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Showing papers by "University of London published in 2012"


Journal ArticleDOI
Rafael Lozano1, Mohsen Naghavi1, Kyle J Foreman2, Stephen S Lim1  +192 moreInstitutions (95)
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2010 aimed to estimate annual deaths for the world and 21 regions between 1980 and 2010 for 235 causes, with uncertainty intervals (UIs), separately by age and sex, using the Cause of Death Ensemble model.

11,809 citations


Journal ArticleDOI
Stephen S Lim1, Theo Vos, Abraham D. Flaxman1, Goodarz Danaei2  +207 moreInstitutions (92)
TL;DR: In this paper, the authors estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010.

9,324 citations


Journal ArticleDOI
Theo Vos, Abraham D. Flaxman1, Mohsen Naghavi1, Rafael Lozano1  +360 moreInstitutions (143)
TL;DR: Prevalence and severity of health loss were weakly correlated and age-specific prevalence of YLDs increased with age in all regions and has decreased slightly from 1990 to 2010, but population growth and ageing have increased YLD numbers and crude rates over the past two decades.

7,021 citations


Journal ArticleDOI
Christopher J L Murray1, Theo Vos2, Rafael Lozano1, Mohsen Naghavi1  +366 moreInstitutions (141)
TL;DR: The results for 1990 and 2010 supersede all previously published Global Burden of Disease results and highlight the importance of understanding local burden of disease and setting goals and targets for the post-2015 agenda taking such patterns into account.

6,861 citations


Journal ArticleDOI
TL;DR: Worldwide, regional, and national estimates of preterm birth rates for 184 countries in 2010 with time trends for selected countries are reported, and a quantitative assessment of the uncertainty surrounding these estimates is provided.

3,742 citations


Journal ArticleDOI
TL;DR: The latest estimates of causes of child mortality in 2010 with time trends since 2000 show that only tetanus, measles, AIDS, and malaria (in Africa) decreased at an annual rate sufficient to attain the Millennium Development Goal 4.

3,441 citations


Journal ArticleDOI
TL;DR: Longer diabetes duration and poorer glycemic and blood pressure control are strongly associated with DR, and these data highlight the substantial worldwide public health burden of DR and the importance of modifiable risk factors in its occurrence.
Abstract: OBJECTIVE To examine the global prevalence and major risk factors for diabetic retinopathy (DR) and vision-threatening diabetic retinopathy (VTDR) among people with diabetes. RESEARCH DESIGN AND METHODS A pooled analysis using individual participant data from population-based studies around the world was performed. A systematic literature review was conducted to identify all population-based studies in general populations or individuals with diabetes who had ascertained DR from retinal photographs. Studies provided data for DR end points, including any DR, proliferative DR, diabetic macular edema, and VTDR, and also major systemic risk factors. Pooled prevalence estimates were directly age-standardized to the 2010 World Diabetes Population aged 20–79 years. RESULTS A total of 35 studies (1980–2008) provided data from 22,896 individuals with diabetes. The overall prevalence was 34.6% (95% CI 34.5–34.8) for any DR, 6.96% (6.87–7.04) for proliferative DR, 6.81% (6.74–6.89) for diabetic macular edema, and 10.2% (10.1–10.3) for VTDR. All DR prevalence end points increased with diabetes duration, hemoglobin A 1c , and blood pressure levels and were higher in people with type 1 compared with type 2 diabetes. CONCLUSIONS There are approximately 93 million people with DR, 17 million with proliferative DR, 21 million with diabetic macular edema, and 28 million with VTDR worldwide. Longer diabetes duration and poorer glycemic and blood pressure control are strongly associated with DR. These data highlight the substantial worldwide public health burden of DR and the importance of modifiable risk factors in its occurrence. This study is limited by data pooled from studies at different time points, with different methodologies and population characteristics.

3,282 citations


Journal ArticleDOI
TL;DR: In this paper, a systematic review of epidemiological surveys of autistic disorder and pervasive developmental disorders (PDDs) worldwide was provided, where the authors considered the possible impact of geographic, cultural/ethnic/ethnic, and socioeconomic factors on prevalence estimates and on clinical presentation of PDD.
Abstract: We provide a systematic review of epidemiological surveys of autistic disorder and pervasive developmental disorders (PDDs) worldwide. A secondary aim was to consider the possible impact of geographic, cultural/ethnic, and socioeconomic factors on prevalence estimates and on clinical presentation of PDD. Based on the evidence reviewed, the median of prevalence estimates of autism spectrum disorders was 62/10 000. While existing estimates are variable, the evidence reviewed does not support differences in PDD prevalence by geographic region nor of a strong impact of ethnic/cultural or socioeconomic factors. However, power to detect such effects is seriously limited in existing data sets, particularly in low-income countries. While it is clear that prevalence estimates have increased over time and these vary in different neighboring and distant regions, these findings most likely represent broadening of the diagnostic concets, diagnostic switching from other developmental disabilities to PDD, service availability, and awareness of autistic spectrum disorders in both the lay and professional public. The lack of evidence from the majority of the world's population suggests a critical need for further research and capacity building in low- and middle-income countries. Autism Res 2012, 5: 160–179. © 2012 International Society for Autism Research, Wiley Periodicals, Inc.

2,085 citations


Journal ArticleDOI
TL;DR: A 2-year follow-up of patients in the PARTNER trial supports TAVR as an alternative to surgery in high-risk patients, but paravalvular regurgitation was more frequent after T AVR and was associated with increased late mortality.
Abstract: The rates of death from any cause were similar in the TAVR and surgery groups (hazard ratio with TAVR, 0.90; 95% confidence interval [CI], 0.71 to 1.15; P = 0.41) and at 2 years (Kaplan–Meier analysis) were 33.9% in the TAVR group and 35.0% in the surgery group (P = 0.78). The frequency of all strokes during follow-up did not differ significantly between the two groups (hazard ratio, 1.22; 95% CI, 0.67 to 2.23; P = 0.52). At 30 days, strokes were more frequent with TAVR than with surgical replacement (4.6% vs. 2.4%, P = 0.12); subsequently, there were 8 additional strokes in the TAVR group and 12 in the surgery group. Improvement in valve areas was similar with TAVR and surgical replacement and was maintained for 2 years. Paravalvular regurgitation was more frequent after TAVR (P<0.001), and even mild paravalvular regurgitation was associated with increased late mortality (P<0.001). Conclusions A 2-year follow-up of patients in the PARTNER trial supports TAVR as an alternative to surgery in high-risk patients. The two treatments were similar with respect to mortality, reduction in symptoms, and improved valve hemodynamics, but paravalvular regurgitation was more frequent after TAVR and was associated with increased late mortality. (Funded by Edwards Lifesciences; ClinicalTrials.gov number, NCT00530894.)

2,012 citations


Journal ArticleDOI
20 Mar 2012-BMJ
TL;DR: In European hospitals, improvement of hospital work environments might be a relatively low cost strategy to improve safety and quality in hospital care and to increase patient satisfaction.
Abstract: Objective To determine whether hospitals with a good organisation of care (such as improved nurse staffing and work environments) can affect patient care and nurse workforce stability in European countries. Design Cross sectional surveys of patients and nurses. Setting Nurses were surveyed in general acute care hospitals (488 in 12 European countries; 617 in the United States); patients were surveyed in 210 European hospitals and 430 US hospitals. Participants 33 659 nurses and 11 318 patients in Europe; 27 509 nurses and more than 120 000 patients in the US. Main outcome measures Nurse outcomes (hospital staffing, work environments, burnout, dissatisfaction, intention to leave job in the next year, patient safety, quality of care), patient outcomes (satisfaction overall and with nursing care, willingness to recommend hospitals). Results The percentage of nurses reporting poor or fair quality of patient care varied substantially by country (from 11% (Ireland) to 47% (Greece)), as did rates for nurses who gave their hospital a poor or failing safety grade (4% (Switzerland) to 18% (Poland)). We found high rates of nurse burnout (10% (Netherlands) to 78% (Greece)), job dissatisfaction (11% (Netherlands) to 56% (Greece)), and intention to leave (14% (US) to 49% (Finland, Greece)). Patients’ high ratings of their hospitals also varied considerably (35% (Spain) to 61% (Finland, Ireland)), as did rates of patients willing to recommend their hospital (53% (Greece) to 78% (Switzerland)). Improved work environments and reduced ratios of patients to nurses were associated with increased care quality and patient satisfaction. In European hospitals, after adjusting for hospital and nurse characteristics, nurses with better work environments were half as likely to report poor or fair care quality (adjusted odds ratio 0.56, 95% confidence interval 0.51 to 0.61) and give their hospitals poor or failing grades on patient safety (0.50, 0.44 to 0.56). Each additional patient per nurse increased the odds of nurses reporting poor or fair quality care (1.11, 1.07 to 1.15) and poor or failing safety grades (1.10, 1.05 to 1.16). Patients in hospitals with better work environments were more likely to rate their hospital highly (1.16, 1.03 to 1.32) and recommend their hospitals (1.20, 1.05 to 1.37), whereas those with higher ratios of patients to nurses were less likely to rate them highly (0.94, 0.91 to 0.97) or recommend them (0.95, 0.91 to 0.98). Results were similar in the US. Nurses and patients agreed on which hospitals provided good care and could be recommended. Conclusions Deficits in hospital care quality were common in all countries. Improvement of hospital work environments might be a relatively low cost strategy to improve safety and quality in hospital care and to increase patient satisfaction.

1,587 citations


Journal ArticleDOI
TL;DR: Prophylaxis with TDF-FTC did not significantly reduce the rate of HIV infection and was associated with increased rates of side effects, as compared with placebo, and drug adherence appeared to be low.
Abstract: Background Preexposure prophylaxis with antiretroviral drugs has been effective in the prevention of human immunodeficiency virus (HIV) infection in some trials but not in others. Methods In this randomized, double-blind, placebo-controlled trial, we assigned 2120 HIV-negative women in Kenya, South Africa, and Tanzania to receive either a combination of tenofovir disoproxil fumarate and emtricitabine (TDF–FTC) or placebo once daily. The primary objective was to assess the effectiveness of TDF–FTC in preventing HIV acquisition and to evaluate safety. Results HIV infections occurred in 33 women in the TDF–FTC group (incidence rate, 4.7 per 100 person-years) and in 35 in the placebo group (incidence rate, 5.0 per 100 person-years), for an estimated hazard ratio in the TDF-FTC group of 0.94 (95% confidence interval, 0.59 to 1.52; P=0.81). The proportions of women with nausea, vomiting, or elevated alanine aminotransferase levels were significantly higher in the TDF–FTC group (P=0.04, P<0.001, and P=0.03, resp...

Journal ArticleDOI
TL;DR: CPMDs are more prevalent in low- and lower-middle-income countries, particularly among poorer women with gender-based risks or a psychiatric history.
Abstract: OBJECTIVE: To review the evidence about the prevalence and determinants of non-psychotic common perinatal mental disorders (CPMDs) in World Bank categorized low- and lower-middle-income countries. METHODS: Major databases were searched systematically for English-language publications on the prevalence of non-psychotic CPMDs and on their risk factors and determinants. All study designs were included. FINDINGS: Thirteen papers covering 17 low- and lower-middle-income countries provided findings for pregnant women, and 34, for women who had just given birth. Data on disorders in the antenatal period were available for 9 (8%) countries, and on disorders in the postnatal period, for 17 (15%). Weighted mean prevalence was 15.6% (95% confidence interval, CI: 15.4-15.9) antenatally and 19.8% (19.5-20.0) postnatally. Risk factors were: socioeconomic disadvantage (odds ratio [OR] range: 2.1-13.2); unintended pregnancy (1.6-8.8); being younger (2.1-5.4); being unmarried (3.4-5.8); lacking intimate partner empathy and support (2.0-9.4); having hostile in-laws (2.1-4.4); experiencing intimate partner violence (2.11-6.75); having insufficient emotional and practical support (2.8-6.1); in some settings, giving birth to a female (1.8-2.6), and having a history of mental health problems (5.1-5.6). Protective factors were: having more education (relative risk: 0.5; P = 0.03); having a permanent job (OR: 0.64; 95% CI: 0.4-1.0); being of the ethnic majority (OR: 0.2; 95% CI: 0.1-0.8) and having a kind, trustworthy intimate partner (OR: 0.52; 95% CI: 0.3-0.9). CONCLUSION: CPMDs are more prevalent in low- and lower-middle-income countries, particularly among poorer women with gender-based risks or a psychiatric history.

Journal ArticleDOI
Joshua A. Salomon1, Theo Vos, Daniel R Hogan1, Michael L. Gagnon1, Mohsen Naghavi2, Ali Mokdad2, Nazma Begum3, Razibuzzaman Shah1, Muhammad Karyana, Soewarta Kosen, Mario Reyna Farje, Gilberto Moncada, Arup Dutta, Sunil Sazawal, Andrew Dyer4, Jason F. S. Seiler4, Victor Aboyans, Lesley Baker2, Amanda J Baxter5, Emelia J. Benjamin6, Kavi Bhalla1, Aref A. Bin Abdulhak, Fiona M. Blyth, Rupert R A Bourne, Tasanee Braithwaite7, Peter Brooks, Traolach S. Brugha8, Claire Bryan-Hancock, Rachelle Buchbinder, Peter Burney9, Bianca Calabria10, Honglei Chen11, Sumeet S. Chugh12, Rebecca Cooley2, Michael H. Criqui13, Marita Cross5, Kaustubh Dabhadkar, Nabila Dahodwala14, Adrian Davis15, Louisa Degenhardt16, Cesar Diaz-Torne17, E. Ray Dorsey3, Tim Driscoll, Karen Edmond18, Alexis Elbaz19, Majid Ezzati20, Valery L. Feigin21, Cleusa P. Ferri22, Abraham D. Flaxman2, Louise Flood8, Marlene Fransen, Kana Fuse, Belinda J. Gabbe23, Richard F. Gillum24, Juanita A. Haagsma25, James Harrison8, Rasmus Havmoeller16, Roderick J. Hay26, Abdullah Hel-Baqui, Hans W. Hoek27, Howard J. Hoffman28, Emily Hogeland29, Damian G Hoy5, Deborah Jarvis2, Ganesan Karthikeyan1, Lisa M. Knowlton30, Tim Lathlean8, Janet L Leasher31, Stephen S Lim2, Steven E. Lipshultz32, Alan D. Lopez, Rafael Lozano2, Ronan A Lyons33, Reza Malekzadeh, Wagner Marcenes, Lyn March6, David J. Margolis14, Neil McGill, John J. McGrath34, George A. Mensah35, Ana-Claire Meyer, Catherine Michaud36, Andrew E. Moran, Rintaro Mori37, Michele E. Murdoch38, Luigi Naldi39, Charles R. Newton12, Rosana E. Norman, Saad B. Omer40, Richard H. Osborne, Neil Pearce18, Fernando Perez-Ruiz, Norberto Perico41, Konrad Pesudovs8, David Phillips42, Farshad Pourmalek43, Martin Prince, Jürgen Rehm, G. Remuzzi41, Kathryn Richardson, Robin Room44, Sukanta Saha45, Uchechukwu Sampson, Lidia Sanchez-Riera46, Maria Segui-Gomez47, Saeid Shahraz48, Kenji Shibuya, David Singh49, Karen Sliwa50, Emma Smith50, Isabelle Soerjomataram51, Timothy J. Steiner, Wilma A. Stolk, Lars Jacob Stovner, Christopher R. Sudfeld1, Hugh R. Taylor, Imad M. Tleyjeh4, Marieke J. van der Werf52, Wendy L. Watson53, David J. Weatherall12, Robert G. Weintraub, Marc G. Weisskopf1, Harvey Whiteford, James D. Wilkinson32, Anthony D. Woolf52, Zhi-Jie Zheng54, Christopher J L Murray2 
Harvard University1, University of Queensland2, Johns Hopkins University3, ICF International4, Centre for Mental Health5, Boston University6, University of Sydney7, University of Melbourne8, Imperial College London9, University of New South Wales10, University of California, San Diego11, Emory University12, University of Pennsylvania13, Autonomous University of Barcelona14, University of London15, National Institutes of Health16, French Institute of Health and Medical Research17, Medical Research Council18, Auckland University of Technology19, Federal University of São Paulo20, National Institute of Population and Social Security Research21, Howard University22, Flinders University23, Erasmus University Rotterdam24, King's College London25, Karolinska Institutet26, University of California, San Francisco27, All India Institute of Medical Sciences28, Nova Southeastern University29, University of Miami30, Swansea University31, Tehran University of Medical Sciences32, Queen Mary University of London33, Allen Institute for Brain Science34, University of Cape Town35, Columbia University36, Watford General Hospital37, Centro Studi GISED38, University of Oxford39, Deakin University40, University of British Columbia41, University of Toronto42, Box Hill Hospital43, Vanderbilt University44, University of Washington45, Brandeis University46, University of Tokyo47, The Queen's Medical Center48, Norwegian University of Science and Technology49, China Medical Board50, University of Cambridge51, Royal Cornwall Hospital52, Cedars-Sinai Medical Center53, Shanghai Jiao Tong University54
TL;DR: In this paper, a comprehensive re-estimation of disability weights for the Global Burden of Disease Study 2010 through a large-scale empirical investigation in which judgments about health losses associated with many causes of disease and injury were elicited from the general public in diverse communities through a new, standardised approach.

Journal ArticleDOI
Stephen Kaptoge1, Emanuele Di Angelantonio1, Lisa Pennells1, Angela M. Wood1, Ian R. White2, Pei Gao1, Matthew G. Walker1, Alexander M. W. Cargill Thompson1, Nadeem Sarwar1, Muriel J. Caslake3, Adam S. Butterworth1, Philippe Amouyel4, Gerd Assmann, Stephan J. L. Bakker5, Elizabeth L M Barr6, Elizabeth Barrett-Connor7, Emelia J. Benjamin8, Cecilia Björkelund9, Hermann Brenner10, Eric J. Brunner11, Robert Clarke12, Jackie A. Cooper11, Peter Cremer13, Mary Cushman14, Gilles R. Dagenais, Ralph B. D'Agostino8, Rachel Dankner, George Davey-Smith15, Dorly J. H. Deeg16, Jacqueline M. Dekker16, Gunnar Engström17, Aaron R. Folsom18, F. Gerry R. Fowkes19, John Gallacher20, J. Michael Gaziano21, Simona Giampaoli22, Richard F. Gillum23, Albert Hofman24, Barbara V. Howard25, Erik Ingelsson26, Hiroyasu Iso27, Torben Jørgensen28, Stefan Kiechl29, Akihiko Kitamura, Yutaka Kiyohara30, Wolfgang Koenig31, Daan Kromhout32, Lewis H. Kuller33, Debbie A Lawlor15, Tom W. Meade34, Aulikki Nissinen35, Børge G. Nordestgaard28, Altan Onat36, Demosthenes B. Panagiotakos37, Bruce M. Psaty38, Beatriz L. Rodriguez39, Annika Rosengren9, Veikko Salomaa35, Jussi Kauhanen40, Jukka T. Salonen41, Jonathan A. Shaffer42, Steven Shea42, Ian Ford3, Coen D.A. Stehouwer43, Timo E. Strandberg44, Robert W. Tipping45, Alberto Tosetto, Sylvia Wassertheil-Smoller46, Patrik Wennberg47, Rudi G. J. Westendorp48, Peter H. Whincup49, Lars Wilhelmsen9, Mark Woodward50, Gordon D.O. Lowe3, Nicholas J. Wareham2, Kay-Tee Khaw1, Naveed Sattar3, Chris J. Packard3, Vilmundur Gudnason51, Paul M. Ridker21, Mark B. Pepys11, Simon G. Thompson1, John Danesh1 
TL;DR: It is estimated that under current treatment guidelines, assessment of the CRP or fibrinogen level in people at intermediate risk for a cardiovascular event could help prevent one additional event over a period of 10 years for every 400 to 500 people screened.
Abstract: Background There is debate about the value of assessing levels of C-reactive protein (CRP) and other biomarkers of inflammation for the prediction of first cardiovascular events. Methods We analyzed data from 52 prospective studies that included 246,669 participants without a history of cardiovascular disease to investigate the value of adding CRP or fibrinogen levels to conventional risk factors for the prediction of cardiovascular risk. We calculated measures of discrimination and reclassification during follow-up and modeled the clinical implications of initiation of statin therapy after the assessment of CRP or fibrinogen. Results The addition of information on high-density lipoprotein cholesterol to a prognostic model for cardiovascular disease that included age, sex, smoking status, blood pressure, history of diabetes, and total cholesterol level increased the C-index, a measure of risk discrimination, by 0.0050. The further addition to this model of information on CRP or fibrinogen increased the C-index by 0.0039 and 0.0027, respectively (P = 20%) (P = 20% and for those with certain other risk factors, such as diabetes, irrespective of their 10-year predicted risk), additional targeted assessment of CRP or fibrinogen levels in the 13,199 remaining participants at intermediate risk could help prevent approximately 30 additional cardiovascular events over the course of 10 years. Conclusions In a study of people without known cardiovascular disease, we estimated that under current treatment guidelines, assessment of the CRP or fibrinogen level in people at intermediate risk for a cardiovascular event could help prevent one additional event over a period of 10 years for every 400 to 500 people screened. (Funded by the British Heart Foundation and others.)

Journal ArticleDOI
Daniel I. Swerdlow1, Michael V. Holmes1, Karoline Kuchenbaecker2, Engmann Jel.1, Tina Shah1, Reecha Sofat1, Yiran Guo, C Chung1, Anne Peasey1, Roman Pfister3, Simon P. Mooijaart4, Helen Ireland1, Maarten Leusink5, Claudia Langenberg3, KaWah Li1, Jutta Palmen1, Phil Howard1, Jackie A. Cooper1, Fotios Drenos1, John Hardy1, Mike A. Nalls6, Yun Li7, Gordon D.O. Lowe8, Marlene C. W. Stewart9, S. J. Bielinski10, Julian Peto11, Nicholas J. Timpson12, John Gallacher13, Malcolm G. Dunlop9, Richard S. Houlston, Ian Tomlinson14, Ioanna Tzoulaki15, Jian'an Luan2, Boer Jma.2, Nita G. Forouhi2, N. C. Onland-Moret5, Y. T. van der Schouw16, Renate B. Schnabel16, Jaroslav A. Hubacek, Růžena Kubínová, Migle Baceviciene17, Abdonas Tamosiunas17, Andrzej Pajak18, Roman Topor-Madry18, Sofia Malyutina19, Damiano Baldassarre, Bengt Sennblad20, Elena Tremoli, U de Faire21, Luigi Ferrucci21, S Bandenelli, Tetsu Tanaka21, James F. Meschia10, AB Singleton6, Gerjan Navis22, I. Mateo Leach22, Bakker Sjl.22, Ron T. Gansevoort, Ian Ford8, Stephen E. Epstein23, Mary-Susan Burnett23, Joe Devaney23, Johan Wouter Jukema4, Westendorp Rgj.5, G Jan de Borst5, Y. van der Graaf5, P A de Jong5, Mailand-van der Zee A-H.5, Olaf H. Klungel5, A. de Boer5, P. A. Doevendans5, Jeffrey W. Stephens24, Charles B. Eaton25, Jennifer G. Robinson26, JoAnn E. Manson27, F G Fowkes28, Timothy M. Frayling28, Jenna Price9, Peter H. Whincup11, Richard W Morris1, Debbie A Lawlor12, George Davey Smith12, Yoav Ben-Shlomo12, Susan Redline27, Leslie A. Lange29, Meena Kumari1, Nicholas J. Wareham2, Verschuren Wmm.30, Emelia J. Benjamin30, John C. Whittaker11, Anders Hamsten20, Frank Dudbridge11, Delaney Jac.31, Andrew Wong31, Diana Kuh31, Rebecca Hardy31, Berta Almoguera Castillo7, John Connolly7, P. van der Harst, Eric J. Brunner1, Michael Marmot1, Christina L. Wassel32, Steve E. Humphries1, P.J. Talmud1, Mika Kivimäki1, Folkert W. Asselbergs5, Mikhail I. Voevoda19, Martin Bobak1, Hynek Pikhart1, James G. Wilson33, Hakon Hakonarson7, Alexander P. Reiner34, Brendan J. Keating7, Naveed Sattar8, Aroon D. Hingorani1, Juan P. Casas11 
TL;DR: IL6R blockade could provide a novel therapeutic approach to prevention of coronary heart disease that warrants testing in suitably powered randomised trials and could help to validate and prioritise novel drug targets or to repurpose existing agents and targets for new therapeutic uses.

Journal ArticleDOI
TL;DR: It is suggested that aspirin might help in treatment of some cancers and provides proof of principle for pharmacological intervention specifically to prevent distant metastasis in patients who developed cancer during trials of daily aspirin versus control.

Journal ArticleDOI
TL;DR: There has been international support and an enthusiastic response to the principle of prospective registration of protocols for systematic reviews and to the development of PROSPERO, the international prospective register of systematic reviews with health-related outcomes.
Abstract: Background: Following publication of the PRISMA statement, the UK Centre for Reviews and Dissemination (CRD) at the University of York in England began to develop an international prospective register of systematic reviews with health-related outcomes. The objectives were to reduce unplanned duplication of reviews and provide transparency in the review process, with the aim of minimizing reporting bias. Methods: An international advisory group was formed and a consultation undertaken to establish the key items necessary for inclusion in the register and to gather views on various aspects of functionality. This article describes the development of the register, now called PROSPERO, and the process of registration. Results: PROSPERO offers free registration and free public access to a unique prospective register of systematic reviews across all areas of health from all around the world. The dedicated web-based interface is electronically searchable and available to all prospective registrants. At the moment, inclusion in PROSPERO is restricted to systematic reviews of the effects of interventions and strategies to prevent, diagnose, treat, and monitor health conditions, for which there is a health-related outcome. Ideally, registration should take place before the researchers have started formal screening against inclusion criteria but reviews are eligible as long as they have not progressed beyond the point of completing data extraction. The required dataset captures the key attributes of review design as well as the administrative details necessary for registration. Submitted registration forms are checked against the scope for inclusion in PROSPERO and for clarity of content before being made publicly available on the register, rejected, or returned to the applicant for clarification. The public records include an audit trail of major changes to planned methods, details of when the review has been completed, and links to resulting publications when provided by the authors. Conclusions: There has been international support and an enthusiastic response to the principle of prospective registration of protocols for systematic reviews and to the development of PROSPERO. In October 2011, PROSPERO contained 200 records of systematic reviews being undertaken in 26 countries around the world on a diverse range of interventions.

Journal ArticleDOI
Lam C. Tsoi1, Sarah L. Spain2, Sarah L. Spain1, Jo Knight1  +212 moreInstitutions (52)
TL;DR: A meta-analysis of genome-wide association studies and independent data sets genotyped on the Immunochip identified 15 new susceptibility loci, increasing to 36 the number associated with psoriasis in European individuals, and identified five independent signals within previously known loci.
Abstract: To gain further insight into the genetic architecture of psoriasis, we conducted a meta-analysis of 3 genome-wide association studies (GWAS) and 2 independent data sets genotyped on the Immunochip, including 10,588 cases and 22,806 controls. We identified 15 new susceptibility loci, increasing to 36 the number associated with psoriasis in European individuals. We also identified, using conditional analyses, five independent signals within previously known loci. The newly identified loci shared with other autoimmune diseases include candidate genes with roles in regulating T-cell function (such as RUNX3, TAGAP and STAT3). Notably, they included candidate genes whose products are involved in innate host defense, including interferon-mediated antiviral responses (DDX58), macrophage activation (ZC3H12C) and nuclear factor (NF)-κB signaling (CARD14 and CARM1). These results portend a better understanding of shared and distinctive genetic determinants of immune-mediated inflammatory disorders and emphasize the importance of the skin in innate and acquired host defense.

Journal ArticleDOI
TL;DR: The short-term reductions in cancer incidence and mortality and the decrease in risk of major extracranial bleeds with extended use, and their low case-fatality, add to the case for daily aspirin in prevention of cancer.

Journal ArticleDOI
Nobuyuki Hamajima, Kaoru Hirose, K. Tajima, T E Rohan1  +289 moreInstitutions (81)
TL;DR: The effects of menarche and menopause on breast cancer risk might not be acting merely by lengthening women's total number of reproductive years, and endogenous ovarian hormones are more relevant for oestrogen receptor-positive disease than for ostrogens receptor-negative disease and for lobular than for ductal tumours.
Abstract: BACKGROUND:Menarche and menopause mark the onset and cessation, respectively, of ovarian activity associated with reproduction, and affect breast cancer risk. Our aim was to assess the strengths of their effects and determine whether they depend on characteristics of the tumours or the affected women.METHODS:Individual data from 117 epidemiological studies, including 118 964 women with invasive breast cancer and 306 091 without the disease, none of whom had used menopausal hormone therapy, were included in the analyses. We calculated adjusted relative risks (RRs) associated with menarche and menopause for breast cancer overall, and by tumour histology and by oestrogen receptor expression.FINDINGS:Breast cancer risk increased by a factor of 1·050 (95% CI 1·044-1·057; p<0·0001) for every year younger at menarche, and independently by a smaller amount (1·029, 1·025-1·032; p<0·0001), for every year older at menopause. Premenopausal women had a greater risk of breast cancer than postmenopausal women of an identical age (RR at age 45-54 years 1·43, 1·33-1·52, p<0·001). All three of these associations were attenuated by increasing adiposity among postmenopausal women, but did not vary materially by women's year of birth, ethnic origin, childbearing history, smoking, alcohol consumption, or hormonal contraceptive use. All three associations were stronger for lobular than for ductal tumours (p<0·006 for each comparison). The effect of menopause in women of an identical age and trends by age at menopause were stronger for oestrogen receptor-positive disease than for oestrogen receptor-negative disease (p<0·01 for both comparisons).INTERPRETATION:The effects of menarche and menopause on breast cancer risk might not be acting merely by lengthening women's total number of reproductive years. Endogenous ovarian hormones are more relevant for oestrogen receptor-positive disease than for oestrogen receptor-negative disease and for lobular than for ductal tumours.

Journal ArticleDOI
20 May 2012-BMJ
TL;DR: Cumulative meta-analysis showed that reliable evidence that tranexamic acid reduces the need for transfusion has been available for over 10 years and surgical patients should be made aware of this evidence so that they can make an informed choice.
Abstract: Objective To assess the effect of tranexamic acid on blood transfusion, thromboembolic events, and mortality in surgical patients. Design Systematic review and meta-analysis. Data sources Cochrane central register of controlled trials, Medline, and Embase, from inception to September 2011, the World Health Organization International Clinical Trials Registry Platform, and the reference lists of relevant articles. Study selection Randomised controlled trials comparing tranexamic acid with no tranexamic acid or placebo in surgical patients. Outcome measures of interest were the number of patients receiving a blood transfusion; the number of patients with a thromboembolic event (myocardial infarction, stroke, deep vein thrombosis, and pulmonary embolism); and the number of deaths. Trials were included irrespective of language or publication status. Results 129 trials, totalling 10 488 patients, carried out between 1972 and 2011 were included. Tranexamic acid reduced the probability of receiving a blood transfusion by a third (risk ratio 0.62, 95% confidence interval 0.58 to 0.65; P Conclusions Strong evidence that tranexamic acid reduces blood transfusion in surgery has been available for many years. Further trials on the effect of tranexamic acid on blood transfusion are unlikely to add useful new information. However, the effect of tranexamic acid on thromboembolic events and mortality remains uncertain. Surgical patients should be made aware of this evidence so that they can make an informed choice.


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20 Nov 2012-Vaccine
TL;DR: There exists a substantial evidence base to support that HPV testing is advantageous both in triage of women with equivocal abnormal cytology, in surveillance after treatment of CIN lesions and in primary screening of women aged 30 years or older, however, the possible advantages offered by HPV-based screening require a well organised program with good compliance with screening and triage policies.

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Selidji T Agnandji1, Selidji T Agnandji2, Bertrand Lell1, Bertrand Lell2  +165 moreInstitutions (14)
TL;DR: The RTS,S/AS01 vaccine coadministered with EPI vaccines provided modest protection against both clinical and severe malaria in young infants.
Abstract: BACKGROUND: The candidate malaria vaccine RTS,S/AS01 reduced episodes of both clinical and severe malaria in children 5 to 17 months of age by approximately 50% in an ongoing phase 3 trial. We studied infants 6 to 12 weeks of age recruited for the same trial. METHODS: We administered RTS,S/AS01 or a comparator vaccine to 6537 infants who were 6 to 12 weeks of age at the time of the first vaccination in conjunction with Expanded Program on Immunization (EPI) vaccines in a three-dose monthly schedule. Vaccine efficacy against the first or only episode of clinical malaria during the 12 months after vaccination, a coprimary end point, was analyzed with the use of Cox regression. Vaccine efficacy against all malaria episodes, vaccine efficacy against severe malaria, safety, and immunogenicity were also assessed. RESULTS: The incidence of the first or only episode of clinical malaria in the intention-to-treat population during the 14 months after the first dose of vaccine was 0.31 per person-year in the RTS,S/AS01 group and 0.40 per person-year in the control group, for a vaccine efficacy of 30.1% (95% confidence interval [CI], 23.6 to 36.1). Vaccine efficacy in the per-protocol population was 31.3% (97.5% CI, 23.6 to 38.3). Vaccine efficacy against severe malaria was 26.0% (95% CI, -7.4 to 48.6) in the intention-to-treat population and 36.6% (95% CI, 4.6 to 57.7) in the per-protocol population. Serious adverse events occurred with a similar frequency in the two study groups. One month after administration of the third dose of RTS,S/AS01, 99.7% of children were positive for anti-circumsporozoite antibodies, with a geometric mean titer of 209 EU per milliliter (95% CI, 197 to 222). CONCLUSIONS: The RTS,S/AS01 vaccine coadministered with EPI vaccines provided modest protection against both clinical and severe malaria in young infants. (Funded by GlaxoSmithKline Biologicals and the PATH Malaria Vaccine Initiative; RTS,S ClinicalTrials.gov number, NCT00866619.).

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TL;DR: Increasing population fatness could have the same implications for world food energy demands as an extra half a billion people living on the earth.
Abstract: The energy requirement of species at each trophic level in an ecological pyramid is a function of the number of organisms and their average mass. Regarding human populations, although considerable attention is given to estimating the number of people, much less is given to estimating average mass, despite evidence that average body mass is increasing. We estimate global human biomass, its distribution by region and the proportion of biomass due to overweight and obesity. For each country we used data on body mass index (BMI) and height distribution to estimate average adult body mass. We calculated total biomass as the product of population size and average body mass. We estimated the percentage of the population that is overweight (BMI > 25) and obese (BMI > 30) and the biomass due to overweight and obesity. In 2005, global adult human biomass was approximately 287 million tonnes, of which 15 million tonnes were due to overweight (BMI > 25), a mass equivalent to that of 242 million people of average body mass (5% of global human biomass). Biomass due to obesity was 3.5 million tonnes, the mass equivalent of 56 million people of average body mass (1.2% of human biomass). North America has 6% of the world population but 34% of biomass due to obesity. Asia has 61% of the world population but 13% of biomass due to obesity. One tonne of human biomass corresponds to approximately 12 adults in North America and 17 adults in Asia. If all countries had the BMI distribution of the USA, the increase in human biomass of 58 million tonnes would be equivalent in mass to an extra 935 million people of average body mass, and have energy requirements equivalent to that of 473 million adults. Increasing population fatness could have the same implications for world food energy demands as an extra half a billion people living on the earth.

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TL;DR: The guidance from the Medical Research Council as discussed by the authors emphasizes that natural experiments can provide convincing evidence of impact even when effects are small or take time to appear, and careful choice and combination of methods, testing of assumptions and transparent reporting is vital.
Abstract: Natural experimental studies are often recommended as a way of understanding the health impact of policies and other large scale interventions. Although they have certain advantages over planned experiments, and may be the only option when it is impossible to manipulate exposure to the intervention, natural experimental studies are more susceptible to bias. This paper introduces new guidance from the Medical Research Council to help researchers and users, funders and publishers of research evidence make the best use of natural experimental approaches to evaluating population health interventions. The guidance emphasises that natural experiments can provide convincing evidence of impact even when effects are small or take time to appear. However, a good understanding is needed of the process determining exposure to the intervention, and careful choice and combination of methods, testing of assumptions and transparent reporting is vital. More could be learnt from natural experiments in future as experience of promising but lesser used methods accumulates.

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TL;DR: The UCL Lancet Commission met from November, 2009, to June, 2011, bringing together an interdisciplinary team of experts to under stand how better health outcomes can be delivered through interventions in the urban environment in cities across the world, and to generate policy recommendations.


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TL;DR: In this article, a systematic review of studies assessing the association between socioeconomic status (SES) and measured obesity in low and middle-income countries (defined by the World Bank as countries with per capita income up to US$12,275) among children, men and women was conducted.
Abstract: We undertook a systematic review of studies assessing the association between socioeconomic status (SES) and measured obesity in low- and middle-income countries (defined by the World Bank as countries with per capita income up to US$12,275) among children, men and women. The evidence on the subject has grown significantly since an earlier influential review was published in 2004. We find that in low-income countries or in countries with low human development index (HDI), the association between SES and obesity appears to be positive for both men and women: the more affluent and/or those with higher educational attainment tend to be more likely to be obese. However, in middle-income countries or in countries with medium HDI, the association becomes largely mixed for men and mainly negative for women. This particular shift appears to occur at an even lower level of per capita income than suggested by an influential earlier review. By contrast, obesity in children appears to be predominantly a problem of the rich in low- and middle-income countries.

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TL;DR: The effects of mobile phone messaging applications designed to facilitate self-management of long-term illnesses, in terms of impact on health outcomes and patients' capacity to self-manage their condition are assessed.
Abstract: Background Long-term illnesses affect a significant proportion of the population in developed and developing countries Mobile phone messaging applications, such as Short Message Service (SMS) and Multimedia Message Service (MMS), may present convenient, cost-effective ways of supporting self-management and improving patients' self-efficacy skills through, for instance, medication reminders, therapy adjustments or supportive messages Objectives To assess the effects of mobile phone messaging applications designed to facilitate self-management of long-term illnesses, in terms of impact on health outcomes and patients' capacity to self-manage their condition Secondary objectives include assessment of: user evaluation of the intervention; health service utilisation and costs; and possible risks and harms associated with the intervention Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL,The Cochrane Library 2009, Issue 2), MEDLINE (OvidSP) (January 1993 to June 2009), EMBASE (OvidSP) (January 1993 to June 2009), PsycINFO (OvidSP) (January 1993 to June 2009), CINAHL (EbscoHOST) (January 1993 to June 2009), LILACS (January 1993 to June 2009) and African Health Anthology (January 1993 to June 2009) We also reviewed grey literature (including trial registers) and reference lists of articles Selection criteria We included randomised controlled trials (RCTs), quasi-randomised controlled trials (QRCTs), controlled before-after (CBA) studies, or interrupted time series (ITS) studies with at least three time points before and after the intervention We selected only studies where it was possible to assess the effects of mobile phone messaging independent of other technologies or interventions Data collection and analysis Two review authors independently assessed all studies against the inclusion criteria, with any disagreements resolved by a third review author Study design features, characteristics of target populations, interventions and controls, and results data were extracted by two review authors and confirmed by a third Primary outcomes of interest were health outcomes as a result of the intervention and capacity to self-manage long-term conditions We also considered patients' and providers' evaluation of the intervention, perceptions of safety, health service utilisation and costs, and potential harms or adverse effects The included studies were heterogeneous in type of condition addressed, intervention characteristics and outcome measures Therefore, a meta-analysis to derive an overall effect size for the main outcome categories was not considered justified and findings are presented narratively Main results We included four randomised controlled trials involving 182 participants For the primary outcome of health outcomes, including physiological measures, there is moderate quality evidence from two studies involving people with diabetes showing no statistical difference from text messaging interventions compared with usual care or email reminders for glycaemic control (HbA1c), the frequency of diabetic complications, or body weight There is moderate quality evidence from one study of hypertensive patients that the mean blood pressure and the proportion of patients who achieved blood pressure control were not significantly different in the intervention and control groups, and that there was no statistically significant difference in mean body weight between the groups There is moderate quality evidence from one study that asthma patients receiving a text messaging intervention experienced greater improvements on peak expiratory flow variability (mean difference (MD) -1112, 95% confidence interval (CI) -1956 to -268) and the pooled symptom score comprising four items (cough, night symptoms, sleep quality, and maximum tolerated activity) (MD -036, 95% CI -056 to -017) compared with the control group However, the study found no significant differences between the groups in impact on forced vital capacity or forced expiratory flow in 1 second For the primary outcome of capacity to self-manage the condition, there is moderate quality evidence from one study that diabetes patients receiving the text messaging intervention demonstrated improved scores on measures of self-management capacity (Self-Efficacy for Diabetes score (MD 610, 95% CI 045 to 1175), Diabetes Social Support Interview pooled score (MD 439, 95% CI 285 to 592)), but did not show improved knowledge of diabetes There is moderate quality evidence from three studies of the effects on treatment compliance One study showed an increase in hypertensive patients' rates of medication compliance in the intervention group (MD 890, 95% CI 018 to 1762) compared with the control group, but in another study there was no statistically significant effect on rates of compliance with peak expiratory flow measurement in asthma patients Text message prompts for diabetic patients initially also resulted in a higher number of blood glucose results sent back (460) than email prompts did (235) For the secondary outcome of participants' evaluation of the intervention, there is very low quality evidence from two studies that patients receiving mobile phone messaging support reported perceived improvement in diabetes self-management, wanted to continue receiving messages, and preferred mobile phone messaging to email as a method to access a computerised reminder system For the secondary outcome of health service utilisation, there is very low quality evidence from two studies Diabetes patients receiving text messaging support made a comparable number of clinic visits and calls to an emergency hotline as patients without the support For asthma patients the total number of office visits was higher in the text messaging group, whereas the number of hospital admissions was higher for the control group Because of the small number of trials included, and the low overall number of participants, for any of the reviewed outcomes the quality of the evidence can at best be considered moderate Authors' conclusions We found some, albeit very limited, indications that in certain cases mobile phone messaging interventions may provide benefit in supporting the self-management of long-term illnesses However, there are significant information gaps regarding the long-term effects, acceptability, costs, and risks of such interventions Given the enthusiasm with which so-called mHealth interventions are currently being implemented, further research into these issues is needed