Cost-effectiveness of Tyrosine Kinase Inhibitor Treatment Strategies for Chronic Myeloid Leukemia in Chronic Phase After Generic Entry of Imatinib in the United States

Background:

We analyzed the cost-effectiveness of treating incident chronic myeloid leukemia in chronic phase (CML-CP) with generic imatinib when it becomes available in United States in 2016. In the year following generic entry, imatinib's price is expected to drop 70% to 90%. We hypothesized that initiating treatment with generic imatinib in these patients and then switching to the other tyrosine-kinase inhibitors (TKIs), dasatinib or nilotinib, because of intolerance or lack of effectiveness ("imatinib-first") would be cost-effective compared with the current standard of care: "physicians' choice" of initiating treatment with any one of the three TKIs.

Methods:

We constructed Markov models to compare the five-year cost-effectiveness of imatinib-first vs physician's choice from a US commercial payer perspective, assuming 3% annual discounting ($US 2013). The models' clinical endpoint was five-year overall survival taken from a systematic review of clinical trial results. Per-person spending on incident CML-CP treatment overall care components was estimated using Truven's MarketScan claims data. The main outcome of the models was cost per quality-adjusted life-year (QALY). We interpreted outcomes based on a willingness-to-pay threshold of $100 000/QALY. A panel of European LeukemiaNet experts oversaw the study's conduct.

Results:

Both strategies met the threshold. Imatinib-first ($277 401, 3.87 QALYs) offered patients a 0.10 decrement in QALYs at a savings of $88 343 over five years to payers compared with physician's choice ($365 744, 3.97 QALYs). The imatinib-first incremental cost-effectiveness ratio was approximately $883 730/QALY. The results were robust to multiple sensitivity analyses.

Conclusion:

When imatinib loses patent protection and its price declines, its use will be the cost-effective initial treatment strategy for CML-CP.

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New Clinical Trial Designs Hasten Approvals for Targeted Therapies

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Stat Bite Percentage of New Caces by Age Group For Lung and Bronchus Cancer (2008-2012)

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American Academy of Pediatrics Wants Smoking and Vaping Age Raised to 21 Years

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PDQ (Physician Data Query)

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Naming and Staging Lung Cancers

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Possible Genetic Pathway to Melanoma

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Relationships between p53 mutation, HPV status and outcome in oropharyngeal squamous cell carcinoma

This study aimed to examine the rate and type of p53 mutation in oropharyngeal cancer (OSCC). Relationships were sought between human papillomavirus (HPV) status and p53 mutation. The role of p53 mutation as a prognostic factor independent of HPV status and as a modifier of the effect of HPV on outcomes was also examined. (Source: Radiotherapy and Oncology)

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Locally advanced hypopharyngeal squamous cell carcinoma: single-institution outcomes in a cohort of patients curatively treated either with or without larynx preservation

Conclusion: The outcomes in the present series are in line with the literature.Resumo Objetivo: O objetivo deste estudo é descrever a experiência de uma instituição no tratamento com intenção curativa de doentes diagnosticados com carcinoma espinocelular da hipofaringe localmente avançado. Materiais e Métodos: Os dados relativos aos doentes portadores de carcinoma espinocelular da hipofaringe localmente avançado tratados entre janeiro de 2006 e junho de 2012 foram revistos. Resultados: Foram incluídos 144 doentes. O tempo mediano de seguimento foi 36,6 meses. A sobrevivência mediana, aos 2 anos e aos 5 anos foi 26 meses, 51% e 30,5%, respectivamente. A sobrevivência livre de recorrência mediana, aos 2 anos e aos 5 anos foi 18 meses, 42,8% e 28,5%, respectivamente. Conclusão: ...

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Interaction between Esophageal Squamous Cell Carcinoma and Adipose Tissue

Esophageal squamous cell carcinoma (ESCC) develops within the squamous epithelial layer and progressively invades the submucosa to the subadventitia that has abundant adipose tissue (AT). AT seems critical to ESCC progression, but the underlying mechanism is unknown. We aimed to address the association between ESCC and AT in vitro. ESCC cells were cultured on rat or human subcutaneous AT-embedded or –non-embedded collagen gel. AT promoted the growth of ESCC cells and inhibited their apoptosis. AT promoted the expression of the squamous differentiation marker involucrin in ESCC cells. (Source: American Journal of Pathology)

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Interaction between Esophageal Squamous Cell Carcinoma and Adipose Tissue

Esophageal squamous cell carcinoma (ESCC) develops within the squamous epithelial layer and progressively invades the submucosa to the subadventitia that has abundant adipose tissue (AT). AT seems critical to ESCC progression, but the underlying mechanism is unknown. We aimed to address the association between ESCC and AT in vitro. ESCC cells were cultured on rat or human subcutaneous AT-embedded or –non-embedded collagen gel. AT promoted the growth of ESCC cells and inhibited their apoptosis. AT promoted the expression of the squamous differentiation marker involucrin in ESCC cells. (Source: American Journal of Pathology)

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Bonnie Raitt on Channeling the ‘Dark Stuff’ For Her New Album and Why She Likes That Bernie Sanders Is Putting … – Billboard

Billboard

Bonnie Raitt on Channeling the 'Dark Stuff' For Her New Album and Why She Likes That Bernie Sanders Is Putting … Billboard I'd lost my family — my brother died of brain cancer and both my parents passed, all within the same period. I wasn't sure how to go on. The darkness was deep. Only Joe's gentle persistence got me back into the studio. "Just come over and relax," he said. and more »

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Medical Complications of Tattoos: A Comprehensive Review

Abstract

Tattoos are defined as the introduction of exogenous pigments into the dermis in order to produce a permanent design. This process may occur unintentional or may be deliberately administered for cosmetic or medical reasons. Tattoos have been around for over 5000 years and over time have evolved to represent a common cosmetic practice worldwide. Currently, adverse reactions are relatively rare and generally unpredictable and predominantly include immune-mediated reactions and skin infections. Along with better healthcare standards and more stringent public health mandates such as the provision of disposable needles, major infectious complications related to hepatitis and human retroviral infections have decreased significantly. When they do occur, skin infections are most frequently associated with Staphylococcus aureus or Streptococcus pyogenes. The aim of this study is to review the types and rates of medical complications of permanent tattoos. PubMed search and search dates were open ended. Acute local inflammation is the most common complication, but infections, allergic contact dermatitis, and other inflammatory or immune responses that are not well-characterized may occur. As many patients with immune reactions to tattoos do not react on skin or patch testing, it is postulated that the antigens contained in dyes or pigments are such small molecules that they need to be haptenized in order to become immunogenic. Red ink is associated more frequently with long-term reactions, including granulomatous and pseudolymphomatous phenomena or morphea-like lesions and vasculitis. Exacerbation of preexisting psoriasis, atopic dermatitis, and pyoderma gangrenosum may occur after tattooing. There is no well-defined association between cancer and tattoos. The treatment of tattoo-related complications may include local destructive measures (cryotherapy, electro-surgery, dermabrasion, chemical destruction, ablative laser destruction), surgical excision, and thermolysis of the pigment using Q-switched laser therapy.

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Effects of optineurin mutants on SH-SY5Y cell survival

Publication date: Available online 5 March 2016
Source:Molecular and Cellular Neuroscience
Author(s): Min Zhu, Ang Li, Junyi Chen, Shenghai Zhang, Jihong Wu
Mutations in the optineurin gene (OPTN) have been found to be associated with glaucoma and amyotrophic lateral sclerosis (ALS). However, the mechanism by which this single gene mutation leads to neurodegeneration in those two diseases remains unrevealed. To study the roles of wild-type (WT) OPTN and its pathogenic mutants in neuronal survival, here we overexpressed SH-SY5Y cells with WT OPTN or its four mutants (E50K, M98K, Q398X and E478G), and detected their effects on neuronal viability under normal or oxidative stress conditions. We found that overexpression of WT OPTN or its glaucoma-linked mutants (E50K and M98K) causes little harm in SH-SY5Y cells, while ALS-associated OPTN mutants (Q398X and E478G) leads to remarkably increased oxidative status and decreased antioxidase activity, which might result in severe mitochondrial dysfunction and neuronal injury. Further investigation suggests that overexpression of WT OPTN promotes endogenous antioxidase activation in the SH-SY5Y cells under oxidative stress and increases neuronal survival. Nevertheless, this neuroprotective effect of WT OPTN is abolished by its four mutants. Our results indicate that oxidative stress may play a central role in the pathogenesis of glaucoma and ALS caused by OPTN mutation.

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Influence of the decoupling degree on the estimation of canopy stomatal conductance for two broadleaf tree species

Publication date: 1 May 2016
Source:Agricultural and Forest Meteorology, Volume 221
Author(s): Zhen Z. Zhang, Ping Zhao, Heather R. McCarthy, Xiu H. Zhao, Jun F. Niu, Li W. Zhu, Guang Y. Ni, Lei Ouyang, Yu Q. Huang
Canopy stomatal conductance (GS) estimation is a critical aspect of evapotranspiration research. Selecting an appropriate model for scaling-up is necessary to study plant water regulation. Two monoculture plantations of broadleaf tree species, Eucalyptus urophylla and Schima superba, were selected to study GS via a widely recognized equation simplified by Köstner (GS1) and an inverse Penman–Monteith equation (GS2). The decoupling coefficient (Ω) was estimated to quantify the decoupling extent of stomata from the atmosphere. We found that both species were well coupled with environmental conditions (0.1±0.06 and 0.22±0.09 for E. urophylla and S. superba). Ω increased exponentially with canopy conductance (GC) and was depressed by the increase of Ga, which implied that there was a combined climatic and physiological regulation on Ω. GS1 for both species (63.7±33.9mmolm−2s−1 and 48.4±18.1mmolm−2s−1 for E. urophylla and S. superba, respectively) was underestimated with the simplified equation compared to GS2 (77.0±52.4mmolm−2s−1and 112.0±52.5mmolm−2s−1 for E. urophylla and S. superba, respectively). The ratio of GS1/GS2 linearly decreased with Ω by a slope of −1.92 and −1.31 for E. urophylla and S. superba, respectively. The increase of the LAI tended to increase the decoupling extent, which further reduced the accuracy of the estimation of GS1. According to our results, the ratio of GS1/GS2 had a mean of 0.94 for 85.3% and 0.6 for 37.6% of all of the data for E. urophylla and S. superba, respectively, implying a better estimation of GS1 for the stand that had a lower LAI. Based on the relationship between the LAI and the ratios of GS1/GS2 (ratio=1.0759×0.02547(0.053LAI+0.054)−0.0078), we can shed some light on the prediction error of stomatal conductance derived from the simplified equation in different forest types.

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Langzeitfolgen körperlicher und psychischer Gewalt

Die Schmerzen bleiben
Das häufigste körperliche Symptom nach extremer Traumatisierung sind chronische Schmerzen. Interdisziplinäre schmerztherapeutische Interventionen können dieses Leiden lindern.

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Corrigendum: Notch signal strength controls cell fate in the haemogenic endothelium

Corrigendum

Nature Communications doi: 10.1038/ncomms10978

Authors: Leonor Gama-Norton, Eva Ferrando, Cristina Ruiz-Herguido, Zhenyi Liu, Jordi Guiu, Abul B. M. M. K. Islam, Sung-Uk Lee, Minhong Yan, Cynthia J. Guidos, Nuria López-Bigas, Takahiro Maeda, Lluis Espinosa, Raphael Kopan, Anna Bigas

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Specular reflection in the signal of LAI-2000 plant canopy analyzer

Publication date: 1 May 2016
Source:Agricultural and Forest Meteorology, Volume 221
Author(s): Andres Kuusk
In a vegetation canopy part of leaves reflect sky radiation specularly to the LAI-2000 sensor. This fraction is smaller in a planophile canopy and higher in an erectophile canopy. As the specularly reflected radiation does not enter the leaf nor it is absorbed by leaf pigments and depending on the incidence angle on the leaf the reflection coefficient may be very high. Depending on the leaf area index (LAI) and leaf angle distribution the scattered sky radiation may cause an overestimation of the gap fraction and consequently an underestimation of LAI up to 20–25% if the LAI measurements with plant canopy analyzer LAI-2000 are carried out under ideal perfectly overcast conditions. Similar biases are present in measurements of gap fraction and LAI with hemispherical photos if these measurement procedures are calibrated against LAI-2000. Considering the scattered sky radiation in optical techniques (LAI-2000, hemispherical photos) of measuring gap fraction in vegetation canopies explains at least part of the observed discrepancies in gap fraction estimated with terrestrial laser scanner and hemispherical photos. The scattered sky radiation in the LAI-2000 signal introduces bias both in the estimated LAI and foliage clumping index.

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Two-colour live-cell nanoscale imaging of intracellular targets

Article

The intracellular applications of STED microscopy are limited by the availability of dyes. Here the authors develop a two-colour labelling strategy based on SiR and ATTO590 dyes, and apply their strategy to image various subcellular membrane compartments.

Nature Communications doi: 10.1038/ncomms10778

Authors: Francesca Bottanelli, Emil B. Kromann, Edward S. Allgeyer, Roman S. Erdmann, Stephanie Wood Baguley, George Sirinakis, Alanna Schepartz, David Baddeley, Derek K. Toomre, James E. Rothman, Joerg Bewersdorf

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Field-free magnetization reversal by spin-Hall effect and exchange bias

Article

Future information storage technology may exploit electrical currents to write the states of ferromagnetic nanoelements via spin torque effects. Here, the authors demonstrate such behaviour promoted by exchange bias from an interfaced antiferromagnet, which may help overcome practical device limitations.

Nature Communications doi: 10.1038/ncomms10854

Authors: A. van den Brink, G. Vermijs, A. Solignac, J. Koo, J. T. Kohlhepp, H. J. M. Swagten, B. Koopmans

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A coral-on-a-chip microfluidic platform enabling live-imaging microscopy of reef-building corals

Article

Studies of coral in laboratory settings are limited by a lack of reliable methods for manipulation of the coral microenvironment and monitoring of coral processes in vitro . Here the authors develop coral-on-a-chip, a microfluidic platform to enable study of coral processes at single-cell resolution.

Nature Communications doi: 10.1038/ncomms10860

Authors: Orr H. Shapiro, Esti Kramarsky-Winter, Assaf R. Gavish, Roman Stocker, Assaf Vardi

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Long-term quality of life in children after open airway surgery for laryngotracheal stenosis

The purpose of this study is to evaluate the long-term health related quality of life (HRQoL) in a cohort of children surgically treated for laryngotracheal stenosis (LTS). (Source: International Journal of Pediatric Otorhinolaryngology)

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TRF2-RAP1 is required to protect telomeres from engaging in homologous recombination-mediated deletions and fusions

Article

While yeast Rap1 regulates telomere length and protects telomeres from non-homologous end joining, its role in higher eukaryotes is controversial. Here the authors present evidence that in mammals, RAP1 cooperates with TRF2 to prevent homologous recombination-mediated repair of telomeres.

Nature Communications doi: 10.1038/ncomms10881

Authors: Rekha Rai, Yong Chen, Ming Lei, Sandy Chang

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Protection from septic peritonitis by rapid neutrophil recruitment through omental high endothelial venules

Article

Neutrophils are critical in preventing the transition of acute peritoneal infection to sepsis. Here the authors show in three mouse models of peritonitis that neutrophils enter the abdominal cavity via high endothelial venules of the greater omentum, and characterize adhesion molecules involved.

Nature Communications doi: 10.1038/ncomms10828

Authors: Konrad Buscher, Huiyu Wang, Xueli Zhang, Paul Striewski, Benedikt Wirth, Gurpanna Saggu, Stefan Lütke-Enking, Tanya N. Mayadas, Klaus Ley, Lydia Sorokin, Jian Song

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Editorial Board

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Low-dose chemo, radiation and surgery means less organ cuts – Daily Trust

Daily Trust

Low-dose chemo, radiation and surgery means less organ cuts Daily Trust The protocol means cancer surgeries combining radiation and chemo will involve less removal of tissues from affected body parts as larynx, breast, rectum, stomach, bones and soft tissue. Singh said the protocol allows for modified doses of both chemo …

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Guidelines for Contributing Authors

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Mariah Carey Irked by James Packer Smoking; Is Engagement in Jeopardy? – TheImproper.com

TheImproper.com

Mariah Carey Irked by James Packer Smoking; Is Engagement in Jeopardy? TheImproper.com Secondhand smoke contains more than 7,000 chemicals, including at least 70 that can cause cancer, the organization says on its Web site. High on the list of organs it can damage are the larynx (voice box), pharynx (throat), nasal sinuses, brain … and more »

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Genetic suppression reveals DNA repair-independent antagonism between BRCA1 and COBRA1 in mammary gland development

Article

COBRA1 is a BRCA1-binding protein and, as part of the negative elongation factor, regulates RNA polymerase II pausing and transcription elongation. Here, the authors show that tissue-specific deletion of mouse Cobra1 inhibits postnatal mammary gland development and that the mammary defects can be rescued by additional deletion of Brca1 in a DNA repair-independent manner.

Nature Communications doi: 10.1038/ncomms10913

Authors: Sreejith J. Nair, Xiaowen Zhang, Huai-Chin Chiang, Md Jamiul Jahid, Yao Wang, Paula Garza, Craig April, Neeraj Salathia, Tapahsama Banerjee, Fahad S. Alenazi, Jianhua Ruan, Jian-Bing Fan, Jeffrey D. Parvin, Victor X. Jin, Yanfen Hu, Rong Li

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Table of Contents

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Editorial Board/Reviewing Committee

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Can migraine aura be provoked experimentally? A systematic review of potential methods for the provocation of migraine aura

Background

The nature of the migraine aura and its role in migraine pathophysiology is incompletely understood. In particular, the mechanisms underlying aura initiation and the causal relation between aura and headache are unknown. The scientific investigation of aura in patients is only possible if aura can be triggered. This paper reviews potential methods for the experimental provocation of migraine aura.

Methods

We systematically searched PubMed for studies of experimental migraine provocation, including case reports of patients with aura and reports of the occurrence of aura following exposure to any kind of suspected trigger.

Results

We identified 21 provocation studies, using 13 different prospective provocation methods, and 34 case reports. In the prospective studies, aura were reported following the administration of intravenous and sublingual glyceryl trinitrate, visual stimulation, physical activity, calcitonin gene-related peptide infusion, chocolate ingestion, and the intravenous injection of insulin. In addition, carotid artery puncture has consistently been reported as a trigger of aura.

Conclusions

No safe and efficient method for aura provocation exists at present, but several approaches could prove useful for this purpose.

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Feedback regulation of apical progenitor fate by immature neurons through Wnt7–Celsr3–Fzd3 signalling

Article

The switch from neurogenesis to gliogenesis in cortical development is only partially understood. Here the authors show that Wnt-Planar cell polarity signaling in immature cortical neurons activates Notch in neural progenitor cells, thereby tuning the timing of their fate decisions.

Nature Communications doi: 10.1038/ncomms10936

Authors: Wei Wang, Yves Jossin, Guoliang Chai, Wen-Hui Lien, Fadel Tissir, Andre M. Goffinet

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A Study of Healthy Adults’ Oro-lingual Effort During Swallowing Using OroPress, A New Portable Wireless Measur ement Tool

Abstract

OroPress is a new, low profile, portable, wireless tool that enables stable measurement of tongue pressure during isometric ('pushing') tasks and, more importantly, during swallowing. Using this tool, a pressure–time product, the OroPress Absolute (OPA) parameter, has been developed as a representative measure of lingual effort during swallowing. In a sample of 57 adults aged 20–80+ years, of both sexes and without dysphagia, tongue-palate contact pressures generated while swallowing 5 ml, 10 ml of water and 5 ml custard, were recorded using OroPress. Data were examined for effects of gender, age and bolus condition (consistency, volume). OPA was tested for stability of measure and then correlated with the criterion standard, peak pressure recorded when swallowing (PMaxSW). Swallowing pressures (PMaxSW, OPA) were positively correlated with bolus viscosity. No significant age and gender differences were found. Excellent stability of measure (test, re-test reliability) was demonstrated and OPA was positively correlated with PMaxSW. OroPress produces valid, reliable and reproducible measurements and improved accuracy of oro-lingual pressure measurement during swallowing. With such a tool, interventions/therapy can be proactive and principled as outcomes are better validated. To enhance specificity of intervention, measurement parameters need to reflect the pressure and temporal qualities of swallow function. OPA has the potential to describe differences in effort made, and ability to sustain pressures, in adults without dysphagia. The results of these studies will enable more accurate examination of the oral phase of swallowing as we establish this highly accurate sensor as a criterion standard for oro-lingual pressure measurement in clinical populations.

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Myoepithelial carcinoma of the hypopharynx

We present an unusual case arising in a 1-year-old boy. He underwent microsuspension direct laryngoscopy with organ preservation. The tumor cells were arranged in nests and lobules separated by thin fibrovascular septae in a background of fibromyxoid stroma. Immunohistochemically, the tumor was positive for S-100 protein, AE1/AE3, and synaptophysin. (Source: International Journal of Pediatric Otorhinolaryngology Extra)

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Sialoblastoma: A Very Rare Cervical Mass in Neonates: a case report

Sialoblastomas are very rare epithelial tumors of the salivary gland that usually occur in the parotid or submandibular gland. Most sialoblastomas present in the neonatal period or early childhood. The biological behavior of these tumors is variable, with a potential for local and systemic recurrences. Only ten cases in the submandibular gland have been reported so far. We are reporting a case of sialoblastoma in a newborn male child presenting in the right submandibular region. Ultrasound visualized a homogeneous solid mass. (Source: International Journal of Pediatric Otorhinolaryngology Extra)

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Editorial Board

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Melanoma cell lysosome secretory burst neutralizes the CTL-mediated cytotoxicity at the lytic synapse

Article

Cytotoxic T lymphocytes recognise and eliminate tumour cells. Here, the authors show that on contact with these immune cells melanoma cells can resist T cell cytotoxicity by modulating the trafficking of their lysosomal compartment, this results in the degradation of the T cell protein perforin by the protease cathepsin B.

Nature Communications doi: 10.1038/ncomms10823

Authors: Roxana Khazen, Sabina Müller, Nicolas Gaudenzio, Eric Espinosa, Marie-Pierre Puissegur, Salvatore Valitutti

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Guidelines for Contributing Authors

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Innate and Adaptive Immune Response to Fungal Products and Allergens

Publication date: Available online 2 January 2016
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): P. Brock Williams, Charles S. Barnes, Jay M. Portnoy
Exposure to fungi and their products is practically ubiquitous, yet most of this is of little consequence to most healthy individuals. This is because there are a number of elaborate mechanisms to deal with these exposures. Most of these mechanisms are designed to recognize and neutralize such exposures. However, in understanding these mechanisms it has become clear that many of them overlap with our ability to respond to disruptions in tissue function caused by trauma or deterioration. These responses involve the innate and adaptive immune systems usually through the activation of nuclear factor kappa B and the production of cytokines that are considered inflammatory accompanied by other factors that can moderate these reactivities. Depending on different genetic backgrounds and the extent of activation of these mechanisms, various pathologies with resulting symptoms can ensue. Complicating this is the fact that these mechanisms can bias toward type 2 innate and adaptive immune responses. Thus, to understand what we refer to as allergens from fungal sources, we must first understand how they influence these innate mechanisms. In doing so it has become clear that many of the proteins that are described as fungal allergens are essentially homologues of our own proteins that signal or cause tissue disruptions.

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