Housing and neighbourhood conditions are widely acknowledged important social determinants of health and health inequalities that persist in developed countries despite general improvements in health outcomes ...
https://ift.tt/2LoYiUL
Παρασκευή 24 Αυγούστου 2018
Crowded living and its association with mental ill-health among recently-arrived migrants in Sweden: a quantitative study
Work related stress and associated factors among Huajian shoe manufacturing employees in Dukem town, central Ethiopia
The objective of this study was to assess the prevalence of work-related stress (WRS) and its determinants among Huajian shoe manufacturing company employees in Dukem town, central Ethiopia. An institutional-b...
https://ift.tt/2wc3uGr
Reactant pairs and reaction organization patterns produced by a new rule-based approach
Improvements in bioinformatics applications for the enzyme identification of biochemical reactions, enzyme classifications, mining for specific inhibitors and pathfinding require the accurate computational det...
https://ift.tt/2LoYhAb
Correction to: MicroRNA-125b reverses oxaliplatin resistance in hepatocellular carcinoma by negatively regulating EVA1A mediated autophagy
Correction to: MicroRNA-125b reverses oxaliplatin resistance in hepatocellular carcinoma by negatively regulating EVA1A mediated autophagy
Correction to: MicroRNA-125b reverses oxaliplatin resistance in hepatocellular carcinoma by negatively regulating EVA1A mediated autophagy, Published online: 24 August 2018; doi:10.1038/s41419-018-0836-y
Correction to: MicroRNA-125b reverses oxaliplatin resistance in hepatocellular carcinoma by negatively regulating EVA1A mediated autophagyhttps://ift.tt/2NjnuNV
Cancers, Vol. 10, Pages 288: p53 Isoforms and Their Implications in Cancer
Cancers, Vol. 10, Pages 288: p53 Isoforms and Their Implications in Cancer
Cancers doi: 10.3390/cancers10090288
Authors: Maximilian Vieler Suparna Sanyal
In this review we focus on the major isoforms of the tumor-suppressor protein p53, dysfunction of which often leads to cancer. Mutations of the TP53 gene, particularly in the DNA binding domain, have been regarded as the main cause for p53 inactivation. However, recent reports demonstrating abundance of p53 isoforms, especially the N-terminally truncated ones, in the cancerous tissues suggest their involvement in carcinogenesis. These isoforms are ∆40p53, ∆133p53, and ∆160p53 (the names indicate their respective N-terminal truncation). Due to the lack of structural and functional characterizations the modes of action of the p53 isoforms are still unclear. Owing to the deletions in the functional domains, these isoforms can either be defective in DNA binding or more susceptive to altered ‘responsive elements’ than p53. Furthermore, they may exert a ‘dominant negative effect’ or induce more aggressive cancer by the ‘gain of function’. One possible mechanism of p53 inactivation can be through tetramerization with the ∆133p53 and ∆160p53 isoforms—both lacking part of the DNA binding domain. A recent report and unpublished data from our laboratory also suggest that these isoforms may inactivate p53 by fast aggregation—possibly due to ectopic overexpression. We further discuss the evolutionary significance of the p53 isoforms.
https://ift.tt/2P4ZheL
Biological issues with cabozantinib in bone metastatic renal cell carcinoma and castration-resistant prostate cancer
Future Oncology, Ahead of Print.
https://ift.tt/2o8Zl1T
Harnessing the CD8+T-cell subsets with stemness for tumor immunotherapy
Future Oncology, Ahead of Print.
https://ift.tt/2BN33I4
Mechanistic insights into the differential effects of thalidomide and lenalidomide in metastatic prostate cancer
Future Oncology, Ahead of Print.
https://ift.tt/2MyVJ7G
Evaluation of curcumin, a natural product in turmeric, on Burkitt lymphoma and acute myeloid leukemia cancer stem cell markers
Future Oncology, Ahead of Print.
https://ift.tt/2OYzTas
Incidence and predictors of 1-year mortality among 9236 breast cancer patients referred for adjuvant chemotherapy
Future Oncology, Ahead of Print.
https://ift.tt/2MyVHwA
Could combinations of new and old drugs enhance tumor cell death?
Future Oncology, Ahead of Print.
https://ift.tt/2P0xFHN
Preoperative fibrinogen to prealbumin ratio as a novel predictor for clinical outcome of hepatocellular carcinoma
Future Oncology, Ahead of Print.
https://ift.tt/2ofFu17
Immune tumor board: integral part in the multidisciplinary management of cancer patients treated with cancer immunotherapy
Abstract
Recent progress in the understanding of immune responses to cancer and how tumor cells evade immune control have led to the successful introduction of cancer immunotherapy, in particular immune checkpoint inhibitors (ICI). Treatment of cancer patients with immunotherapy such as ICIs has led to new challenges, including starting and stopping rules for immunotherapy, the management of immune-related adverse events, and logistic issues for the production of cellular therapies and viral delivery vectors. These challenges are not disease- or organ-specific and several potential biomarkers to predict response to ICI are under investigation. We installed an interdisciplinary discussion platform for managing patient-specific challenges associated with cancer immunotherapy in our institution. Here, we describe an immune tumor board for the management of cancer patients treated with immunotherapy and provide an outlook on how such a platform could be potentially used in the future to discuss rational and personalized combination therapies, and how to improve the management of side effects occurring under immunotherapy.
https://ift.tt/2PzHXzH
Knockdown of Long Noncoding RNA Plasmacytoma Variant Translocation 1 with Antisense Locked Nucleic Acid GapmeRs Exerts Tumor-Suppressive Functions in Human Acute Erythroleukemia Cells Through Downregulation of C-MYC Expression
Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.
https://ift.tt/2MuEch8
Hürthle Cell Carcinomas Exhibit Widespread Loss of Heterozygosity [Research Watch]
Hürthle cell carcinomas (HCC) harbor recurrent somatic DNA mutations and mtDNA mutations.
https://ift.tt/2PzCzfT
PD-1-Blocking scFV-Secreting CAR T Cells Exhibit Antitumor Efficacy [Research Watch]
PD-1–blocking scFv-expressing CAR constructs enhance CAR T-cell efficacy.
https://ift.tt/2LqorT8
T-Cell Mutation Leads to GI Polyps [News in Brief]
LKB1-deficient immune cells spark inflammatory response that promotes Peutz–Jeghers syndrome.
https://ift.tt/2PBZkzJ
Bendamustine, Obinutuzumab, and Venetoclax Achieve Responses in CLL [Research Watch]
Bendamustine followed by obinutuzumab and venetoclax provides clinical benefit without unexpected toxicity.
https://ift.tt/2wqAVo7
An Update on the Histology of Pheochromocytomas: How Does it Relate to Genetics?
Horm Metab Res
DOI: 10.1055/a-0672-1266
Pheochromocytomas are rare neuroendocrine tumors of the adrenal gland, whereas any extra-adrenal tumor with similar histology is designated as paraganglioma. These tumors have a very high rate of germline mutations in a large number of genes, up to 35% to 40%, frequently predisposing for other tumors as well. Therefore, they represent a phenomenal challenge for treating physicians. This review focuses on pheochromocytomas only, with special attention to gross and microscopic clues to the diagnosis of genetic syndromes, including the role of succinate dehydrogenase subunit A and subunit B immunohistochemistry as surrogate markers for genetic analysis in the field of succinate dehydrogenase subunit gene mutations.
[...]
© Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Abstract | Full text
https://ift.tt/2w8MqRE
Amplification of glyceronephosphate O-acyltransferase and recruitment of USP30 stabilize DRP1 to promote hepatocarcinogenesis
Hepatocellular carcinoma is a leading cause of cancer-related death worldwide and the underlying pathophysiology of HCC is highly complex. In this study, we report that, in a bioinformatic screen of 2783 genes encoding metabolic enzymes, GNPAT, which encodes the enzyme glyceronephosphate O-acyltransferase, is amplified, upregulated, and highly correlated with poor clinical outcome in human HCC patients. High GNPAT expression in HCC was due to its amplification and transcriptional activation by the c-Myc/KDM1A complex. GNPAT compensated the oncogenic phenotypes in c-Myc-depleted HCC cells. Mechanistically, GNPAT recruited the enzyme USP30, which deubiquitylated and stabilized dynamin-related protein 1 (DRP1), thereby facilitating regulation of mitochondrial morphology, lipid metabolism, and hepatocarcinogenesis. Inhibition of GNPAT and DRP1 dramatically attenuated lipid metabolism and hepatocarcinogenesis. Furthermore, DRP1 mediated the oncogenic phenotypes driven by GNPAT. Taken together, these results indicate that GNPAT and USP30-mediated stabilizaiton of DRP1 play a critical role in the development of HCC.
https://ift.tt/2Nhch0D
CSTF2-induced shortening of the RAC1 3'UTR promotes the pathogenesis of urothelial carcinoma of the bladder
Shortening of the 3' untranslated regions (3'UTR) of mRNA is an important mechanism for oncogene activation. However, 3'UTR alteration events, their pathological functions, and underlying mechanisms in human urothelial carcinoma of the bladder (UCB) are not clear. Here we combine RNA-seq, bioinformatics, and clinical studies in two independent cohorts of UCB patients to identify a novel RAC1 shorter-3'UTR isoform that is frequently expressed in UCB and is critical in the tumorigenesis and acquisition of a poor prognostic phenotype in patients. Short 3'UTR isoform of RAC1 substantially upregulated RAC1 expression by escaping from miRNA targeted repression and played an essential oncogenic role in UCB pathogenesis. An important cleavage/polyadenylation factor, cleavage stimulation factor 2 (CSTF2), induced 3'UTR shortening of RAC1 in UCB by mediating slow transcriptional elongation at RAC1. Cotranscriptional recruitment of CSTF2 on the GUAAU motif at proximal polyadenylation site (pPAS) of RAC1 attenuated the recruitment of two transcription factors AFF1 and AFF4, causing the defects in elongation. CSTF2 regulated the tumorigenic functions of the shorter RAC1 isoform in UCB cells, enhancing cell proliferation, migration, and invasion. The combination of high expression of CSTF2 and high usage of RAC1 short 3'UTR isoform may be used as a powerful biomarker to predict poor prognosis in UCB. Our findings also suggest a CSTF2-regulated RAC1-3'UTR shortening program as an exploitable therapeutic strategy for UCB patients.
https://ift.tt/2PBYsuX
Sleep quality, daytime sleepiness, fatigue, and quality of life in patients with multiple sclerosis treated with interferon beta-1b: results from a prospective observational cohort study
Sleep disorders and fatigue are common in multiple sclerosis (MS). The underlying causes are not fully understood, and prospective studies are lacking. Therefore, we conducted a prospective, observational coho...
https://ift.tt/2wbr8TE
Intracranial pressure responsiveness to positive end-expiratory pressure is influenced by chest wall elastance: a physiological study in patients with aneurysmal subarachnoid hemorrhage
Respiratory system elastance (ERS) is an important determinant of the responsiveness of intracranial pressure (ICP) to positive end-expiratory pressure (PEEP). However, lung elastance (EL) and chest wall elastanc...
https://ift.tt/2NdH26A
Medicaid Expansion Linked to Increase in Diabetes Rx Fills
FRIDAY, Aug. 24, 2018 -- Expansions in Medicaid eligibility are associated with an increase in Medicaid diabetes prescriptions filled, according to a study published in the August issue of Health Affairs. Rebecca Myerson, M.P.H., Ph.D., from the...
https://ift.tt/2w8KSYc
AMA Adopts Policy Promoting Health Equity As a Goal
FRIDAY, Aug. 24, 2018 -- The American Medical Association (AMA) House of Delegates has adopted a policy that sets health equity as a goal for the U.S. health care system, according to a report published in the organization's AMA Wire. The action,...
https://ift.tt/2NgngXQ
Office Workstation Type Linked to Physical Activity, Stress
FRIDAY, Aug. 24, 2018 -- Workers in open bench seating office workstations are more active and have lower perceived stress at the office, according to a study published online Aug. 20 in Occupational & Environmental Medicine. Casey M. Lindberg,...
https://ift.tt/2PzmKWC
Arkansas Law Restricting Abortion Pills Remains on Hold
FRIDAY, Aug. 24, 2018 -- An Arkansas law that would severely limit the use of abortion pills must remain on hold, a federal appeals court says. Under the law, doctors who provide the pills must have a contract with a doctor who has admitting...
https://ift.tt/2NgneiG
FDA: Illnesses Linked to McDonald's Salads Reach 507
FRIDAY, Aug. 24, 2018 -- The number of confirmed cases of Cyclospora infection linked to salads from McDonald's restaurants was 507 in 15 states and New York City as of Aug. 23, according to the U.S. Food and Drug Administration. The source of the...
https://ift.tt/2w8KRU8
Whole blood profiling of leprosy type 1(reversal) reactions highlights prominence of innate immune response genes
The major factors contributing for nerve damage and permanent disabilities in leprosy are type 1 or reversal reactions (RR) and type 2 or erythema nodosum leprosum (ENL). Gene profiling of leprosy reactions ha...
https://ift.tt/2o7qLF7
Association of the Tyrosine/Nitrotyrosine pathway with death or ICU admission within 30 days for patients with community acquired pneumonia
Oxidative stress is a modifiable risk-factor in infection causing damage to human cells. As an adaptive response, cells catabolize Tyrosine to 3-Nitrotyrosine (Tyr-NO2) by nitrosylation. We investigated whethe...
https://ift.tt/2LoxfJ9
Comparative Effects of Different Assistance Force During Robot-Assisted Gait Training on Locomotor Functions in Patients with Subacute Stroke: An Assessor-Blind, Randomized Controlled Trial
Objective To compare the effects of progressive reducing assistance force (AF) versus full AF controlled robot-assisted gait training (RAGT) combined with conventional physiotherapy on locomotor functions in patients with subacute stroke. Design Inpatients with subacute stroke (N=29; 16 men; Functional Ambulation Category [FAC] score, 1±0.9) were randomly assigned to 1 of 2 groups: a progressive reducing AF group (n=15) or a full AF group (n=14). The progressive reducing AF group performed RAGT sessions from 100%-AF at the outset to 60%-AF at the end of the RAGT, while the full AF group received 100%-AF throughout the RAGT sessions. Both groups performed RAGT combined with conventional physiotherapy 5 days a week for 4 weeks. After intervention, all patients then underwent only conventional physiotherapy 5 days a week for 4-weeks of follow-up. Results The Mann-Whitney U test between-group comparisons showed that improvements were significantly greater in the progressive reducing AF group for the FAC, knee extensors torque, and Berg Balance Scale relative to the full AF group, both at post-intervention and at follow-up. Conclusion Progressive reducing AF control during RAGT combined with conventional physiotherapy may be more beneficial for improving locomotor functions in patients with subacute stroke. *Both first authors have equally contributed to this study as first author. Corresponding author: Yong-Il Shin, MD, PhD, Department of Rehabilitation Medicine, Pusan National University School of Medicine, Yangsan, Republic of Korea, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea, Address: 20 Geumo-ro, Mulgeum-eup, Yangsan, Gyeongsangnam-do 50612, Republic of Korea. Mobile: +82-10-6535-0310. E-mail: rmshin01@gmail.com Author Disclosures: This manuscript has been submitted solely to this journal and has not been published or submitted elsewhere. No conflicts of interest have been reported by the authors or by any individual in control of the content of this manuscript. This research received no specific grant from any funding agency. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2o6bO6l
https://ift.tt/2o6bO6l
Initial Results of a Multicenter Phase II Trial of Stereotactic Ablative Radiation Therapy for Oligometastatic Cancer
Here we report the initial outcomes of an international multi-center phase II prospective trial assessing the role of stereotactic ablative radiotherapy (SABR) for oligometastatic cancer. Our results demonstrate SABR to be a safe an effective treatment modality that demonstrates excellent overall survival and local control. Additionally, we report very low rates of acute and late grade 3 toxicity and show SABR to have no significant adverse effect on patient reported quality of life.
https://ift.tt/2Lobnxe
Novel Biomarkers in Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths and the fifth most common cancer worldwide. Most of these patients are seen with advanced disease at the time of presentation. In spite of its high prevalence, there are not many therapeutic options available for patients with advanced-stage HCC. There is an urgent need for improving early detection and prognostication of patients with HCC. In addition, the development of new therapies targeting specific pathways involved in the pathogenesis of HCC should be a major goal for future research, with the objective of improving outcomes of patients with HCC.
https://ift.tt/2NggB05
HOXB9 inhibits proliferation in gastric carcinoma cells via suppression of phosphorylated-Akt and NF-κB-dependent Snail expression
HOXB9 is a homeobox transcription factor which plays an important role in carcinoma development. This protein has been shown to inhibit cancer cell proliferation. However, the mechanisms that underpin HOXB9-mediated inhibition of cellular proliferation remain to be elucidated.
https://ift.tt/2MQEe26
Comparison of automated and manual drying in the eliminating residual endoscope working channel fluid after reprocessing (with video)
Residual fluid within endoscope working channels after reprocessing may promote growth of pathogens. Current reprocessing guidelines therefore recommend endoscope drying with administration of forced filtered air; however, the duration and modality of administered air are not specified. The new DriScope Aid device enables automated administration of filtered air at controlled pressure through all internal endoscope channels. We systematically compared, for the first time, the impact of manual drying and automated drying on retained working channel fluid and bioburden after reprocessing.
https://ift.tt/2o8tSwN
Endoscopic sleeve gastroplasty versus laparoscopic sleeve gastrectomy: a case-matched study
Endoscopic sleeve gastroplasty (ESG) reduces the gastric lumen to a size comparable to that of laparoscopic sleeve gastrectomy (LSG). Yet, there is a paucity of research comparing outcomes between the 2 procedures. Our study compared the 6-month weight loss outcomes and adverse events of ESG with LSG in a case-matched cohort.
https://ift.tt/2LnYVxO
The suture pulley countertraction method reduces procedure time and technical demand of ESD among novice endoscopists learning ESD: a prospective randomized ex vivo study
The lack of reliable countertraction in endoscopic submucosal dissection (ESD) contributes to its technical demand and increased procedure time. We aimed to prospectively evaluate the efficacy of the suture pulley countertraction method in endoscopists new to both suturing and ESD.
https://ift.tt/2o9mxwE
Wire-guided cannulation over a pancreatic stent method ıncreases the need for needle-knife precutting ın patients with difficult biliary cannulation
Cannulation of the major papilla can be problematic and selective biliary cannulation may fail in up to 18% of cases. Various techniques, such as double-guidewire technique (DGWT), wire-guided cannulation over a pancreatic stent (WGC-PS), the precut endoscopic sphincterotomy (needle-knife precutting technique: NKP), and transpancreatic septotomy, have been used to improve the success rate of biliary cannulation. We conducted a prospective, randomized study in order to compare the biliary cannulation success rates of DGWT and WGC-PS techniques in patients with inadvertent passage of guidewire to pancreatic duct.
https://ift.tt/2Loep4A
The Validity of Drug Effects on Proteinuria, Albuminuria, Serum Creatinine, and Estimated GFR as Surrogate End Points for ESKD: A Systematic Review
Proteinuria, albuminuria, and serum creatinine level are widely used as surrogate end point measures of end-stage kidney disease (ESKD). We evaluated the correlation between antihypertensive drug effects on surrogate renal end points and ESKD.
https://ift.tt/2w8z8VC
The Role for Protein Restriction in Addition to Renin-Angiotensin-Aldosterone System Inhibitors in the Management of CKD
In experimental studies a low-protein diet (LPD) and renin-angiotensin-aldosterone system (RAAS) inhibitors are both reported to slow the progression of chronic kidney disease (CKD) and reduce proteinuria. RAAS activity contributes to increased blood pressure, fluid retention, and positive sodium balance, but also to kidney damage by enhancing glomerular capillary filtration pressure and synthesis of profibrotic molecules such as transforming growth factor β. It has been well established that an LPD decreases glomerular hyperfiltration and the generation of uremic toxins, as well as the burden of acid load, phosphorus, and sodium.
https://ift.tt/2Lqv1su
Patient, Caregiver and Taxpayer Knowledge of Palliative Care and Views on a Model of Community-Based Palliative Care
Palliative care model delivered by two large hospices and palliative care providers.
https://ift.tt/2LogXA3
Delirium Monitoring in Neurocritically Ill Patients: A Systematic Review
Objectives: The Society of Critical Care Medicine recommends routine delirium monitoring, based on data in critically ill patients without primary neurologic injury. We sought to answer whether there are valid and reliable tools to monitor delirium in neurocritically ill patients and whether delirium is associated with relevant clinical outcomes (e.g., survival, length of stay, functional independence, cognition) in this population. Data Sources: We systematically reviewed Cumulative Index to Nursing and Allied Health Literature, Web of Science, and PubMed. Study Selection and Data Extraction: Inclusion criteria allowed any study design investigating delirium monitoring in neurocritically ill patients (e.g., neurotrauma, ischemic, and/or hemorrhagic stroke) of any age. We extracted data relevant to delirium tool sensitivity, specificity, negative predictive value, positive predictive value, interrater reliability, and associated clinical outcomes. Data Synthesis: Among seven prospective cohort studies and a total of 1,173 patients, delirium was assessed in neurocritically patients using validated delirium tools after considering primary neurologic diagnoses and associated complications, finding a pooled prevalence rate of 12–43%. When able to compare against a common reference standard, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, the test characteristics showed a sensitivity of 62–76%, specificity of 74–98%, positive predictive value of 63–91%, negative predictive value of 70–94%, and reliability kappa of 0.64–0.94. Among four studies reporting multivariable analyses, delirium in neurocritically patients was associated with increased hospital length of stay (n = 3) and ICU length of stay (n = 1), as well as worse functional independence (n = 1) and cognition (n = 2), but not survival. Conclusions: These data from studies of neurocritically ill patients demonstrate that patients with primary neurologic diagnoses can meet diagnostic criteria for delirium and that delirious features may predict relevant untoward clinical outcomes. There is a need for ongoing investigations regarding delirium in these complicated neurocritically ill patients. Drs. Patel, Lee, Marra, Pandharipande, and Ely contributed to review structure; Drs. Patel and Lee contributed to literature search; Drs. Patel, Lee, Pandharipande, and Ely contributed data sheets; Drs. Patel, Pandharipande, and Ely contributed to title and abstract screening; Drs. Patel, Pandharipande, and Ely contributed to full text screening; Drs. Patel, Pandharipande, and Ely contributed to data extraction; Drs. Patel, Pandharipande, and Ely contributed to bias assessments; Drs. Patel, Lee, and Ely contributed to systematic review coordination; and all contributed to critical revisions to article. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/29S62lw). Supported, in part, by Veterans Affairs Tennessee Valley Geriatric Research, Education and Clinical Center (Nashville, TN) and the National Institutes of Health AG027472, AG035117, HL111111, GM120484 (Bethesda, MD). Dr. Patel's institution received funding from National Institutes of Health (NIH) HL111111 and NIH GM120484; he received funding from Pfizer/Hospira (education presentation); and he disclosed that funding was provided by federal sources including the Veterans Affairs (VA) Tennessee Valley Geriatric Research, Education and Clinical Center (Nashville, TN) and the NIH AG027472, AG035117, HL111111, GM120484 (Bethesda, MD). Drs. Patel and Ely received support for article research from the NIH. Ms. Klein's institution received funding from Hill Rom Co. Dr. Naidech received support for article research from the Agency for Healthcare Research and Quality (K18 HS023437). Dr. Pun received funding from the Society of Critical Care Medicine, the American Association of Critical Care Medicine, and the France Foundation to provide continuing education. Dr. John disclosed other support from CSL Behring (speaker). Dr. Pandharipande's institution received funding from Hospira. Dr. Ely's institution received funding from NIH and VA funding, and he received funding from Orion Laboratories, Abbott Laboratories, and Pfizer. Dr. Pandharipande has received a research grant from Hospira Inc, in collaboration with the NIH. Dr. Ely has conducted Continuing Medical Education activities sponsored by Abbott, Hospira, and Orion. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: wes.ely@vanderbilt.edu Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
https://ift.tt/2wtfHGq
https://ift.tt/2wtfHGq
An Academic Relative Value Unit System for Incentivizing the Academic Productivity of Surgery Faculty Members
Objective: The objective of this study was to evaluate a new academic relative-value unit (aRVU) scoring system linked to faculty compensation and analyze its association with overall departmental academic productivity. Summary Background Data: Faculty are often not incentivized or financially compensated for educational and research activities crucial to the academic mission. Methods: We launched an online, self-reporting aRVU system in 2015 to document and incentivize the academic productivity of our faculty. The system captured 65 specific weighted scores in 5 major categories of research, education, innovation, academic service, and peer review activities. The aRVU scores were rank-aggregated annually, and bonuses were distributed to faculty members in 3 tiers: top 10%, top third, and top half. We compared pre-aRVU (academic year 2015) to post-aRVU (academic year 2017) departmental achievement metrics. Results: Since 2015, annual aRVU bonuses totaling $493,900 were awarded to 59 faculty members (58% of eligible department faculty). Implementing aRVUs was associated with significant increases in several key departmental academic achievement metrics: presentations (579 to 862; P = 0.02; 49% increase), publications (390 to 446; P = 0.02; 14%), total research funding ($4.6 M to $8.4 M; Phttps://ift.tt/2BaAwvP
President’s Symposia Registrants are now AGA Members
We held two President's Symposia this year - Anne Bronikowski's Quantitative Genetics in the Wild and Rosemary Gillespie's Origins of Adaptive Radiations. The programs and abstracts for both the talks and posters are available for download from the AGA website https://www.theaga.org/
https://ift.tt/2wkV5zW
https://ift.tt/2wkV5zW
A Computational Conundrum: “What is a Computer?” A Historical Overview
Abstract
This introduction begins by posing the question that this Special Issue addresses and briefly considers historical precedents and why the issue is important. The discussion then moves on to the consideration of important milestones in the history of computing, up until the present time. A brief specification of the essential components of computational systems is then offered. The final section introduces the papers that are included in this volume.
https://ift.tt/2P2S9zw
Current status of projects for developing cancer-related clinical practice guidelines in Japan and recommendations for the future
Abstract
Background
The current status and adoption of cancer-related clinical practice guidelines in Japan has not been elucidated yet. The purpose of this study was to propose roles and suggestions to develop future cancer-related clinical guidelines.
Methods
A questionnaire consisting of four domains with a total of 17 questions was developed. We distributed the questionnaire to 28 specific academic organizations in Japan which have developed any cancer-related clinical practice guidelines and which were funded by the Ministry of Health, Labor, and Welfare.
Results
Most organizations have investigated nationwide dissemination and adoption of clinical practice guidelines. The rate of adoption in clinical practice was estimated at approximately ≥ 70%. However, organizations with smaller budgets reported surveying approximately 60% of the time, whereas the ones with larger budgets reported approximately 100% success in surveying about their guidelines. The presidents of the organizations agreed that a new organization operated directly by the national government was necessary.
Conclusion
In Japan, to develop cancer-related clinical practice guidelines, a study of clinical validation is necessary. Sufficient funds must be available to support the project to maintain and revise the guidelines. Furthermore, legal and ethical issues should be solved before establishing any registry system.
https://ift.tt/2BKwMkW
Genetic Incorporation of Biosynthesized L-dihydroxyphenylalanine (DOPA) and Its Application to Protein Conjugation
https://ift.tt/2Ne94i5
Complete and Partial Aortic Occlusion for the Treatment of Hemorrhagic Shock in Swine
Here, we present a protocol demonstrating a hemorrhagic shock model in swine that uses aortic occlusion as a bridge to definitive care in trauma. This model has application in testing a wide range of surgical and pharmacological therapeutic strategies.
https://ift.tt/2MMmVzi
Hyaluronic-Acid Based Hydrogels for 3-Dimensional Culture of Patient-Derived Glioblastoma Cells
Here, we present a protocol for three-dimensional culture of patient-derived glioblastoma cells within orthogonally tunable biomaterials designed to mimic the brain matrix. This approach provides an in vitro, experimental platform that maintains many characteristics of in vivo glioblastoma cells typically lost in culture.
https://ift.tt/2Ne8X69
Hydrocodone Schedule Change Affected Post-Op Opioid Rx
FRIDAY, Aug. 24, 2018 -- Hydrocodone's change from schedule III to schedule II in 2014 was associated with an increase in the amount of opioids filled in the initial prescription after surgery, according to a study published online Aug. 22 in JAMA...
https://ift.tt/2MPydTn
Broader Scope of Practice Linked to Lower Rates of Burnout
FRIDAY, Aug. 24, 2018 -- Early-career family physicians who practice inpatient medicine or obstetrics have reduced odds of burnout, according to a study published in the May/June issue of the Annals of Family Medicine. Amanda K.H. Weidner, M.P.H.,...
https://ift.tt/2Px0Kfb
Generic Substitutes, Therapeutic Interchange Can Save Money
FRIDAY, Aug. 24, 2018 -- Promoting generic substitution and therapeutic interchange can save money compared with spending on brand-name combination medications, according to a study published in the Aug. 21 issue of the Journal of the American...
https://ift.tt/2wobWBQ
Breastfeeding Linked to Lower Risk of Stroke Post-Menopause
FRIDAY, Aug. 24, 2018 -- Breastfeeding is associated with a lower risk of stroke among older women, with a stronger correlation for longer duration of breastfeeding, according to a study published online Aug. 22 in the Journal of the American Heart...
https://ift.tt/2wobV0K
Living in Deprived Area Is Risk Factor for Cognitive Dysfunction
FRIDAY, Aug. 24, 2018 -- Area-level deprivation is an independent risk factor for cognitive dysfunction in older adults, according to a study published in the July issue of the Journal of the American Geriatrics Society. Adrian McCann, Ph.D., from...
https://ift.tt/2PAPWfR
TNFi Not Linked to Increased Cancer Recurrence in RA Patients
FRIDAY, Aug. 24, 2018 -- For patients with rheumatoid arthritis (RA), treatment with tumor necrosis factor inhibitors (TNFi) is not associated with increased risk for cancer recurrence, according to a study published online Aug. 14 in the Annals of...
https://ift.tt/2P2QuKl
Education RE: Herd Immunity Can Up Readiness to Be Vaccinated
FRIDAY, Aug. 24, 2018 -- Educating adults about herd immunity can increase the proportion willing to be vaccinated for influenza, according to a study recently published in Vaccine. Jacqueline Logan, M.P.H., from the University of Minnesota in...
https://ift.tt/2PBOdqz
Decline in Hospital-Acquired Conditions Continues
FRIDAY, Aug. 24, 2018 -- The rate of hospital-acquired conditions (HACs) continued its decline from 2014 to 2016, according to the Agency for Healthcare Research and Quality (AHRQ) National Scorecard on Hospital-Acquired Conditions. For the 2014 to...
https://ift.tt/2wrz4zk
Cardiovascular Health Tied to Dementia Risk in Older Adults
FRIDAY, Aug. 24, 2018 -- For older adults, increased numbers of optimal cardiovascular health metrics are associated with reduced risk of dementia, according to a study published in the Aug. 21 issue of the Journal of the American Medical...
https://ift.tt/2OXqxvC
Lower Post-Op Mortality With Hip Fx Surgery on Day of Admission
FRIDAY, Aug. 24, 2018 -- Postoperative mortality is lower for medically stable older patients who undergo surgery for hip fracture on the day of admission or the following day, according to a study published in the Aug. 7 issue of CMAJ, the journal...
https://ift.tt/2ML5mQc
Association of tamoxifen resistance and lipid reprogramming in breast cancer
Abstract
Background
Tamoxifen treatment of estrogen receptor (ER)-positive breast cancer reduces mortality by 31%. However, over half of advanced ER-positive breast cancers are intrinsically resistant to tamoxifen and about 40% will acquire the resistance during the treatment.
Methods
In order to explore mechanisms underlying endocrine therapy resistance in breast cancer and to identify new therapeutic opportunities, we created tamoxifen-resistant breast cancer cell lines that represent the luminal A or the luminal B. Gene expression patterns revealed by RNA-sequencing in seven tamoxifen-resistant variants were compared with their isogenic parental cells. We further examined those transcriptomic alterations in a publicly available patient cohort.
Results
We show that tamoxifen resistance cannot simply be explained by altered expression of individual genes, common mechanism across all resistant variants, or the appearance of new fusion genes. Instead, the resistant cell lines shared altered gene expression patterns associated with cell cycle, protein modification and metabolism, especially with the cholesterol pathway. In the tamoxifen-resistant T-47D cell variants we observed a striking increase of neutral lipids in lipid droplets as well as an accumulation of free cholesterol in the lysosomes. Tamoxifen-resistant cells were also less prone to lysosomal membrane permeabilization (LMP) and not vulnerable to compounds targeting the lipid metabolism. However, the cells were sensitive to disulfiram, LCS-1, and dasatinib.
Conclusion
Altogether, our findings highlight a major role of LMP prevention in tamoxifen resistance, and suggest novel drug vulnerabilities associated with this phenotype.
https://ift.tt/2MPnybd
Association between cyclooxygenase-2 ( COX-2 ) 8473 T > C polymorphism and cancer risk: a meta-analysis and trial sequential analysis
Abstract
Background
Numerous studies have investigated the relationship between COX-2 8473 T > C polymorphism and cancer susceptibility, however, the results remain controversial. Therefore, we carried out the present meta-analysis to obtain a more accurate assessment of this potential association.
Methods
In this meta-analysis, 79 case-control studies were included with a total of 38,634 cases and 55,206 controls. We searched all relevant articles published in PubMed, EMBASE, OVID, Web of Science, CNKI and Wanfang Data, till September 29, 2017. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of the association. We performed subgroup analysis according to ethnicity, source of controls, genotyping method and cancer type. Moreover, Trial sequential analysis (TSA) was implemented to decrease the risk of type I error and estimate whether the current evidence of the results was sufficient and conclusive.
Results
Overall, our results indicated that 8473 T > C polymorphism was not associated with cancer susceptibility. However, stratified analysis showed that the polymorphism was associated with a statistically significant decreased risk for nasopharyngeal cancer and bladder cancer, but an increased risk for esophageal cancer and skin cancer. Interestingly, TSA demonstrated that the evidence of the result was sufficient in this study.
Conclusion
No significant association between COX-2 8473 T > C polymorphism and cancer risk was detected.
https://ift.tt/2P2PoOJ
Survival and prognostic factors in conventional central chondrosarcoma
Abstract
Background
Chondrosarcoma is the second most frequent primary malignant bone tumor. Treatment is mainly based on surgery. In general, wide resection is advocated at least in G2 and G3 tumors. But which margins should be achieved? Does localization as for example in the pelvis have a higher impact on survival than surgical margins themselves?
Methods
From 1982 to 2014, 87 consecutive patients were treated by resection. The margin was defined as R0 (wide resection), R1 (marginal resection) or, R2 if the tumor was left intentionally. All patients were followed for evidence of local recurrence or distant metastasis. Overall and recurrence-free survival were calculated, significance analysis was performed.
Results
In 54 (62%) cases a R0 resection, in 31 (36%) a R1 and in 2 (2%) patients a R2-resection was achieved. Histology proved to be G1 in 37 patients (43%), G2 in 41 (47%) and G3 in 9 cases (10%). 5-year local recurrence-free survival (LRFS) was 75%. Local recurrence-free survival showed a significant association with the margin status and the localization of the tumor with pelvic lesions doing worst. Metastatic disease was initially seen in 4 patients (4.6%), 19 others developed metastatic disease during follow-up. Overall survival of the entire group at 5 and 10 years were 79 and 75%, respectively. The quality of surgical margins and the presence of local recurrence did not influence overall survival in a multivariate analysis. Pelvic lesions had a worse prognosis as did higher grades of the tumor, metastatic disease and age.
Conclusions
The mainstay of therapy in Chondrosarcoma remains surgery. Risk factors as grading, metastatic disease, age and location significantly influence overall survival. Margin status (R0 vs. R1) did influence local recurrence-free survival but not overall survival. Chondrosarcomas of the pelvis have a higher risk of local recurrence and should be treated more aggressively.
https://ift.tt/2MzmoBy
Plate-based Large-scale Cultivation of Caenorhabditis elegans: Sample Preparation for the Study of Metabolic Alterations in Diabetes
This protocol describes a method for the large-scale cultivation of Caenorhabditis elegans on solid media. As an alternative to liquid culture, this protocol allows obtaining parameters of different scales under plate-based cultivation. This increases the comparability of results by omitting the morphological and metabolic differences between liquid and solid media culture.
https://ift.tt/2P0EERa
In Vitro Canine Neutrophil Extracellular Trap Formation: Dynamic and Quantitative Analysis by Fluorescence Microscopy
https://ift.tt/2Mt7psR
Medical billing company works to create jobs in US
Fellow Health Partners strategically grew their business after listening to the majority of healthcare staff, who said they'd prefer a U.S. based billing manager
https://ift.tt/2w8Rl5m
Webinar: How can prehospital providers quickly identify and treat sepsis?
Learn how you can quickly assess and treat patients with sepsis as an EMS provider
https://ift.tt/2BGtChY
New Research From Psychological Science
Read about the latest findings published in Psychological Science:
How Endogenous Crowd Formation Undermines the Wisdom of the Crowd in Online Ratings
Gaël Le Mens, Balázs Kovács, Judith Avrahami, and Yaakov Kareev
People often rely on ratings from online recommendation platforms before making decisions about purchases or other kinds of consumption. These ratings typically are averaged and accordingly are thought to reflect the wisdom-of-the-crowd phenomenon and thus provide unbiased quality estimates. But what if the way the crowd forms biases the average ratings? Le Mens and colleagues analyzed more than 80 million online ratings and found that items with more ratings tend to attract more additional ratings than items with fewer ratings. This asymmetry indicates an endogenous formation of the crowd that therefore generates a systematic bias. The authors created a model that describes the endogenous formation of crowds and how it might affect ratings and showed that average ratings are negatively biased, especially when average ratings are based on few ratings. Data from an experiment in which participants were presented with ratings from different types of crowds supported the model. Thus, experimental data and data from real online product ratings support the hypothesis that the crowd that rates online products is formed endogenously, provoking a systematic negative bias that penalizes items with few ratings and favors items with many ratings.
Increasing the Similarity of Lineup Fillers to the Suspect Improves the Applied Value of Lineups Without Improving Memory Performance: Commentary on Colloff, Wade, and Strange (2016)
Andrew M. Smith, Gary L. Wells, Laura Smalarz, and James Michael Lampinen
In this commentary, Smith and colleagues reanalyze data from Colloff, Wade, and Strange (2016). Colloff and colleagues suggested that the presence of similar-looking individuals in a lineup improved witnesses' memory performance by helping them determine which features were relevant for the identification, as predicted by the diagnostic-feature-detection theory. Despite agreeing with Colloff et al. that lineups with similar-looking individuals produce better outcomes in the legal system than so-called "unfair" lineups, in which a suspect stands out, Smith et al. argue that high-similarity fillers (similar-looking innocent individuals in the lineup) actually worsen memory performance and that Colloff et al. used the wrong signal detection theory (SDT) model to fit to their data. Smith et al. suggest that, instead of diagnostic-feature detection, differential-filler siphoning occurs in high-similarity lineups. That is, in a lineup with similar-looking individuals, the innocents attract some of the false identifications that in a lineup with very dissimilar individuals would occur only for the innocents who shared most distinctive features with the guilty individual. Thus, high-similarity fillers influence only which innocent the witnesses confuse with the guilty but do not influence the ability to discriminate between the guilty and the innocent. Smith et al. also suggest that a simple SDT model is inadequate because lineup procedures imply both detection and identification, which can be better captured by a compound-SDT model, and that filler-identification rates must also be taken into account.
Filler-Siphoning Theory Does Not Predict the Effect of Lineup Fairness on the Ability to Discriminate Innocent From Guilty Suspects: Reply to Smith, Wells, Smalarz, and Lampinen (2018)
Melissa F. Colloff, Kimberley A. Wade, Deryn Strange, and John T. Wixted
In this reply to the commentary in which Smith et al. argue that lineups with similar-looking individuals do not increase correct suspect identification, present an alternative explanation—differential-filler siphoning–and suggest that Colloff et al. had fit their 2016 data to the wrong model, Colloff et al. compare differential-filler siphoning to a theory of response bias and show that although it is compatible with their 2016 results, it does not predict them. They say that differential-filler siphoning predicts a change in response criterion but not a change in the discrimination between the distributions of innocent and guilty suspects. Colloff et al. also provide data from an experiment in which they did not include innocent fillers therefore differential-filler siphoning could not have occurred. These new results replicate their 2016 findings, showing a shift in the distributions and, consequently, a change in the ability to discriminate between innocent and guilty individuals.
https://ift.tt/2o5ab8Z
Designing CAD/CAM Surgical Guides for Maxillary Reconstruction Using an In-house Approach
Methods for designing a computer-aided design/computer-aided manufacturing (CAD/CAM) surgical guide are shown. Cutting planes are separated, united, and thickened to easily visualize the necessary bone transfer. These designs can be three-dimensional printed and checked for accuracy.
https://ift.tt/2MxsGBI
Differentiation, Maintenance, and Analysis of Human Retinal Pigment Epithelium Cells: A Disease-in-a-dish Model for BEST1 Mutations
Here we present a protocol to differentiate retinal pigment epithelium (RPE) cells from human pluripotent stem cells bearing patient-derived mutations. The mutant cell lines may be used for functional analyses including immunoblotting, immunofluorescence, and patch clamp. This disease-in-a-dish approach circumvents the difficulty of obtaining native human RPE cells.
https://ift.tt/2OYJCh4
Validation of new transmission detector transmission factors for online dosimetry: an experimental study
Abstract
Background
The demand for dose verification during treatment has risen with the increasing use of intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) in modern radiation therapy. This study aims to validate the transmission factors of a new transmission detector, the Dolphin online monitoring system (IBA Dosimetry, Schwarzenbruck, Germany), for clinical use.
Methods
The transmission factors of the Dolphin detector were evaluated using 6 MV, 6 flattening filter free (FFF), 10 MV, and 10 FFF clinical beams from a TrueBeam STx linear accelerator system. Two-dimensional (2D) dose distributions were measured through portal dosimetry with and without Dolphin to derive the transmission factors. The measurements were performed using 10 IMRT and 10 VMAT treatment plans. The transmission factors were calculated using a non-negative least squares problem solver for the 2D dose matrix. Normalized plans were generated using the derived transmission factors. Patient-specific quality assurance with normalized plans was performed using portal dosimetry and an ArcCheck detector to verify the transmission factors. The gamma passing rates were calculated for the 2%/2 mm and 1%/1 mm criteria.
Results
The transmission factors for the 6 MV, 6 FFF, 10 MV, and 10 FFF beams, were 0.878, 0.824, 0.913, and 0.883, respectively. The average dose difference between the original plan without Dolphin and the normalized plan with Dolphin was less than 1.8% for all measurements. The mean passing rates of the gamma evaluation were 98.1 ± 2.1 and 82.9 ± 12.6 for the 2%/2 mm and 1%/1 mm criteria, respectively, for portal dosimetry of the original plan. In the case of the portal dosimetry of the normalized plan, the mean passing rates of the gamma evaluation were 97.2 ± 2.8 and 79.1 ± 14.8 for the 2%/2 mm and 1%/1 mm criteria, respectively.
Conclusions
The Dolphin detector can be used for online dosimetry when valid transmission factors are applied to the clinical plan.
https://ift.tt/2NfMRjV
Priority Ambulance awarded for EMS innovation, safety efforts
The American Ambulance Association named Priority Ambulance the national AMBY Award winner in two categories
https://ift.tt/2Mzw6Uz
ALDH1A3 upregulation and spontaneous metastasis formation is associated with acquired chemoresistance in colorectal cancer cells
Abstract
Background
Efficiency of colorectal carcinoma treatment by chemotherapy is diminished as the resistance develops over time in patients. The same holds true for 5-fluorouracil, the drug used in first line chemotherapy of colorectal carcinoma.
Methods
Chemoresistant derivative of HT-29 cells was prepared by long-term culturing in increasing concentration of 5-fluorouracil. Cells were characterized by viability assays, flow cytometry, gene expression arrays and kinetic imaging. Immunomagnetic separation was used for isolation of subpopulations positive for cancer stem cells-related surface markers. Aldehyde dehydrogenase expression was attenuated by siRNA. In vivo studies were performed on SCID/bg mice.
Results
The prepared chemoresistant cell line labeled as HT-29/EGFP/FUR is assigned with different morphology, decreased proliferation rate and 135-fold increased IC50 value for 5-fluorouracil in comparison to parental counterparts HT-29/EGFP. The capability of chemoresistant cells to form tumor xenografts, when injected subcutaneously into SCID/bg mice, was strongly compromised, however, they formed distant metastases in mouse lungs spontaneously. Derived cells preserved their resistance in vitro and in vivo even without the 5-fluorouracil selection pressure. More importantly, they were resistant to cisplatin, oxaliplatin and cyclophosphamide exhibiting high cross-resistance along with alterations in expression of cancer-stem cell markers such as CD133, CD166, CD24, CD26, CXCR4, CD271 and CD274. We also detected increased aldehyde dehydrogenase (ALDH) activity associated with overexpression of specific ALDH isoform 1A3. Its inhibition by siRNA approach partially sensitized cells to various agents, thus linking for the first time the ALDH1A3 and chemoresistance in colorectal cancer.
Conclusion
Our study demonstrated that acquired chemoresistance goes along with metastatic and migratory phenotype and can be accompanied with increased activity of aldehyde dehydrogenase. We describe here the valuable model to study molecular link between resistance to chemotherapy and metastatic dissemination.
https://ift.tt/2P49Hvm
Cancers, Vol. 10, Pages 287: RKIP: A Key Regulator in Tumor Metastasis Initiation and Resistance to Apoptosis: Therapeutic Targeting and Impact
Cancers, Vol. 10, Pages 287: RKIP: A Key Regulator in Tumor Metastasis Initiation and Resistance to Apoptosis: Therapeutic Targeting and Impact
Cancers doi: 10.3390/cancers10090287
Authors: Apostolos Zaravinos Benjamin Bonavida Ekaterini Chatzaki Stavroula Baritaki
RAF-kinase inhibitor protein (RKIP) is a well-established tumor suppressor that is frequently downregulated in a plethora of solid and hematological malignancies. RKIP exerts antimetastatic and pro-apoptotic properties in cancer cells, via modulation of signaling pathways and gene products involved in tumor survival and spread. Here we review the contribution of RKIP in the regulation of early metastatic steps such as epithelial–mesenchymal transition (EMT), migration, and invasion, as well as in tumor sensitivity to conventional therapeutics and immuno-mediated cytotoxicity. We further provide updated justification for targeting RKIP as a strategy to overcome tumor chemo/immuno-resistance and suppress metastasis, through the use of agents able to modulate RKIP expression in cancer cells.
https://ift.tt/2OX7mlC
Long-term remission in advanced stage hepatocellular carcinoma? A chance for cure?
Summary
Liver resection, transplantation, and local ablation are potential curative treatment options but can only be offered to patients with early stage hepatocellular carcinoma (HCC). Patients with macrovascular tumor invasion and extrahepatic metastases are candidates for palliative systemic therapies. Achieving radiological complete response can be associated with long-term remission and excellent outcome. However, despite recent advancements in the medical treatment of advanced stage HCC, complete remission with available systemic treatment options still remains a rare event. This review summarizes data on radiological complete response to systemic therapies and discusses issues that may complicate the goal of achieving cure in advanced stage HCC.
https://ift.tt/2o7mul2
No Therapeutic Effect of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Retreatment Despite T790M Disappearance: Case Report of 3 Cases
Background: T790M is a major cause of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance, but the clinical significance of T790M disappearance is unknown. Case Report: We report 3 cases of pulmonary adenocarcinoma which did not respond to EGFR-TKI retreatment even with T790M disappearance. T790M mutations were detected in the pleural effusions after the tumors had acquired EGFR-TKI resistance. T790M mutations disappeared from cancer cells in the pleural effusion after a break from the treatment drug and cytotoxic agent administration. However, no therapeutic effect was obtained despite EGFR-TKI reinitiation. Conclusions: Responsiveness to EGFR-TKI might not be restored in some cases, although the disappearance of T790M mutations is confirmed.
Chemotherapy 2018;63:198–202
https://ift.tt/2PCAf8b
Chemotherapy 2018;63:198–202
https://ift.tt/2PCAf8b
Expected Budget Impact and Health Outcomes of Expanded Use of Vagus Nerve Stimulation Therapy for Drug-Resistant Epilepsy
Abstract
Introduction
The objective was to estimate, from the perspective of a managed care organization in the United States, the budget impact and effect on health outcomes of expanded use of vagus nerve stimulation [VNS (VNS Therapy®)] among patients aged ≥ 12 years with drug-resistant epilepsy (DRE) with partial-onset seizures.
Methods
An Excel model was developed to compare the costs of continued anti-epileptic drug (AED) treatment with the costs of VNS plus AED treatment. The number of people eligible for VNS was estimated using published prevalence data and an estimate of the percentage of eligible patients currently without VNS. Costs included VNS device, placement, programming, and battery changes; adverse events associated with VNS (cough, voice alteration, device removal resulting from surgical site infection); AEDs; and seizure-related costs affected by seizure frequency, which affects resource utilization (i.e., hospitalizations, emergency department visits, neurologist visits). To estimate the potential savings with VNS due to a reduction in seizure frequency, the budget impact model uses the results of an underlying Markov model to estimate seizure-related costs by seizure frequency. Transitions occurred among four health states, defined by number of seizures per month (i.e., seizure-free, ≤ 1, > 1 to < 10, ≥ 10) on a 3-month cycle based on published clinical trials and registry data.
Results
VNS resulted in an estimated net cost savings, on average, over 5 years, due to the expected reduction in seizure frequency. The initial cost of the VNS device, placement, and programming was estimated to be offset 1.7 years after VNS device placement. Reductions in hospitalizations were the main contributor to the cost savings with VNS.
Conclusions
VNS is a proven intervention that offers a long-term solution for patients with DRE by reducing seizure frequency, which leads to lower resource utilization and lower costs.
Funding
LivaNova PLC.
https://ift.tt/2BR4TI6
How to transition from the apparatus to a power position
Our co-hosts answer an email from a listener asking for help in transitioning to a position of power from the fire truck
https://ift.tt/2MLffx7
Is Focused MRI Adequate for Treatment Decision-Making in Acute Traumatic Thoracic and Lumbar Spine Fractures seen on Whole spine CT?
Publication date: Available online 23 August 2018
Source: The Spine Journal
Author(s): Bharti Khurana, S. Mohammed Karim, Jay M. Zampini, Hamdi Jimale, Charles H. Cho, Mitchel B. Harris, Aaron D. Sodickson, Christopher M. Bono
Abstract
PURPOSE
To assess whether a focused MRI limited to the region of known acute traumatic thoracic or lumbar fracture(s) would miss any clinically significant injuries that would change patient management.
STUDY DESIGN/SETTING
Multi-center retrospective clinical study.
PATIENT SAMPLE
Adult patients with acute traumatic thoracic and/or lumbar spine fracture(s).
OUTCOME MEASURES
Pathology identified on MRI (ligamentous disruption, epidural hematoma, cord contusion) outside of the focused zone, an alteration in patient management, including surgical and nonsurgical, as a result of the identified pathology outside the focused zone.
METHODS
Records were reviewed for all adult trauma patients who presented to the emergency department between 2008 and 2016 with one or more fracture(s) of the thoracic and/or lumbar spine identified on CT and who underwent MRI of the entire thoracic and lumbar spine within 10 days. Exclusion criteria were patients with > 4 fractured levels, pathologic fractures, isolated transverse and/or spinous process fractures, prior vertebral augmentation, and prior thoracic or lumbar spine instrumentation. Patients with neurologic deficits or cervical spine fractures were also included. MRIs were reviewed independently by one spine surgeon and one musculoskeletal fellowship-trained emergency radiologist for posterior ligamentous complex (PLC) integrity, vertebral injury, epidural hematoma, and cord contusion. The surgeon also commented on the clinical significance of the pathology identified outside the focused zone. All cases in which pathology was identified outside of the focused zone (three levels above & below the fractures) were independently reviewed by a second spine surgeon to determine if the pathology was clinically significant and would alter the treatment plan.
RESULTS
In all, 126 patients with 216 fractures identified on CT were included, with a median age of 49 years old. There were 81 males (64%). Sixty-two (49%) patients had isolated thoracolumbar junction injuries and 36 (29%) had injuries limited to a single fractured level. Forty-seven (37%) patients were managed operatively. PLC injury was identified by both readers in 36 (29%) patients with a percent agreement of 96% and κ coefficient of 0.91 (95% CI 0.87 – 0.95). Both readers independently agreed that there was no pathology identified on the complete thoracic and lumbar spine MRIs outside the focused zone in 107 (85%) patients. Injury outside the focused zone was identified by at least one reader in 19 (15%) patients. None of the readers identified PLC injury, cord edema, or non-contiguous epidural hematoma outside the focused zone. Percent agreement for outside pathology between the two readers was 92% and κ coefficient of 0.60 (95% CI 0.48 – 0.72). The two spine surgeons independently agreed that none of the identified pathology outside of the focused zone altered management.
CONCLUSIONS
A focused MRI protocol of 3 levels above and below known thoracolumbar spine fractures would have missed radiological abnormality in 15% of patients. However, the pathology, such as vertebral body edema not appreciated on CT, was not clinically significant and did not alter patient care. Based on these findings, the investigators conclude that a focused protocol would decrease the imaging time while providing the information of the injured segment with minimal risk of missing any clinically significant injuries.
https://ift.tt/2P2LxRJ
Validation and reliability of the Abbreviated World Health Organization Quality of Life Instrument (WHOQOL-BREF) in the hospitalized trauma population
Publication date: Available online 23 August 2018
Source: Injury
Author(s): N. Kruithof, J.A. Haagsma, M. Karabatzakis, M.C. Cnossen, L. de Munter, C.L.P. van de Ree, M.A.C. de Jongh, S. Polinder
ABSTRACT
Introduction
While the number of trauma patients surviving their injury increase, it is important to measure Quality of Life (QoL). The Abbreviated World Health Organization Quality of Life (WHOQOL-BREF) questionnaire can be used to assess QoL. However, its psychometric properties in trauma patients are unknown and therefore, we aimed to investigate the validity and reliability of the WHOQOL-BREF for the hospitalized trauma population.
Methods
Data were derived from the Brabant Injury Outcome Surveillance. Floor and ceiling effects and missing values of the WHOQOL-BREF were examined. Confirmatory factor analysis (CFA) was performed to examine the underlying 4 dimensions (i.e. physical, psychological, social and environmental) of the questionnaire. Cronbach's alpha (CA) was calculated to determine internal consistency. In total, 42 hypotheses were formulated to determine construct validity and 6 hypotheses were created to determine discriminant validity. To determine construct validity, Spearman's correlations were calculated between the WHOQOL-BREF and the EuroQol-five-dimension-3-level questionnaire, the Health Utility Index Mark 2 and 3, the Hospital Anxiety and Depression Scale and the Impact of Event Scale. Discriminant validity between patients with minor injuries (i.e. Injury Severity Score (ISS)≤8) and moderate/severe injuries (i.e. ISS ≥ 9) was examined by conducting Mann-Whitney-U-tests.
Results
In total, 202 patients (median 63y) participated in this study with a median of 32 days (interquartile range 29-37) post-trauma. The WHOQOL-BREF showed no problematic floor and ceiling effects. The CFA revealed a moderate model fit. The domains showed good internal consistency, with the exception of the social domain. All individual items and domain scores of the WHOQOL-BREF showed nearly symmetrical distributions since mean scores were close to median scores, except of the 'general health' item. The highest percentage of missing values was found on the 'sexual activity' item (i.e. 19.3%). The WHOQOL-BREF showed moderate construct and discriminant validity since in both cases, 67% of the hypotheses were confirmed.
Conclusion
The present study provides support for using the WHOQOL-BREF for the hospitalized trauma population since the questionnaire appears to be valid and reliable. The WHOQOL-BREF can be used to assess QoL in a heterogeneous group of hospitalized trauma patients accurately.
Trail registration
ClinicalTrials.gov identifier: NCT02508675
https://ift.tt/2MONdRx
Non-halophilic endophytes associated to the euhalophyte Arthrocnemum macrostachyum and their plant growth promoting activity potential
Abstract
Numerous microbial taxa establish natural relations with plants, and especially endophytes can be relevant in the development and growth promotion of their host. In this work we explore the diversity of non-halophilic microorganisms inhabiting the endosphere of the halophyte Arthrocnemum macrostachyum.A total of 1,045 isolates were recovered using standard non-saline media, which clustered into 22 operational phylogenetic units (OPUs) including seven putative new species and thirteen OPUs not previously detected as endophytes. The more abundant isolates corresponded to close relatives of Kushneria indalinina/K. marisflavi, Providencia rettgeri, Pseudomonas zhaodongensis and Bacillus safensis, which made up to ∼ 62% of the total isolates. We also isolated OPUs not detected by the culture-independent approach reinforcing the need of culturing to reveal the microbial diversity associated to plants. Additionally, the plant growth promoting activity was evaluated by representative strains of the more abundant OPUs (total = 94 strains) including also some previously isolated halophiles from the same plants. Under both saline and non-saline conditions, some strains principally those affiliated to Paenibacillus borealis, Staphylococcus equorum, Salinicola halophilus and Marinococcus tarijensis, presented growth promoting activity in Arabidopsis thaliana, which was evaluated as an increment of weight and root length.https://ift.tt/2P3xiwi
Innovative training networks: Overview of the Marie Skłodowska-Curie PhD training model
Abstract
Doctoral training has changed in recent years with most PhDs now performed in structured programmes operated by university graduate schools. These schools generally superimpose a training framework onto the traditional research project to improve the education experience of the students and to prepare them for their careers. Often these are in the commercial sector, where the demand is high for graduates with relevant skills and training. The European Union promotes the development of transnational, training-focussed, PhD programmes called Innovative Training Networks (ITNs) through Marie Skłodowska-Curie Actions (MSCA). ITNs share many features of thematic PhD programmes, but they only recruit a single cohort of students, and they align with EU policy goals. These training networks are prestigious and very well-regarded within European academia. The authors of this article were participants in a yeast biotechnology ITN, YEASTCELL, which finished in 2017. Some interesting insights into the more and less successful aspects of the project arose during discussions at the final project workshop. The views of the participants are distilled here in a discussion of how an ITN could be structured to maximise the benefits for the three main stakeholders: students, supervisors, and industry partners.https://ift.tt/2MwKUTF
Alternative splicing in prostate cancer.
| Related Articles |
Alternative splicing in prostate cancer.
Nat Rev Clin Oncol. 2018 Aug 22;:
Authors: Paschalis A, Sharp A, Welti JC, Neeb A, Raj GV, Luo J, Plymate SR, de Bono JS
Abstract
Androgen receptor (AR) splice variants (AR-Vs) have been implicated in the development and progression of metastatic prostate cancer. AR-Vs are truncated isoforms of the AR, a subset of which lack a ligand-binding domain and remain constitutively active in the absence of circulating androgens, thus promoting cancer cell proliferation. Consequently, AR-Vs have been proposed to contribute not only to resistance to anti-androgen therapies but also to resistance to radiotherapy in patients receiving combination therapy by promoting DNA repair. AR-Vs, such as AR-V7, have been associated with unfavourable clinical outcomes in patients; however, attempts to specifically inhibit or prevent the formation of AR-Vs have, to date, been unsuccessful. Thus, novel therapeutic strategies are desperately needed to address the oncogenic effects of AR-Vs, which can drive lethal forms of prostate cancer. Disruption of alternative splicing through modulation of the spliceosome is one such potential therapeutic avenue; however, our understanding of the biology of the spliceosome and how it contributes to prostate cancer remains incomplete, as reflected in the dearth of spliceosome-targeted therapeutic agents. In this Review, the authors outline the current understanding of the role of the spliceosome in the progression of prostate cancer and explore the therapeutic utility of manipulating alternative splicing to improve patient care.
PMID: 30135575 [PubMed - as supplied by publisher]
https://ift.tt/2BQJmzg
Nanovaccine Incorporated with Hydroxychloroquine Enhances Antigen Cross-presentation and Promotes anti-Tumor Immune Responses.
Nanovaccine Incorporated with Hydroxychloroquine Enhances Antigen Cross-presentation and Promotes anti-Tumor Immune Responses.
ACS Appl Mater Interfaces. 2018 Aug 23;:
Authors: Liu J, Liu X, Han Y, Zhang J, Liu D, Ma G, Li C, Liu L, Kong D
Abstract
Induction of effective antigen-specific CD8+ T-cell responses is critical for cancer immunotherapy success. Hydroxychloroquine (HCQ) is a widely used classical antimalarial and antirheumatic drug. HCQ is also an endosomal membrane disrupting agent that can lead to vesicular swelling and membrane permeabilization, which likely facilitates the release of therapeutic agents from lysosomes into the cytoplasm. Here, we develop a minimalistic nanovaccine, which is comprised of poly (lactide-co-glycolide) acid (PLGA) nanoparticles encapsulating a physical mixture of ovalbumin (OVA, a model antigen) and HCQ (HCQ-OVA-PLGA NPs). We tested whether HCQ could spatiotemporally control the cytosolic delivery of antigens, enhance antigen processing and presentation via the MHC-I pathway, and thus generate a sufficient anti-tumor cytotoxic T-cell response. The results of in vitro experiments showed that HCQ-OVA-PLGA NPs significantly enhanced OVA escape from lysosomes into the cytoplasm within bone marrow-derived dendritic cells (BMDCs). We also observed that HCQ-OVA-PLGA NPs enhanced the expression level of MHC-I on dendritic cells (DCs) and improved cross-presentation of antigen, compared to Free OVA or OVA-PLGA NPs. Results of in vivo experiments confirmed that HCQ initiated Th1-type responses and strong CD8+ T-cell responses that induced tumor cell apoptosis. Moreover, vaccination of mice with HCQ-OVA-PLGA NPs effectively generated memory immune responses in vivo and prevented tumor progression. We conclude that co-encapsulation of HCQ with antigens in nanovaccines can boost antigen-specific antitumor immune responses, particularly through CD8+ T-cells, serving as a simple and effective platform for the treatment of tumors and infectious diseases.
PMID: 30136844 [PubMed - as supplied by publisher]
https://ift.tt/2MMxXVm
CD40L-adjuvanted DNA vaccine carrying EBV-LMP2 antigen enhances anti-tumor effect in NPC transplantation tumor animal.
| Related Articles |
CD40L-adjuvanted DNA vaccine carrying EBV-LMP2 antigen enhances anti-tumor effect in NPC transplantation tumor animal.
Cent Eur J Immunol. 2018;43(2):117-122
Authors: Lei L, Li J, Liu M, Hu X, Zhou Y, Yang S
Abstract
CD40L, a costimulatory molecule for dendritic cells (DCs) and B cells, can serve as an adjuvant for enhancing the specific immune response induced by DNA vaccine carrying tumor-associated antigens. In this study, we investigated the potential of CD40L as an adjuvant to enhance the anti-tumor effect mediated by a DNA vaccine based on the Epstein-Barr virus-latent membrane protein 2 (EBV-LMP2) antigen. The plasmids capable of expressing the fusion protein EBV-LMP2-CD40L were constructed. Expression vector pVAX1 and plasmid expressing the individual antigen EBV-LMP2 were used as control groups. These plasmids were used to immunize female BALB/c mice (4-6 weeks old) at days 0, 7 and 14. The results suggest that immunization with DNA vaccines carrying fusion gene EBV-LMP2-CD40L can induce specific immunity more effectively than the plasmid expression individual antigen EBV-LMP2. In order to evaluate the anti-tumor effect of this DNA vaccine, we constructed a tumor bearing mouse model. After immunization, the tumor bearing mouse model, DNA vaccination with EBV-LMP2-CD40L plasmid significantly inhibited tumor growth in the tumor bearing mouse model and enhanced the tumor inhibition rate. This study demonstrated that encoding the EBV-LMP2 tumor antigen within an EBV-LMP2-CD40L DNA vaccine generates an effective antitumor response against EBV tumor, which may be a promising method to improve the antitumor immunity of DNA vaccine.
PMID: 30135622 [PubMed]
https://ift.tt/2NhKXPT
Hapten-mediated recruitment of polyclonal antibodies to tumors engenders antitumor immunity.
| Related Articles |
Hapten-mediated recruitment of polyclonal antibodies to tumors engenders antitumor immunity.
Nat Commun. 2018 Aug 22;9(1):3348
Authors: Schrand B, Clark E, Levay A, Capote AR, Martinez O, Brenneman R, Castro I, Gilboa E
Abstract
Uptake of tumor antigens by tumor-infiltrating dendritic cells is limiting step in the induction of tumor immunity, which can be mediated through Fc receptor (FcR) triggering by antibody-coated tumor cells. Here we describe an approach to potentiate tumor immunity whereby hapten-specific polyclonal antibodies are recruited to tumors by coating tumor cells with the hapten. Vaccination of mice against dinitrophenol (DNP) followed by systemic administration of DNP targeted to tumors by conjugation to a VEGF or osteopontin aptamer elicits potent FcR dependent, T cell mediated, antitumor immunity. Recruitment of αGal-specific antibodies, the most abundant naturally occurring antibodies in human serum, inhibits tumor growth in mice treated with a VEGF aptamer-αGal hapten conjugate, and recruits antibodies from human serum to human tumor biopsies of distinct origin. Thus, treatment with αGal hapten conjugated to broad-spectrum tumor targeting ligands could enhance the susceptibility of a broad range of tumors to immune elimination.
PMID: 30135425 [PubMed - in process]
https://ift.tt/2MH1zDB
Fecal indicator bacteria and zoonotic pathogens in marine snow and California mussels (Mytilus californianus)
Abstract
Pollution of nearshore waters with disease-causing microorganisms impacts ecosystems health through illness and deaths in people and wildlife, as well as negative socioeconomic consequences of impaired marine resources. Insight on pathogen ecology in coastal habitats is crucial for accurately mitigating inputs and impacts of microbial pollution. Three objectives were addressed to (1) compare fecal pollution in proximity to (i) freshwater runoff, and (ii) endemic marine wildlife; (2) evaluate presence and magnitude of fecal microorganisms in marine snow and mussels; and (3) determine if pathogens in mussels and FIB levels in seawater or mussels are correlated. Sampling during the wet season, proximity to freshwater, and FIB levels in mussel homogenates (but not seawater) were associated with pathogen presence in mussels. Pathogens and FIB were enriched in aggregate-rich fractions, further supporting an important role of marine snow in pathogen transmission. The lack of association between FIB in surrounding waters and presence of pathogens in mussels calls into question current regulations for insuring safe seafood to consumers in the United States, and alternative monitoring approaches such as direct testing for select pathogens should be further evaluated.https://ift.tt/2OYaHkz
Expanding the spectrum of translocations in sclerosing epitheloid fibrosarcoma: a new case with EWSR1‐CREB3L3 fusion
Genes, Chromosomes and Cancer, Volume 0, Issue ja, -Not available-.
https://ift.tt/2LmwIqQ
Successful closure of a complicated duodenal ulcer perforation with an expandable esophageal stent
Asian Journal of Endoscopic Surgery, EarlyView.
https://ift.tt/2MOv9H1
5 tips to provide safe and effective ventilation
Assign someone to monitor the patient's airway visually and with capnography using these five tips
https://ift.tt/2NarCzW
5 tips to provide safe and effective ventilation
Assign someone to monitor the patient's airway visually and with capnography using these five tips
https://ift.tt/2LiCMAQ
Cancers, Vol. 10, Pages 286: Distinct 3D Structural Patterns of Lamin A/C Expression in Hodgkin and Reed-Sternberg Cells
Cancers, Vol. 10, Pages 286: Distinct 3D Structural Patterns of Lamin A/C Expression in Hodgkin and Reed-Sternberg Cells
Cancers doi: 10.3390/cancers10090286
Authors: Fabio Contu Aline Rangel-Pozzo Peter Trokajlo Landon Wark Ludger Klewes Nathalie A. Johnson Tina Petrogiannis-Haliotis John G. Gartner Yuval Garini Roberta Vanni Hans Knecht Sabine Mai
Classical Hodgkin’s lymphoma (cHL) is a B-Cell lymphoma comprised of mononuclear Hodgkin cells (H) and bi- to multi-nucleated Reed-Sternberg (RS) cells. Previous studies revealed that H and RS cells express lamin A/C, a component of the lamina of the nuclear matrix. Since no information was available about the three-dimensional (3D) expression patterns of lamin A/C in H and RS cells, we analyzed the 3D spatial organization of lamin in such cells, using 3D fluorescent microscopy. H and RS cells from cHL derived cell lines stained positive for lamin A/C, in contrast to peripheral blood lymphocytes (PBLs), in which the lamin A/C protein was not detected or weak, although its presence could be transiently increased with lymphocyte activation by lipopolysaccharide (LPS). Most importantly, in H and RS cells, the regular homogeneous and spherically shaped lamin A/C pattern, identified in activated lymphocytes, was absent. Instead, in H and RS cells, lamin staining showed internal lamin A/C structures, subdividing the nuclei into two or more smaller compartments. Analysis of pre-treatment cHL patients’ samples replicated the lamin patterns identified in cHL cell lines. We conclude that the investigation of lamin A/C protein could be a useful tool for understanding nuclear remodeling in cHL.
https://ift.tt/2wpZCkJ
Cryotherapy reduces muscle spasticity but does not affect proprioception in ischemic stroke: a randomized sham-controlled crossover study
Objective To evaluate the immediate effects of cryotherapy (using an ice pack) on ankle joint position sense (JPS) and the degree of spasticity following chronic hemiparetic stroke. Design We used a sham-controlled crossover design. Sixteen chronic hemiparetic patients were randomly assigned to two groups: 1) those who received cryotherapy followed by a control intervention 15 days later (cryotherapy [CT] group) and 2) those who received the control intervention followed by cryotherapy 15 days later (control intervention [CI] group). Ankle JPS was measured on the paretic side using a Biodex Multi-joint System 3 dynamometer before and after 20 min of either application on the calf muscles. Lower absolute error scores were calculated for data analyses and were used to determine JPS. The degree of spasticity of the plantar flexor muscles was scored according to the Modified Ashworth scale. Results Sixteen patients completed the crossover experiment; however, data analysis was successfully conducted in 15 participants. Cryotherapy reduced the degree of spasticity of the plantar flexor muscles without altering ankle JPS. Conclusion Cryotherapy (using an ice pack) may reduce plantar flexor spasticity without influencing proprioception. *Both authors contributed equally to this study. Corresponding Author: Thiago Luiz de Russo and Luccas Cavalcanti Garcia, Laboratório de Pesquisa em Fisioterapia Neurológica. Departamento de Fisioterapia. Universidade Federal de São Carlos – UFSCar. São Carlos, SP, Brazil. Rodovia Washington Luís, Km 235. Zip Code: 13565-905. Telephone: +551633519578. E-mail: thiagoluizrusso@gmail.com or russo@ufscar.br Author Disclosures: This study was supported by the São Paulo Research Foundation – FAPESP (grants: 2013/25805-1, 2014/25845-6 and 2017/13655-6) and the National Council for Scientific and Technological Development – CNPq (funding: 442972/2014-8). The authors have no conflicts of interest to declare. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2BIcrww
https://ift.tt/2BIcrww
Benefits of maxillary expansion for a patient with spinal muscular atrophy type 2
This case report involves a 10-year-old boy diagnosed with spinal muscular atrophy type 2 who underwent nighttime mechanical ventilation with bi-level positive airway pressure. The oral examination revealed restricted mouth opening, lip interposition, dental crowding and maxillary compression. After maxillary expansion the upper airway volume increased 18.6%; 13 episodes of airway infections (20 days of hospitalization) were recorded in the 2 years prior to the maxillary expansion and only 4 episodes (no hospital admissions) in the 2 subsequent years. In conclusion, maxillary expansion in children with systemic disease that involves respiratory impairment may, in some cases, provide functional and clinical improvements, increase upper airway airflows and possibly decrease the number of respiratory infections Correspondence: Pedro Diz Dios, Special Needs Unit, School of Medicine and Dentistry, Santiago de Compostela University, 15782 Santiago de Compostela, Spain. Fax: +34981562226, Telephone: +34881562026. e-mail: pedro.diz@usc.es Author Disclosures: Authors declare no competing interests. No funding or grants or equipment have been provided for the project from any source. There aren´t financial benefits to the authors. Details of this case report have not been previously presented. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2o4hZb3
https://ift.tt/2o4hZb3
Hypothesis testing in superiority, non-inferiority and equivalence clinical trials: Implications in Physical Medicine and Rehabilitation
Abstract: In medical research, it is important to be able to examine whether there is a significant difference between two samples. With this, establishing an appropriate hypothesis is a critical, basic step for correct interpretation of results in inferential statistical data analysis. It is important to note that the aim of hypothesis testing is not to "accept" or "reject" the null hypothesis but to gauge the likelihood that the observed difference is genuine if the null hypothesis is true. Traditionally, the null hypothesis assumes that there is no statistically significant difference between the two groups. As it has become more difficult to develop new treatments that are better than the standard of care. This review article summarizes and explains the methodology of the different types of clinical trials regarding the relevant basic statistical concepts and hypothesis testing. Corresponding Author: Dinesh Kumbhare, MD, PhD, FRCPC, FAAPMR, Department of Medicine, Division of Physical Medicine and Rehabilitation, University of Toronto, Toronto, Ontario, Canada. Email: dinesh.kumbhare@uhn.ca. Tel: 416-597-3422 x 4612 Funding Source: The authors received no funding for this work. Competing Interests of Authors: None declared Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2o3NUZ0
https://ift.tt/2o3NUZ0
Individually-matched etiologic studies: classical estimators made new again
Abstract
With greater access to regression-based methods for confounder control, the etiologic study with individual matching, analyzed by classical (calculator) methods, lost favor in recent decades. This design was costly, and the data sometimes mis-analyzed. Now, with Big Data, individual matching becomes an economical option. To many, however, conditional logistic regression, commonly used to estimate the incidence density ratio parameter, is somewhat of a black box whose output is not easily checked. An epidemiologist-statistician pair recently proposed a new estimator that is easily applied to data from individually-matched series with a 2:1 ratio (and no other confounding variables) using just a hand calculator or spreadsheet. Surprisingly—or possibly not—they overlooked classical estimators developed in earlier decades. This prompts me to re-introduce some of these, to highlight their considerable flexibility and ease of use, and to update them. Nowadays, for any matching ratio (M:1), the Maximum Likelihood result can be easily computed from data gathered under the matched design in two different ways, each using just the summary data. One is via any binomial regression program that allows offsets, applied to just M 'rows' of data. The other is by hand! The aim of this note is not to save on computation; instead, it is to make connections between classical and regression-based methods, to promote terminology that reflects the concepts and structure of the etiologic study, and to focus attention on what parameter is being estimated.
https://ift.tt/2P1Croi
Prognostic value of prehospital quick sequential organ failure assessment score among patients with suspected infection
Objective After the third international consensus on sepsis released its new definitions, the prognostic value of quick sequential organ failure assessment (qSOFA) score has been confirmed in the emergency department. However, its validity in the prehospital setting remains unknown. The objective of the study was to assess its accuracy for prehospital patients cared by emergency physician-staffed ambulances (services mobiles d'urgence et de réanimation SMUR). Patients and methods This was a prospective observational multicenter cohort study (N=6). All consecutive patients with prehospital clinical suspicion of infection by the emergency physician of the SMUR emergency medical service were included. Components of qSOFA were collected, and the patients were followed until hospital discharge. The primary end point was in-hospital mortality, censored at 28 days. Secondary end points included ICU admission longer than 72 h and a composite of 'death or ICU stay more than 72 h'. Results We screened 342 patients and included 332 in the analysis. Their mean age was 73 years, 159 (48%) were women, and the most common site of infection was respiratory (73% of cases). qSOFA was at least 2 in 133 (40%) patients. The overall in-hospital mortality was 27%: 41% in patients with qSOFA of at least 2 versus 18% for qSOFA less than 2 (absolute difference 23%; 95% confidence interval: 13–33%, P
https://ift.tt/2o6wYBe
https://ift.tt/2o6wYBe
Effects of the selective chymase inhibitor TEI‐F00806 on the intrarenal renin–angiotensin system in salt‐treated angiotensin I‐infused hypertensive mice
Experimental Physiology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2LmqTtu
Microsurgical reconstruction using the middle temporal vein: a case report
ANZ Journal of Surgery, EarlyView.
https://ift.tt/2wvb0vN
Diagnosing phyllodes tumours of the breast: how successful are our current preoperative assessment modalities?
ANZ Journal of Surgery, EarlyView.
https://ift.tt/2PzxnZq
Bilateral breast cancers in an Asian population, and a comparison between synchronous and metachronous tumours
ANZ Journal of Surgery, EarlyView.
https://ift.tt/2wvaQVd
High risk re‐do sternotomy and repair of aortic root false aneurysm and obstructed innominate branch of Dacron graft
ANZ Journal of Surgery, EarlyView.
https://ift.tt/2PvJjeZ
Preliminary biomechanical results of a novel pin configuration for external fixation of vertical shear pelvic fractures
ANZ Journal of Surgery, EarlyView.
https://ift.tt/2wm9xrf
Self‐Assembled Fluorescent Organic Nanomaterials for Biomedical Imaging
Advanced Healthcare Materials, EarlyView.
https://ift.tt/2o7Y9M8
Biosensors: 3D‐Ridge Stocked Layers of Nitrogen‐Doped Mesoporous Carbon Nanosheets for Ultrasensitive Monitoring of Dopamine Released from PC12 Cells under K+ Stimulation (Adv. Healthcare Mater. 16/2018)
Advanced Healthcare Materials, Volume 7, Issue 16, August 22, 2018.
https://ift.tt/2BDGgyl
Efficient Perovskite Solar Cells Fabricated Through CsCl‐Enhanced PbI2 Precursor via Sequential Deposition
Advanced Materials, EarlyView.
https://ift.tt/2o3Fml0
Atomic Interlamellar Ion Path in High Sulfur Content Lithium‐Montmorillonite Host Enables High‐Rate and Stable Lithium–Sulfur Battery
Advanced Materials, EarlyView.
https://ift.tt/2BGTNFc
A New Facile Route to Flexible and Semi‐Transparent Electrodes Based on Water Exfoliated Graphene and their Single‐Electrode Triboelectric Nanogenerator
Advanced Materials, EarlyView.
https://ift.tt/2P2u2RM
A Translucent Nanocomposite with Liquid Inclusions of a Responsive Nanoparticle Dispersion
Advanced Materials, EarlyView.
https://ift.tt/2o4AtrZ
Quadruple Junction Polymer Solar Cells with Four Complementary Absorber Layers
Advanced Materials, EarlyView.
https://ift.tt/2BID7NP
High‐Performance Next‐Generation Perovskite Nanocrystal Scintillator for Nondestructive X‐Ray Imaging
Advanced Materials, EarlyView.
https://ift.tt/2o6R5zt
FA0.88Cs0.12PbI3−x(PF6)x Interlayer Formed by Ion Exchange Reaction between Perovskite and Hole Transporting Layer for Improving Photovoltaic Performance and Stability
Advanced Materials, EarlyView.
https://ift.tt/2BHXRVP
Picosecond Capture of Photoexcited Electrons Improves Photovoltaic Conversion in MAPbI3:C70‐Doped Planar and Mesoporous Solar Cells
Advanced Materials, EarlyView.
https://ift.tt/2o6QUnN
Digitally Tunable Microfluidic Bioprinting of Multilayered Cannular Tissues
Advanced Materials, EarlyView.
https://ift.tt/2BID6tf
Cancer Care Using an Array of Radiolabelled Small Molecules
BioEssays, EarlyView.
https://ift.tt/2w6zyLQ
Hypotheses “R” Us − But What's a Hypothesis Anyway?
BioEssays, Volume 40, Issue 9, September 2018.
https://ift.tt/2w6zj3o
Serum Angiopoietin‐2 Predicts Mortality and Kidney Outcomes in Decompensated Cirrhosis
Hepatology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2waCkQh
mTOR signaling in X/A‐like cells contributes to lipid homeostasis in mice
Hepatology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2LnT9fj
Effects of endotoxin on type 3 inositol 1,4,5‐trisphosphate receptor in human cholangiocytes
Hepatology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2wgQGir
Incomplete differentiation of engrafted bone marrow endothelial progenitor cells initiates hepatic fibrosis in the rat
Hepatology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2LnT1fP
Tracking Fenestrae Dynamics in Live Murine Liver Sinusoidal Endothelial Cells
Hepatology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2w6xq6O
HBV core variants, liver fibrosis and hepatocellular carcinoma
Hepatology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2LnSSch
Isolation, Purification of DPAn‐3 from the Seal Oil Ethyl Ester
European Journal of Lipid Science and Technology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2w9jh94
Extraction and process optimization of bael fruit pectin
Food Science &Nutrition, EarlyView.
https://ift.tt/2LnSIlb
RELT negatively regulates the early phase of the T cell response in mice
European Journal of Immunology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2OZmLSM
Local anaesthesia for endovascular repair of ruptured abdominal aortic aneurysm
BJS, EarlyView.
https://ift.tt/2LlUP9q
Radiological characteristics and predisposing factors of venous tumor thrombus in pelvic osteosarcoma: A mono‐institutional retrospective study of 115 cases
Cancer Medicine, EarlyView.
https://ift.tt/2w6vdbw
Evaluation of Pharmacokinetics and Pharmacodynamics of BI 425809, a Novel GlyT1 Inhibitor: Translational Studies
Clinical and Translational Science, EarlyView.
https://ift.tt/2Lj7cTC
Cancers, Vol. 10, Pages 285: Co-Expression of the Epstein-Barr Virus-Encoded Latent Membrane Proteins and the Pathogenesis of Classic Hodgkin Lymphoma
Cancers, Vol. 10, Pages 285: Co-Expression of the Epstein-Barr Virus-Encoded Latent Membrane Proteins and the Pathogenesis of Classic Hodgkin Lymphoma
Cancers doi: 10.3390/cancers10090285
Authors: Katerina Vrzalikova Maha Ibrahim Eszter Nagy Martina Vockerodt Tracey Perry Wenbin Wei Ciaran Woodman Paul Murray
The Epstein-Barr virus (EBV) is present in the tumour cells of a subset of patients with classic Hodgkin lymphoma (cHL), yet the contribution of the virus to the pathogenesis of these tumours remains only poorly understood. The EBV genome in virus-associated cHL expresses a limited subset of genes, restricted to the non-coding Epstein-Barr virus-encoded RNAs (EBERs) and viral miRNA, as well as only three virus proteins; the Epstein-Barr virus nuclear antigen-1 (EBNA1), and the two latent membrane proteins, known as LMP1 and LMP2, the latter of which has two isoforms, LMP2A and LMP2B. LMP1 and LMP2A are of particular interest because they are co-expressed in tumour cells and can activate cellular signalling pathways, driving aberrant cellular transcription in infected B cells to promote lymphomagenesis. This article seeks to bring together the results of recent studies of the latent membrane proteins in different B cell systems, including experiments in animal models as well as a re-analysis of our own transcriptional data. In doing so, we summarise the potentially co-operative and antagonistic effects of the LMPs that are relevant to B cell lymphomagenesis.
https://ift.tt/2PzqgjG
Neoadjuvant chemotherapy with docetaxel, nedaplatin and fluorouracil for resectable esophageal cancer: A phase II study
Cancer Science, Volume 0, Issue ja, -Not available-.
https://ift.tt/2whvQ1e
Wnt signaling in human and mouse breast cancer: focusing on Wnt ligands, receptors and antagonists
Cancer Science, Volume 0, Issue ja, -Not available-.
https://ift.tt/2PzZzLZ
OLFM4, LY6D and S100A7 as potent markers for distant metastasis in estrogen receptor‐positive breast carcinoma
Cancer Science, Volume 0, Issue ja, -Not available-.
https://ift.tt/2wrx62e
Effect of the phase of force production on corticomuscular coherence with agonist and antagonist muscles
European Journal of Neuroscience, Volume 0, Issue ja, -Not available-.
https://ift.tt/2PxqGah
Does Surgical Margin Impact Recurrence in Noninvasive Intraductal Papillary Mucinous Neoplasms?: A Multi-institutional Study
Objective: The relevance of margin positivity on recurrence after resection of intraductal papillary mucinous neoplasms (IPMNs) is poorly defined and represents one reason controversy remains regarding optimal surveillance recommendations. Methods: Patients undergoing surgery for noninvasive IPMN at 8 academic medical centers from the Central Pancreas Consortium were analyzed. A positive margin was defined as presence of IPMN or pancreatic intraepithelial neoplasia. Results: Five hundred two patients underwent surgery for IPMN; 330 (66%) did not have invasive cancer on final pathology and form the study cohort. Of these, 20% harbored high grade dysplasia. A positive margin was found in 20% of cases and was associated with multifocal disease (P = 0.02). The majority of positive margins were associated with low grade dysplasia. At a median follow-up of 36 months, 34 (10.3%) patients recurred, with 6.7% developing recurrent cystic disease and 3.6% developing invasive cancer. On multivariate analysis, margin positivity was not associated with recurrence of either IPMN or invasive cancer (P > 0.05). No association between margin status and development of recurrence at the margin was found. Only 6% of recurrences developed at the resection margin and median time to recurrence was 22 months. Of note, 18% of recurrences occurred > 5 years following surgery. Conclusion: Margin positivity after resection for noninvasive IPMNs is primarily due to low grade dysplasia and is not associated with developing recurrence in the remnant pancreas or at the resection margin. Long-term surveillance is required for all patients, as a significant number of recurrences developed over 5 years after the index operation.https://ift.tt/2B9Jids
Evaluation of 8 melanocytic and neural crest‐associated markers in a well‐characterized series of 124 malignant peripheral nerve sheath tumors (MPNST): useful to distinguish MPNST from melanoma?
Histopathology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2BIuvGT
Oxygen Reserve Index: Validation of a New Variable
BACKGROUND: Pulse oximetry–derived oxygen saturation is typically >97% in normoxia and hyperoxia, limiting its clinical use. The new Oxygen Reserve Index (ORi), a relative indicator of the partial pressure of oxygen dissolved in arterial blood (PaO2) in the range of 100–200 mm Hg, may allow additional monitoring of oxygen status. METHODS: In this prospective validation intervention study, 20 healthy volunteers were breathing standardized oxygen concentrations ranging from mild hypoxia (fraction of inspired oxygen = 0.14) to hyperoxia (fraction of inspired oxygen = 1.0) via a tight-fitting face mask. ORi was measured noninvasively by multiwavelength pulse co-oximetry using 2 finger sensors. These ORi values (unitless scale, 0.00–1.00) were compared with measured PaO2 values. Repeated-measurements correlation analysis was performed to assess the ORi/PaO2 relationship. ORi trending ability was assessed using a 4-quadrant plot. The area under the receiver operating characteristics curve was calculated to assess the prediction of hypoxia (low-ranged PaO2,
https://ift.tt/2PDH0qe
https://ift.tt/2PDH0qe
Dexmedetomidine Pharmacokinetics and a New Dosing Paradigm in Infants Supported With Cardiopulmonary Bypass
BACKGROUND: Dexmedetomidine is increasingly used off-label in infants and children with cardiac disease during cardiopulmonary bypass (CPB) and in the postoperative period. Despite its frequent use, optimal dosing of dexmedetomidine in the setting of CPB has not been identified but is expected to differ from dosing in those not supported with CPB. This study had the following aims: (1) characterize the effect of CPB on dexmedetomidine clearance (CL) and volume of distribution (V) in infants and young children; (2) characterize tolerance and sedation in patients receiving dexmedetomidine; and (3) identify preliminary dosing recommendations for infants and children undergoing CPB. We hypothesized that CL would decrease, and V would increase during CPB compared to pre- or post-CPB states. METHODS: Open-label, single-center, opportunistic pharmacokinetics (PK) and safety study of dexmedetomidine in patients ≤36 months of age administered dexmedetomidine per standard of care via continuous infusion. We analyzed dexmedetomidine PK data using standard nonlinear mixed effects modeling with NONMEM software. We compared model-estimated PK parameters to those from historical patients receiving dexmedetomidine before anesthesia for urologic, lower abdominal, or plastic surgery; after low-risk cardiac or craniofacial surgery; or during bronchoscopy or nuclear magnetic resonance imaging. We investigated the influence of CPB-related factors on PK estimates and used the final model to simulate dosing recommendations, targeting a plasma concentration previously associated with safety and efficacy (0.6 ng/mL). We used the Wilcoxon rank sum test to evaluate differences in dexmedetomidine exposure between infants with hypotension or bradycardia and those who did not develop these adverse events. RESULTS: We collected 213 dexmedetomidine plasma samples from 18 patients. Patients had a median (range) age of 3.3 months (0.1–34.0 months) and underwent CPB for 161 minutes (63–394 minutes). We estimated a CL of 13.4 L/h/70 kg (95% confidence interval, 2.6–24.2 L/h/70 kg) during CPB, compared to 42.1 L/h/70 kg (95% confidence interval, 38.7–45.8 L/h/70 kg) in the historical patients. No specific CPB-related factor had a statistically significant effect on PK. A loading dose of 0.7 µg/kg over 10 minutes before CPB, followed by maintenance infusions through CPB of 0.2 or 0.25 µg/kg/h in infants with postmenstrual ages of 42 or 92 weeks, respectively, maintained targeted concentrations. We identified no association between dexmedetomidine exposure and selected adverse events (P = .13). CONCLUSIONS: CPB is associated with lower CL during CPB in infants and young children compared to those not undergoing CPB. Further study should more closely investigate CPB-related factors that may influence CL. Accepted for publication June 27, 2018. Funding: K.O.Z. is funded by grant KL2TR001115-03 from the Duke Clinical and Translational Science Awards and K23 grant HD091398 from the National Institutes of Health (NIH). H.W. received salary support from grant K23HD0785891 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) for completion of this project. M.L. receives support from the US government for work in neonatal clinical pharmacology, clinical trials, and cohort studies including Food and Drug Administration (FDA) R01 FD005101, Prinicipal Investigator (PI) M.L.; National Heart, Lung and Blood Institute (NHLBI) R34 HL124038, PI M.L.; the NIH Office of the Director, Environmental Influences on Child Health Outcomes (ECHO) Coordinating Center U2C OD023375, PI P.B.S., Duke University School of Medicine; the NICHD Pediatric Trials Network Government Contract HHSN267200700051C, PI Daniel Benjamin Jr, Duke University School of Medicine; and as the satellite site PI for the NICHD Neonatal Research Network NICHD U10 HD040492, PI C. Michael Cotten, Duke University School of Medicine. R.G.G. receives salary support for research from the NIH training grants (5T32HD043029-13), NIH awards (HHSN 275201000003I, HHSN 272201300017I), and from the FDA (HHSF223201610082C). P.B.S. receives salary support for research from the NIH (NIH-1R21HD080606-01ª1) and the National Center for Advancing Translational Sciences of the NIH (UL1TR001117), the NICHD (HHSN275201000003I), and the FDA (1R18-FD005292-01). C.P.H. receives salary support for research from the National Center for Advancing Translational Sciences of the NIH (UL1TR001117) and the US government for his work in pediatric and neonatal clinical pharmacology (Government Contract HHSN267200700051C, PI: Daniel Benjamin Jr under the Best Pharmaceuticals for Children Act). M.C.-W. receives support for research from the NIH (1R01-HD076676-01A1), the National Institute of Allergy and Infectious Disease (HHSN272201500006I and HHSN272201300017I), the NICHD (HHSN275201000003I), the Biomedical Advanced Research and Development Authority (HHSO100201300009C), and industry for drug development in adults and children (https://ift.tt/2PAHZY8). K.M.W. receives support from the Pediatric Critical Care and Trauma Scientist Development Program (5K12HD047349) and the NICHD (1K23HD075891) for his work in pediatric clinical pharmacology. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to Kanecia O. Zimmerman, MD, MPH, Department of Pediatrics, Duke University School of Medicine, Box 3850, Durham, NC 27710. Address e-mail to Kanecia.obie@dm.duke.edu. © 2018 International Anesthesia Research Society
https://ift.tt/2wo5w5B
https://ift.tt/2wo5w5B
Εγγραφή σε:
Αναρτήσεις (Atom)
-
Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
-
heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
-
https://ift.tt/2MQ8Ai8
