A randomised comparison evaluating changes in bone mineral density in advanced prostate cancer: luteinising hormone-releasing hormone agonists versus transdermal oestradiol

Background Luteinising hormone-releasing hormone agonists (LHRHa), used as androgen deprivation therapy (ADT) in prostate cancer (PCa) management, reduce serum oestradiol as well as testosterone, causing bone mineral density (BMD) loss. Transdermal oestradiol is a potential alternative to LHRHa. Objective To compare BMD change in men receiving either LHRHa or oestradiol patches (OP). Design, setting, and participants Men with locally advanced or metastatic PCa participating in the randomised UK Prostate Adenocarcinoma TransCutaneous Hormones (PATCH) trial (allocation ratio of 1:2 for LHRHa:OP, 2006–2011; 1:1, thereafter) were recruited into a BMD study (2006–2012). Dual-energy x-ray absorptiometry scans were performed at baseline, 1 yr, and 2 yr. Interventions LHRHa as per local practice, OP (FemSeven 100 μg/24 h patches). Outcome measurements and statistical analysis The primary outcome was 1-yr change in lumbar spine (LS) BMD from baseline compared between randomised arms using analysis of covariance. Results and limitations A total of 74 eligible men (LHRHa 28, OP 46) participated from seven centres. Baseline clinical characteristics and 3-mo castration rates (testosterone ≤1.7 nmol/l, LHRHa 96% [26 of 27], OP 96% [43 of 45]) were similar between arms. Mean 1-yr change in LS BMD was −0.021 g/cm3 for patients randomised to the LHRHa arm (mean percentage change −1.4%) and +0.069 g/cm3 for the OP arm (+6.0%; p < 0.001). Similar patterns were seen in hip and total body measurements. The largest difference between arms was at 2 yr for those remaining on allocated treatment only: LS BMD mean percentage change LHRHa −3.0% and OP +7.9% (p < 0.001). Conclusions Transdermal oestradiol as a single agent produces castration levels of testosterone while mitigating BMD loss. These early data provide further supporting evidence for the ongoing phase 3 trial

Development and evaluation of a web-based breast cancer cultural competency course for primary healthcare providers

<p>Abstract</p> <p>Background</p> <p>To develop and evaluate a continuing medical education (CME) course aimed at improving healthcare provider knowledge about breast cancer health disparities and the importance of cross-cultural communication in provider-patient interactions about breast cancer screening.</p> <p>Methods</p> <p>An interactive web-based CME course was developed and contained information about breast cancer disparities, the role of culture in healthcare decision making, and demonstrated a model of cross-cultural communication. A single group pre-/post-test design was used to assess knowledge changes. Data on user satisfaction was also collected.</p> <p>Results</p> <p>In all, 132 participants registered for the CME with 103 completing both assessments. Differences between pre-/post-test show a significant increase in knowledge (70% vs. 94%; p < .001). Ninety-five percent of participants agreed that the web based training was an appropriate tool to train healthcare providers about cultural competency and health disparities.</p> <p>Conclusion</p> <p>There was an overall high level of satisfaction among all users. Users felt that learning objectives were met and the web-based format was appropriate and easy to use and suggests that web-based CME formats are an appropriate tool to teach cultural competency skills. However, more information is needed to understand how the CME impacted practice behaviors.</p

Enzootic Rabies Elimination from Dogs and Reemergence in Wild Terrestrial Carnivores, United States

Independent enzootics in wild terrestrial carnivores resulted from spillover events from long-term enzootics associated with dogs

Current worldwide nuclear cardiology practices and radiation exposure: results from the 65 country IAEA Nuclear Cardiology Protocols Cross-Sectional Study (INCAPS)

Aims To characterize patient radiation doses from nuclear myocardial perfusion imaging (MPI) and the use of radiation-optimizing ‘best practices' worldwide, and to evaluate the relationship between laboratory use of best practices and patient radiation dose. Methods and results We conducted an observational cross-sectional study of protocols used for all 7911 MPI studies performed in 308 nuclear cardiology laboratories in 65 countries for a single week in March-April 2013. Eight ‘best practices' relating to radiation exposure were identified a priori by an expert committee, and a radiation-related quality index (QI) devised indicating the number of best practices used by a laboratory. Patient radiation effective dose (ED) ranged between 0.8 and 35.6 mSv (median 10.0 mSv). Average laboratory ED ranged from 2.2 to 24.4 mSv (median 10.4 mSv); only 91 (30%) laboratories achieved the median ED ≤ 9 mSv recommended by guidelines. Laboratory QIs ranged from 2 to 8 (median 5). Both ED and QI differed significantly between laboratories, countries, and world regions. The lowest median ED (8.0 mSv), in Europe, coincided with high best-practice adherence (mean laboratory QI 6.2). The highest doses (median 12.1 mSv) and low QI (4.9) occurred in Latin America. In hierarchical regression modelling, patients undergoing MPI at laboratories following more ‘best practices' had lower EDs. Conclusion Marked worldwide variation exists in radiation safety practices pertaining to MPI, with targeted EDs currently achieved in a minority of laboratories. The significant relationship between best-practice implementation and lower doses indicates numerous opportunities to reduce radiation exposure from MPI globall

Mutational Analysis of EGFR and Related Signaling Pathway Genes in Lung Adenocarcinomas Identifies a Novel Somatic Kinase Domain Mutation in FGFR4

BACKGROUND: Fifty percent of lung adenocarcinomas harbor somatic mutations in six genes that encode proteins in the EGFR signaling pathway, i.e., EGFR, HER2/ERBB2, HER4/ERBB4, PIK3CA, BRAF, and KRAS. We performed mutational profiling of a large cohort of lung adenocarcinomas to uncover other potential somatic mutations in genes of this signaling pathway that could contribute to lung tumorigenesis. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed genomic DNA from a total of 261 resected, clinically annotated non-small cell lung cancer (NSCLC) specimens. The coding sequences of 39 genes were screened for somatic mutations via high-throughput dideoxynucleotide sequencing of PCR-amplified gene products. Mutations were considered to be somatic only if they were found in an independent tumor-derived PCR product but not in matched normal tissue. Sequencing of 9MB of tumor sequence identified 239 putative genetic variants. We further examined 22 variants found in RAS family genes and 135 variants localized to exons encoding the kinase domain of respective proteins. We identified a total of 37 non-synonymous somatic mutations; 36 were found collectively in EGFR, KRAS, BRAF, and PIK3CA. One somatic mutation was a previously unreported mutation in the kinase domain (exon 16) of FGFR4 (Glu681Lys), identified in 1 of 158 tumors. The FGFR4 mutation is analogous to a reported tumor-specific somatic mutation in ERBB2 and is located in the same exon as a previously reported kinase domain mutation in FGFR4 (Pro712Thr) in a lung adenocarcinoma cell line. CONCLUSIONS/SIGNIFICANCE: This study is one of the first comprehensive mutational analyses of major genes in a specific signaling pathway in a sizeable cohort of lung adenocarcinomas. Our results suggest the majority of gain-of-function mutations within kinase genes in the EGFR signaling pathway have already been identified. Our findings also implicate FGFR4 in the pathogenesis of a subset of lung adenocarcinomas

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

The Earth BioGenome Project 2020: Starting the clock

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The Earth BioGenome Project 2020: Starting the clock.

© The Author(s), 2022. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Lewin, H. A., Richards, S., Lieberman Aiden, E., Allende, M. L., Archibald, J. M., Bálint, M., Barker, K. B., Baumgartner, B., Belov, K., Bertorelle, G., Blaxter, Mark L., Cai, J., Caperello, N. D., Carlson, K., Castilla-Rubio, J. C., Chaw, S-M., Chen, L., Childers, A. K., Coddington, J. A., Conde, D. A., Corominas, M., Crandall, K. A., Crawford, A. J., DiPalma, F., Durbin, R., Ebenezer, T. E., Edwards, S. V., Fedrigo, O., Flicek, P., Formenti, G., Gibbs, R. A., Gilbert, M. Thomas P., Goldstein, M. M., Graves, J. M., Greely, H. T., Grigoriev, I. V., Hackett, K. J., Hall, N., Haussler, D., Helgen, K. M., Hogg, C. J., Isobe, S., Jakobsen, K. S., Janke, A., Jarvis, E. D., Johnson, W. E., Jones, S. J. M., Karlsson, E. K., Kersey, P. J., Kim, J-H., Kress, W. J., Kuraku, S., Lawniczak, M. K. N., Leebens-Mack, J. H., Li, X., Lindblad-Toh, K., Liu, X., Lopez, J. V., Marques-Bonet, T., Mazard, S., Mazet, J. A. K., Mazzoni, C. J., Myers, E. W., O’Neill, R. J., Paez, S., Park, H., Robinson, G. E., Roquet, C., Ryder, O. A., Sabir, J. S. M., Shaffer, H. B., Shank, T. M., Sherkow, J. S., Soltis, P. S., Tang, B., Tedersoo, L., Uliano-Silva, M., Wang, K., Wei, X., Wetzer, R., Wilson, J. L., Xu, X., Yang, H., Yoder, A. D., Zhang, G. The Earth BioGenome Project 2020: starting the clock. Proceedings of the National Academy of Sciences of the United States of America, 119(4), (2022): e2115635118, https://doi.org/10.1073/pnas.2115635118.November 2020 marked 2 y since the launch of the Earth BioGenome Project (EBP), which aims to sequence all known eukaryotic species in a 10-y timeframe. Since then, significant progress has been made across all aspects of the EBP roadmap, as outlined in the 2018 article describing the project’s goals, strategies, and challenges (1). The launch phase has ended and the clock has started on reaching the EBP’s major milestones. This Special Feature explores the many facets of the EBP, including a review of progress, a description of major scientific goals, exemplar projects, ethical legal and social issues, and applications of biodiversity genomics. In this Introduction, we summarize the current status of the EBP, held virtually October 5 to 9, 2020, including recent updates through February 2021. References to the nine Perspective articles included in this Special Feature are cited to guide the reader toward deeper understanding of the goals and challenges facing the EBP