13 results
Effectiveness of Bio-K+ for the prevention of Clostridioides difficile infection: Stepped-wedge cluster-randomized controlled trial
- Jenine Leal, Ye Shen, Peter Faris, Bruce Dalton, Deana Sabuda, Wrechelle Ocampo, Lauren Bresee, Blanda Chow, Jared R. Fletcher, Elizabeth Henderson, Jaime Kaufman, Joseph Kim, Maitreyi Raman, Scott Kraft, Nicole C. Lamont, Oscar Larios, Bayan Missaghi, Jayna Holroyd-Leduc, Thomas Louie, John Conly
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- Journal:
- Infection Control & Hospital Epidemiology / Volume 45 / Issue 4 / April 2024
- Published online by Cambridge University Press:
- 11 December 2023, pp. 443-451
- Print publication:
- April 2024
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Objective:
To evaluate the impact of administering probiotics to prevent Clostridioides difficile infection (CDI) among patients receiving therapeutic antibiotics.
Design:Stepped-wedge cluster-randomized trial between September 1, 2016, and August 31, 2019.
Setting:This study was conducted in 4 acute-care hospitals across an integrated health region.
Patients:Hospitalized patients, aged ≥55 years.
Methods:Patients were given 2 probiotic capsules daily (Bio-K+, Laval, Quebec, Canada), containing 50 billion colony-forming units of Lactobacillus acidophilus CL1285, L. casei LBC80R, and L. rhamnosus CLR2. We measured hospital-acquired CDI (HA-CDI) and the number of positive C. difficile tests per 10,000 patient days as well as adherence to administration of Bio-K+ within 48 and 72 hours of antibiotic administration. Mixed-effects generalized linear models, adjusted for influenza admissions and facility characteristics, were used to evaluate the impact of the intervention on outcomes.
Results:Overall adherence of Bio-K+ administration ranged from 76.9% to 84.6% when stratified by facility and periods. Rates of adherence to administration within 48 and 72 hours of antibiotic treatment were 60.2% –71.4% and 66.7%–75.8%, respectively. In the adjusted analysis, there was no change in HA-CDI (incidence rate ratio [IRR], 0.92; 95% confidence interval [CI], 0.68–1.23) or C. difficile positivity rate (IRR, 1.05; 95% CI, 0.89–1.24). Discharged patients may not have received a complete course of Bio-K+. Our hospitals had a low baseline incidence of HA-CDI. Patients who did not receive Bio-K+ may have differential risks of acquiring CDI, introducing selection bias.
Conclusions:Hospitals considering probiotics as a primary prevention strategy should consider the baseline incidence of HA-CDI in their population and timing of probiotics relative to the start of antimicrobial administration.
6 - A Critical Analysis of Past and Present Campaigns to Challenge Online Racism in English Professional Football
- Edited by Imran Awan, Birmingham City University, Irene Zempi, Nottingham Trent University
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- Book:
- Hate Crime in Football
- Published by:
- Bristol University Press
- Published online:
- 03 April 2024
- Print publication:
- 13 November 2023, pp 83-102
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Summary
Introduction
Inside Wembley Stadium, the men’s England manager, Gareth Southgate, huddles his players together for a final team talk before the players step up to take their penalty kicks. First for England is Harry Kane, who scores with a shot that is low and to the goalkeeper’s right. Next is Harry Maguire, who smashes the ball into the top right of the goal. However, Marcus Rashford hits the post and Jadon Sancho’s and Bukayo Saka’s efforts are saved by Italian goalkeeper Gianluigi Donnarumma. It is the final of the UEFA (Union of European Football Associations) European Football Championship (Euro 2020), held in July 2021 due to the COVID-19 pandemic, and England have been defeated on penalties. Sadly, the online racist abuse which followed soured what should have been a proud moment for English football, as the national men’s team had reached their first major tournament final since 1966.
After the penalty kicks, in the ensuing moments online, the three young England players who missed theirs were rendered Black and ‘foreign’ above anything else, thereby exposing people’s deeply held views concerning race relations. Of particular interest here is the fact that a Fédération Internationale de Football Association (FIFA) report released in June 2022 highlighted that more than a third of the online abuse during the final came from online accounts based in the United Kingdom (UK). To offer further context, the abuse mirrored online reactions a decade prior towards Black English players Ashley Cole and Ashley Young, who also missed penalties against Italy during Euro 2012 (Press Association, 2012). The Euro 2020 case illustrates both the ease with which online racism is expressed and its frequency – it sadly represents yet another chapter in the history of online racism within football. What is clear is that forms of hate and forms of racism are evolving, with much of this moving online. Indeed, while racist chants and insults, and even bananas, were once hurled at players inside football stadiums, we can now observe these epithets in multiple digital forms. Many strategies (past and present) have sought to challenge online racism in football, some being more effective than others.
Impact of Seasonality and Influenza Rates on Interventions to Reduce Hospital-Acquired Clostridioides difficile Rates
- Jenine Leal, Peter Faris, Ye Shen, Lauren Bresee, Kathryn Bush, Blanda Chow, Bruce Dalton, Jared Fletcher, Sara Hartman, Jaime Kaufman, Joseph Kim, Maitreyi Kothandaraman, Scott Kraft, Nicole Lamont, Oscar Larios, Braden Manns, Bayan Missaghi, Wrechelle Ocampo, Paule Poulin, Deana Sabuda, Jayna Holroyd-Leduc, Thomas Louie, John Conly
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- Journal:
- Infection Control & Hospital Epidemiology / Volume 41 / Issue S1 / October 2020
- Published online by Cambridge University Press:
- 02 November 2020, pp. s265-s266
- Print publication:
- October 2020
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Background: Hospital-acquired Clostridioides difficile infection (HA-CDI) rates are highly variable over time, posing problems for research assessing interventions that might improve rates. By understanding seasonality in HA-CDI rates and the impacts that other factors such as influenza admissions might have on these rates, we can account for them when establishing the relationship between interventions and infection rates. We assessed whether there were seasonal trends in HA-CDI and whether they could be accounted for by influenza rates. Methods: We assessed HA-CDI rates per 10,000 patient days, and the rate of hospitalized patients with influenza per 1,000 admissions in 4 acute-care facilities (n = 2,490 beds) in Calgary, Alberta, from January 2016 to December 2018. We used 4 statistical approaches in R (version 3.5.1 software): (1) autoregressive integrated moving average (ARIMA) to assess dependencies and trends in each of the monthly HA-CDI and influenza series; (2) cross correlation to assess dependencies between the HA-CDI and influenza series lagged over time; (3) Poisson harmonic regression models (with sine and cosine components) to assess the seasonality of the rates; and (4) Poisson regression to determine whether influenza rates accounted for seasonality in the HA-CDI rates. Results: Conventional ARIMA approaches did not detect seasonality in the HA-CDI rates, but we found strong seasonality in the influenza rates. A cross-correlation analysis revealed evidence of correlation between the series at a lag of zero (R = 0.41; 95% CI, 0.10–0.65) and provided an indication of a seasonal relationship between the series (Fig. 1). Poisson regression suggested that influenza rates predicted CDI rates (P < .01). Using harmonic regression, there was evidence of seasonality in HA-CDI rates (2 [2 df] = 6.62; P < .05) and influenza rates (2 [2 df] = 1,796.6; P < .001). In a Poisson model of HA-CDI rates with both the harmonic components and influenza admission rates, the harmonic components were no longer predictive of HA-CDI rates. Conclusions: Harmonic regression provided a sensitive means of identifying seasonality in HA-CDI rates, but the seasonality effect was accounted for by influenza admission rates. The relationship between HA-CDI and influenza rates is likely mediated by antibiotic prescriptions, which needs to be assessed. To improve precision and reduce bias, research on interventions to reduce HA-CDI rates should assess historic seasonality in HA-CDI rates and should account for influenza admissions.
Funding: None
Disclosures: None
Implementation Strategies of a Quality Improvement Initiative for Hospital-Acquired Clostridioides difficile Infection Prevention
- Nicole Lamont, Lauren Bresee, Kathryn Bush, Blanda Chow, Bruce Dalton, Cody Doolan, Peter Faris, Jared Fletcher, Sara Hartman, Jaime Kaufman, Maida Khan, Joseph Kim, Maitreyi Kothandaraman, Scott Kraft, Oscar Larios, Jenine Leal, Braden Manns, Bayan Missaghi, Wrechelle Ocampo, Dylan Pillai, Paule Poulin, Deana Sabuda, Ye Shen, Thomas Louie, Jayna Holroyd-Leduc, John Conly
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- Journal:
- Infection Control & Hospital Epidemiology / Volume 41 / Issue S1 / October 2020
- Published online by Cambridge University Press:
- 02 November 2020, pp. s279-s280
- Print publication:
- October 2020
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Background:Clostridioides difficile infection (CDI) is the most common cause of infectious diarrhea in hospitalized patients. Probiotics have been studied as a measure to prevent CDI. Timely probiotic administration to at-risk patients receiving systemic antimicrobials presents significant challenges. We sought to determine optimal implementation methods to administer probiotics to all adult inpatients aged 55 years receiving a course of systemic antimicrobials across an entire health region. Methods: Using a randomized stepped-wedge design across 4 acute-care hospitals (n = 2,490 beds), the probiotic Bio-K+ was prescribed daily to patients receiving systemic antimicrobials and was continued for 5 days after antimicrobial discontinuation. Focus groups and interviews were conducted to identify barriers, and the implementation strategy was adapted to address the key identified barriers. The implementation strategy included clinical decision support involving a linked flag on antibiotic ordering and a 1-click order entry within the electronic medical record (EMR), provider and patient education (written/videos/in-person), and local site champions. Protocol adherence was measured by tracking the number of patients on therapeutic antimicrobials that received BioK+ based on the bedside nursing EMR medication administration records. Adherence rates were sorted by hospital and unit in 48- and 72-hour intervals with recording of percentile distribution of time (days) to receipt of the first antimicrobial. Results: In total, 340 education sessions with >1,800 key stakeholders occurred before and during implementation across the 4 involved hospitals. The overall adherence of probiotic ordering for wards with antimicrobial orders was 78% and 80% at 48 and 72 hours, respectively over 72 patient months. Individual hospital adherence rates varied between 77% and 80% at 48 hours and between 79% and 83% at 72 hours. Of 246,144 scheduled probiotic orders, 94% were administered at the bedside within a median of 0.61 days (75th percentile, 0.88), 0.47 days (75th percentile, 0.86), 0.71 days (75th percentile, 0.92) and 0.67 days (75th percentile, 0.93), respectively, at the 4 sites after receipt of first antimicrobial. The key themes from the focus groups emphasized the usefulness of the linked flag alert for probiotics on antibiotic ordering, the ease of the EMR 1-click order entry, and the importance of the education sessions. Conclusions: Electronic clinical decision support, education, and local champion support achieved a high implementation rate consistent across all sites. Use of a 1-click order entry in the EMR was considered a key component of the success of the implementation and should be considered for any implementation strategy for a stewardship initiative. Achieving high prescribing adherence allows more precision in evaluating the effectiveness of the probiotic strategy.
Funding: Partnerships for Research and Innovation in the Health System, Alberta Innovates/Health Solutions Funding: Award
Disclosures: None
10 - Saturn’s Seasonally Changing Atmosphere
- Edited by Kevin H. Baines, University of Wisconsin, Madison, F. Michael Flasar, NASA-Goddard Space Flight Center, Norbert Krupp, Tom Stallard, University of Leicester
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- Book:
- Saturn in the 21st Century
- Published online:
- 13 December 2018
- Print publication:
- 06 December 2018, pp 251-294
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Summary
The longevity of Cassini’s exploration of Saturn’s atmosphere (a third of a Saturnian year) means that we have been able to track the seasonal evolution of atmospheric temperatures, chemistry and cloud opacity over almost every season, from solstice to solstice and from perihelion to aphelion. Cassini has built upon the decades-long ground-based record to observe seasonal shifts in atmospheric temperature, finding a thermal response that lags behind the seasonal insolation with a lag time that increases with depth into the atmosphere, in agreement with radiative climate models. Seasonal hemispheric contrasts are perturbed at smaller scales by atmospheric circulation, such as belt/zone dynamics, the equatorial oscillations and the polar vortices. Temperature asymmetries are largest in the middle stratosphere and become insignificant near the radiative-convective boundary. Cassini has also measured southern-summertime asymmetries in atmospheric composition, including ammonia (the key species forming the topmost clouds), phosphine and para-hydrogen (both disequilibrium species) in the upper troposphere; and hydrocarbons deriving from the UV photolysis of methane in the stratosphere (principally ethane and acetylene). These chemical asymmetries are now altering in subtle ways due to (i) the changing chemical efficiencies with temperature and insolation and (ii) vertical motions associated with large-scale overturning in response to the seasonal temperature contrasts. Similarly, hemispheric contrasts in tropospheric aerosol opacity and coloration that were identified during the earliest phases of Cassini’s exploration have now reversed, suggesting an intricate link between the clouds and the temperatures. Finally, comparisons of observations between Voyager and Cassini (both observing in early northern spring, one Saturn year apart) show tantalizing suggestions of non-seasonal variability. Disentangling the competing effects of radiative balance, chemistry and dynamics in shaping the seasonal evolution of Saturn’s temperatures, clouds and composition remains the key challenge for the next generation of observations and numerical simulations.
Developing a Minimum Summary Sheet for Sudden Onset Disasters: The UK, EMT Approach
- Anisa J.N. Jafar, Chrissy Alcock, Rachel Fletcher, Thomas C. Hughes, Brigid Hayden, Philip Gaffney, John Simpson, Anthony Redmond
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- Journal:
- Prehospital and Disaster Medicine / Volume 32 / Issue S1 / April 2017
- Published online by Cambridge University Press:
- 20 April 2017, p. S60
- Print publication:
- April 2017
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NOTES
- F. B. Caulfield, J Fletcher, Thomas. W. Fyles
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- The Canadian Entomologist / Volume 22 / Issue 1 / January 1890
- Published online by Cambridge University Press:
- 31 May 2012, pp. 19-20
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Contributors
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- By Gregory H. Adkisson, Ozan Akça, Nawar Al-Rawas, John T. Anderson, Richard M. Bednarski, Francesca Bernabè, David G. Bjoraker, Lluis Blanch, Stephan H. Böhm, Edwin A. Bowe, Philip G. Boysen, Justin C. Cahill, Ira M. Cheifetz, David C. Cone, Nancy Craig, Daniel P. Davis, John B. Downs, Ronald Dueck, Jay L. Falk, Roger Fletcher, Michael A. Frakes, Andrea Gabrielli, Thomas J. Gallagher, Geoff Gilmartin, J. S. Gravenstein, Antonino Gullo, Donna Hamel, John W. Huang, Amy V. Isenberg, Michael B. Jaffe, Michael C. K. Khoo, Robert R. Kirby, E. F. Klein, A. Joseph Layon, Umberto Lucangelo, Emilio Maldonado, Paul E. Marik, Alicia E. Meuret, Timothy E. Morey, William Muir, Joseph A. Orr, Mehmet S. Ozcan, Lucía Isabel Passoni, David A. Paulus, Yong G. Peng, Carl W. Peters, George A. Ralls, Adriana G. Scandurra, Peter W. Scherer, Gerd Schmalisch, Adam Seiver, Salvatore Silvestri, Bob Smalhout, Fernando Suarez-Sipmann, Daniel E. Supkis, John Thompson, Patrick Troy, Jonathon D. Truwit, Gerardo Tusman, Joseph Varon, Ajeet G. Vinayak, Kevin R. Ward, Marvin A. Wayne, Charles Weissman, Dafna Willner, Kai Zhao, Christian C. Zuver
- Edited by J. S. Gravenstein, University of Florida, Michael B. Jaffe, Nikolaus Gravenstein, University of Florida, David A. Paulus, University of Florida
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- Book:
- Capnography
- Published online:
- 05 August 2011
- Print publication:
- 17 March 2011, pp ix-xii
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Influence of Education on Subcortical Hyperintensities and Global Cognitive Status in Vascular Dementia
- Elizabeth M. Lane, Robert H. Paul, David J. Moser, Thomas D. Fletcher, Ronald A. Cohen
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- Journal of the International Neuropsychological Society / Volume 17 / Issue 3 / May 2011
- Published online by Cambridge University Press:
- 09 March 2011, pp. 531-536
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Subcortical hyperintensities (SH) on neuroimaging are a prominent feature of vascular dementia (VaD) and SH severity correlates with cognitive impairment in this population. Previous studies demonstrated that SH burden accounts for a degree of the cognitive burden among VaD patients, although it remains unclear if individual factors such as cognitive reserve influence cognitive status in VaD. To address this issue, we examined 36 individuals diagnosed with probable VaD (age = 77.56; education = 12). All individuals underwent MMSE evaluations and MRI brain scans. We predicted that individuals with higher educational attainment would exhibit less cognitive difficulty despite similar levels of SH volume, compared to individuals with less educational attainment. A regression analysis revealed that greater SH volume was associated with lower scores on the MMSE. Additionally, education moderated the relationship between SH volume and MMSE score, demonstrating that individuals with higher education had higher scores on the MMSE despite similar degrees of SH burden. These results suggest that educational attainment buffers the deleterious effects of SH burden on cognitive status among VaD patients. (JINS, 2011, 17, 531–536)
Beccles Triple Post Alignment, Beccles Marshes, Suffolk: Excavation and Palaeoenvironmental Analyses of an Iron Age Wetland Site
- Benjamin R. Gearey, Henry P. Chapman, Andrew J. Howard, Kristina Krawiec, Michael Bamforth, William G. Fletcher, Thomas C.B. Hill, Peter Marshall, Emma Tetlow, Ian Tyers
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- Proceedings of the Prehistoric Society / Volume 77 / 2011
- Published online by Cambridge University Press:
- 05 March 2013, pp. 231-250
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- 2011
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This paper describes the results of two seasons of excavation and associated palaeoenvironmental analyses of a wetland site on Beccles Marshes, Beccles, Suffolk. The site has been identified as a triple post alignment of oak timbers (0.6–2.0 m long), over 100 m in length, and 3–4 m wide, running north-west to south-east towards the River Waveney. It was constructed in a single phase which has been dated dendrochronologically to 75 BC, although discrete brushwood features identified as possible short trackways have been dated by radiocarbon to both before and after the alignment was built. It is unclear if the posts ever supported a superstructure but notches (‘halving lap joints’) in some of the posts appear to have held timbers to support the posts and/or aid in their insertion. In addition, fragments of both Iron Age and Romano-British pottery were recovered. A substantial assemblage of worked wooden remains appears to reflect the construction of the post row itself and perhaps the on-site clearance of floodplain vegetation. This assemblage also contains waste material derived from the reduction splitting of timbers larger than the posts of the alignment, but which have not been recovered from the site. Environmental analyses indicate that the current landscape context of the site with respect to the River Waveney is probably similar to that which pertained in prehistory. The coleoptera (beetle) record illustrates a series of changes in the on-site vegetation in the period before, during and after the main phase of human activity which may be related to a range of factors including floodplain hydrology and anthropogenic utilisation of Beccles Marshes. The possible form and function of the site is discussed in relation to the later prehistoric period in Suffolk.
The science of EChO
- Giovanna Tinetti, James Y-K. Cho, Caitlin A. Griffith, Olivier Grasset, Lee Grenfell, Tristan Guillot, Tommi T. Koskinen, Julianne I. Moses, David Pinfield, Jonathan Tennyson, Marcell Tessenyi, Robin Wordsworth, Alan Aylward, Roy van Boekel, Angioletta Coradini, Therese Encrenaz, Ignas Snellen, Maria R. Zapatero-Osorio, Jeroen Bouwman, Vincent Coudé du Foresto, Mercedes Lopez-Morales, Ingo Mueller-Wodarg, Enric Pallé, Franck Selsis, Alessandro Sozzetti, Jean-Philippe Beaulieu, Thomas Henning, Michael Meyer, Giuseppina Micela, Ignasi Ribas, Daphne Stam, Mark Swain, Oliver Krause, Marc Ollivier, Emanuele Pace, Bruce Swinyard, Peter A.R. Ade, Nick Achilleos, Alberto Adriani, Craig B. Agnor, Cristina Afonso, Carlos Allende Prieto, Gaspar Bakos, Robert J. Barber, Michael Barlow, Peter Bernath, Bruno Bézard, Pascal Bordé, Linda R. Brown, Arnaud Cassan, Céline Cavarroc, Angela Ciaravella, Charles Cockell, Athéna Coustenis, Camilla Danielski, Leen Decin, Remco De Kok, Olivier Demangeon, Pieter Deroo, Peter Doel, Pierre Drossart, Leigh N. Fletcher, Matteo Focardi, Francois Forget, Steve Fossey, Pascal Fouqué, James Frith, Marina Galand, Patrick Gaulme, Jonay I. González Hernández, Davide Grassi, Matt J. Griffin, Ulrich Grözinger, Manuel Guedel, Pactrick Guio, Olivier Hainaut, Robert Hargreaves, Peter H. Hauschildt, Kevin Heng, David Heyrovsky, Ricardo Hueso, Pat Irwin, Lisa Kaltenegger, Patrick Kervella, David Kipping, Geza Kovacs, Antonino La Barbera, Helmut Lammer, Emmanuel Lellouch, Giuseppe Leto, Mercedes Lopez Morales, Miguel A. Lopez Valverde, Manuel Lopez-Puertas, Christophe Lovi, Antonio Maggio, Jean-Pierre Maillard, Jesus Maldonado Prado, Jean-Baptiste Marquette, Francisco J. Martin-Torres, Pierre Maxted, Steve Miller, Sergio Molinari, David Montes, Amaya Moro-Martin, Olivier Mousis, Napoléon Nguyen Tuong, Richard Nelson, Glenn S. Orton, Eric Pantin, Enzo Pascale, Stefano Pezzuto, Ennio Poretti, Raman Prinja, Loredana Prisinzano, Jean-Michel Réess, Ansgar Reiners, Benjamin Samuel, Jorge Sanz Forcada, Dimitar Sasselov, Giorgio Savini, Bruno Sicardy, Alan Smith, Lars Stixrude, Giovanni Strazzulla, Gautam Vasisht, Sandrine Vinatier, Serena Viti, Ingo Waldmann, Glenn J. White, Thomas Widemann, Roger Yelle, Yuk Yung, Sergey Yurchenko
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- Journal:
- Proceedings of the International Astronomical Union / Volume 6 / Issue S276 / October 2010
- Published online by Cambridge University Press:
- 10 November 2011, pp. 359-370
- Print publication:
- October 2010
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The science of extra-solar planets is one of the most rapidly changing areas of astrophysics and since 1995 the number of planets known has increased by almost two orders of magnitude. A combination of ground-based surveys and dedicated space missions has resulted in 560-plus planets being detected, and over 1200 that await confirmation. NASA's Kepler mission has opened up the possibility of discovering Earth-like planets in the habitable zone around some of the 100,000 stars it is surveying during its 3 to 4-year lifetime. The new ESA's Gaia mission is expected to discover thousands of new planets around stars within 200 parsecs of the Sun. The key challenge now is moving on from discovery, important though that remains, to characterisation: what are these planets actually like, and why are they as they are?
In the past ten years, we have learned how to obtain the first spectra of exoplanets using transit transmission and emission spectroscopy. With the high stability of Spitzer, Hubble, and large ground-based telescopes the spectra of bright close-in massive planets can be obtained and species like water vapour, methane, carbon monoxide and dioxide have been detected. With transit science came the first tangible remote sensing of these planetary bodies and so one can start to extrapolate from what has been learnt from Solar System probes to what one might plan to learn about their faraway siblings. As we learn more about the atmospheres, surfaces and near-surfaces of these remote bodies, we will begin to build up a clearer picture of their construction, history and suitability for life.
The Exoplanet Characterisation Observatory, EChO, will be the first dedicated mission to investigate the physics and chemistry of Exoplanetary Atmospheres. By characterising spectroscopically more bodies in different environments we will take detailed planetology out of the Solar System and into the Galaxy as a whole.
EChO has now been selected by the European Space Agency to be assessed as one of four M3 mission candidates.
12 - Antiretroviral drug interactions
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- By Thomas N. Kakuda, Department of Medical Affairs, Hoffman LaRoche, Nutley, NJ, Courtney V. Fletcher, University of Colorado Health Sciences Center, Denver, CO
- Edited by Steven L. Zeichner, National Cancer Institute, Bethesda, Maryland, Jennifer S. Read
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- Book:
- Handbook of Pediatric HIV Care
- Published online:
- 23 December 2009
- Print publication:
- 04 May 2006, pp 360-381
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Summary
Treatment of HIV-infected patients requires polypharmacy, during which drug interactions can occur. Pharmacokinetic interactions are those that affect the absorption, distribution, metabolism, or excretion of a drug. Pharmacodynamic interactions produce antagonistic, additive, or synergistic effects. Interactions can be adverse or beneficial. This chapter provides a framework for understanding HIV-related drug interactions through the principles of pharmacology.
Pharmacokinetic drug interactions
Absorption
Fasting, gastric pH, and enteric P-glycoprotein (PGP) expression all can affect absorption. Table 12.1 delineates drug–food interactions and lists antiretroviral drugs that may be administered without regard to food. Antacids (including the buffer in older formulations of didanosine), H2-receptor antagonists, and proton pump inhibitors increase gastric pH, impairing the bioavailability of drugs that require low pH for optimal absorption (e.g., delavirdine, indinavir, itraconazole, ketoconazole). This interaction usually can be avoided by administrating the gastric pH-raising agent 1 to 2 hours later [1–3]. Didanosine is much better absorbed in an alkaline environment because it is acid labile. The original formulation of didanosine included a buffer (calcium carbonate and magnesium hydroxide in tablets or citrate-phosphate in sachets) or had to be reconstituted in antacid. The buffer in didanosine does not affect dapsone absorption but significantly decreases ciprofloxacin absorption [4, 5]. Didanosine or antacids do not interfere with nevirapine. The new formulation of didanosine (Videx® EC) does not have significant interactions with ciprofloxacin, indinavir, or azole antifungals [6, 7]. Drug absorption also can be affected by transporters in the gut.
19 - Antiretroviral drug interactions
- from Part III - Antiretroviral therapy
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- By Thomas N. Kakuda, Associate Clinical Research Scientist, Abbott Laboratories, Courtney V. Fletcher, Professor, University of Colorado Health Sciences Center, Denver, CO, USA
- Edited by Steven L. Zeichner, National Cancer Institute, Bethesda, Maryland, Jennifer S. Read, National Cancer Institute, Bethesda, Maryland
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- Book:
- Textbook of Pediatric HIV Care
- Published online:
- 03 February 2010
- Print publication:
- 28 April 2005, pp 305-318
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Summary
Treatment of HIV-infected patients requires unavoidable polypharmacy, during which drug interactions can occur. Pharmacokinetic interactions are those that affect the absorption, distribution, metabolism, or excretion of a drug. Interactions that produce antagonistic, additive, or synergistic effects are considered pharmacodynamic interactions. Not all interactions are clinically adverse and in some cases, interactions can be beneficial. The objective of this chapter is to provide the clinician with a framework for understanding drug interactions by applying the principles of pharmacology in the context of HIV medicine.
Pharmacokinetic drug interactions
Absorption
The absorption of oral drugs is affected by several conditions such as fasting, gastric pH, and enteric P-glycoprotein (PGP) expression. Drug—food interactions are delineated in Table 19.1; also listed are antiretroviral drugs that may be administered without regard to food. Drugs that increase gastric pH include antacids (including the buffer in older formulations of didanosine), H2-receptor antagonists, and proton pump inhibitors. These drugs can impair the bioavailability of drugs that require a low pH for optimal absorption such as delavirdine, indinavir, itraconazole, and ketoconazole. This interaction can usually be avoided by administrating the gastric pH-raising agent 1–2 hours later [1–3]. Didanosine is an example of a drug much better absorbed in an alkaline environment because it is acid labile. The original formulation of didanosine included a buffer (calcium carbonate and magnesium hydroxide in tablets or citrate-phosphate in sachets) or had to be reconstituted in antacid.