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5. Increased Platelet Counts Are Associated With Female Sex and Asthma Severity

Author

Solanki, N., primary, Attaway, A., additional, Bleecker, E.R., additional, Cahill, K., additional, Castro, M., additional, Comhair, S.A.A., additional, Denlinger, L.C., additional, Erzurum, S.C., additional, Fahy, J.V., additional, Gaston, B., additional, Hawkins, G.A., additional, Hazen, S., additional, Israel, E., additional, Jarjour, N.N., additional, Levy, B.D., additional, Li, X., additional, Mauger, D., additional, Meyers, D.A., additional, Moore, W.C., additional, Newcomb, D.C., additional, Ortega, V.E., additional, Peters, M.C., additional, Townsend, E.A., additional, Wenzel, S.E., additional, and Zein, J.G., additional

Published
2023
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7. Lattice Effective Actions and Light-Quark Confinement

Author

Cahill, K. and Herling, G.

Subjects
High Energy Physics - Lattice
Abstract

The positive-plaquette Manton action at weak coupling is a reasonable action for short-distance phenomena. We propose an iterative scheme for evolving this action into an effective action for longer distance scales. We report on the first step of this scheme in which we have measured ``blocked'' Creutz ratios with lattice spacing 2a at beta = 16 on a 32^4 lattice and have searched for an effective action that yields the same ratios on a 16^4 lattice. We also suggest a mechanism for quark confinement that relies upon the lightness of the u and d quarks and formulate a way of testing it in lattice simulations of QCD., Comment: LATTICE98(algorithms), 3 pages

Published
1998
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9. Toolbox for Research and Exploration (TREX): Investigations of Fine-Grained Materials on Small Bodies

Author

Domingue, D. L, Allain, J.-P, Banks, M, Christoffersen, R, Cintala, M, Clark, R, Cloutis, E, Graps, A, Hendrix, A. R, Hsieh, H, Lane, M. D, Lederer, S, Li, J.-Y, Dobrea, E. Noe, Prettyman, T, Savin, D. W, Schorghofer, N, Stockstill-Cahill, K, and Vilas, F

Subjects
Space Sciences (General)
Abstract

The Toolbox for Research and Exploration (TREX) is a NASA SSERVI (Solar System Exploration Research Virtual Institute) node. TREX (trex.psi.edu) aims to decrease risk to future missions, specifically to the Moon, the Martian moons, and near- Earth asteroids, by improving mission success and assuring the safety of astronauts, their instruments, and spacecraft. TREX studies will focus on characteristics of the fine grains that cover the surfaces of these target bodies - their spectral characteristics and the potential resources (such as H2O) they may harbor. TREX studies are organized into four Themes (Laboratory- Studies, Moon-Studies, Small-Bodies Studies, and Field-Work). In this presentation, we focus on the work targeted by the Small-Bodies Theme. The Small-Bodies' Theme delves into several topics, many which overlap or are synergistic with the other TREX Themes. The main topics include photometry, spectral modeling, laboratory simulations of space weathering processes relevant to asteroids, the assembly of an asteroid regolith database, the dichotomy between nuclear and reflectance spectroscopy, and the dynamical evolution of asteroids and the implications for the retention of volatiles.

Published
2018

23. Initial Teacher Education for Inclusion Phase 1 and 2 Report: NCSE Research Report No. 26

Author

Peter Hick, Solomon, Y., Mintz, J., Matziari, A., Ó Murchú, F., Hall, K., Cahill, K., Curtin, C., and Margariti, D.

Abstract

Executive Summary Background to the project The context for this project is a growing international consensus on the importance of policy initiatives to both raise the quality of teaching (OECD, 2005) and to better prepare teachers to respond to increasing diversity in communities and classrooms (EADSNE, 2011). The DES and the Teaching Council of Ireland developed policies requiring higher education institutions providing Initial Teacher Education (ITE) to undergo a re-accreditation process from 2012. This involved both an extension and a reconceptualization of programmes, with mandatory additional content related to inclusive education and differentiation, together with the opportunity for a wider range of school placement experiences. All concurrent (undergraduate) programmes of initial teacher education must be of four years' duration and all consecutive (postgraduate) programmes of initial teacher education must be of two years' duration. The latter were re-accredited at Masters Level 9 on the National Framework of Qualifications. Following this major reform, the National Council for Special Education (NCSE) in Ireland commissioned a study of ‘Initial Teacher Education for Inclusion’ in 2015. NCSE’s research aim was: ‘to establish what the components of inclusive/special education are within Initial Teacher Education (ITE) programmes in Ireland and to explore if the recent changes prepare newly qualified teachers to be inclusive using the indicators set out in the EASNIE’s Profile of Inclusive Teachers’. The European Agency for Special Needs and Inclusive Education (EASNIE) conducted a four-year project on Teacher Education for Inclusion, involving representatives of twenty five countries. A key output was a proposed ‘Profile of Inclusive Teachers’ (EADSNE, 2012), which outlines a range of attitudes, knowledge and skills in relation to four core values and eight areas of competence, to be addressed in initial teacher education to prepare all new teachers to become more inclusive. The NCSE proposed the EASNIE Profile of Inclusive Teachers as the baseline definition of inclusive teaching for the project and it is used by the research team as the framework and starting point for analysis. The ‘Initial Teacher Education for Inclusion’ project (ITE4I), runs from 2015-2018. The research team is led by Manchester Metropolitan University in partnership with University College Cork and University College London, Institute of Education. We understand this project may be one of the first system-wide, longitudinal studies of initial teacher education for inclusive teaching in Europe. This report relates to the first year of the project in 2015/16, which analysed the content of ITE programmes and studied the experiences of the first cohort of student teachers to graduate from the extended and reconceptualised programmes, in their final year of study. This comprised two phases of data collection: in Phase 1 we analysed programme documents and surveyed teacher educators; in Phase 2 we surveyed student teachers and interviewed a sample of student teachers and teacher educators. At the same time, a literature review was developed setting out definitional debates on inclusive education and outlining the scope of the international literature on inclusive teaching. Research design The Research Questions formulated by National Council for Special Education (NCSE) were as follows: 1. What are the components of inclusive/special education within Initial Teacher Education (ITE) programmes in Ireland for primary and post-primary teachers? 2. Do the recent changes to ITE prepare newly qualified teachers to be inclusive as identified by European Agency for Special Needs and Inclusive Education (EASNIE) Profile of Inclusive Teachers? 3. What is the intended impact of the changes in ITE on outcomes for students with special educational needs (SEN) and do student/newly qualified teachers perceive their learning during initial teacher education makes an impact on outcomes for students with SEN? 4. What gaps are there in how current ITE programmes prepare student teachers to be inclusive as per the EASNIE Profile of Inclusive Teachers and what aspects need to be strengthened to better prepare student teachers to be inclusive? 5. What lessons can be identified from this research for initial teacher education in Ireland and subsequent phases in the continuum of teacher education? The Project Phases were planned around data collection over the three years of the project: Phase 1 (Sept. – Jan. 2016): Analysing ITE Programme Content Data collection in Phase 1 included documentary analysis and a survey of teacher educators. Documentation relating to some 30 programmes (out of 59 nationally) from 13 ITE providers (out of 19 in total) was obtained with the support of the Teaching Council. These were primarily standard proforma submitted for re-accreditation, with module outlines appended in some cases; in addition, reviews of these submissions published by the Teaching Council were analysed, together with the criteria used for re-accreditation. The documentary analysis started from a typology derived from the EASNIE Profile of Inclusive Teachers, to examine how and where inclusive teaching is represented within ITE programme documents. A survey of teacher educators was conducted at the same time, to collect initial data on the range of views expressed by teacher educators in relation to issues of inclusive teaching in ITE programmes. The survey was constructed to reflect areas of competence within the EASNIE Profile of Inclusive Teachers, and to collect free-text comments. Following piloting, 21 respondents (programme leaders, module leaders, heads of departments) provided complete or near-complete responses giving information relating to 27 programmes from 13 institutions (some survey responses related to more than one programme). Phase 2 (Feb. – Aug. 2016): Understanding the ITE Student Experience Data collection in Phase 2 included a survey of student teachers, together with interviews with student teachers and with teacher educators at five case study sites. The five ITE providers were selected to represent a range of primary, post-primary, consecutive and concurrent programmes; and to provide a geographical spread of institutions. The survey of student teachers elicited data about their experiences of initial teacher education and their understandings of inclusive teaching. The questionnaire captured demographic information, key areas of experience prior to and during the respondents’ ITE programme, and a series of statements mapped to an analysis of the attitude, knowledge and skills components of the EASNIE profile. A total of 430 valid responses were received, representing a sample of approximately 13% of the national cohort of student teachers. The interviews with student teachers aimed to elicit their views about their course and how their studies related to their school placement experiences; their understandings of inclusive teaching; their approaches to inclusive teaching in practice; and their reflections on their own professional development in relation to inclusive teaching and how their courses might be developed. A total of 47 students were interviewed in person or by Skype, with 32 recruited at the five case study sites and a further 15 recruited by survey responses from other institutions. The interviews with teacher educators sought their views on issues of inclusive teaching and ITE in Ireland, and on the impact of the extension and reconceptualization of ITE programmes; their responses to emergent themes and issues arising from the survey of teacher educators and the documentary analysis; and their reflections on aspects of the EASNIE Profile of Inclusive Teachers. A total of 11 staff interviews were conducted across the five case study sites, typically including the Head of School or a Programme Leader and a lecturer in inclusive or special education.

Published
2018

24. Sensations, natural properties, and the private language argument

Author

Child, T, Cahill, K, and Raleigh, T

Abstract

Wittgenstein’s philosophy involves a general anti-platonism about properties or standards of similarity. On his view, what it is for one thing to have the same property as another is not dictated by reality itself; it depends on our classificatory practices and the standards of similarity they embody. Wittgenstein’s anti-platonism plays an important role in the private language sections and in his discussion of the conceptual problem of other minds. In sharp contrast to Wittgenstein’s views stands the contemporary doctrine of natural properties, which holds that there is an objective hierarchy of naturalness amongst properties, a hierarchy that is completely independent of our concepts or practices. Some authors have appealed to the natural properties view to offer an explicitly anti-Wittgensteinian account of sensation concepts. The paper discusses these competing views of properties and sensation concepts. It is argued that, if our account of concepts of conscious states starts from a commitment to natural properties, we are bound to recognize that our actual classificatory practices also play a crucial role in determining which properties our concepts pick out. On the other hand, if we start from the anti-platonist position, we are bound to recognize that we also need a notion of sameness of property that extends beyond our limited capacity to recognize similarity or sameness of property. The correct view, it is concluded, must occupy a middle position between an extreme anti-realism about properties and an extreme version of the natural properties view. It is suggested that Wittgenstein’s own view does just that.

Published
2018

28. Mass media interventions for smoking cessation in adults

Author

Bala, MM, Strzeszynski, L, Topor-Madry, R, and Cahill, K

Subjects
Medicine General & Introductory Medical Sciences, Adult, Smoking prevention, medicine.medical_treatment, Health Behavior, MEDLINE, Psychological intervention, Smoking Prevention, Health Promotion, 03 medical and health sciences, 0302 clinical medicine, Environmental health, Humans, Medicine, Pharmacology (medical), Mass Media, 030212 general & internal medicine, Mass media, Tobacco harm reduction, 030505 public health, business.industry, Tobacco control, Smoking cessation, Smoking Cessation, Health behavior, 0305 other medical science, business
Abstract

BACKGROUND: Mass media tobacco control campaigns can reach large numbers of people. Much of the literature is focused on the effects of tobacco control advertising on young people, but there are also a number of evaluations of campaigns targeting adult smokers, which show mixed results. Campaigns may be local, regional or national, and may be combined with other components of a comprehensive tobacco control policy. OBJECTIVES: To assess the effectiveness of mass media interventions in reducing smoking among adults. SEARCH METHODS: The Cochrane Tobacco Addiction Group search strategy was combined with additional searches for any studies that referred to tobacco/smoking cessation, mass media and adults. We also searched the Cochrane Central Register of Controlled Trials (CENTRAL) and a number of electronic databases. The last search was carried out in November 2016. SELECTION CRITERIA: Controlled trials allocating communities, regions or states to intervention or control conditions; interrupted time series. Adults, 25 years or older, who regularly smoke cigarettes. Studies which cover all adults as defined in studies were included. Mass media are defined here as channels of communication such as television, radio, newspapers, billboards, posters, leaflets or booklets intended to reach large numbers of people, and which are not dependent on person‐to‐person contact. The purpose of the mass media campaign must be primarily to encourage smokers to quit. They could be carried out alone or in conjunction with tobacco control programmes. The primary outcome was change in smoking behaviour. This could be reported as changes in prevalence, changes in cigarette consumption, quit rates, or odds of being a smoker. DATA COLLECTION AND ANALYSIS: Two authors independently assessed all studies for inclusion criteria and for study quality (MB, LS, RTM). One author (MB) extracted data, and a second author (LS) checked them. Results were not pooled due to heterogeneity of the included studies and are presented narratively and in table form. MAIN RESULTS: Eleven campaigns met the inclusion criteria for this review. Studies differed in design, settings, duration, content and intensity of intervention, length of follow‐up, methods of evaluation and also in definitions and measures of smoking behaviour used. Among seven campaigns reporting smoking prevalence, significant decreases were observed in the California and Massachusetts statewide tobacco control campaigns compared with the rest of the USA. Some positive effects on prevalence in the whole population or in the subgroups were observed in three of the remaining seven studies. Three large‐scale campaigns of the seven presenting results for tobacco consumption found statistically significant decreases. Among the eight studies presenting abstinence or quit rates, four showed some positive effect, although in one of them the effect was measured for quitting and cutting down combined. Among the three that did not show significant decreases, one demonstrated a significant intervention effect on smokers and ex‐smokers combined. AUTHORS' CONCLUSIONS: There is evidence that comprehensive tobacco control programmes which include mass media campaigns can be effective in changing smoking behaviour in adults, but the evidence comes from a heterogeneous group of studies of variable methodological quality. One state‐wide tobacco control programme (Massachusetts) showed positive results up to eight years after the campaign. Another (California) showed positive results during the period of adequate funding and implementation and in final evaluation since the beginning of the programme. Six of nine studies carried out in communities or regions showed some positive effects on smoking behaviour and at least one significant change in smoking prevalence (Sydney). The intensity and duration of mass media campaigns may influence effectiveness, but length of follow‐up and concurrent secular trends and events can make this difficult to quantify. No consistent relationship was observed between campaign effectiveness and age, education, ethnicity or gender.

Published
2017

31. Circulating microRNAs in Sera Correlate with Soluble Biomarkers of Immune Activation but Do Not Predict Mortality in ART Treated Individuals with HIV-1 Infection: A Case Control Study

Author

Murray, D. D., Suzuki, K., Law, M., Trebicka, J., Neuhaus, J., Wentworth, D., Johnson, M., Vjecha, M. J., Kelleher, A. D., Emery, S., Aagaard, B., Aragon, E., Arnaiz, J., Borup, L., Clotet, B., Dragsted, U., Fau, A., Gey, D., Grarup, J., Hengge, U., Herrero, P., Jansson, P., Jensen, B., Jensen, K., Juncher, H., Lopez, P., Lundgren, J. D., Matthews, C., Mollerup, D., Pearson, M., Phillips, A., Reilev, S., Tillmann, K., Varea, S., Angus, B., Babiker, A., Cordwell, B., Darbyshire, J., Dodds, W., Fleck, S., Horton, J., Hudson, F., Moraes, Y., Pacciarini, F., Palfreeman, A., Paton, N., Smith, N., Van Hooff, F., Bebchuk, J., Collins, G., Denning, E., Duchene, A., Fosdick, L., Harrison, M., Herman-Lamin, K., Krum, E., Larson, G., Neaton, J., Nelson, R., Quan, K., Quan, S., Schultz, T., Thompson, G., Wyman, N., Carey, C., Chan, F., Cooper, D., Courtney-Rodgers, D., Drummond, F., Harrod, M., Jacoby, S., Kearney, L., Lin, E., Pett, S., Robson, R., Seneviratne, N., Stewart, M., Watts, E., Finley, E., Gordin, F., Sanchez, A., Standridge, B., Belloso, W., Davey, R., Duprez, D., Gatell, J., Hoy, J., Lifson, A., Pederson, C., Perez, G., Price, R., Prineas, R., Rhame, F., Sampson, J., Worley, J., Modlin, J., Beral, V., Chaisson, R., Fleming, T., Hill, C., Kim, K., Murray, B., Pick, B., Seligmann, M., Weller, I., Cahill, K., Fox, L., Luzar, M., Martinez, A., Mcnay, L., Pierson, J., Tierney, J., Vogel, S., Costas, V., Eckstrand, J., Brown, S., Abusamra, L., Angel, E., Aquilia, S., Benetucci, J., Bittar, V., Bogdanowicz, E., Cahn, P., Casiro, A., Contarelli, J., Corral, J., Daciuk, L., David, D., Dobrzanski, W., Duran, A., Ebenrstejin, J., Ferrari, I., Fridman, D., Galache, V., Guaragna, G., Ivalo, S., Krolewiecki, A., Lanusse, I., Laplume, H., Lasala, M., Lattes, R., Lazovski, J., Lopardo, G., Losso, M., Lourtau, L., Lupo, S., Maranzana, A., Marson, C., Massera, L., Moscatello, G., Olivia, S., Otegui, I., Palacios, L., Parlante, A., Salomon, H., Sanchez, M., Somenzini, C., Suarez, C., Tocci, M., Toibaro, J., Zala, C., Agrawal, S., Ambrose, P., Anderson, C., Anderson, J., Baker, D., Beileiter, K., Blavius, K., Bloch, M., Boyle, M., Bradford, D., Britton, P., Brown, P., Busic, T., Cain, A., Carrall, L., Carson, S., Chenoweth, I., Chuah, J., Clark, F., Clemons, J., Clezy, K., Cortissos, P., Cunningham, N., Curry, M., Daly, L., D'Arcy-Evans, C., Del Rosario, R., Dinning, S., Dobson, P., Donohue, W., Doong, N., Downs, C., Edwards, E., Edwards, S., Egan, C., Ferguson, W., Finlayson, R., Forsdyke, C., Foy, L., Franic, T., Frater, A., French, M., Gleeson, D., Gold, J., Habel, P., Haig, K., Hardy, S., Holland, R., Hudson, J., Hutchison, R., Hyland, N., James, R., Johnston, C., Kelly, M., King, M., Kunkel, K., Lau, H., Leamy, J., Lester, D., Leung, J., Lohmeyer, A., Lowe, K., Macrae, K., Magness, C., Martinez, O., Maruszak, H., Medland, N., Miller, S., Murray, J., Negus, P., Newman, R., Ngieng, M., Nowlan, C., Oddy, J., Orford, N., Orth, D., Patching, J., Plummer, M., Price, S., Primrose, R., Prone, I., Ree, H., Remington, C., Richardson, R., Robinson, S., Rogers, G., Roney, J., Roth, N., Russell, D., Ryan, S., Sarangapany, J., Schmidt, T., Schneider, K., Shields, C., Silberberg, C., Shaw, D., Skett, J., Smith, D., Soo, T. M., Sowden, D., Street, A., Tee, B. K., Thomson, J., Topaz, S., Vale, R., Villella, C., Walker, A., Watson, A., Wendt, N., Williams, L., Youds, D., Aichelburg, A., Cichon, P., Gemeinhart, B., Rieger, A., Schmied, B., Touzeau-Romer, V., Vetter, N., Colebunders, R., Clumeck, N., Deroo, A., Kabeya, K., O'Doherty, E., De Wit, S., De Salles Amorim, C., Basso, C., Flint, S., Kallas, E., Levi, G., Lewi, D., Pereira, L., Da Silva, M., Souza, T., Toscano, A., Angel, J., Arsenault, M., Bast, M., Beckthold, B., Bouchard, P., Chabot, I., Clarke, R., Cohen, J., Cote, P., Ellis, M., Gagne, C., Gill, J., Houde, M., Johnston, B., Jubinville, N., Kato, C., Lamoureux, N., Latendre-Paquette, J., Lindemulder, A., Mcneil, A., Mcfarland, N., Montaner, J., Morrisseau, C., O'Neill, R., Page, G., Piche, A., Pongracz, B., Preziosi, H., Puri, L., Rachlis, A., Ralph, E., Raymond, I., Rouleau, D., Routy, J. P., Sandre, R., Seddon, T., Shafran, S., Sikora, C., Smaill, F., Stromberg, D., Trottier, S., Walmsley, S., Weiss, K., Williams, K., Zarowny, D., Baadegaard, B., Andersen, A. B., Boedker, K., Collins, P., Gerstoft, J., Jensen, L., Moller, H., Andersen, P. L., Loftheim, I., Mathiesen, L., Nielsen, H., Obel, N., Pedersen, C., Petersen, D., Jensen, L. P., Black, F. T., Aboulker, J. P., Aouba, A., Bensalem, M., Berthe, H., Blanc, C., Bornarel, D., Bouchaud, O., Boue, F., Bouvet, E., Brancon, C., Breaud, S., Brosseau, D., Brunet, A., Capitant, C., Ceppi, C., Chakvetadze, C., Cheneau, C., Chennebault, J. M., De Truchis, P., Delavalle, A. M., Delfraissy, J. F., Dellamonica, P., Dumont, C., Edeb, N., Fabre, G., Ferrando, S., Foltzer, A., Foubert, V., Gastaut, J. A., Gerbe, J., Girard, P. M., Goujard, C., Hoen, B., Honore, P., Hue, H., Hynh, T., Jung, C., Kahi, S., Katlama, C., Lang, J. M., Le Baut, V., Lefebvre, B., Leturque, N., Levy, Y., Loison, J., Maddi, G., Maignan, A., Majerholc, C., De Boever, C., Meynard, J. L., Michelet, C., Michon, C., Mole, M., Netzer, E., Pialoux, G., Poizot-Martin, I., Raffi, F., Ratajczak, M., Ravaux, I., Reynes, J., Salmon-Ceron, D., Sebire, M., Simon, A., Tegna, L., Tisne-Dessus, D., Tramoni, C., Viard, J. P., Vidal, M., Viet-Peaucelle, C., Weiss, L., Zeng, A., Zucman, D., Adam, A., Arasteh, K., Behrens, G., Bergmann, F., Bickel, M., Bittner, D., Bogner, J., Brockmeyer, N., Darrelmann, N., Deja, M., Doerler, M., Esser, S., Faetkenheuer, G., Fenske, S., Gajetzki, S., Goebel, F., Gorriahn, D., Harrer, E., Harrer, T., Hartl, H., Hartmann, M., Heesch, S., Jakob, W., Jager, H., Klinker, H., Kremer, G., Ludwig, C., Mantzsch, K., Mauss, S., Meurer, A., Niedermeier, A., Pittack, N., Plettenberg, A., Potthoff, A., Probst, M., Rittweger, M., Rockstroh, J., Ross, B., Rotty, J., Rund, E., Ruzicka, T., Schmidt, R., Schmutz, G., Schnaitmann, E., Schuster, D., Sehr, T., Spaeth, B., Staszewski, S., Stellbrink, H. J., Stephan, C., Stockey, T., Stoehr, A., Trein, A., Vaeth, T., Vogel, M., Wasmuth, J., Wengenroth, C., Winzer, R., Wolf, E., Mulcahy, F., Reidy, D., Cohen, Y., Drora, G., Eliezer, I., Godo, O., Kedem, E., Magen, E., Mamorsky, M., Pollack, S., Sthoeger, Z., Vered, H., Yust, I., Aiuti, F., Bechi, M., Bergamasco, A., Bertelli, D., Bruno, R., Butini, L., Cagliuso, M., Carosi, G., Casari, S., Chrysoula, V., Cologni, G., Conti, V., Costantini, A., Corpolongo, A., D'Offizi, G., Gaiottino, F., Di Pietro, M., Esposito, R., Filice, G., Francesco, M., Gianelli, E., Graziella, C., Magenta, L., Martellotta, F., Maserati, R., Mazzotta, F., Murdaca, G., Nardini, G., Nozza, S., Puppo, F., Pogliaghi, M., Ripamonti, D., Ronchetti, C., Rusconi, S., Rusconi, V., Sacchi, P., Silvia, N., Suter, F., Tambussi, G., Uglietti, A., Vechi, M., Vergani, B., Vichi, F., Vitiello, P., Iwamoto, A., Kikuchi, Y., Miyazaki, N., Mori, M., Nakamura, T., Odawara, T., Oka, S., Shirasaka, T., Tabata, M., Takano, M., Ueta, C., Watanabe, D., Yamamoto, Y., Erradey, I., Himmich, H., El Filali, K. M., Blok, W., Van Boxtel, R., Doevelaar, K. B. H., Van Eeden, A., Grijsen, M., Groot, M., Juttmann, J., Kuipers, M., Ligthart, S., Van Der Meulen, P., Lange, J., Langebeek, N., Reiss, P., Richter, C., Schoemaker, M., Schrijnders-Gudde, L., Septer-Bijleveld, E., Sprenger, H., Vermeulen, J., Ten Kate, R., Van De Ven, B., Bruun, J., Kvale, D., Maeland, A., Bakowska, E., Beniowski, M., Boron-Kaczmarska, A., Gasiorowski, J., Horban, A., Inglot, M., Knysz, B., Mularska, E., Parczewski, M., Pynka, M., Rymer, W., Szymczak, A., Aldir, M., Antunes, F., Baptista, C., Da Conceicao Vera, J., Doroana, M., Mansinho, K., Dos Santos, C. R. A., Valadas, E., Vaz Pinto, I., Chia, E., Foo, E., Karim, F., Lim, P. L., Panchalingam, A., Quek, A., Alcazar-Caballero, R., Arribas, J., Arrizabalaga, J., De Barron, X., Blanco, F., Bouza, E., Bravo, I., Calvo, S., Carbonero, L., Carpena, I., Castro, M., Cortes, L., Del Toro, M., Domingo, P., Elias, M., Espinosa, J., Estrada, V., Fernandez-Cruz, E., Fernandez, P., Freud, H., Fuster, M., Garcia, A., Garcia, G., Garrido, R., Gijon, P., Gonzalez-Garcia, J., Gil, I., Gonzalez, A., Gonzalez-Lahoz, J., Grosso, P. 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M., Peters, S., Peto, T. E. A., Portsmouth, S. D., Rajamanoharan, S., Ronan, Schwenk, A., Slinn, M. A., Stroud, C. J., Thomas, R. C., Wansbrough-Jones, M. H., Whiles, H. J., White, D. J., Williams, E., Williams, G., Youle, M., Abrams, D. I., Acosta, E. A., Adamski, A., Antoniskis, D., Aragon, D. R., Barnett, B. J., Baroni, C., Barron, M., Baxter, J. D., Beers, D., Beilke, M., Bemenderfer, Bernard, A., Besch, C. L., Bessesen, M. T., Bethel, J. T., Blue, S., Blum, J. D., Boarden, S., Bolan, R. K., Borgman, J. B., Brar, I., Braxton, B. K., Bredeek, U. F., Brennan, R., Britt, D. E., Bulgin-Coleman, D., Bullock, E., Campbell, B., Caras, S., Carroll, J., Casey, K. K., Chiang, F., Cindrich, R. B., Cohen, C., Coley, J., Condoluci, D. V., Contreras, R., Corser, J., Cozzolino, J., Crane, L. R., Daley, L., Dandridge, D., D'Antuono, V., Darcourt Rizo Patron, J. G., Dehovitz, J. A., Dejesus, E., Desjardin, J., Dietrich, C., Dolce, A., Erickson, D., Faber, L. L., Falbo, J., Farrough, M. 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K., Visnegarwala, F., Wade, H., Weis, S. E., Weise, J. A., Weissman, S., Wilkin, M., Witter, J. H., Wojtusic, L., Wright, T. J., Yeh, V., Young, B., Zeana, C., Zeh, J., Savio, E., Vacarezza, M., and Pacheco, Antonio Guilherme

Subjects
Adult, CD4-Positive T-Lymphocytes, Male, General Science & Technology, Anti-HIV Agents, T cell, lcsh:Medicine, Antiretroviral Therapy, HIV Infections, Biology, Essential hypertension, Logistic regression, Malignancy, Acquired immunodeficiency syndrome (AIDS), Clinical Research, Antiretroviral Therapy, Highly Active, microRNA, medicine, Genetics, 2.1 Biological and endogenous factors, Humans, Highly Active, Aetiology, lcsh:Science, Genetic Association Studies, Multidisciplinary, lcsh:R, Case-control study, Middle Aged, medicine.disease, 3. Good health, Circulating MicroRNA, MicroRNAs, medicine.anatomical_structure, Infectious Diseases, Good Health and Well Being, INSIGHT ESPRIT and SMART Study Groups, Immunology, HIV-1, HIV/AIDS, lcsh:Q, Female, Infection, Biomarkers, Biotechnology, Research Article
Abstract

Introduction The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR-145 correlated with nadir CD4+ T cell count. Discussion No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection.

Published
2015

32. Development and validation of a risk score for chronic kidney disease in HIV infection using prospective cohort data from the D:A:D study

Author

Mocroft, Amanda, Lundgren, Jens D., Ross, Michael, Law, Matthew, Reiss, Peter, Kirk, Ole, Smith, Colette, Wentworth, Deborah, Neuhaus, Jacqueline, Fux, Christoph A., Moranne, Olivier, Morlat, Phillipe, Johnson, Margaret A., Ryom, Lene, Lundgren, J. D., Powderly, B., Shortman, N., Moecklinghoff, C., Reilly, G., Franquet, X., Sabin, C. A., Phillips, A., Kirk, O., Reiss, P., Weber, R., Pradier, C., Law, M., d'Arminio Monforte, A., Dabis, F., El-Sadr, W. M., De Wit, S., Ryom, L., Kamara, D., Smith, C., Mocroft, A., Tverland, J., Mansfeld, M., Nielsen, J., Raben, D., Salbøl Brandt, R., Rickenbach, M., Fanti, I., Krum, E., Hillebregt, M., Geffard, S., Sundström, A., Delforge, M., Fontas, E., Torres, F., Mcmanus, H., Wright, S., Kjær, J., Sjøl, A., Meidahl, P., Helweg-Larsen, J., Schmidt Iversen, J., Ross, M., Fux, C. A., Morlat, P., Moranne, O., Kesselring, A. M., Kamara, D. A., Friis-Møller, N., Kowalska, J., Sabin, C., Bruyand, M., Bower, M., Fätkenheuer, G., Donald, A., Grulich, A., Prins, J. M., Kuijpers, T. W., Scherpbier, H. J., van der Meer, J. T. M., Wit, F. W. M. N., Godfried, M. H., van der Poll, T., Nellen, F. J. B., Geerlings, S. E., van Vugt, M., Pajkrt, D., Bos, J. C., Wiersinga, W. J., van der Valk, M., Goorhuis, A., Hovius, J. W., van Eden, J., Henderiks, A., van Hes, A. M. H., Mutschelknauss, M., Nobel, H. E., Pijnappel, F. J. J., Westerman, A. M., Jurriaans, S., Back, N. K. T., Zaaijer, H. L., Berkhout, B., Cornelissen, M. T. E., Schinkel, C. J., Thomas, X. V., van den Berge, M., Stegeman, A., Baas, S., Hage de Looff, L., Versteeg, D., Pronk, M. J. H., Ammerlaan, H. S. M., Korsten-Vorstermans, E. M. H. M., de Munnik, E. S., Jansz, A. R., Tjhie, J., Wegdam, M. C. A., Deiman, B., Scharnhorst, V., van der Plas, A., Weijsenfeld, A. M., van der Ende, M. E., de Vries-Sluijs, T. E. M. S., C. M. van Gorp, E., Schurink, C. A. M., Nouwen, J. L., Verbon, A., Rijnders, B. J. A., Bax, H. I., Hassing, R. J., van der Feltz, M., Bassant, N., van Beek, J. E. A., Vriesde, M., van Zonneveld, L. M., de Oude-Lubbers, A., van den Berg-Cameron, H. J., Bruinsma-Broekman, F. B., de Groot, J., de Zeeuw- de Man, M., Broekhoven-Kruijne, M. J., Schutten, M., Osterhaus, A. D. M. E., Boucher, C. A. B., Driessen, G. J. A., van Rossum, A. M. C., van der Knaap, L. C., Visser, E., Branger, J., H. M. Duijf-van de Ven, C. J., Schippers, E. F., van Nieuwkoop, C., Brimicombe, R. W., van IJperen, J. M., van der Hut, G., Franck, P. F. H., van Eeden, A., Brokking, W., Groot, M., Damen, M., Kwa, I. S., Groeneveld, P. H. P., Bouwhuis, J. W., van den Berg, J. F., van Hulzen, A. G. W., van der Bliek, G. L., Bor, P. C. J., Bloembergen, P., Wolfhagen, M. J. H. M., Ruijs, G. J. H. M., van Lelyveld, S. F. L., Soetekouw, R., Hulshoff, N., van der Prijt, L. M. M., Schoemaker, M., Bermon, N., van der Reijden, W. A., Jansen, R., Herpers, B. L., Veenendaal, D., Kroon, F. P., Arend, S. M., de Boer, M. G. J., Bauer, M. P., Jolink, H., Vollaard, A. M., Dorama, W., Moons, C., Claas, E. C. J., Kroes, A. C. M., den Hollander, J. G., Pogany, K., Kastelijns, M., Smit, J. V., Smit, E., Bezemer, M., van Niekerk, T., Pontesilli, O., Lowe, S. H., Oude Lashof, A., Posthouwer, D., Ackens, R. P., Schippers, J., Vergoossen, R., Weijenberg Maes, B., Savelkoul, P. H. M., Loo, I. H., Weijer, S., El Moussaoui, R., Heitmuller, M., Kortmann, W., van Twillert, G., Cohen Stuart, J. W. T., Diederen, B. M. W., Pronk, D., van Truijen-Oud, F. A., Leyten, E. M. S., Gelinck, L. B. S., van Hartingsveld, A., Meerkerk, C., Wildenbeest, G. S., Mutsaers, J. A. E. M., Jansen, C. L., van Vonderen, M. G. A., van Houte, D. P. F., Dijkstra, K., Faber, S., Weel, J., Kootstra, G. J., Delsing, C. E., van der Burg-van de Plas, M., Heins, H., Lucas, E., Brinkman, K., Frissen, P. H. J., Blok, W. L., Schouten, W. E. M., Bosma, A. S., Brouwer, C. J., Geerders, G. 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W., Howe-Pittman, M., Hubbard, J., Hudson, R., Hunter, H., Hutelmyer, C., Insignares, M. T., Jackson, L., Jenny, L., Johnson, D. L., Johnson, G., Johnson, J., Kaatz, J., Kaczmarski, J., Kagan, S., Kantor, C., Kempner, T., Kieckhaus, K., Kimmel, N., Klaus, B. M., Koeppe, J. R., Koirala, J., Kopka, J., Kostman, J. R., Kozal, M. J., Kumar, A., Lampiris, H., Lamprecht, C., Lattanzi, K. M., Lee, J., Leggett, J., Long, C., Loquere, A., Loveless, K., Lucasti, C. J., Macveigh, M., Makohon, L. H., Markowitz, N. P., Marks, C., Martorell, C., Mcfeaters, E., Mcgee, B., Mcintyre, D. M., Mcmanus, E., Melecio, L. G., Melton, D., Mercado, S., Merrifield, E., Mieras, J. A., Mogyoros, M., Moran, F. M., Murphy, K., Mutic, S., Nadeem, I., Nadler, J. P., Ognjan, A., O'Hearn, M., O'Keefe, K., Okhuysen, P. C., Oldfield, E., Olson, D., Orenstein, R., Ortiz, R., Parpart, F., Pastore-Lange, V., Paul, S., Pavlatos, A., Pearce, D. D., Pelz, R., Peterson, S., Pitrak, D., Powers, S. L., Pujet, H. C., Raaum, J. 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J., Yeh, V., Young, B., Zeana, C., Zeh, J., Savio, E., Vacarezza, M., University College of London [London] (UCL), University of Copenhagen = Københavns Universitet (KU), University of New South Wales [Sydney] (UNSW), University of Amsterdam [Amsterdam] (UvA), University of Minnesota [Twin Cities] (UMN), University of Minnesota System, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Nice (CHU Nice), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Med Microbiol, Infect Dis & Infect Prev, RS: NUTRIM - R3 - Chronic inflammatory disease and wasting, RS: CAPHRI School for Public Health and Primary Care, RS: CAPHRI - R4 - Health Inequities and Societal Participation, Interne Geneeskunde, Chemical Biology, Mocroft, A, Lundgren, J, Ross, M, Law, M, Reiss, P, Kirk, O, Smith, C, Wentworth, D, Neuhaus, J, Fux, C, Moranne, O, Morlat, P, Johnson, M, Ryom, L, Gori, A, Internal medicine, CCA - Innovative therapy, ICaR - Circulation and metabolism, Medical Microbiology and Infection Prevention, CCA - Disease profiling, CCA - Immuno-pathogenesis, Plastic, Reconstructive and Hand Surgery, Mocroft, Amanda, Lundgren, Jens D., Ross, Michael, Law, Matthew, Reiss, Peter, Kirk, Ole, Smith, Colette, Wentworth, Deborah, Neuhaus, Jacqueline, Fux, Christoph A., Moranne, Olivier, Morlat, Phillipe, Johnson, Margaret A., Ryom, Lene, D:a:d Study, Group, Castagna, Antonella, the Royal Free Hospital Clinic, Cohort, and the, Insight, Smart, and ESPRIT, Study, Clinicum, Department of Medicine, Herrada, Anthony, University of Copenhagen = Københavns Universitet (UCPH), AII - Amsterdam institute for Infection and Immunity, APH - Amsterdam Public Health, Global Health, Other departments, Infectious diseases, Paediatric Infectious Diseases / Rheumatology / Immunology, General Internal Medicine, Center of Experimental and Molecular Medicine, Graduate School, Gastroenterology and Hepatology, Dermatology, ACS - Amsterdam Cardiovascular Sciences, Other Research, Anesthesiology, and Bartlett, John

Subjects
Male, Adult, Age Factors, Anti-HIV Agents, CD4 Lymphocyte Count, Clinical Decision-Making, Comorbidity, Female, HIV, HIV Infections, HIV Seropositivity, Humans, Incidence, Kidney, Middle Aged, Prospective Studies, Renal Insufficiency, Chronic, Risk, Risk Assessment, Sex Factors, urologic and male genital diseases, Biochemistry, 0302 clinical medicine, ANTIRETROVIRAL THERAPY, Adult, Age Factors, Anti-HIV Agents, CD4 Lymphocyte Count, Clinical Decision-Making, Comorbidity, Female, HIV, HIV Infections, HIV Seropositivity, Humans, Incidence, Kidney, Male, Middle Aged, Prospective Studies, Renal Insufficiency, Chronic, Risk, Risk Assessment, Sex Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Age Factor, Chronic, STAGE RENAL-DISEASE, PROTEINURIA, virus diseases, 11 Medical And Health Sciences, General Medicine, ASSOCIATION, 6. Clean water, female genital diseases and pregnancy complications, 3. Good health, HIV/AIDS, Medicine, Infection, psychological phenomena and processes, Human, medicine.medical_specialty, Renal function, NEFROPATIAS, chronic kidney disease, risk score model, 12. Responsible consumption, ESPRIT study group, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Clinical Research, D:A:D study group, Intensive care medicine, medicine (all), Molecular Biology, Royal Free Hospital Clinic Cohort, Prevention, Anti-HIV Agent, medicine.disease, Prospective Studie, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Immunology, Kidney Disease, PREDICTION, POSITIVE PERSONS, 030232 urology & nephrology, Sex Factor, SDG 3 – Goede gezondheid en welzijn, Medical and Health Sciences, GLOMERULAR-FILTRATION-RATE, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, INSIGHT study group, HIV Infection, LIFE EXPECTANCY, 030212 general & internal medicine, Renal Insufficiency, Prospective cohort study, Framingham Risk Score, Incidence (epidemiology), adult, age factors, anti-hiv agents, CD4 lymphocyte count, clinical decision-making, comorbidity, female, hiv, hiv infections, hiv seropositivity, humans, incidence, kidney, male, middle aged, prospective studies, renal insufficiency, chronic, risk, risk assessment, sex factors, SMART study group, 6.1 Pharmaceuticals, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Patient Safety, Risk assessment, Biotechnology, Research Article, Settore MED/17 - MALATTIE INFETTIVE, NO, A:D study group [D], General & Internal Medicine, Diabetes mellitus, mental disorders, medicine, EXPOSURE, business.industry, Evaluation of treatments and therapeutic interventions, Cell Biology, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, INDIVIDUALS, Good Health and Well Being, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 3121 General medicine, internal medicine and other clinical medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Kidney disease
Abstract

Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with ≥3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR ≤ 60 ml/min/1.73 m2. Poisson regression was used to develop a risk score, externally validated on two independent cohorts. In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7–6.7; median follow-up 6.1 y, range 0.3–9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was −2 (interquartile range –4 to 2). There was a 1:393 chance of developing CKD in the next 5 y in the low risk group (risk score < 0, 33 events), rising to 1:47 and 1:6 in the medium (risk score 0–4, 103 events) and high risk groups (risk score ≥ 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166–3,367); NNTH was 202 (95% CI 159–278) and 21 (95% CI 19–23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506–1462), 88 (95% CI 69–121), and 9 (95% CI 8–10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3–12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6–8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD., Editors’ Summary Background About 35 million people are currently infected with HIV, the virus that causes AIDS. HIV destroys CD4 lymphocytes and other immune system cells, leaving infected individuals susceptible to other infections. HIV infection can be controlled, but not cured, using combination antiretroviral therapy (cART), and, nowadays, the life expectancy of many HIV-positive individuals is similar to that of HIV-negative people. HIV-positive individuals nevertheless experience some illnesses more frequently than HIV-negative people do. For example, up to a third of HIV-positive individuals develop chronic kidney disease (CKD), which is associated with an increased risk of cardiovascular disease and death. Persons with CKD may have an impaired effect of the filtration units in the kidneys that remove waste products and excess water from the blood to make urine, thereby leading to a reduced blood filtration rate (the estimated glomerular filtration rate [eGFR]) and waste product accumulation in the blood. Symptoms of CKD, which rarely occur until the disease is advanced, include tiredness, swollen feet, and frequent urination. Advanced stages of CKD cannot be cured, but its progression can be slowed by, for example, controlling hypertension (high blood pressure) and diabetes (two CDK risk factors) and by adopting a healthy lifestyle. Why Was This Study Done? The burden of CKD may increase among HIV-positive individuals as they age, and clinicians need to know which individuals are at high risk of developing CKD when choosing cART regimens for their patients. In addition, clinicians need to be able to identify those HIV-positive individuals at greatest risk of CKD so that they can monitor them for early signs of kidney disease. Some antiretroviral drugs—for example, tenofovir and atazanavir/ritonavir (a boosted protease inhibitor)—are associated with kidney damage. Clinicians may need to weigh the benefits and risks of giving such potentially nephrotoxic drugs to individuals who already have a high CKD risk. Here, the researchers develop and validate a simple, widely applicable risk score (a risk prediction model) for CKD among HIV-positive individuals and investigate the relationship between CKD and potentially nephrotoxic antiretroviral drugs among individuals with different CKD risk score profiles. What Did the Researchers Do and Find? To develop their CKD risk score, the researchers used clinical and demographic data collected from 17,954 HIV-positive individuals enrolled in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study who had an eGFR > 60 ml/min/1.73 m2 and were not taking a potentially nephrotoxic antiretroviral at baseline. During 103,185 person-years of follow-up, 641 individuals developed CKD. Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease predicted CKD. The researchers included these nine factors in their risk score model (which is available online) and defined three risk groups: low (risk score < 0), medium (risk score 0–4), and high (risk score ≥ 5) risk of CKD development in the next five years. Specifically, there was a 1 in 393, 1 in 47, and 1 in 6 chance of developing CKD in the next five years in the low, medium, and high risk groups, respectively. Because some patients started to use potentially nephrotoxic antiretroviral drugs during follow-up, the researchers were able to use their risk score model to calculate how many patients would have to be treated with one of these drugs for an additional patient to develop CKD over five years in each risk group. This “number needed to harm” (NNTH) for patients starting treatment with tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor was 739, 88, and 9 in the low, medium, and high risk groups, respectively. Finally, the researchers validated the accuracy of their risk score in two independent HIV study groups. What Do These Findings Mean? These findings provide a simple, validated risk score for CKD and indicate that the NNTH when starting potentially nephrotoxic antiretrovirals was low among HIV-positive individuals at the highest risk of CKD (i.e., treating just nine individuals with nephrotoxic antiretroviral drugs will likely lead to an additional case of CKD in five years). Although various aspects of the study, including the lack of data on race, limit the accuracy of these findings, these findings highlight the need for monitoring, screening, and chronic disease prevention to minimize the risk of HIV-positive individuals developing diabetes, hypertension, or cardiovascular disease, or becoming coinfected with hepatitis C, all of which contribute to the CKD risk score. Moreover, the development of a tool for estimating an individual’s five-year risk of developing CKD with or without the addition of potentially nephrotoxic antiretroviral drugs will enable clinicians and patients to weigh the benefits of certain antiretroviral drugs against the risk of CKD and make informed decisions about treatment options. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001809. Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS NAM/aidsmap provides basic information about HIV/AIDS, summaries of recent research findings on HIV care and treatment, and personal stories about living with AIDS/HIV Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including personal stories about living with HIV/AIDS The World Health Organization provides information on all aspects of HIV/AIDS (in several languages), including its guidelines on the use of ART for treating and preventing HIV infection The UNAIDS World AIDS Day Report 2014 provides up-to-date information about the AIDS epidemic and efforts to halt it The UK National Health Service Choices website provides information for patients on chronic kidney disease, including some personal stories The US National Kidney Foundation, a not-for-profit organization, provides information about chronic kidney disease (in English and Spanish) A tool for calculating the CDK risk score developed in this study is available Additional information about the D:A:D study is available, Amanda Mocroft and colleagues develop and validate a model for determining risk of developing chronic kidney disease for individuals with HIV if treated with different antiretroviral therapies.

Published
2015

33. Reliability of Estimating Ductions in Thyroid Eye Disease An International Thyroid Eye Disease Society Multicenter Study

Author

Dolman PJ, Cahill K, Czyz CN, Douglas RS, Elner VM, Feldon S, Kazim M, Lucarelli M, Sivak Collcott J, Stacey AW, Uddin J., STRIANESE, DIEGO, Dolman, Pj, Cahill, K, Czyz, Cn, Douglas, R, Elner, Vm, Feldon, S, Kazim, M, Lucarelli, M, Sivak Collcott, J, Stacey, Aw, Strianese, Diego, and Uddin, J.

Subjects
Thyroid Eye Disease, ocular motility, reliability of ductions examination, UNIOCULAR FIELDS
Abstract

Purpose: To determine intraobserver and interobserver reliability of 3 clinical techniques for measuring ocular ductions in patients with thyroid eye disease and to compare these with an established method using a Goldmann perimeter. Our secondary goals were to compare the clinical methods for test duration, ease of learning and performance, and whether these differed between novices and experts. Design: Multicenter, prospective, comparative trial. Participants: We recruited 38 patients with thyroid orbitopathy and reduced ocular motility from 7 academic centers. Methods: At each center, 2 novices and 2 experts measured the ocular ductions of each eye of each patient in 4 directions (0 degrees, 90 degrees, 180 degrees, and 270 degrees) using 3 techniques (best guess [BG], light reflex [LR], and a ruler measuring [RU] technique). Test duration and clinicians' feedback were recorded. A subjective and objective measurement for ocular ductions using a Goldmann perimeter was performed for each subject by a trained technician. The 3 clinical measurements and the perimetry measurements were performed twice, separated by >= 1 hour. Main Outcome Measures: We measured the intraobserver and interobserver reliability of the 3 clinical techniques and intraobserver reliability of Goldmann perimeter. Clinical testing reliability was compared between experts and novices. We also examined test duration and clinician feedback. Results: The LR technique had significantly better intraobserver and interobserver repeatability compared with the BG or RU clinical measurements and statistically was equivalent to the gold-standard perimetric technique. Reliability was constant regardless of the amount of restriction in ocular movement. There was no difference between reliability values for experts and novices. The LR and BG techniques were significantly faster than the RU or perimetry techniques and were considered easiest to learn and perform, but clinicians had most confidence in the LR technique results. Conclusions: The LR technique for measuring ocular ductions in thyroid orbitopathy is more reliable than other clinical techniques and as reliable as the established technique using the perimeter. However, unlike the latter method, it is easier to learn and perform by both novices and experts, is significantly faster, and can be performed by the clinician without machinery or a trained technician

Published
2011

34. Efficacy of interventions to combat tobacco addiction: Cochrane update of 2013 reviews

Author

Hartmann-Boyce, J, Stead, L, Cahill, K, and Lancaster, T

Abstract

AIMS: The Cochrane Collaboration is an international not-for profit organization which produces and disseminates systematic reviews. This paper is the second in a series of annual updates of Cochrane reviews on tobacco addiction interventions, covering new and updated reviews from 2013. METHODS: In 2013, the Group published two new reviews and updated 11 others. This update summarizes and comments on these reviews as well as on a review of psychosocial interventions for smoking cessation in pregnant women, and presents pooled results from reviews of cessation interventions. RESULTS: New reviews in 2013 found: low-quality evidence that behavioural interventions with mood management components could significantly increase long-term quit rates in people with current [risk ratio (RR) = 1.47, 95% confidence interval (CI) = 1.13-1.92) and past (RR = 1.41, 95% CI = 1.13-1.77] depression; evidence from network meta-analysis that varenicline and combined forms of nicotine replacement therapy (NRT) are associated with higher quit rates than bupropion or single-form NRT (varenicline versus single-form NRT odds ratio (OR) = 1.57, 95% credibility interval (CredI) = 1.29-1.91; versus bupropion OR = 1.59, 95% CredI = 1.29-1.96); and no evidence of a significant increase in serious adverse events in trial participants randomized to varenicline or bupropion when compared to placebo controls. New evidence emerging from updated reviews suggests that counselling interventions can increase quit rates in pregnant women and that school-based smoking programmes with social competence curricula can lead to a significant reduction in uptake of smoking at more than a year. Updated reviews also suggested that naltrexone, selective serotonin re-uptake inhibitors and St John's wort do not have a significant effect on long-term smoking cessation. CONCLUSIONS: Cochrane systematic review evidence from 2013 suggests that adding mood management to behavioural support may improve cessation outcomes in smokers with current or past depression and strengthens evidence for previous conclusions, including the safety of varenicline and bupropion and the benefits of behavioural support for smoking cessation in pregnancy.

Published
2014

35. Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Author

Mocroft, A., Lundgren, J. D., Ross, M., Law, M., Reiss, P., Kirk, O., Smith, C., Wentworth, D., Neuhaus, J., Fux, C. A., Moranne, O., Morlat, P., Johnson, M. A., Ryom, L., Powderly, B., Shortman, N., Moecklinghoff, C., Reilly, G., Franquet, X., Sabin, C. A., Phillips, A., Weber, R., Pradier, C., d'Arminio Monforte, A., Dabis, F., El-Sadr, W. M., De Wit, S., Kamara, D., Tverland, J., Mansfeld, M., Nielsen, J., Raben, D., Salbol Brandt, R., Rickenbach, M., Fanti, I., Krum, E., Hillebregt, M., Geffard, S., Sundstrom, A., Delforge, M., Fontas, E., Torres, F., Mcmanus, H., Wright, S., Kjaer, J., Sjol, A., Meidahl, P., Helweg-Larsen, J., Schmidt Iversen, J., Kesselring, A. M., Friis-Moller, N., Kowalska, J., Sabin, C., Bruyand, M., Kamara, D. A., Bower, M., Fatkenheuer, G., Donald, A., Grulich, A., Prins, J. M., Kuijpers, T. W., Scherpbier, H. J., van der Meer, J. T. M., Wit, F. W. M. N., Godfried, M. H., van der Poll, T., Nellen, F. J. B., Geerlings, S. E., van Vugt, M., Pajkrt, D., Bos, J. C., Wiersinga, W. J., van der Valk, M., Goorhuis, A., Hovius, J. W., van Eden, J., Henderiks, A., van Hes, A. M. H., Mutschelknauss, M., Nobel, H. E., Pijnappel, F. J. J., Westerman, A. M., Jurriaans, S., Back, N. K. T., Zaaijer, H. L., Berkhout, B., Cornelissen, M. T. E., Schinkel, C. J., Thomas, X. V., van den Berge, M., Stegeman, A., Baas, S., Hage de Looff, L., Versteeg, D., Pronk, M. J. H., Ammerlaan, H. S. M., Korsten-Vorstermans, E. M. H. M., de Munnik, E. S., Jansz, A. R., Tjhie, J., Wegdam, M. C. A., Deiman, B., Scharnhorst, V., van der Plas, A., Weijsenfeld, A. M., van der Ende, M. E., de Vries-Sluijs, T. E. M. S., C. M. van Gorp, E., Schurink, C. A. M., Nouwen, J. L., Verbon, A., Rijnders, B. J. A., Bax, H. I., Hassing, R. J., van der Feltz, M., Bassant, N., van Beek, J. E. A., Vriesde, M., van Zonneveld, L. M., de Oude-Lubbers, A., van den Berg-Cameron, H. J., Bruinsma-Broekman, F. B., de Groot, J., de Zeeuw- de Man, M., Broekhoven-Kruijne, M. J., Schutten, M., Osterhaus, A. D. M. E., Boucher, C. A. B., Driessen, G. J. A., van Rossum, A. M. C., van der Knaap, L. C., Visser, E., Branger, J., H. M. Duijf-van de Ven C., J., Schippers, E. F., van Nieuwkoop, C., Brimicombe, R. W., van IJperen, J. M., van der Hut, G., Franck, P. F. H., van Eeden, A., Brokking, W., Groot, M., Damen, M., Kwa, I. S., Groeneveld, P. H. P., Bouwhuis, J. W., van den Berg, J. F., van Hulzen, A. G. W., van der Bliek, G. L., Bor, P. C. J., Bloembergen, P., Wolfhagen, M. J. H. M., Ruijs, G. J. H. M., van Lelyveld, S. F. L., Soetekouw, R., Hulshoff, N., van der Prijt, L. M. M., Schoemaker, M., Bermon, N., van der Reijden, W. A., Jansen, R., Herpers, B. L., Veenendaal, D., Kroon, F. P., Arend, S. M., de Boer, M. G. J., Bauer, M. P., Jolink, H., Vollaard, A. M., Dorama, W., Moons, C., Claas, E. C. J., Kroes, A. C. M., den Hollander, J. G., Pogany, K., Kastelijns, M., Smit, J. V., Smit, E., Bezemer, M., van Niekerk, T., Pontesilli, O., Lowe, S. H., Oude Lashof, A., Posthouwer, D., Ackens, R. P., Schippers, J., Vergoossen, R., Weijenberg Maes, B., Savelkoul, P. H. M., Loo, I. H., Weijer, S., El Moussaoui, R., Heitmuller, M., Kortmann, W., van Twillert, G., Cohen Stuart, J. W. T., Diederen, B. M. W., Pronk, D., van Truijen-Oud, F. A., Leyten, E. M. S., Gelinck, L. B. S., van Hartingsveld, A., Meerkerk, C., Wildenbeest, G. S., Mutsaers, J. A. E. M., Jansen, C. L., van Vonderen, M. G. A., van Houte, D. P. F., Dijkstra, K., Faber, S., Weel, J., Kootstra, G. J., Delsing, C. E., van der Burg-van de Plas, M., Heins, H., Lucas, E., Brinkman, K., Frissen, P. H. J., Blok, W. L., Schouten, W. E. M., Bosma, A. S., Brouwer, C. J., Geerders, G. F., Hoeksema, K., Kleene, M. J., van der Meche, I. B., Toonen, A. J. M., Wijnands, S., van Ogtrop, M. L., Koopmans, P. P., Keuter, M., van der Ven, A. J. A. M., ter Hofstede, H. J. M., Dofferhoff, A. S. M., van Crevel, R., Albers, M., Bosch, M. E. W., Grintjes-Huisman, K. J. T., Zomer, B. J., Stelma, F. F., Burger, D., Richter, C., van der Berg, J. P., Gisolf, E. H., ter Beest, G., van Bentum, P. H. M., Langebeek, N., Tiemessen, R., Swanink, C. M. A., Veenstra, J., Lettinga, K. D., Spelbrink, M., Sulman, H., Witte, E., Peerbooms, P. G. H., Mulder, J. W., Vrouenraets, S. M. E., Lauw, F. N., van Broekhuizen, M. C., Paap, H., Vlasblom, D. J., Oudmaijer Sanders, E., Smits, P. H. M., Rosingh, A. W., Verhagen, D. W. M., Geilings, J., van Kasteren, M. E. E., Brouwer, A. E., de Kruijf-van de Wiel, B. A. F. M., Kuipers, M., Santegoets, R. M. W. J., van der Ven, B., Marcelis, J. H., G. M. Buiting, A., Kabel, P. J., Bierman, W. F. W., Sprenger, H. G., Scholvinck, E. H., van Assen, S., Wilting, K. R., Stienstra, Y., de Groot-de Jonge, H., van der Meulen, P. A., de Weerd, D. A., Niesters, H. G. M., Riezebos-Brilman, A., van Leer-Buter, C. C., Hoepelman, A. I. M., Schneider, M. M. E., Mudrikova, T., Ellerbroek, P. M., Oosterheert, J. J., Arends, J. E., Barth, R. E., Wassenberg, M. W. M., van Elst-Laurijssen, D. H. M., Laan, L. M., van Oers-Hazelzet, E. E. B., Patist, J., Vervoort, S., Nieuwenhuis, H. E., Frauenfelder, R., Schuurman, R., Verduyn-Lunel, F., Wensing, A. M. J., Peters, E. J. G., van Agtmael, M. A., Perenboom, R. M., Bomers, M., de Vocht, J., Elsenburg, L. J. M., Pettersson, A. M., Vandenbroucke-Grauls, C. M. J. E., Ang, C. W., Geelen, S. P. M., Wolfs, T. F. W., Bont, L. J., Nauta, N., Bezemer, D. O., Gras, L., van Sighem, A. I., Smit, C., Zaheri, S., Kimmel, V., Tong, Y., Lascaris, B., van den Boogaard, R., Hoekstra, P., de Lang, A., Berkhout, M., Grivell, S., Jansen, A., de Groot, L., van den Akker, M., Bergsma, D., Lodewijk, C., Meijering, R., Peeck, B., Raethke, M., Ree, C., Regtop, R., Ruijs, Y., Schoorl, M., Tuijn, E., Veenenberg, L., Woudstra, T., Bakker, Y., de Jong, A., Broekhoven, M., Claessen, E., Rademaker, M. J., Munjishvili, L., Kruijne, E., Tuk, B., Bonnet, F., Dupon, M., Chene, G., Breilh, D., Fleury, H., Malvy, D., Mercie, P., Pellegrin, I., Neau, D., Bouchet, S., Gaborieau, V., Lacoste, D., Tchamgoue, S., Thiebaut, R., Lawson-Ayayi, S., Wittkop, L., Bernard, N., Hessamfar, M., Vandenhende, M. A., Dauchy, F. A., Dutronc, H., Longy-Boursier, M., Duffau, P., Roger Schmeltz, J., Pistone, T., Receveur, M. C., Cazanave, C., Ochoa, A., Vareil, M. O., Pellegrin, J. L., Viallard, J. F., Greib, C., Lazaro, E., Lafon, M. E., Reigadas, S., Trimoulet, P., Molimard, M., Titier, K., Moreau, J. F., Haramburu, F., Miremont-Salame, G., Dupont, A., Gerard, Y., Caunegre, L., Andre, K., Bonnal, F., Farbos, S., Gemain, M. C., Ceccaldi, J., De Witte, S., Courtault, C., Monlun, E., Lataste, P., Meraud, J. P., Chossat, I., Blaizeau, M. J., Conte, V., Decoin, M., Delaune, J., Delveaux, S., Diarra, F., D'Ivernois, C., Frosch, A., Hannapier, C., Lenaud, E., Leleux, O., Le Marec, F., Leray, J., Louis, I., Palmer, G., Pougetoux, A., Sicard, X., Touchard, D., Uwamaliya-Nziyumvira, B., Petoumenos, K., Bendall, C., Moore, R., Edwards, S., Watson, K., Roth, N., Nicholson, J., Bloch, M., Franic, T., Baker, D., Vale, R., Carr, A., Cooper, D., Chuah, J., Ngieng, M., Nolan, D., Skett, J., Calvo, G., Mateu, S., Domingo, P., Sambeat, M. A., Gatell, J., Del Cacho, E., Cadafalch, J., Fuster, M., Codina, C., Sirera, G., Vaque, A., Clumeck, N., Necsoi, C., Gennotte, A. F., Gerard, M., Kabeya, K., Konopnicki, D., Libois, A., Martin, C., Payen, M. C., Semaille, P., Van Laethem, Y., Neaton, J., Bartsch, G., Thompson, G., Luskin-Hawk, R., Telzak, E., Abrams, D. I., Cohn, D., Markowitz, N., Arduino, R., Mushatt, D., Friedland, G., Perez, G., Tedaldi, E., Fisher, E., Gordin, F., Crane, L. R., Sampson, J., Baxter, J., Cozzi-Lepri, A., Grint, D., Podlekareva, D., Peters, L., Reekie, J., Fischer, A. H., Losso, M., Elias, C., Vetter, N., Zangerle, R., Karpov, I., Vassilenko, A., Mitsura, V. M., Suetnov, O., Colebunders, R., Vandekerckhove, L., Hadziosmanovic, V., Kostov, K., Begovac, J., Machala, L., Jilich, D., Sedlacek, D., Kronborg, G., Benfield, T., Larsen, M., Gerstoft, J., Katzenstein, T., Hansen, A. -B. E., Skinhoj, P., Pedersen, C., Ostergaard, L., Zilmer, K., Smidt, J., Ristola, M., Katlama, C., Viard, J. -P., Girard, P. -M., Livrozet, J. M., Vanhems, P., Rockstroh, J., Schmidt, R., van Lunzen, J., Degen, O., Stellbrink, H. J., Staszewski, S., Bickel, M., Kosmidis, J., Gargalianos, P., Xylomenos, G., Perdios, J., Panos, G., Filandras, A., Karabatsaki, E., Sambatakou, H., Banhegyi, D., Mulcahy, F., Yust, I., Turner, D., Burke, M., Pollack, S., Hassoun, G., Maayan, S., Vella, S., Esposito, R., Mazeu, I., Mussini, C., Arici, C., Pristera, R., Mazzotta, F., Gabbuti, A., Vullo, V., Lichtner, M., Chirianni, A., Montesarchio, E., Gargiulo, M., Antonucci, G., Testa, A., Narciso, P., Vlassi, C., Zaccarelli, M., Lazzarin, A., Castagna, A., Gianotti, N., Galli, M., Ridolfo, A., Rozentale, B., Zeltina, I., Chaplinskas, S., Hemmer, R., Staub, T., Ormaasen, V., Maeland, A., Bruun, J., Knysz, B., Gasiorowski, J., Horban, A., Bakowska, E., Grzeszczuk, A., Flisiak, R., Boron-Kaczmarska, A., Pynka, M., Parczewski, M., Beniowski, M., Mularska, E., Trocha, H., Jablonowska, E., Malolepsza, E., Wojcik, K., Antunes, F., Doroana, M., Caldeira, L., Mansinho, K., Maltez, F., Duiculescu, D., Rakhmanova, A., Zakharova, N., Buzunova, S., Jevtovic, D., Mokras, M., Stanekova, D., Tomazic, J., Gonzalez-Lahoz, J., Soriano, V., Labarga, P., Medrano, J., Moreno, S., Rodriguez, J. M., Clotet, B., Jou, A., Paredes, R., Tural, C., Puig, J., Bravo, I., Miro, J. M., Gutierrez, M., Mateo, G., Karlsson, A., Flamholc, L., Ledergerber, B., Francioli, P., Cavassini, M., Hirschel, B., Boffi, E., Furrer, H., Battegay, M., Elzi, L., Kravchenko, E., Chentsova, N., Frolov, V., Kutsyna, G., Servitskiy, S., Krasnov, M., Barton, S., Johnson, A. M., Mercey, D., Murphy, M., Weber, J., Scullard, G., Fisher, M., Leen, C., Morfeldt, L., Thulin, G., Akerlund, B., Koppel, K., Hakangard, C., Moroni, M., Angarano, G., Antinori, A., Armignacco, O., Castelli, F., Cauda, Roberto, Di Perri, G., Iardino, R., Ippolito, G., Perno, C. F., von Schloesser, F., Viale, P., Ceccherini-Silberstein, F., Girardi, E., Lo Caputo, S., Puoti, M., Andreoni, M., Ammassari, A., Balotta, C., Bonora, S., Borderi, M., Capobianchi, R., Ceccherini- Silberstein, F., Cingolani, A., Cinque, P., De Luca, A., Di Biagio, A., Gori, A., Guaraldi, G., Lapadula, G., Madeddu, G., Maggiolo, F., Marchetti, G., Marcotullio, S., Monno, L., Quiros Roldan, E., Rusconi, S., Cicconi, P., Formenti, T., Galli, L., Lorenzini, P., Giacometti, A., Costantini, A., Santoro, C., Suardi, C., Vanino, E., Verucchi, G., Minardi, C., Quirino, T., Abeli, C., Manconi, P. E., Piano, P., Vecchiet, J., Falasca, K., Sighinolfi, L., Segala, D., Cassola, G., Viscoli, G., Alessandrini, A., Piscopo, R., Mazzarello, G., Mastroianni, C., Belvisi, V., Bonfanti, P., Caramma, I., Castelli, A. P., Rizzardini, G., Ridolfo, A. L., Piolini, R., Salpietro, S., Carenzi, L., Moioli, M. C., Puzzolante, C., Abrescia, N., Guida, M. 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J., Mooka, B., Mamorksy, M. G., Agmon-Levin, N., Karplus, R., Shahar, E., Biglino, A., De Gioanni, M., Montroni, M., Raise, E., Honda, M., Ishisaka, M., Caplinskas, S., Uzdaviniene, V., Schmit, J. C., Mills, G. D., Blackmore, T., Masters, J. A., Morgan, J., Pithie, A., Brunn, J., Ormasssen, V., La Rosa, A., Guerra, O., Espichan, M., Gutierrez, L., Mendo, F., Salazar, R., Knytz, B., Kwiatkowski, J., Castro, R. S., Horta, A., Miranda, A. C., Pinto, I. V., Vera, J., Vinogradova, E., Yakovlev, A., Wood, R., Orrel, C., Arnaiz, J. A., Carrillo, R., Dalmau, D., Jordano, Q., Knobel, H., Larrousse, M., Moreno, J. S., Oretaga, E., Pena, J. N., Spycher, R., Bottone, S., Christen, A., Franc, C., Furrer, H. J., Gayet-Ageron, A., Genne, D., Hochstrasser, S., Moens, C., Nuesch, R., Ruxrungtham, K., Pumpradit, W., Dangthongdee, S., Kiertiburanakul, S., Klinbuayaem, V., Mootsikapun, P., Nonenoy, S., Piyavong, B., Prasithsirikul, W., Raksakulkarn, P., Gazzard, B. G., Ainsworth, J. G., Angus, B. J., Barber, T. J., Brook, M. G., Care, C. D., Chadwick, D. R., Chikohora, M., Churchill, D. R., Cornforth, D., Dockrell, D. H., Easterbrook, P. J., Fox, P. A., Gomez, P. A., Gompels, M. M., Harris, G. M., Herman, S., Jackson, A. G. A., Jebakumar, S. P. R., Kinghorn, G. R., Kuldanek, K. A., Larbalestier, N., Lumsden, M., Maher, T., Mantell, J., Muromba, L., Orkin, C. M., Palfreeman, A. J., Peters, B. S., Peto, T. E. A., Portsmouth, S. D., Rajamanoharan, S., Ronan, A., Schwenk, A., Slinn, M. A., Stroud, C. J., Thomas, R. C., Wansbrough-Jones, M. H., Whiles, H. J., White, D. J., Williams, E., Williams, I. G., Acosta, E. A., Adamski, A., Antoniskis, D., Aragon, D. R., Barnett, B. J., Baroni, C., Barron, M., Baxter, J. D., Beers, D., Beilke, M., Bemenderfer, D., Bernard, A., Besch, C. L., Bessesen, M. T., Bethel, J. T., Blue, S., Blum, J. D., Boarden, S., Bolan, R. K., Borgman, J. B., Brar, I., Braxton, B. K., Bredeek, U. F., Brennan, R., Britt, D. E., Bulgin-Coleman, D., Bullock, D. E., Campbell, B., Caras, S., Carroll, J., Casey, K. K., Chiang, F., Cindrich, R. B., Clark, C., Cohen, C., Coley, J., Condoluci, D. V., Contreras, R., Corser, J., Cozzolino, J., Daley, L., Dandridge, D., D'Antuono, V., Darcourt Rizo Patron, J. G., Dehovitz, J. A., Dejesus, E., Desjardin, J., Dietrich, C., Dolce, E., Erickson, D., Faber, L. L., Falbo, J., Farrough, M. J., Farthing, C. F., Ferrell-Gonzalez, P., Flynn, H., Frank, M., Freeman, K. F., French, N., Fujita, N., Gahagan, L., Gilson, I., Goetz, M. B., Goodwin, E., Guity, C. K., Gulick, P., Gunderson, E. R., Hale, C. M., Hannah, K., Henderson, H., Hennessey, K., Henry, W. K., Higgins, D. T., Hodder, S. L., Horowitz, H. W., Howe-Pittman, M., Hubbard, J., Hudson, R., Hunter, H., Hutelmyer, C., Insignares, M. T., Jackson, L., Jenny, L., Johnson, D. L., Johnson, G., Johnson, J., Kaatz, J., Kaczmarski, J., Kagan, S., Kantor, C., Kempner, T., Kieckhaus, K., Kimmel, N., Klaus, B. M., Koeppe, J. R., Koirala, J., Kopka, J., Kostman, J. R., Kozal, M. J., Kumar, A., Lampiris, H., Lamprecht, C., Lattanzi, K. M., Lee, J., Leggett, J., Long, C., Loquere, A., Loveless, K., Lucasti, C. J., Macveigh, M., Makohon, L. H., Markowitz, N. P., Marks, C., Martorell, C., Mcfeaters, E., Mcgee, B., Mcintyre, D. M., Mcmanus, E., Melecio, L. G., Melton, D., Mercado, S., Merrifield, E., Mieras, J. A., Mogyoros, M., Moran, F. M., Murphy, K., Mutic, S., Nadeem, I., Nadler, J. P., Ognjan, A., O'Hearn, M., O'Keefe, K., Okhuysen, P. C., Oldfield, E., Olson, D., Orenstein, R., Ortiz, R., Parpart, F., Pastore-Lange, V., Paul, S., Pavlatos, A., Pearce, D. D., Pelz, R., Peterson, S., Pitrak, D., Powers, S. L., Pujet, H. C., Raaum, J. W., Ravishankar, J., Reeder, J., Reilly, N. A., Reyelt, C., Riddell, J., Rimland, D., Robinson, M. L., Rodriguez, A. E., Rodriguez-Barradas, M. C., Rodriguez Derouen, V., Rosmarin, C., Rossen, W. L., Rouff, J. R., Sampson, J. H., Sands, M., Savini, C., Schrader, S., Schulte, M. M., Scott, R., Seedhom, H., Sension, M., Sheble-Hall, A., Shuter, J., Slater, L. N., Slotten, R., Smith, M., Snap, S., States, D. M., Stringer, G., Summers, K. K., Swanson, K., Sweeton, I. B., Szabo, S., Telzak, E. E., Thompson, M. A., Thompson, S., Ting Hong Bong, C., Vaccaro, A., Vasco, L. M., Vecino, I., Verlinghieri, G. K., Visnegarwala, F., Wade, B. H., Weis, S. E., Weise, J. A., Weissman, S., Wilkin, A. M., Witter, J. H., Wojtusic, L., Wright, T. J., Yeh, V., Young, B., Zeana, C., Zeh, J., Savio, E., Vacarezza, M., and Cauda R. (ORCID:0000-0002-1498-4229)

Abstract

Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with ≥3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR ≤ 60 ml/min/1.73 m2. Poisson regression was used to develop a risk score, externally validated on two independent cohorts. In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7–6.7; median follow-up 6.1 y, range 0.3–9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was −2 (interquartile range –4 to 2). There was a 1:393 chance of developing CKD in the next 5 y in the low risk group (risk score < 0, 33 events), rising to 1:47 and 1:6 in the medium (risk score 0–4, 103 events) and high risk groups (risk score ≥ 5, 505 events)

Published
2015

40. Some Observations on Imaging Inter-aquifer Leakage Using Airborne EM Technologies

Author

Munday, T., Fitzpatrick, A., Esben Auken, Berens, V., and Cahill, K.

Subjects
SkyTEM, aquifer, electromagnetics, EM, AEM, quality, Airborne, imaging, ground water
Abstract

Nøglen til en effektiv forvaltning af naturlige økosystemer, som karakteriserer flodsletter af MurrayBasin i det sydøstlige Australien, og vedligeholdelse af floden sundhed (en kritisk vandressourcerne) i en settingwhere svær tilsaltning er en allestedsnærværende trussel, kræver en solid forståelse af overflade watergroundwaterprocesses . Denne afhandling præsenterer resultaterne fra en undersøgelse af hydrogeophysics, specificallyairborne elektromagnetisme (AEM) data indhentet ved SkyTEM tid domæne helikopter EM-system, som ameans til at forbedre vores viden om rumlige mønstre i forbindelse med inter-grundvandsmagasin blanding wheregroundwater flow er kompleks. I den sydøstlige del af Murray bassinet, AEM data showsconsiderable løfte som et middel til forståelse af grundvandets kvalitet og dens laterale variation. I theBookpurnong og Loxton kunstvanding områder, den store øjeblik evne SkyTEM tillader os at investigatevariations i kvaliteten af grundvandet i dybde (> 100m), som igen giver os mulighed for at visualisere howgroundwater kan bevæge sig på tværs af aquitards og inden for bestemte grundvandsmagasin systemer. Key to the effective management of natural ecosystems that characterise the floodplains of the MurrayBasin in south eastern Australia, and maintenance of river health (a critical water resource) in a settingwhere severe salinisation is an ever-present threat, requires a sound understanding of surface watergroundwaterprocesses. This paper presents results from an examination of hydrogeophysics, specificallyairborne electromagnetics (AEM) data acquired by the SkyTEM time domain helicopter EM system, as ameans for improving our knowledge of spatial patterns associated with inter-aquifer mixing wheregroundwater flow is complex. In the south-eastern part of the Murray Basin, AEM data showsconsiderable promise as a means for understanding of groundwater quality and its lateral variability. In theBookpurnong and Loxton irrigation areas the high moment capability of SkyTEM permits us to investigatevariations in the quality of groundwater at depth (>100m), which in turn allows us to visualise howgroundwater may be moving across aquitards and within particular aquifer systems.

Published
2009

41. Cannabinoid type I receptor antagonists (rimonabant) for smoking cessation

Author

Cahill, K and Ussher, M

Abstract

Rimonabant is a selective type 1 cannabinoid ( CB1) receptor antagonist. It may assist with smoking cessation by restoring the balance of the endocannabinoid system, which can be disrupted by prolonged use of nicotine. Rimonabant also seeks to address many smokers' reluctance to persist with a quit attempt because of concerns about weight gain.ObjectivesTo determine whether selective CB1 receptor antagonists increase the numbers of people stopping smokingTo assess their effects on weight change in successful quitters and in those who try to quit but fail.Search strategyWe searched the Cochrane Tobacco Addiction Review Group specialized register for trials, using the terms 'rimonabant' and 'smoking' in the title or abstract, or as keywords. We also searched MEDLINE, EMBASE, CINAHL and PsycINFO, using major MESH terms. We acquired electronic or paper copies of posters of preliminary trial results presented at the American Thoracic Society Meeting in 2005, and at the Society for Research on Nicotine and Tobacco European Meeting 2006. We also attempted to contact the authors of ongoing studies of rimonabant, and Sanofi Aventis ( manufacturers of rimonabant).Selection criteriaTypes of studiesRandomized controlled trialsTypes of participantsAdult smokersTypes of interventionsSelective CB1 receptor antagonists, such as rimonabant.Types of outcome measuresThe primary outcome is smoking status at a minimum of six months after the start of treatment. We preferred sustained cessation rates to point prevalence, and biochemically verified cessation to self-reported quitting. We regarded smokers who drop out or are lost to follow up as continuing smokers. We have noted any adverse effects of treatment.A secondary outcome is weight change associated with the cessation attempt.Data collection and analysisTwo authors checked the abstracts for relevance, and attempted to acquire full trial reports. One author extracted the data, and a second author checked them.Main resultsWe found three trials which met our inclusion criteria, covering 1567 smokers ( cessation: STRATUS-EU and STRATUS-US), and 1661 quitters ( relapse prevention: STRATUS-WW). At one year, the pooled odds ratio ( OR) for quitting with rimonabant 20 mg was 1.61 ( 95% confidence interval ( CI) 1.12 to 2.30). No significant benefit was demonstrated for rimonabant at 5 mg dosage. Adverse events included nausea and upper respiratory tract infections.In the relapse prevention trial, smokers who had quit on the 20 mg regimen were 1 times more likely to remain abstinent on either active regimen than on placebo; the OR for the 20 mg maintenance group was 1.49 ( 95% CI 1.09 to 2.04, and for the 5 mg maintenance group 1.51 ( 95% CI 1.11 to 2.07). There appeared to be no significant benefit of maintenance treatment for the 5 mg quitters. Weight gain was reported to be significantly lower among the 20 mg quitters than in the 5 mg or placebo quitters. During treatment, overweight or obese smokers tended to lose weight, while normal weight smokers did not.Authors' conclusionsFrom the preliminary trial reports available, rimonabant 20 mg may increase the odds of quitting approximately 1 1/2-fold.Adverse events include nausea and upper respiratory tract infections; the risk of serious adverse events is reported to be low.The evidence for rimonabant in maintaining abstinence is inconclusive.Rimonabant 20 mg may moderate weight gain in the long term.

Published
2007

42. Progress in Drug Research / Fortschritte der Arzneimittelforschung / Progrès des recherches pharmaceutiques

Author

Archer, S., primary, Browne, S. G., additional, Cahill, K. M., additional, Colbourne, M. J., additional, Dastur, D. K., additional, Ramamohan, Y., additional, Dabholkar, A. S., additional, deSa, A. E., additional, Deshmukh, M. D., additional, Kulkarni, K. G., additional, Virdi, S. S., additional, Elslager, E. F., additional, Hawking, F., additional, Janssen, P. A. J., additional, Kean, B. H., additional, Kradolfer, F., additional, Miller, M. J., additional, Nanavati, A. N. D., additional, Rao, V. N., additional, Rott, R., additional, Sasa, M., additional, Sant, M. V., additional, Gatlewar, W. N., additional, Menon, T. U. K., additional, Smith, C. E. G., additional, Steck, E. A., additional, Vakil, B. J., additional, Dalal, N. J., additional, Aviado, D. M., additional, and Horváth, G., additional

Published
1974
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46. Nfkb1 is a haploinsufficient DNA damage-specific tumor suppressor

Author

Voce, D J, primary, Schmitt, A M, additional, Uppal, A, additional, McNerney, M E, additional, Bernal, G M, additional, Cahill, K E, additional, Wahlstrom, J S, additional, Nassiri, A, additional, Yu, X, additional, Crawley, C D, additional, White, K P, additional, Onel, K, additional, Weichselbaum, R R, additional, and Yamini, B, additional

Published
2014
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