Oseltamivir induced sinus bradycardia: an area of potential concern

Oseltamivir was approved for the prevention and treatment of influenza in 1999 by the USFDA (US Food and Drug Administration). The use of Oseltamivir is increasing rapidly all over the world, especially after the 2009 “Swine Flu” pandemic. Less data is published as far as the cardiovascular side effects of Oseltamivir are concerned, but it could be associated with some serious cardiovascular side effects. This study presented a case series of 5 cases suspected to be suffering from seasonal influenza H1N1 (“Swine Flu”), who developed sinus bradycardia while they were on Oseltamivir therapy

Lower Back Injuries in National Collegiate Athletic Association Football Players: A 5-Season Epidemiological Study

Background: Low back injuries are common in collegiate football players and can frequently lead to persistent pain, reinjuries, and time lost from participation. Purpose: To describe the epidemiology of back injuries in National Collegiate Athletic Association (NCAA) football players during the 2009/2010 through 2013/2014 academic years utilizing the NCAA Injury Surveillance Program (ISP) database. Study Design: Descriptive epidemiology study. Methods: A convenience sample of NCAA varsity football teams was utilized to determine the rates and patterns of back injuries as well as to generate national injury estimates. The rates and distribution of back injuries were identified within the context of mechanism of injury, injury chronicity, and time lost from sport. Injury rates were calculated as the number of injuries divided by the total number of athlete-exposures (AEs). Incidence rate ratios were calculated to compare the rates of injury between season, event type, mechanism of injury, injury chronicity, and time lost from sport. Results: Nationally, there were 267 low back injuries reported in the database. These were used to estimate 7076 back injuries over the 5-year period, approximately 82% of which were new injuries. The injuries occurred at a rate of 2.70 per 10,000 AEs. Overall, injuries were 3.12 times more likely to occur in competitions than in practices. Athletes were 4.67 times more likely to sustain a back injury during the preseason compared with the postseason but were 1.41 times more likely to sustain a low back injury during the preseason compared with the regular season. Both contact and noncontact were reported equally as the mechanism of injury (37.8% and 38.3%, respectively), and unspecified low back pain was the most common injury (64.2%). Only 1.6% of patients required surgery for their injury, and the majority of athletes (59.6%) returned to play within 24 hours. Conclusion: There was a relatively high rate of lumbar back injuries at the collegiate level (2.70/10,000 AEs), the majority of which were new injuries. About 18% of reported injuries were reinjuries. Although very few required surgery, a careful examination and work-up should be conducted to evaluate each injury. Regimented physical therapy and reconditioning programs are recommended to avert reinjuries.NCAAOpen access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Identification of publicly available data sources to inform the conduct of Health Technology Assessment in India

Background: Health technology assessment (HTA) provides a globally-accepted and structured approach to synthesising evidence for cost and clinical effectiveness alongside ethical and equity considerations to inform evidence-based priorities. India is one of the most recent countries to formally commit to institutionalising HTA as an integral component of the heath resource allocation decision-making process. The effective conduct of HTA depends on the availability of reliable data. Methods: We draw from our experience of collecting, synthesizing, and analysing health-related datasets in India and internationally, to highlight the complex requirements for undertaking HTA, and explore the availability of such data in India. We first outlined each of the core data components required for the conduct of HTA, and their availability in India, drawing attention to where data can be accessed, and different ways in which researchers can overcome the challenges of missing or low quality data. Results: We grouped data into the following categories: clinical efficacy; cost; epidemiology; quality of life; service use/consumption; and equity. We identified numerous large local data sources containing epidemiological information. There was a marked absence of other locally-collected data necessary for informing HTA, particularly data relating to cost, service use, and quality of life. Conclusions: The introduction of HTA into the health policy space in India provides an opportunity to comprehensively assess the availability and quality of health data capture across the country. While epidemiological information is routinely collected across India, other data inputs necessary for HTA are not readily available. This poses a significant bottleneck to the efficient generation and deployment of HTA into the health decision space. Overcoming these data gaps by strengthening the routine collection of comprehensive and verifiable health data will have important implications not only for embedding economic analyses into the priority setting process, but for strengthening the health system as a whole

Fibrinolytic protease production by new Streptomyces sp. DPUA 1576 from amazon lichens

Background Streptomyces sp. DPUA 1576 from Amazon lichens was studied to protease and fibrinolytic production. A 22 factorial experimental design was applied to optimize its protease enzyme production using two independent variables, namely soybean flour and glucose concentrations. Results The optimal conditions to obtain high protease production (83.42 U/mL) were 1.26% soybean flour and 1.23% glucose concentration. A polynomial model was fitted to correlate the relationship between the two variables and protease activity. In relation to fibrinolytic activity, the highest activity of 706.5 mm2 was obtained at 1.7% soybean flour and 1.0% glucose concentration, which was 33% higher than plasmin. Fibrinolytic production was not optimized in the studied conditions. Conclusions These results show that the optimization of the culture medium can enhance protease production, thus becoming a good process for further research. In addition, Streptomyces sp. DPUA 1576, isolated from Amazon lichens, might be a potential strain for fibrinolytic protease production.The authors thank CAPES (National Council for the Improvement of Higher Education) for the scholarship and CNPq/RENORBIO (National Counsel of Technological and Scientific Development, N. 55146/2010-3) and FACEPE (Fundacao de Amparo a Ciencia e Tecnologia do Estado de Pernambuco, 0158-2.12/11) for the financial support

Integration of copy number and transcriptomics provides risk stratification in prostate cancer: A discovery and validation cohort study.

BACKGROUND: Understanding the heterogeneous genotypes and phenotypes of prostate cancer is fundamental to improving the way we treat this disease. As yet, there are no validated descriptions of prostate cancer subgroups derived from integrated genomics linked with clinical outcome. METHODS: In a study of 482 tumour, benign and germline samples from 259 men with primary prostate cancer, we used integrative analysis of copy number alterations (CNA) and array transcriptomics to identify genomic loci that affect expression levels of mRNA in an expression quantitative trait loci (eQTL) approach, to stratify patients into subgroups that we then associated with future clinical behaviour, and compared with either CNA or transcriptomics alone. FINDINGS: We identified five separate patient subgroups with distinct genomic alterations and expression profiles based on 100 discriminating genes in our separate discovery and validation sets of 125 and 103 men. These subgroups were able to consistently predict biochemical relapse (p = 0.0017 and p = 0.016 respectively) and were further validated in a third cohort with long-term follow-up (p = 0.027). We show the relative contributions of gene expression and copy number data on phenotype, and demonstrate the improved power gained from integrative analyses. We confirm alterations in six genes previously associated with prostate cancer (MAP3K7, MELK, RCBTB2, ELAC2, TPD52, ZBTB4), and also identify 94 genes not previously linked to prostate cancer progression that would not have been detected using either transcript or copy number data alone. We confirm a number of previously published molecular changes associated with high risk disease, including MYC amplification, and NKX3-1, RB1 and PTEN deletions, as well as over-expression of PCA3 and AMACR, and loss of MSMB in tumour tissue. A subset of the 100 genes outperforms established clinical predictors of poor prognosis (PSA, Gleason score), as well as previously published gene signatures (p = 0.0001). We further show how our molecular profiles can be used for the early detection of aggressive cases in a clinical setting, and inform treatment decisions. INTERPRETATION: For the first time in prostate cancer this study demonstrates the importance of integrated genomic analyses incorporating both benign and tumour tissue data in identifying molecular alterations leading to the generation of robust gene sets that are predictive of clinical outcome in independent patient cohorts.Cambridge work was funded by a CRUK programme grant awarded to DEN; Swedish work and tissue collections were funded by grants from the Linne Centre for Breast and Prostate Cancer (CRISP, grant 70867901), Karolinska Institutet, the Swedish Research Council (K2010-70X-20430-04-3), and the Swedish Cancer Society (11-0287).This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.ebiom.2015.07.01

Integration of copy number and transcriptomics provides risk stratification in prostate cancer : a discovery and validation cohort study

Study data are deposited in NCBI GEO (unique identifier number GSE70770).Background : Understanding the heterogeneous genotypes and phenotypes of prostate cancer is fundamental to improving the way we treat this disease. As yet, there are no validated descriptions of prostate cancer subgroups derived from integrated genomics linked with clinical outcome. Methods : In a study of 482 tumour, benign and germline samples from 259 men with primary prostate cancer, we used integrative analysis of copy number alterations (CNA) and array transcriptomics to identify genomic loci that affect expression levels of mRNA in an expression quantitative trait loci (eQTL) approach, to stratify patients into subgroups that we then associated with future clinical behaviour, and compared with either CNA or transcriptomics alone. Findings : We identified five separate patient subgroups with distinct genomic alterations and expression profiles based on 100 discriminating genes in our separate discovery and validation sets of 125 and 103 men. These subgroups were able to consistently predict biochemical relapse (p = 0.0017 and p = 0.016 respectively) and were further validated in a third cohort with long-term follow-up (p = 0.027). We show the relative contributions of gene expression and copy number data on phenotype, and demonstrate the improved power gained from integrative analyses. We confirm alterations in six genes previously associated with prostate cancer ( MAP3K7, MELK, RCBTB2, ELAC2, TPD52, ZBTB4), and also identify 94 genes not previously linked to prostate cancer progression that would not have been detected using either transcript or copy number data alone. We confirm a number of previously published molecular changes associated with high risk disease, including MYC amplification, and NKX3-1, RB1 and PTEN deletions, as well as over-expression of PCA3 and AMACR, and loss of MSMB in tumour tissue. A subset of the 100 genes outperforms established clinical predictors of poor prognosis (PSA, Gleason score), as well as previously published gene signatures (p = 0.0001). We further show how our molecular profiles can be used for the early detection of aggressive cases in a clinical setting, and inform treatment decisions. Interpretation : For the first time in prostate cancer this study demonstrates the importance of integrated genomic analyses incorporating both benign and tumour tissue data in identifying molecular alterations leading to the generation of robust gene sets that are predictive of clinical outcome in independent patient cohorts.Publisher PDFPeer reviewe

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts