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Most Cited The Lancet Articles
The most cited articles published since 2011, extracted from Scopus.
Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: A systematic analysis for the Global Burden of Disease Study 2010Rafael Lozano | Mohsen Naghavi | Kyle Foreman | Stephen Lim | Kenji Shibuya | Victor Aboyans | Jerry Abraham | Timothy Adair | Rakesh Aggarwal | Stephanie Y. Ahn | Miriam Alvarado | H. Ross Anderson | Laurie M. Anderson | Kathryn G. Andrews | Charles Atkinson | Larry M. Baddour | Suzanne Barker-Collo | David H. Bartels | Michelle L. Bell | Emelia J. Benjamin | Derrick Bennett | Kavi Bhalla | Boris Bikbov | Aref Bin Abdulhak | Gretchen Birbeck | Fiona Blyth | Ian Bolliger | Soufiane Boufous | Chiara Bucello | Michael Burch | Peter Burney | Jonathan Carapetis | Honglei Chen | David Chou | Sumeet S. Chugh | Luc E. Coffeng | Steven D. Colan | Samantha Colquhoun | K. Ellicott Colson | John Condon | Myles D. Connor | Leslie T. Cooper | Matthew Corriere | Monica Cortinovis | Karen Courville De Vaccaro | William Couser | Benjamin C. Cowie | Michael H. Criqui | Marita Cross | Kaustubh C. Dabhadkar | Nabila Dahodwala | Diego De Leo | Louisa Degenhardt | Allyne Delossantos | Julie Denenberg | Don C. Des Jarlais | Samath D. Dharmaratne | E. Ray Dorsey | Tim Driscoll | Herbert Duber | Beth Ebel | Patricia J. Erwin | Patricia Espindola | Majid Ezzati | Valery Feigin | Abraham D. Flaxman | Mohammad H. Forouzanfar | Francis Gerry R Fowkes | Richard Franklin | Marlene Fransen | Michael K. Freeman | Sherine E. Gabriel | Emmanuela Gakidou | Flavio Gaspari | Richard F. Gillum | Diego Gonzalez-Medina | Yara A. Halasa | Diana Haring | James E. Harrison | Rasmus Havmoeller | Roderick J. Hay | Bruno Hoen | Peter J. Hotez | Damian Hoy | Kathryn H. Jacobsen | Spencer L. James | Rashmi Jasrasaria | Sudha Jayaraman | Nicole Johns | Ganesan Karthikeyan | Nicholas Kassebaum
Volume 380, Issue 9859, December 2012, Pages 2095-2128
Background Reliable and timely information on the leading causes of death in populations, and how these are changing, is a crucial input into health policy debates. In the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010), we aimed to estimate annual deaths for the world and 21 regions between 1980 and 2010 for 235 causes, with uncertainty intervals (UIs); 1separately by age and sex. Methods We attempted to identify all available data on causes of death for 187 countries from 1980 to 2010 from vital registration, verbal autopsy, mortality surveillance, censuses, surveys, hospitals, police records, and mortuaries. We assessed data quality for completeness, diagnostic accuracy, missing data, stochastic variations, and probable causes of death. We applied six different modelling strategies to estimate cause-specific mortality trends depending on the strength of the data. For 133 causes and three special aggregates we used the Cause of Death Ensemble model; (CODEm) approach, which uses four families of statistical models testing a large set of different models using different permutations of covariates. Model ensembles were developed from these component models. We assessed model performance with rigorous out-of-sample testing of prediction error and the validity of 95% UIs. For 13 causes with low observed numbers of deaths, we developed negative binomial models with plausible covariates. For 27 causes for which death is rare, we modelled the higher level cause in the cause hierarchy of the GBD 2010 and then allocated deaths across component causes proportionately, estimated from all available data in the database. For selected causes (African trypanosomiasis, congenital syphilis, whooping cough, measles, typhoid and parathyroid, leishmaniasis, acute hepatitis E, and HIV/AIDS); we used natural history models based on information on incidence, prevalence, and case-fatality. We separately estimated cause fractions by aetiology for diarrhoea, lower respiratory infections, and meningitis, as well as disaggregations by subcause for chronic kidney disease, maternal disorders, cirrhosis, and liver cancer. For deaths due to collective violence and natural disasters, we used mortality shock regressions. For every cause, we estimated 95% UIs that captured both parameter estimation uncertainty and uncertainty due to model specification where CODEm was used. We constrained cause-specific fractions within every age-sex group to sum to total mortality based on draws from the uncertainty distributions. Findings In 2010, there were 52 8 million deaths globally. At the most aggregate level, communicable, maternal, neonatal, and nutritional causes were 24 9% of deaths worldwide in 2010, down from 15 9 million (34 1%) of 46 5 million in 1990. This decrease was largely due to decreases in mortality from diarrhoeal disease (from 2 5 to 1 4 million); 1lower respiratory infections (from 3 4 to 2 8 million); 1neonatal disorders; (from 3 1 to 2 2 million); 1measles; (from 0 63 to 0 13 million)l; 1and tetanus; (from 0 27 to 0 06 million). Deaths from HIV/AIDS increased from 0 30 million in 1990 to 1 5 million in 2010, reaching a peak of 1 7 million in 2006. Malaria mortality also rose by an estimated 19 9% since 1990 to 1 17 million deaths in 2010. Tuberculosis killed 1 2 million people in 2010. Deaths from non-communicable diseases rose by just under 8 million between 1990 and 2010, accounting for two of every three deaths (34 5 million) worldwide by 2010. 8 million people died from cancer in 2010, 38% more than two decades ago; of these, 1 5 million (19%) were from trachea, bronchus, and lung cancer. Ischaemic heart disease and stroke collectively killed 12 9 million people in 2010, or one in four deaths worldwide, compared with one in five in 1990; 1 3 million deaths were due to diabetes, twice as many as in 1990. The fraction of global deaths due to injuries (5 1 million deaths) was marginally higher in 2010 (9 6%) compared with two decades earlier (8 8%). This was driven by a 46% rise in deaths worldwide due to road traffic accidents (1 3 million in 2010) and a rise in deaths from falls. Ischaemic heart disease, stroke, chronic obstructive pulmonary disease (COPD); 1lower respiratory infections, lung cancer, and HIV/AIDS were the leading causes of death in 2010. Ischaemic heart disease, lower respiratory infections, stroke, diarrhoeal disease, malaria, and HIV/AIDS were the leading causes of years of life lost due to premature mortality; (YLLs) in 2010, similar to what was estimated for 1990, except for HIV/AIDS and preterm birth complications. YLLs from lower respiratory infections and diarrhoea decreased by 45-54% since 1990; ischaemic heart disease and stroke YLLs increased by 17-28%. Regional variations in leading causes of death were substantial. Communicable, maternal, neonatal, and nutritional causes still accounted for 76% of premature mortality in sub- Saharan Africa in 2010. Age standardised death rates from some key disorders rose (HIV/AIDS, Alzheimer's disease, diabetes mellitus, and chronic kidney disease in particular); 1but for most diseases, death rates fell in the past two decades; including major vascular diseases, COPD, most forms of cancer, liver cirrhosis, and maternal disorders. For other conditions, notably malaria, prostate cancer, and injuries, little change was noted. Interpretation Population growth, increased average age of the world's population, and largely decreasing age-specific, sex-specific, and cause-specific death rates combine to drive a broad shift from communicable, maternal, neonatal, and nutritional causes towards non-communicable diseases. Nevertheless, communicable, maternal, neonatal, and nutritional causes remain the dominant causes of YLLs in sub-Saharan Africa. Overlaid on this general pattern of the epidemiological transition, marked regional variation exists in many causes, such as interpersonal violence, suicide, liver cancer, diabetes, cirrhosis, Chagas disease, African trypanosomiasis, melanoma, and others. Regional heterogeneity highlights the importance of sound epidemiological assessments of the causes of death on a regular basis.
A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: A systematic analysis for the Global Burden of Disease Study 2010Stephen S. Lim | Theo Vos | Abraham D. Flaxman | Goodarz Danaei | Kenji Shibuya | Heather Adair-Rohani | Markus Amann | H. Ross Anderson | Kathryn G. Andrews | Martin Aryee | Charles Atkinson | Loraine J. Bacchus | Adil N. Bahalim | Kalpana Balakrishnan | John Balmes | Suzanne Barker-Collo | Amanda Baxter | Michelle L. Bell | Jed D. Blore | Fiona Blyth | Carissa Bonner | Guilherme Borges | Rupert Bourne | Michel Boussinesq | Michael Brauer | Peter Brooks | Nigel G. Bruce | Bert Brunekreef | Claire Bryan-Hancock | Chiara Bucello | Rachelle Buchbinder | Fiona Bull | Richard T. Burnett | Tim E. Byers | Bianca Calabria | Jonathan Carapetis | Emily Carnahan | Zoe Chafe | Fiona Charlson | Honglei Chen | Jian Shen Chen | Andrew Tai Ann Cheng | Jennifer Christine Child | Aaron Cohen | K. Ellicott Colson | Benjamin C. Cowie | Sarah Darby | Susan Darling | Adrian Davis | Louisa Degenhardt | Frank Dentener | Don C. Des Jarlais | Karen Devries | Mukesh Dherani | Eric L. Ding | E. Ray Dorsey | Tim Driscoll | Karen Edmond | Suad Eltahir Ali | Rebecca E. Engell | Patricia J. Erwin | Saman Fahimi | Gail Falder | Farshad Farzadfar | Alize Ferrari | Mariel M. Finucane | Seth Flaxman | Francis Gerry R Fowkes | Greg Freedman | Michael K. Freeman | Emmanuela Gakidou | Santu Ghosh | Edward Giovannucci | Gerhard Gmel | Kathryn Graham | Rebecca Grainger | Bridget Grant | David Gunnell | Hialy R. Gutierrez | Wayne Hall | Hans W. Hoek | Anthony Hogan | H. Dean Hosgood | Damian Hoy | Howard Hu | Bryan J. Hubbell | Sally J. Hutchings | Sydney E. Ibeanusi | Gemma L. Jacklyn | Rashmi Jasrasaria | Jost B. Jonas | Haidong Kan | John A. Kanis
Volume 380, Issue 9859, December 2012, Pages 2224-2260
Background Quantification of the disease burden caused by different risks informs prevention by providing an account of health loss different to that provided by a disease-by-disease analysis. No complete revision of global disease burden caused by risk factors has been done since a comparative risk assessment in 2000, and no previous analysis has assessed changes in burden attributable to risk factors over time. Methods We 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. We estimated exposure distributions for each year, region, sex, and age group, and relative risks per unit of exposure by systematically reviewing and synthesising published and unpublished data. We used these estimates, together with estimates of cause-specific deaths and DALYs from the Global Burden of Disease Study 2010, to calculate the burden attributable to each risk factor exposure compared with the theoretical-minimum-risk exposure. We incorporated uncertainty in disease burden, relative risks, and exposures into our estimates of attributable burden. Findings In 2010, the three leading risk factors for global disease burden were high blood pressure (7 0% [95% uncertainty interval 6 2-7 7] of global DALYs); tobacco smoking including second-hand smoke (6 3% [5 5-7 0]), and alcohol use (5 5% [5 0-5 9]). In 1990, the leading risks were childhood underweight (7 9% [6 8-9 4]), household air pollution from solid fuels; (HAP; 7 0% [5 6-8 3]), and tobacco smoking including second-hand smoke (6 1% [5 4-6 8]). Dietary risk factors and physical inactivity collectively accounted for 10 0% (95% UI 9 2-10 8) of global DALYs in 2010, with the most prominent dietary risks being diets low in fruits and those high in sodium. Several risks that primarily affect childhood communicable diseases, including unimproved water and sanitation and childhood micronutrient deficiencies, fell in rank between 1990 and 2010, with unimproved water ' and sanitation accounting for 0 9% (0 4-1 6) of global DALYs in 2010. However, in most of sub-Saharan Africa childhood underweight, HAP, and non-exclusive and discontinued breastfeeding were the leading risks in 2010, while HAP was the leading risk in south Asia. The leading risk factor in Eastern Europe, most of Latin America, and southern sub-Saharan Africa in 2010 was alcohol use; in most of Asia, North Africa and Middle East, and central Europe it was high blood pressure. Despite declines, tobacco smoking including second-hand smoke remained the leading risk in high-income north America and western Europe. High body-mass index has increased globally and it is the leading risk in Australasia and southern Latin America, and also ranks high in other high-income regions, North Africa and Middle East, and Oceania. Interpretation Worldwide, the contribution of different risk factors to disease burden has changed substantially, with a shift away from risks for communicable diseases in children towards those for non-communicable diseases in adults. These changes are related to the ageing population, decreased mortality among children younger than 5 years, changes in cause-of-death composition, and changes in risk factor exposures. New evidence has led to changes in the magnitude of key risks including unimproved water and sanitation, vitamin A and zinc deficiencies, and ambient particulate matter pollution. The extent to which the epidemiological shift has occurred and what the leading risks currently are varies greatly across regions. In much of sub-Saharan Africa, the leading risks are still those associated with poverty and those that affect children.
Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: A systematic analysis for the Global Burden of Disease Study 2010Christopher J L Murray | Theo Vos | Rafael Lozano | Mohsen Naghavi | Abraham D. Flaxman | Catherine Michaud | Majid Ezzati | Kenji Shibuya | Joshua A. Salomon | Safa Abdalla | Victor Aboyans | Jerry Abraham | Ilana Ackerman | Rakesh Aggarwal | Stephanie Y. Ahn | Mohammed K. Ali | Miriam Alvarado | H. Ross Anderson | Laurie M. Anderson | Kathryn G. Andrews | Charles Atkinson | Larry M. Baddour | Adil N. Bahalim | Suzanne Barker-Collo | Lope H. Barrero | David H. Bartels | Maria Gloria Basáñez | Amanda Baxter | Michelle L. Bell | Emelia J. Benjamin | Derrick Bennett | Eduardo Bernabé | Kavi Bhalla | Bishal Bhandari | Boris Bikbov | Aref Bin Abdulhak | Gretchen Birbeck | James A. Black | Hannah Blencowe | Jed D. Blore | Fiona Blyth | Ian Bolliger | Audrey Bonaventure | Soufiane Boufous | Rupert Bourne | Michel Boussinesq | Tasanee Braithwaite | Carol Brayne | Lisa Bridgett | Simon Brooker | Peter Brooks | Traolach S. Brugha | Claire Bryan-Hancock | Chiara Bucello | Rachelle Buchbinder | Geoffrey Buckle | Christine M. Budke | Michael Burch | Peter Burney | Roy Burstein | Bianca Calabria | Benjamin Campbell | Charles E. Canter | Hélène Carabin | Jonathan Carapetis | Loreto Carmona | Claudia Cella | Fiona Charlson | Honglei Chen | Andrew Tai Ann Cheng | David Chou | Sumeet S. Chugh | Luc E. Coffeng | Steven D. Colan | Samantha Colquhoun | K. Ellicott Colson | John Condon | Myles D. Connor | Leslie T. Cooper | Matthew Corriere | Monica Cortinovis | Karen Courville De Vaccaro | William Couser | Benjamin C. Cowie | Michael H. Criqui | Marita Cross | Kaustubh C. Dabhadkar | Manu Dahiya | Nabila Dahodwala | James Damsere-Derry | Goodarz Danaei | Adrian Davis | Diego De Leo | Louisa Degenhardt | Robert Dellavalle | Allyne Delossantos | Julie Denenberg
Volume 380, Issue 9859, January 2012, Pages 2197-2223
Background Measuring disease and injury burden in populations requires a composite metric that captures both premature mortality and the prevalence and severity of ill-health. The 1990 Global Burden of Disease study proposed disability-adjusted life years (DALYs) to measure disease burden. No comprehensive update of disease burden worldwide incorporating a systematic reassessment of disease and injury-specific epidemiology has been done since the 1990 study. We aimed to calculate disease burden worldwide and for 21 regions for 1990, 2005, and 2010 with methods to enable meaningful comparisons over time. Methods We calculated DALYs as the sum of years of life lost (YLLs) and years lived with disability (YLDs). DALYs were calculated for 291 causes, 20 age groups, both sexes, and for 187 countries, and aggregated to regional and global estimates of disease burden for three points in time with strictly comparable definitions and methods. YLLs were calculated from age-sex-country-time-specific estimates of mortality by cause, with death by standardised lost life expectancy at each age. YLDs were calculated as prevalence of 1160 disabling sequelae, by age, sex, and cause, and weighted by new disability weights for each health state. Neither YLLs nor YLDs were age-weighted or discounted. Uncertainty around cause-specific DALYs was calculated incorporating uncertainty in levels of all-cause mortality, cause-specific mortality, prevalence, and disability weights. Findings Global DALYs remained stable from 1990 (2 503 billion) to 2010 (2 490 billion). Crude DALYs per 1000 decreased by 23% (472 per 1000 to 361 per 1000). An important shift has occurred in DALY composition with the contribution of deaths and disability among children (younger than 5 years of age) declining from 41% of global DALYs in 1990 to 25% in 2010. YLLs typically account for about half of disease burden in more developed regions (high-income Asia Pacific, western Europe, high-income North America, and Australasia); rising to over 80% of DALYs in sub-Saharan Africa. In 1990, 47% of DALYs worldwide were from communicable, maternal, neonatal, and nutritional disorders, 43% from non-communicable diseases, and 10% from injuries. By 2010, this had shifted to 35%, 54%, and 11%, respectively. Ischaemic heart disease was the leading cause of DALYs worldwide in 2010; (up from fourth rank in 1990, increasing by 29%), followed by lower respiratory infections (top rank in 1990; 44% decline in DALYs); stroke; (fifth in 1990; 19% increase); diarrhoeal diseases; (second in 1990; 51% decrease); and HIV/AIDS (33rd in 1990; 351% increase). Major depressive disorder increased from 15th to 11th rank (37% increase) and road injury from 12th to 10th rank (34% increase). Substantial heterogeneity exists in rankings of leading causes of disease burden among regions. Interpretation Global disease burden has continued to shift away from communicable to non-communicable diseases and from premature death to years lived with disability. In sub-Saharan Africa, however, many communicable, maternal, neonatal, and nutritional disorders remain the dominant causes of disease burden. The rising burden from mental and behavioural disorders, musculoskeletal disorders, and diabetes will impose new challenges on health systems. Regional heterogeneity highlights the importance of understanding local burden of disease and setting goals and targets for the post-2015 agenda taking such patterns into account. Because of improved definitions, methods, and data, these results for 1990 and 2010 supersede all previously published Global Burden of Disease results.
National, regional, and global trends in body-mass index since 1980: Systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9·1 million participantsMariel M. Finucane | Gretchen A. Stevens | Melanie J. Cowan | Goodarz Danaei | John K. Lin | Christopher J. Paciorek | Gitanjali M. Singh | Hialy R. Gutierrez | Yuan Lu | Adil N. Bahalim | Farshad Farzadfar | Leanne M. Riley | Majid Ezzati
Volume 377, Issue 9765, February 2011, Pages 557-567
Excess bodyweight is a major public health concern. However, few worldwide comparative analyses of long-term trends of body-mass index (BMI) have been done, and none have used recent national health examination surveys. We estimated worldwide trends in population mean BMI. We estimated trends and their uncertainties of mean BMI for adults 20 years and older in 199 countries and territories. We obtained data from published and unpublished health examination surveys and epidemiological studies (960 country-years and 9·1 million participants). For each sex, we used a Bayesian hierarchical model to estimate mean BMI by age, country, and year, accounting for whether a study was nationally representative. Between 1980 and 2008, mean BMI worldwide increased by 0·4 kg/m2 per decade (95 uncertainty interval 0·2-0·6, posterior probability of being a true increase >0·999) for men and 0·5 kg/m2 per decade (0·3-0·7, posterior probability >0·999) for women. National BMI change for women ranged from non-significant decreases in 19 countries to increases of more than 2·0 kg/m2 per decade (posterior probabilities >0·99) in nine countries in Oceania. Male BMI increased in all but eight countries, by more than 2 kg/m2 per decade in Nauru and Cook Islands (posterior probabilities >0·999). Male and female BMIs in 2008 were highest in some Oceania countries, reaching 33·9 kg/m2 (32·8-35·0) for men and 35·0 kg/m2 (33·6-36·3) for women in Nauru. Female BMI was lowest in Bangladesh (20·5 kg/m2, 19·8-21·3) and male BMI in Democratic Republic of the Congo 19·9 kg/m2 (18·2-21·5), with BMI less than 21·5 kg/m2 for both sexes in a few countries in sub-Saharan Africa, and east, south, and southeast Asia. The USA had the highest BMI of high-income countries. In 2008, an estimated 1·46 billion adults (1·41-1·51 billion) worldwide had BMI of 25 kg/m2 or greater, of these 205 million men (193-217 million) and 297 million women (280-315 million) were obese. Globally, mean BMI has increased since 1980. The trends since 1980, and mean population BMI in 2008, varied substantially between nations. Interventions and policies that can curb or reverse the increase, and mitigate the health effects of high BMI by targeting its metabolic mediators, are needed in most countries. Bill Melinda Gates Foundation and WHO.
Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: A systematic analysis for the Global Burden of Disease Study 2010Theo Vos | Abraham D. Flaxman | Mohsen Naghavi | Rafael Lozano | Catherine Michaud | Majid Ezzati | Kenji Shibuya | Joshua A. Salomon | Safa Abdalla | Victor Aboyans | Jerry Abraham | Ilana Ackerman | Rakesh Aggarwal | Stephanie Y. Ahn | Mohammed K. Ali | Miriam Alvarado | H. Ross Anderson | Laurie M. Anderson | Kathryn G. Andrews | Charles Atkinson | Larry M. Baddour | Adil N. Bahalim | Suzanne Barker-Collo | Lope H. Barrero | David H. Bartels | Maria Gloria Basáñez | Amanda Baxter | Michelle L. Bell | Emelia J. Benjamin | Derrick Bennett | Eduardo Bernabé | Kavi Bhalla | Bishal Bhandari | Boris Bikbov | Aref Bin Abdulhak | Gretchen Birbeck | James A. Black | Hannah Blencowe | Jed D. Blore | Fiona Blyth | Ian Bolliger | Audrey Bonaventure | Soufiane Boufous | Rupert Bourne | Michel Boussinesq | Tasanee Braithwaite | Carol Brayne | Lisa Bridgett | Simon Brooker | Peter Brooks | Traolach S. Brugha | Claire Bryan-Hancock | Chiara Bucello | Rachelle Buchbinder | Geoffrey Buckle | Christine M. Budke | Michael Burch | Peter Burney | Roy Burstein | Bianca Calabria | Benjamin Campbell | Charles E. Canter | Hélène Carabin | Jonathan Carapetis | Loreto Carmona | Claudia Cella | Fiona Charlson | Honglei Chen | Andrew Tai Ann Cheng | David Chou | Sumeet S. Chugh | Luc E. Coffeng | Steven D. Colan | Samantha Colquhoun | K. Ellicott Colson | John Condon | Myles D. Connor | Leslie T. Cooper | Matthew Corriere | Monica Cortinovis | Karen Courville De Vaccaro | William Couser | Benjamin C. Cowie | Michael H. Criqui | Marita Cross | Kaustubh C. Dabhadkar | Manu Dahiya | Nabila Dahodwala | James Damsere-Derry | Goodarz Danaei | Adrian Davis | Diego De Leo | Louisa Degenhardt | Robert Dellavalle | Allyne Delossantos | Julie Denenberg | Sarah Derrett
Volume 380, Issue 9859, January 2012, Pages 2163-2196
Background Non-fatal health outcomes from diseases and injuries are a crucial consideration in the promotion and monitoring of individual and population health. The Global Burden of Disease (GBD) studies done in 1990 and 2000 have been the only studies to quantify non-fatal health outcomes across an exhaustive set of disorders at the global and regional level. Neither effort quantified uncertainty in prevalence or years lived with disability (YLDs). Methods Of the 291 diseases and injuries in the GBD cause list, 289 cause disability. For 1160 sequelae of the 289 diseases and injuries, we undertook a systematic analysis of prevalence, incidence, remission, duration, and excess mortality. Sources included published studies, case notification, population-based cancer registries, other disease registries, antenatal clinic serosurveillance, hospital discharge data, ambulatory care data, household surveys, other surveys, and cohort studies. For most sequelae, we used a Bayesian meta-regression method, DisMod-MR, designed to address key limitations in descriptive epidemiological data, including missing data, inconsistency, and large methodological variation between data sources. For some disorders, we used natural history models, geospatial models, back-calculation models (models calculating incidence from population mortality rates and case fatality); or registration completeness models; (models adjusting for incomplete registration with health-system access and other covariates). Disability weights for 220 unique health states were used to capture the severity of health loss. YLDs by cause at age, sex, country, and year levels were adjusted for comorbidity with simulation methods. We included uncertainty estimates at all stages of the analysis. Findings Global prevalence for all ages combined in 2010 across the 1160 sequelae ranged from fewer than one case per 1 million people to 350 000 cases per 1 million people. Prevalence and severity of health loss were weakly correlated (correlation coefficient -0 37). In 2010, there were 777 million YLDs from all causes, up from 583 million in 1990. The main contributors to global YLDs were mental and behavioural disorders, musculoskeletal disorders, and diabetes or endocrine diseases. The leading specific causes of YLDs were much the same in 2010 as they were in 1990: low back pain, major depressive disorder, iron-deficiency anaemia, neck pain, chronic obstructive pulmonary disease, anxiety disorders, migraine, diabetes, and falls. Age-specific prevalence of YLDs increased with age in all regions and has decreased slightly from 1990 to 2010. Regional patterns of the leading causes of YLDs were more similar compared with years of life lost due to premature mortality. Neglected tropical diseases, HIV/AIDS, tuberculosis, malaria, and anaemia were important causes of YLDs in sub-Saharan Africa. Interpretation Rates of YLDs per 100 000 people have remained largely constant over time but rise steadily with age. Population growth and ageing have increased YLD numbers and crude rates over the past two decades. Prevalences of the most common causes of YLDs, such as mental and behavioural disorders and musculoskeletal disorders, have not decreased. Health systems will need to address the needs of the rising numbers of individuals with a range of disorders that largely cause disability but not mortality. Quantification of the burden of non-fatal health outcomes will be crucial to understand how well health systems are responding to these challenges. Effective and affordable strategies to deal with this rising burden are an urgent priority for health systems in most parts of the world.
National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: Systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2·7 million participantsGoodarz Danaei | Mariel M. Finucane | Yuan Lu | Gitanjali M. Singh | Melanie J. Cowan | Christopher J. Paciorek | John K. Lin | Farshad Farzadfar | Young Ho Khang | Gretchen A. Stevens | Mayuree Rao | Mohammed K. Ali | Leanne M. Riley | Carolyn A. Robinson | Majid Ezzati
Volume 378, Issue 9785, July 2011, Pages 31-40
Data for trends in glycaemia and diabetes prevalence are needed to understand the effects of diet and lifestyle within populations, assess the performance of interventions, and plan health services. No consistent and comparable global analysis of trends has been done. We estimated trends and their uncertainties in mean fasting plasma glucose (FPG) and diabetes prevalence for adults aged 25 years and older in 199 countries and territories. We obtained data from health examination surveys and epidemiological studies (370 country-years and 2·7 million participants). We converted systematically between different glycaemic metrics. For each sex, we used a Bayesian hierarchical model to estimate mean FPG and its uncertainty by age, country, and year, accounting for whether a study was nationally, subnationally, or community representative. In 2008, global age-standardised mean FPG was 5·50 mmol/L (95 uncertainty interval 5·37-5·63) for men and 5·42 mmol/L (5·29-5·54) for women, having risen by 0·07 mmol/L and 0·09 mmol/L per decade, respectively. Age-standardised adult diabetes prevalence was 9·8 (8·6- 11·2) in men and 9·2 (8·0-10·5) in women in 2008, up from 8·3 (6·5-10·4) and 7·5 (5·8-9·6) in 1980. The number of people with diabetes increased from 153 (127-182) million in 1980, to 347 (314-382) million in 2008. We recorded almost no change in mean FPG in east and southeast Asia and central and eastern Europe. Oceania had the largest rise, and the highest mean FPG (6·09 mmol/L, 5·73-6·49 for men; 6·08 mmol/L, 5·72-6·46 for women) and diabetes prevalence (15·5, 11·6-20·1 for men; and 15·9, 12·1-20·5 for women) in 2008. Mean FPG and diabetes prevalence in 2008 were also high in south Asia, Latin America and the Caribbean, and central Asia, north Africa, and the Middle East. Mean FPG in 2008 was lowest in sub-Saharan Africa, east and southeast Asia, and high-income Asia-Pacific. In high-income subregions, western Europe had the smallest rise, 0·07 mmol/L per decade for men and 0·03 mmol/L per decade for women; North America had the largest rise, 0·18 mmol/L per decade for men and 0·14 mmol/L per decade for women. Glycaemia and diabetes are rising globally, driven both by population growth and ageing and by increasing age-specific prevalences. Effective preventive interventions are needed, and health systems should prepare to detect and manage diabetes and its sequelae. Bill & Melinda Gates Foundation and WHO. © 2011 Elsevier Ltd.
Hepatocellular carcinomaAlejandro Forner | Josep M. Llovet | Jordi Bruix
Volume 379, Issue 9822, March 2012, Pages 1245-1255
Hepatocellular carcinoma is the sixth most prevalent cancer and the third most frequent cause of cancer-related death. Patients with cirrhosis are at highest risk of developing this malignant disease, and ultrasonography every 6 months is recommended. Surveillance with ultrasonography allows diagnosis at early stages when the tumour might be curable by resection, liver transplantation, or ablation, and 5-year survival higher than 50 can be achieved. Patients with small solitary tumours and very well preserved liver function are the best candidates for surgical resection. Liver transplantation is most beneficial for individuals who are not good candidates for resection, especially those within Milano criteria (solitary tumour ≤5 cm and up to three nodules ≤3 cm). Donor shortage greatly limits its applicability. Percutaneous ablation is the most frequently used treatment but its effectiveness is limited by tumour size and localisation. In asymptomatic patients with multifocal disease without vascular invasion or extrahepatic spread not amenable to curative treatments, chemoembolisation can provide survival benefit. Findings of randomised trials of sorafenib have shown survival benefits for individuals with advanced hepatocellular carcinoma, suggesting that molecular-targeted therapies could be effective in this chemoresistant cancer. Research is active in the area of pathogenesis and treatment of hepatocellular carcinoma. © 2012 Elsevier Ltd.
Effect of physical inactivity on major non-communicable diseases worldwide: An analysis of burden of disease and life expectancyI. Min Lee | Eric J. Shiroma | Felipe Lobelo | Pekka Puska | Steven N. Blair | Peter T. Katzmarzyk | Jasem R. Alkandari | Lars Bo Andersen | Adrian E. Bauman | Ross C. Brownson | Fiona C. Bull | Cora L. Craig | Ulf Ekelund | Shifalika Goenka | Regina Guthold | Pedro C. Hallal | William L. Haskell | Gregory W. Heath | Shigeru Inoue | Sonja Kahlmeier | Harold W. Kohl | Estelle Victoria Lambert | Grit Leetongin | Ruth J F Loos | Bess Marcus | Brian W. Martin | Neville Owen | Diana C. Parra | Michael Pratt | David Ogilvie | Rodrigo S. Reis | James F. Sallis | Olga Lucia Sarmiento | Jonathan C. Wells
Volume 380, Issue 9838, July 2012, Pages 219-229
Background Strong evidence shows that physical inactivity increases the risk of many adverse health conditions, including major non-communicable diseases such as coronary heart disease, type 2 diabetes, and breast and colon cancers, and shortens life expectancy. Because much of the world's population is inactive, this link presents a major public health issue. We aimed to quantify the effect of physical inactivity on these major non-communicable diseases by estimating how much disease could be averted if inactive people were to become active and to estimate gain in life expectancy at the population level. Methods For our analysis of burden of disease, we calculated population attributable fractions (PAFs) associated with physical inactivity using conservative assumptions for each of the major non-communicable diseases, by country, to estimate how much disease could be averted if physical inactivity were eliminated. We used life-table analysis to estimate gains in life expectancy of the population. Findings Worldwide, we estimate that physical inactivity causes 6% (ranging from 3.2% in southeast Asia to 7.8% in the eastern Mediterranean region) of the burden of disease from coronary heart disease, 7% (3.9-9.6) of type 2 diabetes, 10% (5.6-14.1) of breast cancer, and 10% (5.7-13.8) of colon cancer. Inactivity causes 9% (range 5.1-12.5) of premature mortality, or more than 5.3 million of the 57 million deaths that occurred worldwide in 2008. If inactivity were not eliminated, but decreased instead by 10% or 25%, more than 533 000 and more than 1.3 million deaths, respectively, could be averted every year. We estimated that elimination of physical inactivity would increase the life expectancy of the world's population by 0.68 (range 0.41-0.95) years. Interpretation Physical inactivity has a major health effect worldwide. Decrease in or removal of this unhealthy behaviour could improve health substantially. Funding None.
Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: A systematic analysis for the Global Burden of Disease Study 2013Marie Ng | Tom Fleming | Margaret Robinson | Blake Thomson | Nicholas Graetz | Christopher Margono | Erin C. Mullany | Stan Biryukov | Cristiana Abbafati | Semaw Ferede Abera | Jerry P. Abraham | Niveen M E Abu-Rmeileh | Tom Achoki | Fadia S. Albuhairan | Zewdie A. Alemu | Rafael Alfonso | Mohammed K. Ali | Raghib Ali | Nelson Alvis Guzman | Walid Ammar | Palwasha Anwari | Amitava Banerjee | Simon Barquera | Sanjay Basu | Derrick A. Bennett | Zulfiqar Bhutta | Jed Blore | Norberto Cabral | Ismael Campos Nonato | Jung Chen Chang | Rajiv Chowdhury | Karen J. Courville | Michael H. Criqui | David K. Cundiff | Kaustubh C. Dabhadkar | Lalit Dandona | Adrian Davis | Anand Dayama | Samath D. Dharmaratne | Eric L. Ding | Adnan M. Durrani | Alireza Esteghamati | Farshad Farzadfar | Derek F J Fay | Valery L. Feigin | Abraham Flaxman | Mohammad H. Forouzanfar | Atsushi Goto | Mark A. Green | Rajeev Gupta | Nima Hafezi-Nejad | Graeme J. Hankey | Heather C. Harewood | Rasmus Havmoeller | Simon Hay | Lucia Hernandez | Abdullatif Husseini | Bulat T. Idrisov | Nayu Ikeda | Farhad Islami | Eiman Jahangir | Simerjot K. Jassal | Sun Ha Jee | Mona Jeffreys | Jost B. Jonas | Edmond K. Kabagambe | Shams Eldin Ali Hassan Khalifa | Andre Pascal Kengne | Yousef Saleh Khader | Young Ho Khang | Daniel Kim | Ruth W. Kimokoti | Jonas M. Kinge | Yoshihiro Kokubo | Soewarta Kosen | Gene Kwan | Taavi Lai | Mall Leinsalu | Yichong Li | Xiaofeng Liang | Shiwei Liu | Giancarlo Logroscino | Paulo A. Lotufo | Yuan Lu | Jixiang Ma | Nana Kwaku Mainoo | George A. Mensah | Tony R. Merriman | Ali H. Mokdad | Joanna Moschandreas | Mohsen Naghavi | Aliya Naheed | Devina Nand | K. M Venkat Narayan | Erica Leigh Nelson | Marian L. Neuhouser | Muhammad Imran Nisar | Takayoshi Ohkubo
Volume 384, Issue 9945, January 2014, Pages 766-781
Background In 2010, overweight and obesity were estimated to cause 3·4 million deaths, 3·9% of years of life lost, and 3·8% of disability-adjusted life-years (DALYs) worldwide. The rise in obesity has led to widespread calls for regular monitoring of changes in overweight and obesity prevalence in all populations. Comparable, up-to-date information about levels and trends is essential to quantify population health effects and to prompt decision makers to prioritise action. We estimate the global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013. Methods We systematically identified surveys, reports, and published studies (n=1769) that included data for height and weight, both through physical measurements and self-reports. We used mixed effects linear regression to correct for bias in self-reports. We obtained data for prevalence of obesity and overweight by age, sex, country, and year (n=19 244) with a spatiotemporal Gaussian process regression model to estimate prevalence with 95% uncertainty intervals (UIs). Findings Worldwide, the proportion of adults with a body-mass index (BMI) of 25 kg/m2 or greater increased between 1980 and 2013 from 28·8% (95% UI 28·4-29·3) to 36·9% (36·3-37·4) in men, and from 29·8% (29·3- 30·2) to 38·0% (37·5-38·5) in women. Prevalence has increased substantially in children and adolescents in developed countries; 23·8% (22·9-24·7) of boys and 22·6% (21·7-23·6) of girls were overweight or obese in 2013. The prevalence of overweight and obesity has also increased in children and adolescents in developing countries, from 8·1% (7·7-8·6) to 12·9% (12·3-13·5) in 2013 for boys and from 8·4% (8·1-8·8) to 13·4% (13·0-13·9) in girls. In adults, estimated prevalence of obesity exceeded 50% in men in Tonga and in women in Kuwait, Kiribati, Federated States of Micronesia, Libya, Qatar, Tonga, and Samoa. Since 2006, the increase in adult obesity in developed countries has slowed down. Interpretation Because of the established health risks and substantial increases in prevalence, obesity has become a major global health challenge. Not only is obesity increasing, but no national success stories have been reported in the past 33 years. Urgent global action and leadership is needed to help countries to more effectively intervene. Funding Bill & Melinda Gates Foundation. © 2014 Elsevier Ltd.
Global, regional, and national causes of child mortality: An updated systematic analysis for 2010 with time trends since 2000Li Liu | Hope L. Johnson | Simon Cousens | Jamie Perin | Susana Scott | Joy E. Lawn | Igor Rudan | Harry Campbell | Richard Cibulskis | Mengying Li | Colin Mathers | Robert E. Black
Volume 379, Issue 9832, June 2012, Pages 2151-2161
Background: Information about the distribution of causes of and time trends for child mortality should be periodically updated. We report the latest estimates of causes of child mortality in 2010 with time trends since 2000. Methods: Updated total numbers of deaths in children aged 0-27 days and 1-59 months were applied to the corresponding country-specific distribution of deaths by cause. We did the following to derive the number of deaths in children aged 1-59 months: we used vital registration data for countries with an adequate vital registration system; we applied a multinomial logistic regression model to vital registration data for low-mortality countries without adequate vital registration; we used a similar multinomial logistic regression with verbal autopsy data for high-mortality countries; for India and China, we developed national models. We aggregated country results to generate regional and global estimates. Findings: Of 7·6 million deaths in children younger than 5 years in 2010, 64·0 (4·879 million) were attributable to infectious causes and 40·3 (3·072 million) occurred in neonates. Preterm birth complications (14·1; 1·078 million, uncertainty range [UR] 0·916-1·325), intrapartum-related complications (9·4; 0·717 million, 0·610-0·876), and sepsis or meningitis (5·2; 0·393 million, 0·252-0·552) were the leading causes of neonatal death. In older children, pneumonia (14·1; 1·071 million, 0·977-1·176), diarrhoea (9·9; 0·751 million, 0·538-1·031), and malaria (7·4; 0·564 million, 0·432-0·709) claimed the most lives. Despite tremendous efforts to identify relevant data, the causes of only 2·7 (0·205 million) of deaths in children younger than 5 years were medically certified in 2010. Between 2000 and 2010, the global burden of deaths in children younger than 5 years decreased by 2 million, of which pneumonia, measles, and diarrhoea contributed the most to the overall reduction (0·451 million [0·339-0·547], 0·363 million [0·283-0·419], and 0·359 million [0·215- 0·476], respectively). However, only tetanus, measles, AIDS, and malaria (in Africa) decreased at an annual rate sufficient to attain the Millennium Development Goal 4. Interpretation: Child survival strategies should direct resources toward the leading causes of child mortality, with attention focusing on infectious and neonatal causes. More rapid decreases from 2010-15 will need accelerated reduction for the most common causes of death, notably pneumonia and preterm birth complications. Continued efforts to gather high-quality data and enhance estimation methods are essential for the improvement of future estimates. Funding: The Bill & Melinda Gates Foundation. © 2012 Elsevier Ltd.
Dabrafenib in BRAF-mutated metastatic melanoma: A multicentre, open-label, phase 3 randomised controlled trialAxel Hauschild | Jean Jacques Grob | Lev V. Demidov | Thomas Jouary | Ralf Gutzmer | Michael Millward | Piotr Rutkowski | Christian U. Blank | Wilson H. Miller | Eckhart Kaempgen | Salvador Martín-Algarra | Boguslawa Karaszewska | Cornelia Mauch | Vanna Chiarion-Sileni | Anne Marie Martin | Suzanne Swann | Patricia Haney | Beloo Mirakhur | Mary E. Guckert | Vicki Goodman | Paul B. Chapman
Volume 380, Issue 9839, July 2012, Pages 358-365
Background Dabrafenib, an inhibitor of mutated BRAF, has clinical activity with a manageable safety profile in studies of phase 1 and 2 in patients with BRAFV600-mutated metastatic melanoma. We studied the efficacy of dabrafenib in patients with BRAFV600E-mutated metastatic melanoma. Methods We enrolled patients in this open-label phase 3 trial between Dec 23, 2010, and Sept 1, 2011. This report is based on a data cutoff date of Dec 19, 2011. Patients aged 18 years or older with previously untreated, stage IV or unresectable stage III BRAFV600E mutation-positive melanoma were randomly assigned (3:1) to receive dabrafenib (150 mg twice daily, orally) or dacarbazine (1000 mg/m2 intravenously every 3 weeks). Patients were stratified according to American Joint Committee on Cancer stage (unresectable III+IVM1a+IVM1b vs IVM1c). The primary endpoint was investigator-assessed progression-free survival and was analysed by intention to treat; safety was assessed per protocol. This study is registered with ClinicalTrials.gov, number NCT01227889. Findings Of the 733 patients screened, 250 were randomly assigned to receive either dabrafenib (187 patients) or dacarbazine (63 patients). Median progression-free survival was 5 1 months for dabrafenib and 2 7 months for dacarbazine, with a hazard ratio (HR) of 0 30 (95% CI 0 18-0 51; p<0 0001). At data cutoff, 107 (57%) patients in the dabrafenib group and 14 (22%) in the dacarbazine group remained on randomised treatment. Treatment-related adverse events (grade 2 or higher) occurred in 100 (53%) of the 187 patients who received dabrafenib and in 26 (44%) of the 59 patients who received dacarbazine. The most common adverse events with dabrafenib were skin-related toxic effects, fever, fatigue, arthralgia, and headache.The most common adverse events with dacarbazine were nausea, vomiting, neutropenia, fatigue, and asthenia. Grade 3-4 adverse events were uncommon in both groups. Interpretation Dabrafenib significantly improved progression-free survival compared with dacarbazine.
The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): A randomised placebo-controlled trialColin Baigent | Martin J. Landray | Christina Reith | Jonathan Emberson | David C. Wheeler | Charles Tomson | Christoph Wanner | Vera Krane | Alan Cass | Jonathan Craig | Bruce Neal | Lixin Jiang | Lai Seong Hooi | Adeera Levin | Lawrence Agodoa | Mike Gaziano | Bertram Kasiske | Robert Walker | Ziad A. Massy | Bo Feldt-Rasmussen | Udom Krairittichai | Vuddidhej Ophascharoensuk | Bengt Fellström | Hallvard Holdaas | Vladimir Tesar | Andrzej Wiecek | Diederick Grobbee | Dick De Zeeuw | Carola Grönhagen-Riska | Tanaji Dasgupta | David Lewis | William Herrington | Marion Mafham | William Majoni | Karl Wallendszus | Richard Grimm | Terje Pedersen | Jonathan Tobert | Jane Armitage | Alex Baxter | Christopher Bray | Yiping Chen | Zhengming Chen | Michael Hill | Carol Knott | Sarah Parish | David Simpson | Peter Sleight | Alan Young | Rory Collins
Volume 377, Issue 9784, June 2011, Pages 2181-2192
Lowering LDL cholesterol with statin regimens reduces the risk of myocardial infarction, ischaemic stroke, and the need for coronary revascularisation in people without kidney disease, but its effects in people with moderate-to-severe kidney disease are uncertain. The SHARP trial aimed to assess the efficacy and safety of the combination of simvastatin plus ezetimibe in such patients. This randomised double-blind trial included 9270 patients with chronic kidney disease (3023 on dialysis and 6247 not) with no known history of myocardial infarction or coronary revascularisation. Patients were randomly assigned to simvastatin 20 mg plus ezetimibe 10 mg daily versus matching placebo. The key prespecified outcome was first major atherosclerotic event (non-fatal myocardial infarction or coronary death, non-haemorrhagic stroke, or any arterial revascularisation procedure). All analyses were by intention to treat. This trial is registered at ClinicalTrials.gov, NCT00125593, and ISRCTN54137607. 4650 patients were assigned to receive simvastatin plus ezetimibe and 4620 to placebo. Allocation to simvastatin plus ezetimibe yielded an average LDL cholesterol difference of 0·85 mmol/L (SE 0·02; with about two-thirds compliance) during a median follow-up of 4·9 years and produced a 17 proportional reduction in major atherosclerotic events (526 [11·3] simvastatin plus ezetimibe vs 619 [13·4] placebo; rate ratio [RR] 0·83, 95 CI 0·74-0·94; log-rank p=0·0021). Non-significantly fewer patients allocated to simvastatin plus ezetimibe had a non-fatal myocardial infarction or died from coronary heart disease (213 [4·6] vs 230 [5·0]; RR 0·92, 95 CI 0·76-1·11; p=0·37) and there were significant reductions in non-haemorrhagic stroke (131 [2·8] vs 174 [3·8]; RR 0·75, 95 CI 0·60-0·94; p=0·01) and arterial revascularisation procedures (284 [6·1] vs 352 [7·6]; RR 0·79, 95 CI 0·68-0·93; p=0·0036). After weighting for subgroup-specific reductions in LDL cholesterol, there was no good evidence that the proportional effects on major atherosclerotic events differed from the summary rate ratio in any subgroup examined, and, in particular, they were similar in patients on dialysis and those who were not. The excess risk of myopathy was only two per 10 000 patients per year of treatment with this combination (9 [0·2] vs 5 [0·1]). There was no evidence of excess risks of hepatitis (21 [0·5] vs 18 [0·4]), gallstones (106 [2·3] vs 106 [2·3]), or cancer (438 [9·4] vs 439 [9·5], p=0·89) and there was no significant excess of death from any non-vascular cause (668 [14·4] vs 612 [13·2], p=0·13). Reduction of LDL cholesterol with simvastatin 20 mg plus ezetimibe 10 mg daily safely reduced the incidence of major atherosclerotic events in a wide range of patients with advanced chronic kidney disease. Merck/Schering-Plough Pharmaceuticals; Australian National Health and Medical Research Council; British Heart Foundation; UK Medical Research Council. © 2011 Elsevier Ltd.
Radiation exposure from CT scans in childhood and subsequent risk of leukaemia and brain tumours: A retrospective cohort studyMark S. Pearce | Jane A. Salotti | Mark P. Little | Kieran McHugh | Choonsik Lee | Kwang Pyo Kim | Nicola L. Howe | Cecile M. Ronckers | Preetha Rajaraman | Alan W. Craft | Louise Parker | Amy Berrington De González
Volume 380, Issue 9840, August 2012, Pages 499-505
Background Although CT scans are very useful clinically, potential cancer risks exist from associated ionising radiation, in particular for children who are more radiosensitive than adults. We aimed to assess the excess risk of leukaemia and brain tumours after CT scans in a cohort of children and young adults. Methods In our retrospective cohort study, we included patients without previous cancer diagnoses who were fi rst examined with CT in National Health Service (NHS) centres in England, Wales, or Scotland (Great Britain) between 1985 and 2002, when they were younger than 22 years of age. We obtained data for cancer incidence, mortality, and loss to follow-up from the NHS Central Registry from Jan 1, 1985, to Dec 31, 2008. We estimated absorbed brain and red bone marrow doses per CT scan in mGy and assessed excess incidence of leukaemia and brain tumours cancer with Poisson relative risk models. To avoid inclusion of CT scans related to cancer diagnosis, follow-up for leukaemia began 2 years after the fi rst CT and for brain tumours 5 years after the fi rst CT. Findings During follow-up, 74 of 178 604 patients were diagnosed with leukaemia and 135 of 176 587 patients were diagnosed with brain tumours. We noted a positive association between radiation dose from CT scans and leukaemia (excess relative risk [ERR] per mGy 0·036, 95% CI 0·005-0·120; p=0·0097) and brain tumours (0·023, 0·010-0·049; p<0·0001). Compared with patients who received a dose of less than 5 mGy, the relative risk of leukaemia for patients who received a cumulative dose of at least 30 mGy (mean dose 51·13 mGy) was 3·18 (95% CI 1·46-6·94) and the relative risk of brain cancer for patients who received a cumulative dose of 50-74 mGy (mean dose 60·42 mGy) was 2·82 (1·33-6·03). Interpretation Use of CT scans in children to deliver cumulative doses of about 50 mGy might almost triple the risk of leukaemia and doses of about 60 mGy might triple the risk of brain cancer. Because these cancers are relatively rare, the cumulative absolute risks are small: in the 10 years after the fi rst scan for patients younger than 10 years, one excess case of leukaemia and one excess case of brain tumour per 10 000 head CT scans is estimated to occur. Nevertheless, although clinical benefi ts should outweigh the small absolute risks, radiation doses from CT scans ought to be kept as low as possible and alternative procedures, which do not involve ionising radiation, should be considered if appropriate.
The global obesity pandemic: Shaped by global drivers and local environmentsBoyd A. Swinburn | Gary Sacks | Kevin D. Hall | Klim McPherson | Diane T. Finegood | Marjory L. Moodie | Steven L. Gortmaker
Volume 378, Issue 9793, August 2011, Pages 804-814
The simultaneous increases in obesity in almost all countries seem to be driven mainly by changes in the global food system, which is producing more processed, affordable, and effectively marketed food than ever before. This passive overconsumption of energy leading to obesity is a predictable outcome of market economies predicated on consumption-based growth. The global food system drivers interact with local environmental factors to create a wide variation in obesity prevalence between populations. Within populations, the interactions between environmental and individual factors, including genetic makeup, explain variability in body size between individuals. However, even with this individual variation, the epidemic has predictable patterns in subpopulations. In low-income countries, obesity mostly affects middle-aged adults (especially women) from wealthy, urban environments; whereas in high-income countries it affects both sexes and all ages, but is disproportionately greater in disadvantaged groups. Unlike other major causes of preventable death and disability, such as tobacco use, injuries, and infectious diseases, there are no exemplar populations in which the obesity epidemic has been reversed by public health measures. This absence increases the urgency for evidence-creating policy action, with a priority on reduction of the supply-side drivers. © 2011 Elsevier Ltd.
Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: A randomised, double-blind studyKarim Fizazi | Michael Carducci | Matthew Smith | Ronaldo Damião | Janet Brown | Lawrence Karsh | Piotr Milecki | Neal Shore | Michael Rader | Huei Wang | Qi Jiang | Sylvia Tadros | Roger Dansey | Carsten Goessl
Volume 377, Issue 9768, March 2011, Pages 813-822
Bone metastases are a major burden in men with advanced prostate cancer. We compared denosumab, a human monoclonal antibody against RANKL, with zoledronic acid for prevention of skeletal-related events in men with bone metastases from castration-resistant prostate cancer. In this phase 3 study, men with castration-resistant prostate cancer and no previous exposure to intravenous bisphosphonate were enrolled from 342 centres in 39 countries. An interactive voice response system was used to assign patients (1:1 ratio), according to a computer-generated randomisation sequence, to receive 120 mg subcutaneous denosumab plus intravenous placebo, or 4 mg intravenous zoledronic acid plus subcutaneous placebo, every 4 weeks until the primary analysis cutoff date. Randomisation was stratified by previous skeletal-related event, prostate-specific antigen concentration, and chemotherapy for prostate cancer within 6 weeks before randomisation. Supplemental calcium and vitamin D were strongly recommended. Patients, study staff, and investigators were masked to treatment assignment. The primary endpoint was time to first on-study skeletal-related event (pathological fracture, radiation therapy, surgery to bone, or spinal cord compression), and was assessed for non-inferiority. The same outcome was further assessed for superiority as a secondary endpoint. Efficacy analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00321620, and has been completed. 1904 patients were randomised, of whom 950 assigned to denosumab and 951 assigned to receive zoledronic acid were eligible for the efficacy analysis. Median duration on study at primary analysis cutoff date was 12·2 months (IQR 5·9-18·5) for patients on denosumab and 11·2 months (IQR 5·6-17·4) for those on zoledronic acid. Median time to first on-study skeletal-related event was 20·7 months (95 CI 18·8-24·9) with denosumab compared with 17·1 months (15·0-19·4) with zoledronic acid (hazard ratio 0·82, 95 CI 0·71-0·95; p=0·0002 for non-inferiority; p=0·008 for superiority). Adverse events were recorded in 916 patients (97) on denosumab and 918 patients (97) on zoledronic acid, and serious adverse events were recorded in 594 patients (63) on denosumab and 568 patients (60) on zoledronic acid. More events of hypocalcaemia occurred in the denosumab group (121 [13]) than in the zoledronic acid group (55 [6]; p<0·0001). Osteonecrosis of the jaw occurred infrequently (22 [2] vs 12 [1]; p=0·09). Denosumab was better than zoledronic acid for prevention of skeletal-related events, and potentially represents a novel treatment option in men with bone metastases from castration-resistant prostate cancer. Amgen. © 2011 Elsevier Ltd.
Epidemiology of multimorbidity and implications for health care, research, and medical education: A cross-sectional studyKaren Barnett | Stewart W. Mercer | Michael Norbury | Graham Watt | Sally Wyke | Bruce Guthrie
Volume 380, Issue 9836, July 2012, Pages 37-43
Background Long-term disorders are the main challenge facing health-care systems worldwide, but health systems are largely configured for individual diseases rather than multimorbidity. We examined the distribution of multimorbidity, and of comorbidity of physical and mental health disorders, in relation to age and socioeconomic deprivation. Methods In a cross-sectional study we extracted data on 40 morbidities from a database of 1 751 841 people registered with 314 medical practices in Scotland as of March, 2007. We analysed the data according to the number of morbidities, disorder type (physical or mental), sex, age, and socioeconomic status. We defined multimorbidity as the presence of two or more disorders. Findings 42.2% (95% CI 42.1-42.3) of all patients had one or more morbidities, and 23.2% (23.08-23.21) were multimorbid. Although the prevalence of multimorbidity increased substantially with age and was present in most people aged 65 years and older, the absolute number of people with multimorbidity was higher in those younger than 65 years (210 500 vs 194 996). Onset of multimorbidity occurred 10-15 years earlier in people living in the most deprived areas compared with the most affluent, with socioeconomic deprivation particularly associated with multimorbidity that included mental health disorders (prevalence of both physical and mental health disorder 11.0%, 95% CI 10.9-11.2% in most deprived area vs 5.9%, 5.8%-6.0% in least deprived). The presence of a mental health disorder increased as the number of physical morbidities increased (adjusted odds ratio 6.74, 95% CI 6.59-6.90 for five or more disorders vs 1.95, 1.93-1.98 for one disorder), and was much greater in more deprived than in less deprived people (2.28, 2.21-2.32 vs 1.08, 1.05-1.11). Interpretation Our findings challenge the single-disease framework by which most health care, medical research, and medical education is configured. A complementary strategy is needed, supporting generalist clinicians to provide personalised, comprehensive continuity of care, especially in socioeconomically deprived areas. Funding Scottish Government Chief Scientist Office.
Global physical activity levels: Surveillance progress, pitfalls, and prospectsPedro C. Hallal | Lars Bo Andersen | Fiona C. Bull | Regina Guthold | William Haskell | Ulf Ekelund | Jasem R. Alkandari | Adrian E. Bauman | Steven N. Blair | Ross C. Brownson | Cora L. Craig | Shifalika Goenka | Gregory W. Heath | Shigeru Inoue | Sonja Kahlmeier | Peter T. Katzmarzyk | Harold W. Kohl | Estelle Victoria Lambert | I. Min Lee | Grit Leetongin | Felipe Lobelo | Ruth J F Loos | Bess Marcus | Brian W. Martin | Neville Owen | Diana C. Parra | Michael Pratt | Pekka Puska | David Ogilvie | Rodrigo S. Reis | James F. Sallis | Olga Lucia Sarmiento | Jonathan C. Wells
Volume 380, Issue 9838, July 2012, Pages 247-257
To implement effective non-communicable disease prevention programmes, policy makers need data for physical activity levels and trends. In this report, we describe physical activity levels worldwide with data for adults (15 years or older) from 122 countries and for adolescents (13-15-years-old) from 105 countries. Worldwide, 31.1% (95% CI 30.9-31.2) of adults are physically inactive, with proportions ranging from 17.0% (16.8-17.2) in southeast Asia to about 43% in the Americas and the eastern Mediterranean. Inactivity rises with age, is higher in women than in men, and is increased in high-income countries. The proportion of 13-15-year-olds doing fewer than 60 min of physical activity of moderate to vigorous intensity per day is 80.3% (80.1-80.5); boys are more active than are girls. Continued improvement in monitoring of physical activity would help to guide development of policies and programmes to increase activity levels and to reduce the burden of non-communicable diseases.
Global malaria mortality between 1980 and 2010: A systematic analysisChristopher J L Murray | Lisa C. Rosenfeld | Stephen S. Lim | Kathryn G. Andrews | Kyle J. Foreman | Diana Haring | Nancy Fullman | Mohsen Naghavi | Rafael Lozano | Alan D. Lopez
Volume 379, Issue 9814, February 2012, Pages 413-431
Background: During the past decade, renewed global and national efforts to combat malaria have led to ambitious goals. We aimed to provide an accurate assessment of the levels and time trends in malaria mortality to aid assessment of progress towards these goals and the focusing of future efforts. Methods: We systematically collected all available data for malaria mortality for the period 1980-2010, correcting for misclassification bias. We developed a range of predictive models, including ensemble models, to estimate malaria mortality with uncertainty by age, sex, country, and year. We used key predictors of malaria mortality such as Plasmodium falciparum parasite prevalence, first-line antimalarial drug resistance, and vector control. We used out-of-sample predictive validity to select the final model. Findings: Global malaria deaths increased from 995 000 (95 uncertainty interval 711 000-1 412 000) in 1980 to a peak of 1 817 000 (1 430 000-2 366 000) in 2004, decreasing to 1 238 000 (929 000-1 685 000) in 2010. In Africa, malaria deaths increased from 493 000 (290 000-747 000) in 1980 to 1 613 000 (1 243 000-2 145 000) in 2004, decreasing by about 30 to 1 133 000 (848 000-1 591 000) in 2010. Outside of Africa, malaria deaths have steadily decreased from 502 000 (322 000-833 000) in 1980 to 104 000 (45 000-191 000) in 2010. We estimated more deaths in individuals aged 5 years or older than has been estimated in previous studies: 435 000 (307 000-658 000) deaths in Africa and 89 000 (33 000-177 000) deaths outside of Africa in 2010. Interpretation: Our findings show that the malaria mortality burden is larger than previously estimated, especially in adults. There has been a rapid decrease in malaria mortality in Africa because of the scaling up of control activities supported by international donors. Donor support, however, needs to be increased if malaria elimination and eradication and broader health and development goals are to be met. Funding: The Bill & Melinda Gates Foundation. © 2012 Elsevier Ltd.
Health and economic burden of the projected obesity trends in the USA and the UKY. Claire Wang | Klim McPherson | Tim Marsh | Steven L. Gortmaker | Martin Brown
Volume 378, Issue 9793, August 2011, Pages 815-825
Rising prevalence of obesity is a worldwide health concern because excess weight gain within populations forecasts an increased burden from several diseases, most notably cardiovascular diseases, diabetes, and cancers. In this report, we used a simulation model to project the probable health and economic consequences in the next two decades from a continued rise in obesity in two ageing populations - the USA and the UK. These trends project 65 million more obese adults in the USA and 11 million more obese adults in the UK by 2030, consequently accruing an additional 6-8·5 million cases of diabetes, 5·7-7·3 million cases of heart disease and stroke, 492 000-669 000 additional cases of cancer, and 26-55 million quality-adjusted life years forgone for USA and UK combined. The combined medical costs associated with treatment of these preventable diseases are estimated to increase by $48-66 billion/year in the USA and by £1·9-2 billion/year in the UK by 2030. Hence, effective policies to promote healthier weight also have economic benefits. © 2011 Elsevier Ltd.
Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): A randomised phase 3 trialBrian I. Rini | Bernard Escudier | Piotr Tomczak | Andrey Kaprin | Cezary Szczylik | Thomas E. Hutson | M. Dror Michaelson | Vera A. Gorbunova | Martin E. Gore | Igor G. Rusakov | Sylvie Negrier | Yen Chuan Ou | Daniel Castellano | Ho Yeong Lim | Hirotsugu Uemura | Jamal Tarazi | David Cella | Connie Chen | Brad Rosbrook | Sinil Kim | Robert J. Motzer
Volume 378, Issue 9807, December 2011, Pages 1931-1939
The treatment of advanced renal cell carcinoma has been revolutionised by targeted therapy with drugs that block angiogenesis. So far, no phase 3 randomised trials comparing the effectiveness of one targeted agent against another have been reported. We did a randomised phase 3 study comparing axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor (VEGF) receptors, with sorafenib, an approved VEGF receptor inhibitor, as second-line therapy in patients with metastatic renal cell cancer. We included patients coming from 175 sites (hospitals and outpatient clinics) in 22 countries aged 18 years or older with confirmed renal clear-cell carcinoma who progressed despite first-line therapy containing sunitinib, bevacizumab plus interferon-alfa, temsirolimus, or cytokines. Patients were stratified according to Eastern Cooperative Oncology Group performance status and type of previous treatment and then randomly assigned (1:1) to either axitinib (5 mg twice daily) or sorafenib (400 mg twice daily). Axitinib dose increases to 7 mg and then to 10 mg, twice daily, were allowed for those patients without hypertension or adverse reactions above grade 2. Participants were not masked to study treatment. The primary endpoint was progression-free survival (PFS) and was assessed by a masked, independent radiology review and analysed by intention to treat. This trial was registered on ClinicalTrials.gov, number NCT00678392. A total of 723 patients were enrolled and randomly assigned to receive axitinib (n=361) or sorafenib (n=362). The median PFS was 6·7 months with axitinib compared to 4·7 months with sorafenib (hazard ratio 0·665; 95 CI 0·544-0·812; one-sided p<0·0001). Treatment was discontinued because of toxic effects in 14 (4) of 359 patients treated with axitinib and 29 (8) of 355 patients treated with sorafenib. The most common adverse events were diarrhoea, hypertension, and fatigue in the axitinib arm, and diarrhoea, palmar-plantar erythrodysaesthesia, and alopecia in the sorafenib arm. Axitinib resulted in significantly longer PFS compared with sorafenib. Axitinib is a treatment option for second-line therapy of advanced renal cell carcinoma. Pfizer Inc. © 2011 Elsevier Ltd.
Maternal and child undernutrition and overweight in low-income and middle-income countriesRobert E. Black | Cesar G. Victora | Susan P. Walker | Zulfiqar A. Bhutta | Parul Christian | Mercedes De Onis | Majid Ezzati | Sally Grantham-Mcgregor | Joanne Katz | Reynaldo Martorell | Ricardo Uauy
Volume 382, Issue 9890, June 2013, Pages 427-451
Maternal and child malnutrition in low-income and middle-income countries encompasses both undernutrition and a growing problem with overweight and obesity. Low body-mass index, indicative of maternal undernutrition, has declined somewhat in the past two decades but continues to be prevalent in Asia and Africa. Prevalence of maternal overweight has had a steady increase since 1980 and exceeds that of underweight in all regions. Prevalence of stunting of linear growth of children younger than 5 years has decreased during the past two decades, but is higher in south Asia and sub-Saharan Africa than elsewhere and globally affected at least 165 million children in 2011; wasting affected at least 52 million children. Deficiencies of vitamin A and zinc result in deaths; deficiencies of iodine and iron, together with stunting, can contribute to children not reaching their developmental potential. Maternal undernutrition contributes to fetal growth restriction, which increases the risk of neonatal deaths and, for survivors, of stunting by 2 years of age. Suboptimum breastfeeding results in an increased risk for mortality in the first 2 years of life. We estimate that undernutrition in the aggregate - including fetal growth restriction, stunting, wasting, and deficiencies of vitamin A and zinc along with suboptimum breastfeeding - is a cause of 3·1 million child deaths annually or 45% of all child deaths in 2011. Maternal overweight and obesity result in increased maternal morbidity and infant mortality. Childhood overweight is becoming an increasingly important contributor to adult obesity, diabetes, and non-communicable diseases. The high present and future disease burden caused by malnutrition in women of reproductive age, pregnancy, and children in the first 2 years of life should lead to interventions focused on these groups. © 2013 Elsevier Ltd.
Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: Meta-analysis of individual patient data for 10 801 women in 17 randomised trialsS. Darby | P. McGale | C. Correa | C. Taylor | R. Arriagada | M. Clarke | D. Cutter | C. Davies | M. Ewertz | J. Godwin | R. Gray | L. Pierce | T. Whelan | Y. Wang | R. Peto | K. Albain | S. Anderson | W. Barlow | J. Bergh | J. Bliss | M. Buyse | D. Cameron | E. Carrasco | A. Coates | R. Collins | J. Costantino | J. Cuzick | N. Davidson | K. Davies | A. Delmestri | A. Di Leo | M. Dowsett | P. Elphinstone | V. Evans | R. Gelber | L. Gettins | C. Geyer | A. Goldhirsch | C. Gregory | D. Hayes | C. Hill | J. Ingle | R. Jakesz | S. James | M. Kaufmann | A. Kerr | E. MacKinnon | T. McHugh | L. Norton | Y. Ohashi | S. Paik | H. C. Pan | E. Perez | M. Piccart | K. Pritchard | G. Pruneri | V. Raina | P. Ravdin | J. Robertson | E. Rutgers | Y. F Shao | S. Swain | P. Valagussa | G. Viale | E. Winer | W. Wood
Volume 378, Issue 9804, November 2011, Pages 1707-1716
After breast-conserving surgery, radiotherapy reduces recurrence and breast cancer death, but it may do so more for some groups of women than for others. We describe the absolute magnitude of these reductions according to various prognostic and other patient characteristics, and relate the absolute reduction in 15-year risk of breast cancer death to the absolute reduction in 10-year recurrence risk. We undertook a meta-analysis of individual patient data for 10 801 women in 17 randomised trials of radiotherapy versus no radiotherapy after breast-conserving surgery, 8337 of whom had pathologically confirmed node-negative (pN0) or node-positive (pN+) disease. Overall, radiotherapy reduced the 10-year risk of any (ie, locoregional or distant) first recurrence from 35·0 to 19·3 (absolute reduction 15·7, 95 CI 13·7-17·7, 2p<0·00001) and reduced the 15-year risk of breast cancer death from 25·2 to 21·4 (absolute reduction 3·8, 1·6-6·0, 2p=0·00005). In women with pN0 disease (n=7287), radiotherapy reduced these risks from 31·0 to 15·6 (absolute recurrence reduction 15·4, 13·2-17·6, 2p<0·00001) and from 20·5 to 17·2 (absolute mortality reduction 3·3, 0·8-5·8, 2p=0·005), respectively. In these women with pN0 disease, the absolute recurrence reduction varied according to age, grade, oestrogen-receptor status, tamoxifen use, and extent of surgery, and these characteristics were used to predict large (≥20), intermediate (10-19), or lower (<10) absolute reductions in the 10-year recurrence risk. Absolute reductions in 15-year risk of breast cancer death in these three prediction categories were 7·8 (95 CI 3·1-12·5), 1·1 (-2·0 to 4·2), and 0·1 (-7·5 to 7·7) respectively (trend in absolute mortality reduction 2p=0·03). In the few women with pN+ disease (n=1050), radiotherapy reduced the 10-year recurrence risk from 63·7 to 42·5 (absolute reduction 21·2, 95 CI 14·5-27·9, 2p<0·00001) and the 15-year risk of breast cancer death from 51·3 to 42·8 (absolute reduction 8·5, 1·8-15·2, 2p=0·01). Overall, about one breast cancer death was avoided by year 15 for every four recurrences avoided by year 10, and the mortality reduction did not differ significantly from this overall relationship in any of the three prediction categories for pN0 disease or for pN+ disease. After breast-conserving surgery, radiotherapy to the conserved breast halves the rate at which the disease recurs and reduces the breast cancer death rate by about a sixth. These proportional benefits vary little between different groups of women. By contrast, the absolute benefits from radiotherapy vary substantially according to the characteristics of the patient and they can be predicted at the time when treatment decisions need to be made. Cancer Research UK, British Heart Foundation, and UK Medical Research Council. © 2011 Elsevier Ltd.
Identifi cation of risk loci with shared eff ects on fi ve major psychiatric disorders: A genome-wide analysisJordan W. Smoller
Volume 381, Issue 9875, April 2013, Pages 1371-1379
Background Findings from family and twin studies suggest that genetic contributions to psychiatric disorders do not in all cases map to present diagnostic categories. We aimed to identify specifi c variants underlying genetic eff ects shared between the fi ve disorders in the Psychiatric Genomics Consortium: autism spectrum disorder, attention defi cit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia. Methods We analysed genome-wide single-nucleotide polymorphism (SNP) data for the fi ve disorders in 33 332 cases and 27 888 controls of European ancestory. To characterise allelic eff ects on each disorder, we applied a multinomial logistic regression procedure with model selection to identify the best-fi tting model of relations between genotype and phenotype. We examined cross-disorder eff ects of genome-wide signifi cant loci previously identifi ed for bipolar disorder and schizophrenia, and used polygenic risk-score analysis to examine such eff ects from a broader set of common variants. We undertook pathway analyses to establish the biological associations underlying genetic overlap for the fi ve disorders. We used enrichment analysis of expression quantitative trait loci (eQTL) data to assess whether SNPs with cross-disorder association were enriched for regulatory SNPs in post-mortem brain-tissue samples. Findings SNPs at four loci surpassed the cutoff for genome-wide signifi cance (p< 5×10-8) in the primary analysis: regions on chromosomes 3p21 and 10q24, and SNPs within two L-type voltage-gated calcium channel subunits, CACNA1C and CACNB2. Model selection analysis supported eff ects of these loci for several disorders. Loci previously associated with bipolar disorder or schizophrenia had variable diagnostic specifi city. Polygenic risk scores showed cross-disorder associations, notably between adult-onset disorders. Pathway analysis supported a role for calcium channel signalling genes for all fi ve disorders. Finally, SNPs with evidence of cross-disorder association were enriched for brain eQTL markers. Interpretation Our fi ndings show that specifi c SNPs are associated with a range of psychiatric disorders of childhood onset or adult onset. In particular, variation in calcium-channel activity genes seems to have pleiotropic eff ects on psychopathology. These results provide evidence relevant to the goal of moving beyond descriptive syndromes in psychiatry, and towards a nosology informed by disease cause.
Alzheimer's diseaseClive Ballard | Serge Gauthier | Anne Corbett | Carol Brayne | Dag Aarsland | Emma Jones
Volume 377, Issue 9770, March 2011, Pages 1019-1031
An estimated 24 million people worldwide have dementia, the majority of whom are thought to have Alzheimer's disease. Thus, Alzheimer's disease represents a major public health concern and has been identified as a research priority. Although there are licensed treatments that can alleviate symptoms of Alzheimer's disease, there is a pressing need to improve our understanding of pathogenesis to enable development of disease-modifying treatments. Methods for improving diagnosis are also moving forward, but a better consensus is needed for development of a panel of biological and neuroimaging biomarkers that support clinical diagnosis. There is now strong evidence of potential risk and protective factors for Alzheimer's disease, dementia, and cognitive decline, but further work is needed to understand these better and to establish whether interventions can substantially lower these risks. In this Seminar, we provide an overview of recent evidence regarding the epidemiology, pathogenesis, diagnosis, and treatment of Alzheimer's disease, and discuss potential ways to reduce the risk of developing the disease. © 2011 Elsevier Ltd.
Radial versus femoral access for coronary angiography and intervention in patients with acute coronary syndromes (RIVAL): A randomised, parallel group, multicentre trialSanjit S. Jolly | Salim Yusuf | John Cairns | Kari Niemelä | Denis Xavier | Petr Widimsky | Andrzej Budaj | Matti Niemelä | Vicent Valentin | Basil S. Lewis | Alvaro Avezum | Philippe Gabriel Steg | Sunil V. Rao | Peggy Gao | Rizwan Afzal | Campbell D. Joyner | Susan Chrolavicius | Shamir R. Mehta
Volume 377, Issue 9775, April 2011, Pages 1409-1420
Background: Small trials have suggested that radial access for percutaneous coronary intervention (PCI) reduces vascular complications and bleeding compared with femoral access. We aimed to assess whether radial access was superior to femoral access in patients with acute coronary syndromes (ACS) who were undergoing coronary angiography with possible intervention. Methods: The RadIal Vs femorAL access for coronary intervention (RIVAL) trial was a randomised, parallel group, multicentre trial. Patients with ACS were randomly assigned (1:1) by a 24 h computerised central automated voice response system to radial or femoral artery access. The primary outcome was a composite of death, myocardial infarction, stroke, or non-coronary artery bypass graft (non-CABG)-related major bleeding at 30 days. Key secondary outcomes were death, myocardial infarction, or stroke; and non-CABG-related major bleeding at 30 days. A masked central committee adjudicated the primary outcome, components of the primary outcome, and stent thrombosis. All other outcomes were as reported by the investigators. Patients and investigators were not masked to treatment allocation. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, NCT01014273. Findings: Between June 6, 2006, and Nov 3, 2010, 7021 patients were enrolled from 158 hospitals in 32 countries. 3507 patients were randomly assigned to radial access and 3514 to femoral access. The primary outcome occurred in 128 (3·7) of 3507 patients in the radial access group compared with 139 (4·0) of 3514 in the femoral access group (hazard ratio [HR] 0·92, 95 CI 0·72-1·17; p=0·50). Of the six prespecified subgroups, there was a significant interaction for the primary outcome with benefit for radial access in highest tertile volume radial centres (HR 0·49, 95 CI 0·28-0·87; p=0·015) and in patients with ST-segment elevation myocardial infarction (0·60, 0·38-0·94; p=0·026). The rate of death, myocardial infarction, or stroke at 30 days was 112 (3·2) of 3507 patients in the radial group compared with 114 (3·2) of 3514 in the femoral group (HR 0·98, 95 CI 0·76-1·28; p=0·90). The rate of non-CABG-related major bleeding at 30 days was 24 (0·7) of 3507 patients in the radial group compared with 33 (0·9) of 3514 patients in the femoral group (HR 0·73, 95 CI 0·43-1·23; p=0·23). At 30 days, 42 of 3507 patients in the radial group had large haematoma compared with 106 of 3514 in the femoral group (HR 0·40, 95 CI 0·28-0·57; p<0·0001). Pseudoaneurysm needing closure occurred in seven of 3507 patients in the radial group compared with 23 of 3514 in the femoral group (HR 0·30, 95 CI 0·13-0·71; p=0·006). Interpretation: Radial and femoral approaches are both safe and effective for PCI. However, the lower rate of local vascular complications may be a reason to use the radial approach. Funding: Sanofi-Aventis, Population Health Research Institute, and Canadian Network for Trials Internationally (CANNeCTIN), an initiative of the Canadian Institutes of Health Research. © 2011 Elsevier Ltd. All Rights Reserved.


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Wilsonville Oregon Real Estate Broker
Welcome we are your Real Estate source for The Portland Metro Area.
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subset: commoncrawl


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Twitter Updates
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David Olusegun Agbaje
David Olusegun Agbaje (26 September,1958 / Owo, Ondo State, Nigeria.)
I Am A Nigerian - Poem by David Olusegun Agbaje
Whenever I meet you,
Wherever you meet me,
Don't ask after my tribe,
Don't ask after my state,
All I know is I am a Nigerian.
Whenever I meet you,
Wherever you meet me,
Don't ask after my faith,
Don't ask after my denomination,
All I know is I am a Nigerian.
An Hausa, an Ibo, a Yoruba you might be,
A Muslim, a Christian, a free-thinker you might be,
A Catholic, an Anglican, an 'Aladura' you might be,
Brothers we are; united like a bunch of brooms we should be,
To sweep our country clean,
To make our nation great.
Comments about I Am A Nigerian by David Olusegun Agbaje
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Poem Submitted: Saturday, October 19, 2013
Poem Edited: Tuesday, October 22, 2013
David Olusegun Agbaje's Other Poems
Famous Poems
Phenomenal Woman
Maya Angelou
Still I Rise
Maya Angelou
The Road Not Taken
Robert Frost
If You Forget Me
Pablo Neruda
Langston Hughes
Annabel Lee
Edgar Allan Poe
Caged Bird
Maya Angelou
Rudyard Kipling
Stopping By Woods On A Snowy Evening
Robert Frost
A Dream Within A Dream
Edgar Allan Poe


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Chrome's Incognito Mode Broken in iOS 7
The Incognito browsing mode in Google's browser for iOS isn't staying private.
UK security firm Parallax has discovered that the private browsing Incognito mode in Google Chrome isn't working correctly in iOS 7. Specifically, the bug allows search terms used in Incognito mode to display as search history on the Google mobile site.
"This is especially important as Google Chrome has a unified search and URL bar, meaning that people often search rather than typing full URLs," commented Tom Faller, project manager at Parallax.
Google has yet to comment on this security flaw. Check out the video below for a demonstration of the bug.
Google Chrome Incognito Mode Broken
Follow Marcus Yam @MarcusYam. Follow us @tomsguide, on Facebook and on Google+.
This thread is closed for comments
HallusHamazing.. not.
the1kingbobHahah, too speed things up. HallusH link states at the bottom that, "On Chrome for iOS, due to platform limitation regular and incognito* tabs share HTML5 local storage, which is typically used by sites to store files on your device (client-side caching) or to provide offline functionality. This means the same sites can always access their data in this storage in both regular and incognito* tabs. Incognito* tabs will still keep browsing history and cookies separate from regular tabs, which are cleared once those tabs are closed."
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text:
Now we know where John McCain has been getting his campaign ideas: 1960s camp television. My friends, who is the Batman? And why is he always palling around with criminals?
Hat tip to George Edelman
Watch it:
Posted on Oct 26, 2016
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text:
DeMarcus Cousins C #15
Current Team: Sacramento Kings
Born: Aug 13, 1990 (26 years old)
Birthplace: Mobile, Alabama (United States)
Nationality: United States
Height: 6-11 (211cm) Weight: 270 (122kg)
Hand: Right
Twitter: @boogiecousins
Facebook: http://www.facebook.com/pages/DeMarcus-Cousins/142630122457234
Instagram: https://www.instagram.com/boogiecousins/
Current NBA Status: Under Contract (Sacramento Kings)
Free Agent: UFA-2018
Current Agent: Dan Fegan, Jarinn Akana
Draft Entry: 2010 NBA Draft
Early Entry Info: 2010 Early Entrant
Drafted: Round 1, Pick 5, Sacramento Kings
Pre-Draft Team: Kentucky (Fr)
High School: LeFlore Magnet High School [Mobile, Alabama]
DeMarcus Cousins News
Mavs Expected To Pursue DeMarcus Cousins In 2018
DeMarcus Cousins signed a four-year, $62 million contract extension in 2013 with the Kings.
George Karl's Attempts To Trade DeMarcus Cousins Confirmed
Vivek Ranadive confirmed that George Karl attempted to trade DeMarcus Cousins when he was head coach of the Kings.
DeMarcus Cousins 'Loves' Dave Joerger's Offense
Dave Joerger plans on using DeMarcus Cousins in the high post more this season as he implements his offense for the Kings.
DeMarcus Cousins Open To Playing In 2020 Olympics
DeMarcus Cousins won a gold medal in his first Olympics for the United States.
Execs Don't Expect DeMarcus Cousins To Re-Sign With Kings In 2018
The Kings have two trade deadlines and one offseason to consider trading DeMarcus Cousins before he's free to leave on his own.
DeMarcus Cousins Calls Carmelo Anthony 'My Favorite Player Of All-Time'
DeMarcus Cousins sometimes resembles a wing player in the body of a big at 6'11, 270 pounds.
DeMarcus Cousins Selected For USA's Olympic Team
The United States also selected DeMarcus Cousins for their 2014 FIBA Basketball World Cup.
Kings Won't Trade DeMarcus Cousins 'This Year For Sure'
The Kings will have three more trade windows before DeMarcus Cousins becomes a free agent if he begins the 16-17 season with the team.
Vlade Divac Wants To Keep DeMarcus Cousins But Willing To Test Market For First Time
The sense within the organization is Vlade Divac has become increasingly frustrated by DeMarcus Cousins' ongoing issues and is willing to test the trade market for the first time.
Kings Unlikely To Make DeMarcus Cousins Available Until 2017 Deadline
DeMarcus Cousins still has two seasons remaining on his contract.
DeMarcus Cousins: Suspension Was From Head Coach
DeMarcus Cousins and George Karl have been at odds since the end of last season.
Kings Make It Clear DeMarcus Cousins Not Available
The Kings considered trading DeMarcus Cousins last June amid a difference of personalities between he and George Karl.
DeMarcus Cousins, Kemba Walker Named Players Of The Week
DeMarcus Cousins and Kemba Walker have been named the NBA's Players of the Week.
Cousins: Rondo's Intentions Are Same As Mine
Rajon Rondo has become the veteran mentor for DeMarcus Cousins the way Kevin Garnett was earlier in his career with the Celtics.
Kings Expect Suspension For DeMarcus Cousins
DeMarcus Cousins had to be restrained by teammates before being escorted off the court.
Rajon Rondo 'Gravitates' Toward DeMarcus Cousins
Rajon Rondo is the first player who can relate to the pressure and perceptions DeMarcus Cousins deals with.
Rondo, Cousins Pulled George Karl In For 'Powerful' Two-Hour Meeting
Rajon Rondo and DeMarcus Cousins were also able to get some lingering frustrations off their chest, and Karl offered back his thoughts.
DeMarcus Cousins Receives One-Game Suspension For Forearm To Horford
DeMarcus Cousins will serve his suspension when the Kings play at the Heat.
DeMarcus Cousins, Nicolas Batum Named Players Of The Week
DeMarcus Cousins led the Kings to a 3-1 week behind averages of 32.5 points (tied-first in the conference) and 11.0 rebounds (third in the conference).
DeMarcus Cousins Doesn't Want George Karl Fired
Both sides believe the relationship between DeMarcus Cousins and George Karl is "salvageable."
DeMarcus Cousins Ready To Be 'Scapegoat' If It Results In Wins
DeMarcus Cousins had 33 points and nine rebounds as the Kings ended their losing streak.
DeMarcus Cousins Went On Profane Tirade Against George Karl
Vlade Divac said George Karl did not have authority to suspend DeMarcus Cousins nor would he grant permission.
DeMarcus Cousins Wants Kings To Have Players-Only Meeting
The Kings have used seven different starting lineups this season.
DeMarcus Cousins: MVP Is Mine To Grab
DeMarcus Cousins has become one of the NBA's best bigs and is the best player in the league to have never appeared in a playoff game.
George Karl Apologized To DeMarcus Cousins In Offseason
George Karl had suggested every player on the Kings was tradeable.
'Vast Majority' Within Kings' Organization In Favor Of Trading DeMarcus Cousins
Vlade Divac has tried to make the situation between DeMarcus Cousins and George Karl tenable.
Divac: Everything Is Going To Be Alright Between Cousins, Karl
George Karl and DeMarcus Cousins shared an awkward handshake at Summer League on Monday.
Divac: Karl-Cousins' Relationship Not 'Pretty Right Now'
Vlade Divac expects both George Karl and DeMarcus Cousins to be with the franchise at the start of next season.
Kings Considering Firing George Karl
No potential replacement for George Karl has been mentioned or considered.
Lakers, Kings Discuss Framework Of DeMarcus Cousins Deal
The Kings started to engage with teams and explore possible DeMarcus Cousins' trade scenarios beyond the Lakers on Wednesday.


text:
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