to 52 days and 62 to 67 days. The median OS for TTI of 46 to 52 days or fewer versus 53 to 67 days versus greater than 67 days was 71.9 months (95% CI, 70.3 to 73.5 months) versus 61 months (95% CI, 57 to 66.1 months) versus 46.6 months (95% CI, 42.8 to 50.7 months), respectively (P &lt; .001). In the most recent year with available data (2011), 25% of patients had TTI of greater than 46 days. Conclusion TTI independently affects survival. One in four patients experienced treatment delay. TTI of greater than 46 to 52 days introduced an increased risk of death that was most consistently detrimental beyond 60 days. Prolonged TTI is currently affecting survival.
La résistance antimicrobienne en Italie: résultats préliminaires du projet AR-ISS
Authors: D Boccia, A Pantosti, F D'Ancona, S Giannitelli, M. Monaco, S Salmaso
Journal: Eurosurveillance (2002)

La resistance antimicrobienne represente, de nos jours, un probleme majeur en medecine humaine, tant sur le plan clinique qu'economique. En 1999, le Conseil de l'Union europeenne a inclut la resistance aux antibiotiques parmi les priorites de sante publique de la Communaute, et une resolution appelee  une strategie contre la menace microbienne  a ete emise (1). D'apres ce document, la mise en place ou le renforcement d'un systeme de surveillance assurant le recueil de donnees fiables et comparables aux niveaux national et international, font partie des principales interventions necessaires pour controler et prevenir la resistance aux antibiotiques. De plus, ces systemes de surveillance devraient egalement integrer les donnees sur l'utilisation et la prescription d'antibiotiques (2).
Harm minimisation is a way of lessening effects of more harmful drugs
Authors: J R Robertson
Journal: BMJ (1996)

Legalisation would have to be accompanied by personal responsibility EDrrOR,-Richard Smith argues for the legalisation of those psychoactive substances whose distribution or possession is currently a crime.'The argument is presented in terms of the impossibility of stopping people from wanting to take illicit drugs, the failure of prohibitionist policies, the desirability of a reduction in the costs of enforce- ment, the possibility of education about drugs, the attraction of purer preparations of drugs being manufactured by large companies, and the right of
Updated Safety and Efficacy from a Phase I Study of Azd9291 in Patients (Pts) with Egfr-Tki-Resistant Non-Small Cell Lung Cancer (Nsclc)
Authors: J.C. Yang, D. Kim, D. Planchard, Y. Ohe, S.S. Ramalingam, M. Ahn, S. Kim, W. Su, L. Horn, D. Haggstrom, E. Felip, J. Kim, P. Frewer, M. Cantarini, S. Ghiorghiu, M. Ranson, P.A. Janne
Journal: Annals of Oncology (2014)
Prednisone versus prednisone plus ciclosporin versus prednisone plus methotrexate in new-onset juvenile dermatomyositis: a randomised trial
Authors: Nicolino Ruperto, Angela Pistorio, Sheila Oliveira, Francesco Zulian, Ruben Cuttica, Angelo Ravelli, Michel Fischbach, Bo Magnusson, Gary Sterba, Tadej Avcin, Karine Brochard, Fabrizia Corona, Frank Dressler, Valeria Gerloni, Maria T Apaz, Claudia Bracaglia, Adriana Cespedes-Cruz, Rolando Cimaz, Gerard Couillault, Rik Joos, Pierre Quartier, Ricardo Russo, Marc Tardieu, Nico Wulffraat, Blanca Bica, Pavla Dolezalova, Virginia Ferriani, Berit Flato, Ana G Bernard-Medina, Troels Herlin, Maria Trachana, Antonella Meini, Emma Allain-Launay, Clarissa Pilkington, Veronika Vargova, Carine Wouters, Simona Angioloni, Alberto Martini
Journal: The Lancet (2015)
Kyoto global consensus report on<i>Helicobacter pylori</i>gastritis
Authors: Kentaro Sugano, Jan Tack, Ernst J Kuipers, David Y Graham, Emad M El-Omar, Soichiro Miura, Ken Haruma, Masahiro Asaka, Naomi Uemura, Peter Malfertheiner
Journal: Gut (2015)

<h3>Objective</h3> To present results of the Kyoto Global Consensus Meeting, which was convened to develop global consensus on (1) classification of chronic gastritis and duodenitis, (2) clinical distinction of dyspepsia caused by <i>Helicobacter pylori</i> from functional dyspepsia, (3) appropriate diagnostic assessment of gastritis and (4) when, whom and how to treat <i>H. pylori</i> gastritis. <h3>Design</h3> Twenty-three clinical questions addressing the above-mentioned four domains were drafted for which expert panels were asked to formulate relevant statements. A Delphi method using an anonymous electronic system was adopted to develop the consensus, the level of which was predefined as ≥80%. Final modifications of clinical questions and consensus were achieved at the face-to-face meeting in Kyoto. <h3>Results</h3> All 24 statements for 22 clinical questions after extensive modifications and omission of one clinical question were achieved with a consensus level of &gt;80%. To better organise classification of gastritis and duodenitis based on aetiology, a new classification of gastritis and duodenitis is recommended for the 11th international classification. A new category of <i>H. pylori</i>-associated dyspepsia together with a diagnostic algorithm was proposed. The adoption of grading systems for gastric cancer risk stratification, and modern image-enhancing endoscopy for the diagnosis of gastritis, were recommended. Treatment to eradicate <i>H. pylori</i> infection before preneoplastic changes develop, if feasible, was recommended to minimise the risk of more serious complications of the infection. <h3>Conclusions</h3> A global consensus for gastritis was developed for the first time, which will be the basis for an international classification system and for further research on the subject.
Community Care: The First Year: Community care in Northern Ireland: a promising start
Authors: A. Tonks
Journal: BMJ (1994)

Integrated health and social services, generous funding, and a special sense of community have got Northern Ireland off to a promising start after the government's community care reforms. Public ignorance about the new arrangements remains a problem, but there is little evidence of serious hardship in any client group. The biggest threat is to nursing and residential homes, which face closure as increasing numbers of elderly and disabled people opt to stay at home. After only a year and without the benefit of formal evaluation, however, the real problems for disabled people and their carers may not yet have emerged.
Oestrogen therapy for prevention of reinfarction in postmenopausal women: a randomised placebo controlled trial
Authors: Nicola Cherry, Kyle Gilmour, Philip Hannaford, Anthony Heagerty, Mohammed Amjed Khan, Henry Kitchener, Roseanne McNamee, Max Elstein, Clifford Kay, Mourad Seif, Hilary Buckley
Journal: The Lancet (2002)
Echinacea for Treating the Common Cold
Authors: Bruce Barrett, Roger Brown, Dave Rakel, Marlon Mundt, Kerry Bone, Shari Barlow, Tola Ewers
Journal: Annals of Internal Medicine (2010)

Echinacea is a popular herbal treatment for the common cold, but its efficacy continues to be debated. In this randomized, controlled trial, illness duration and severity did not significantly decr...
Phase II clinical trial of ixabepilone in metastatic breast cancer (MBC) patients previously untreated with taxanes
Authors: N. Denduluri, J. J. Lee, J. M. Walshe, S. X. Yang, U. Vatas, C. K. Chow, S. M. Steinberg, M. C. Cox, J. A. Low, S. M. Swain
Journal: Journal of Clinical Oncology (2006)

651 Background: Ixabepilone, an epothilone B analog, stabilizes microtubules by binding to tubulin. The response rate (RR) in taxane-pretreated patients at our institution was 22%. Methods: Patients (pts) were eligible if they had MBC previously untreated with taxanes and measurable disease by RECIST criteria. Ixabepilone was given at 6mg/m 2 /d intravenously days 1–5 every 3 weeks until unacceptable toxicity or disease progression. Primary objectives included RR and toxicity. Pts underwent pre and/or post treatment tumor biopsies for correlative studies. Acetylated α-tubulin, Tau-1, and p53 were stained with anti-acetylated α-tubulin, anti-Tau-1, and anti-p53 antibodies in samples from 13 pts. Staining was scored quantitatively using the Automated Cellular Imaging System. Results: Twenty-three pts received 197 cycles (C). Median of 7C (range 2–22) per pt were administered. Median age was 55 (range 22–79). Seven pts received 1 prior metastatic chemotherapy regimen. Ten of 23 or 43% (exact 95% confidence interval: 23.2% to 65.5%) pts had partial responses (PR), 9 (39%) stable disease (SD) (2 unconfirmed PRs), and 4 (17%) progressive disease (PD). Median time to progression was 5.3 months; median duration of response was 5.4 months from date of best response. Four pts required dose reductions for neutropenia, neuropathy or fatigue. Grade 3/4 toxicities included neutropenia (22%), fatigue (13%), anorexia (9%), infection without neutropenia (9%), motor neuropathy (4%), and muscle weakness (4%). No grade 3/4 sensory neuropathy was seen, but 35% and 13% of pts had grades 1 and 2 neuropathy respectively. Median acetylated α-tubulin at baseline was 0.2 in responders and 17.6 in non-responders (p=0.069). There were no differences in response according to Tau-1 or p53 expression at baseline. Conclusion: Ixabepilone is an effective treatment for MBC with a 43% RR in 23 pts previously untreated with taxanes. There was minimal hematologic toxicity and no grade 3 sensory neuropathy. The use of baseline level of acetylated α-tubulin to predict response may warrant further study. No significant financial relationships to disclose.
Study links negative news stories about statins to patients’ likelihood of giving them up
Authors: Nigel Hawkes
Journal: BMJ (2015)

Negative news stories about statins are followed by reduced compliance, a study in Denmark has found. Positive stories have the opposite effect.

The authors, Sune Fallgaard Nielsen and Borge Gronne Nordestgaard of Copenhagen University Hospital, said that although they could not conclude that the negative stories caused early discontinuation, their findings indicated that this was likely.

“If negative statin related news stories did not exist at all, then early statin discontinuation would decrease by 1.3% in the whole of the population,” Nordestgaard said in a press release accompanying the paper, published in European Heart Journal . In the paper itself the authors were more cautious, saying that “great care should be taken in the interpretation of the present results.”1

They reached their conclusions by looking at more than 670 000 people prescribed statins between 1995 and 2010—all those …
Prevalence of current asthma and COPD, and their overlap in adults in Phnom Penh, Cambodia
Authors: Sohei Makino, Clyde Ito, Kimihiro Nakae, Hironori Sagara
Journal: European Respiratory Journal (2014)

Background: Survey of prevalence of asthma and COPD using international methods has not been carried out in Cambodia. Asthma is described as a risk factor of COPD. Aim of this survey was to know the prevalence of asthma and COPD in Cambodia, and their overlap in adults 40 years and over. Subjects: Randomly recruited 1,365 of adults 20 years of age and over (male: 625, female: 740), out of them 660 adults 40 years and over (male 308,female:352). Methods: Diagnosis of current asthma: Current asthma was defined as wheezes or whistling for the past 12 months companied with at least one of asthma-specific symptoms (ECRHS questionnaires). Diagnosis of COPD: COPD was defined as FEV1/FVC
NCCN Task Force Report: Tyrosine Kinase Inhibitor Therapy Selection in the Management of Patients With Chronic Myelogenous Leukemia
Authors: Susan O'Brien, Ellin Berman, Joseph O. Moore, Javier Pinilla-Ibarz, Jerald P. Radich, Paul J. Shami, B. Douglas Smith, David S. Snyder, Hema M. Sundar, Moshe Talpaz, Meir Wetzler
Journal: Journal of the National Comprehensive Cancer Network (2011)

The advent of imatinib has dramatically improved outcomes in patients with chronic myelogenous leukemia (CML). It has become the standard of care for all patients with newly diagnosed chronic-phase CML based on its successful induction of durable responses in most patients. However, its use is complicated by the development of resistance in some patients. Dose escalation might overcome this resistance if detected early. The second-generation tyrosine kinase inhibitors (TKIs) dasatinib and nilotinib provide effective therapeutic options for managing patients resistant or intolerant to imatinib. Recent studies have shown that dasatinib and nilotinib provide quicker and potentially better responses than standard-dose imatinib when used as a first-line treatment. The goal of therapy for patients with CML is the achievement of a complete cytogenetic response, and eventually a major molecular response, to prevent disease progression to accelerated or blast phase. Selecting the appropriate TKI depends on many factors, including disease phase, primary or secondary resistance to TKI, the agent's side effect profile and its relative effectiveness against BCR-ABL mutations, and the patient's tolerance to therapy. In October 2010, NCCN organized a task force consisting of a panel of experts from NCCN Member Institutions with expertise in the management of patients with CML to discuss these issues. This report provides recommendations regarding the selection of TKI therapy for the management of patients with CML based on the evaluation of available published clinical data and expert opinion among the task force members.
Effective intrahepatic CD8+ T-cell immune responses are induced by low but not high numbers of antigen-expressing hepatocytes
Authors: Aaron Ochel, Marcin Cebula, Mathias Riehn, Upneet Hillebrand, Christoph Lipps, Reinhold Schirmbeck, Hansjörg Hauser, Dagmar Wirth
Journal: Cellular and Molecular Immunology (2015)

Liver infections with hepatotropic viruses, such as hepatitis B virus and hepatitis C virus are accompanied by viral persistence and immune failure. CD8+ T cells are crucial mediators of the intrahepatic antiviral immune response. Chronic infections of the liver and other organs correlate with T-cell exhaustion. It was previously suggested that high antigen load could result in T-cell exhaustion. We aimed at elucidating the impact of different intrahepatic antigen loads on the quality of CD8+ T-cell-mediated immunity by employing an infection-free transgenic mouse model expressing ovalbumin (Ova) as the target antigen. Adoptive transfer of OT-I cells induced a transient intrahepatic immune response toward both high and low Ova levels. However, antigen clearance was achieved only in mice expressing low antigen levels. In contrast, T cells exposed to high antigen levels underwent exhaustion and became depleted, causing antigen persistence. Moreover, when functional T cells were exposed to high intrahepatic antigen levels, a complete transition toward exhaustion was observed. Thus, this study shows that the antigen expression level in the liver correlates inversely with T-cell immunity in vivo and governs the efficiency of immune responses upon antigen presentation.
Tumor and host characteristics of small cell lung cancer (SCLC) in U.S. community oncology practice
Authors: Donald Richards, Si G Li, Thomas Anderson, Marc Monte, Brian Ulrich, David A Smith, Mahesh Seetharam, Paul Kaywin, Ray Page, Kimary Kulig, Cory Batenchuk, Maen Hussein
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts The majority of lung cancer in the U.S. is treated in the community. A prospective cohort study of stage IV NSCLC and extensive disease (ED) SCLC is being conducted in 70 U.S. community practices to assess outcomes during the pre- and post-immunotherapy eras of lung cancer
Amsacrine-associated cardiotoxicity: an analysis of 82 cases.
Authors: R B Weiss, A J Grillo-López, S Marsoni, J G Posada, F Hess, B J Ross
Journal: Journal of Clinical Oncology (1986)

Amsacrine is an antileukemia drug being widely used in North America, Europe, Australia, and New Zealand. In the initial clinical trials, patients treated with amsacrine developed occasional instances of acute cardiac arrhythmias and cardiomyopathy. We review and analyze the features of cardiac abnormalities associated with amsacrine in 82 patients, 27 of whom have not been previously reported. The rest have been reported in the literature, but we have included a large amount of additional information about these patients in our analysis. We conclude that amsacrine-related cardiac events are less common than those related to anthracycline chemotherapeutic agents. Manifestations of such toxicity include ECG abnormalities, ventricular and atrial arrhythmias, sudden death, and congestive heart failure. There is little or no cumulative dose effect. Hypokalemia may be a risk factor for development of serious tachyarrhythmias, but such problems can occur despite a normal serum potassium level. Amsacrine appears to affect depolarization and repolarization of the heart, but the mechanism is unknown.
Identification of Variant-Specific Functions of <i>PIK3CA</i> by Rapid Phenotyping of Rare Mutations
Authors: Turgut Dogruluk, Yiu Huen Tsang, Maribel Espitia, Fengju Chen, Tenghui Chen, Zechen Chong, Vivek Appadurai, Armel Dogruluk, Agna Karina Eterovic, Penelope E. Bonnen, Chad J. Creighton, Ken Chen, Gordon B. Mills, Kenneth L. Scott
Journal: Cancer Research (2015)

Large-scale sequencing efforts are uncovering the complexity of cancer genomes, which are composed of causal "driver" mutations that promote tumor progression along with many more pathologically neutral "passenger" events. The majority of mutations, both in known cancer drivers and uncharacterized genes, are generally of low occurrence, highlighting the need to functionally annotate the long tail of infrequent mutations present in heterogeneous cancers. Here we describe a mutation assessment pipeline enabled by high-throughput engineering of molecularly barcoded gene variant expression clones identified by tumor sequencing. We first used this platform to functionally assess tail mutations observed in PIK3CA, which encodes the catalytic subunit alpha of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) frequently mutated in cancer. Orthogonal screening for PIK3CA variant activity using in vitro and in vivo cell growth and transformation assays differentiated driver from passenger mutations, revealing that PIK3CA variant activity correlates imperfectly with its mutation frequency across breast cancer populations. Although PIK3CA mutations with frequencies above 5% were significantly more oncogenic than wild-type in all assays, mutations occurring at 0.07% to 5.0% included those with and without oncogenic activities that ranged from weak to strong in at least one assay. Proteomic profiling coupled with therapeutic sensitivity assays on PIK3CA variant-expressing cell models revealed variant-specific activation of PI3K signaling as well as other pathways that include the MEK1/2 module of mitogen-activated protein kinase pathway. Our data indicate that cancer treatments will need to increasingly consider the functional relevance of specific mutations in driver genes rather than considering all mutations in drivers as equivalent.