[Show abstract][Hide abstract] ABSTRACT: Open fractures are considered orthopedic emergencies that are traditionally treated with surgical debridement within 6 h of injury to prevent infection. However, this proclaimed "6-h rule" is arbitrary and not based on rigorous scientific evidence. The aim of our study was to systematically review the literature that compares late (>6 h from the time of injury) to early (<6 h from the time of injury) surgical debridement of pediatric open fractures.
We searched several databases from 1946 to 2013 for any observational or experimental studies that evaluated late and early surgical debridement of pediatric open fractures. We performed a meta-analysis using a random effects model to pool odds ratios for a comparison of infection rates between children undergoing late versus early surgical debridement. We also investigated the infection rates in upper- and lower-limb pediatric open fractures. Descriptive, quantitative, and qualitative data were extracted.
Of the 12 articles identified, three studies (retrospective cohort studies) were eligible for the meta-analysis, encompassing a total of 714 open fractures. The pooled odds ratio (OR = 0.79) for infection between late and early surgical debridement was in favor of late surgical debridement but was not statistically significant (95 % CI 0.32, 1.99; p = 0.38, I (2) = 0 %). No significant difference in infection rate was detected between pediatric open fractures in the upper and lower limbs according to the time threshold in the included studies (OR = 0.72, 95 % CI 0.29, 1.82; p = 0.40, I (2) = 0 %).
The cumulative evidence does not, at present, indicate an association between late surgical debridement and higher infection rates in pediatric open fractures. However, initial expedient surgical debridement of open fractures in children should always remain the rule. Thus, multi-center randomized controlled trials or prospective cohort studies will be able to answer this question with more certainty and a higher level of evidence.
[Show abstract][Hide abstract] ABSTRACT: Infective endocarditis (IE) is a life-threatening disease associated with serious complications. The GBD 2010 (Global Burden of Disease, Injuries, and Risk Factors) study IE expert group conducted a systematic review of IE epidemiology literature to inform estimates of the burden on IE in 21 world regions in 1990 and 2010. The disease model of IE for the GBD 2010 study included IE death and 2 sequelae: stroke and valve surgery. Several medical and science databases were searched for IE epidemiology studies in GBD high-, low-, and middle-income regions published between 1980 and 2008. The epidemiologic parameters of interest were IE incidence, proportions of IE patients who developed stroke or underwent valve surgery, and case fatality. Literature searches yielded 1,975 unique papers, of which 115 published in 10 languages were included in the systematic review. Eligible studies were population-based (17%), multicenter hospital-based (11%), and single-center hospital-based studies (71%). Population-based studies were reported from only 6 world regions. Data were missing or sparse in many low- and middle-income regions. The crude incidence of IE ranged between 1.5 and 11.6 cases per 100,000 people and was reported from 10 countries. The overall mean proportion of IE patients that developed stroke was 0.158 ± 0.091, and the mean proportion of patients that underwent valve surgery was 0.324 ± 0.188. The mean case fatality risk was 0.211 ± 0.104. A systematic review for the GBD 2010 study provided IE epidemiology estimates for many world regions, but highlighted the lack of information about IE in low- and middle-income regions. More complete knowledge of the global burden of IE will require improved IE surveillance in all world regions.
[Show abstract][Hide abstract] ABSTRACT: 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), separately by age and sex.
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.
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), lower respiratory infections (from 3·4 to 2·8 million), neonatal disorders (from 3·1 to 2·2 million), measles (from 0·63 to 0·13 million), and 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), lower 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), but 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.
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.
Bill & Melinda Gates Foundation.
The Lancet 12/2013; 380(9859):2095-128. · 39.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Measurement of the global burden of disease with disability-adjusted life-years (DALYs) requires disability weights that quantify health losses for all non-fatal consequences of disease and injury. There has been extensive debate about a range of conceptual and methodological issues concerning the definition and measurement of these weights. Our primary objective was 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.
We surveyed respondents in two ways: household surveys of adults aged 18 years or older (face-to-face interviews in Bangladesh, Indonesia, Peru, and Tanzania; telephone interviews in the USA) between Oct 28, 2009, and June 23, 2010; and an open-access web-based survey between July 26, 2010, and May 16, 2011. The surveys used paired comparison questions, in which respondents considered two hypothetical individuals with different, randomly selected health states and indicated which person they regarded as healthier. The web survey added questions about population health equivalence, which compared the overall health benefits of different life-saving or disease-prevention programmes. We analysed paired comparison responses with probit regression analysis on all 220 unique states in the study. We used results from the population health equivalence responses to anchor the results from the paired comparisons on the disability weight scale from 0 (implying no loss of health) to 1 (implying a health loss equivalent to death). Additionally, we compared new disability weights with those used in WHO's most recent update of the Global Burden of Disease Study for 2004.
13 902 individuals participated in household surveys and 16 328 in the web survey. Analysis of paired comparison responses indicated a high degree of consistency across surveys: correlations between individual survey results and results from analysis of the pooled dataset were 0·9 or higher in all surveys except in Bangladesh (r=0·75). Most of the 220 disability weights were located on the mild end of the severity scale, with 58 (26%) having weights below 0·05. Five (11%) states had weights below 0·01, such as mild anaemia, mild hearing or vision loss, and secondary infertility. The health states with the highest disability weights were acute schizophrenia (0·76) and severe multiple sclerosis (0·71). We identified a broad pattern of agreement between the old and new weights (r=0·70), particularly in the moderate-to-severe range. However, in the mild range below 0·2, many states had significantly lower weights in our study than previously.
This study represents the most extensive empirical effort as yet to measure disability weights. By contrast with the popular hypothesis that disability assessments vary widely across samples with different cultural environments, we have reported strong evidence of highly consistent results.
Bill & Melinda Gates Foundation.
The Lancet 12/2013; 380(9859):2129-43. · 39.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study sought to perform a meta-analysis of randomized controlled trials comparing device closure with medical therapy in the prevention of recurrent neurological events in patients with cryptogenic stroke and patent foramen ovale.
The optimal strategy for secondary prevention of cryptogenic stroke with a patent foramen ovale is unclear.
Several databases were searched from their inception to March 2013, which yielded 3 eligible studies. The results were pooled as per the different patient populations defined in the studies-intention-to-treat, per-protocol, and as-treated cohorts. A generic inverse method was used based on time-to-event outcomes in a fixed-effect model. A supplementary analysis pooled the results from only 2 trials (RESPECT [Randomized Clinical Trial Comparing the Efficacy of Percutaneous Closure of Patent Foramen Ovale (PFO) With Medical Treatment in Patients With Cryptogenic Embolism]) as a similar device was used in them.
Our meta-analysis yielded effect-estimate hazard ratios of 0.67 (95% confidence interval [CI]: 0.44 to 1.00, I(2) = 0%) in the intention-to-treat cohort, 0.62 (95% CI: 0.40 to 0.95). I(2) = 0%) in the per-protocol cohort, and 0.61 (95% CI: 0.40 to 0.95, I(2) = 38%) in the as-treated cohort, showing beneficial effects of device closure. The results became more robust with pooled results from RESPECT and the PC Trial: The effect-estimate hazard ratios being 0.54 (95% CI: 0.29 to 1.01, I(2) = 0%), 0.48 (95% CI: 0.24 to 0.94, I(2) = 26%), and 0.42 (95% CI: 0.21 to 0.84, I(2) = 26%) in the intention-to-treat, per-protocol, and as-treated populations, respectively.
Our meta-analysis suggests that PFO closure is beneficial as compared to medical therapy in the prevention of recurrent neurological events. This meta-analysis helps to further strengthen the role of device closure in cryptogenic stroke.
[Show abstract][Hide abstract] ABSTRACT: Aims: Cangrelor is a new antiplatelet agent that has been used in percutaneous coronary intervention (PCI) with mixed results. We aim to review the evidence on the efficacy of cangrelor in comparison to clopidogrel in reducing ischaemic endpoints at 48 hours in patients undergoing PCI in large randomised trials. Methods and results: In three large clinical trials involving 25,107 participants, the risk of the primary composite efficacy endpoint of death, MI and ischaemia-driven revascularisation at 48 hours, (pooled OR 0.94; 95% CI: 0.77-1.14, p=0.51, I2=68%), death from all cause (pooled OR 0.72, 95% CI: 0.36-1.43, p=0.34 I2=52%), myocardial infarction (pooled OR 0.94, 95% CI: 0.77-1.14, p=0.51 I2=68%) was not significantly different between cangrelor and clopidogrel. Likewise, severe or life-threatening bleeding was similar between cangrelor and clopidogrel (pooled OR 1.21, 95% CI: 0.70-2.12, p=0.50 I2=0%). The risk of stent thrombosis (pooled OR 0.59, 95% CI: 0.43-0.81, p=0.001, I2=0%), Q-wave myocardial infarction (pooled OR 0.53, 95% CI: 0.30-0.92, p=0.02, I2=0%) and ischaemia-driven revascularisation (pooled OR 0.71, 95% CI: 0.52-0.98, p=0.04, I2=0%) was lower in the cangrelor group. Conclusions: Based on this meta-analysis, we did not find any difference in the risk of the primary composite efficacy endpoint of all-cause death, ischaemia-driven revascularisation, and myocardial infarction at 48 hours between cangrelor and clopidogrel use. Given that cangrelor was associated with a lower risk of stent thrombosis, ischaemia-driven revascularisation and Q-wave myocardial infarction compared to clopidogrel, cangrelor can be considered as a suitable alternative during PCI.
EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 09/2013; · 3.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To examine the safety (defined as bleeding risk) and efficacy (defined as prevention of thromboembolic events) of interrupted dabigatran for peri-procedural anticoagulation in catheter ablation (CA) of atrial fibrillation (AF) in comparison with warfarin.METHODS AND RESULTS: Reviewers independently searched literature databases from January 2010 through April 2013 for studies comparing the safety and efficacy of dabigatran and warfarin in CA of AF and extracted pre-defined data. The Mantel-Haenszel method was used to pool data of bleeding and thromboembolism outcomes into random and fixed effect model meta-analyses, respectively. Odds ratios (ORs), and risk difference (RD) analysis when studies reported no events in either arm, were used to generate an overall effect estimate of both outcomes. Publication bias and heterogeneity were assessed by contour funnel plot and the I(2) test, respectively. Nine citations, including 3036 patients (1073 dabigatran), met the inclusion criteria. There was no significant difference between interrupted dabigatran and warfarin therapy in CA of AF in occurrence of bleeding [dabigatran 58 (5.4%), warfarin 103 (5.2%); OR 0.92 (95% confidence interval (CI) 0.55-1.45); χ(2) = 13.03-P = 0.11; I(2) = 39%] or thromboembolism [dabigatran 5 (0.4%), warfarin 2 (0.1%); OR 2.15 (95% CI-0.58-7.98); χ(2) = 2.14, P = 0.54; I(2) = 0%; RD 0.00 (95% CI-0.00 to 0.01); χ(2) = 3.37, P = 0.81; I(2) = 0%]. Analysis of pre-defined subgroups (published articles vs. abstracts), sensitivity analyses (interrupted warfarin, USA studies, and Japanese studies) and fixed effect model analyses showed similar results. Heterogeneity was mild in the bleeding outcome analysis and zero in thromboembolism. There was no evidence of publication bias in either meta-analysis.CONCLUSION: Meta-analysis of currently available studies showed no significant difference in bleeding and thromboembolism between interrupted dabigatran and warfarin therapy in CA of AF. Dabigatran appears to be safe and effective for peri-procedural anticoagulation in CA of AF.
[Show abstract][Hide abstract] ABSTRACT: The Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) constitutes an unprecedented collaboration of 488 scientists from 303 institutions in 50 countries, focusing on describing the state of health around the world using a uniform method. Results for the world and 21 regions for 1990 and 2010 have been reported for 291 diseases and injuries, 1160 sequelae of these causes, and 67 risk factors or clusters of risk factors. 1–7 The burden of each disease, injury, or risk factor has been quantifi ed in terms of deaths, years of life lost due to premature mortality (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs). Although only global and regional results have been reported so far, the underlying unit of analysis for GBD 2010 was 187 countries. Age-specifi c mortality was analysed for each country for each year from 1970 to 2010. Causes of death were estimated for each country from 1990 to 2010 with country-specifi c data and models. Disease and injury sequelae were estimated in most cases with a Bayesian meta-regression method (DisMod-MR) that includes estimation of systematic diff erences in incidence, prevalence, or excess mortality between countries within regions. 5 Systematic analysis of risk factor exposure, excess health risks associated with each risk–outcome pair, and counterfactual minimum risk levels of exposure were used to compute attributable burden. On the basis of these analyses, GBD 2010 provides a complete assessment of the burden of diseases, injuries, and risk factors for 187 countries including quantifi cation of uncertainty in the estimates for 1990 and 2010, albeit with important limitations because of the scarcity of data for some outcomes in some countries and the need to use a range of statistical models to generate estimates. The availability of standardised estimates for each of the 187 countries over time provides an unprecedented opportunity to undertake comparative assessments, to benchmark country performance in control of critical diseases, injuries, and risks, and to stimulate evidence-based action. Most of the scientists in the GBD 2010 collaboration volunteered their own time or raised their own funds to participate. 8 A key motivation for them was the opportunity to publish more detailed analyses of data, methods, and results for specifi c diseases, injuries, and risk factors. Many reports are in submission or in preparation and provide more detail for specifi c diseases, injuries, risk factors, and countries. 9 Although we expect that these reports will be important contributions to the scientifi c literature, we recognise that country results from the GBD are a global public good that could be a useful or even critical input into a more informed national, regional, and global dialogue about health challenges. Already, governments of several developed and developing countries have approached us seeking access to more detailed results. Because we believe that the dissemination and rapid availability of the detailed results is a moral imperative, we are providing global access to these details on March 5, 2013, through a series of online visualisations. To allow suffi cient time for members of the GBD 2010 collaboration to report their own research fi ndings, we will defer dissemination of public-use datasets of the underlying results presented in the visualisations until Sept 1, 2013. In this way, we believe that we can provide global access to these important results while at the same time respecting the intellectual investment of the collaboration's mem-bers. Nonetheless, anticipating that some governments might wish to have immediate access to more detailed information as an input to national policy dialogue, we have provided and will continue to provide detailed national disease burden results on request. We also encourage use of the visualisations or snapshots of their images for teaching, communication, and other educational purposes. Alongside the reporting of global and regional results in The Lancet, fi ve data visualisations were made available in December, 2012. For visualisation of country-level data, the Institute for Health Metrics and Evaluation (IHME) has developed new visualisations with expanded scope and functionality, which are being launched on March 5. Data visualisations can make complex information accessible and interpretable without advanced statistical or epidemiological training. The primary purpose of these visualisations is to allow health specialists, policy makers, the media, donors, and the general public to explore the patterns of health in diff erent age and sex groups, countries, and time periods. Providing information on patterns of health to this broad audience could enhance the scope and quality of national, regional, and global dialogue about the main For data visualisations see
The Lancet 03/2013; 381(9871):965-70. · 39.06 Impact Factor