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ObjectivesTo report the level and trends of prevalence, incidence and years lived with disability (YLDs) for osteoarthritis (OA) in 195 countries and territories from 1990 to 2017 by age, sex and Socio-demographic index (SDI; a composite of sociodemographic factors).MethodsPublicly available modelled data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 were used. The burden of OA was estimated for 195 countries and territories from 1990 to 2017, through a systematic analysis of prevalence and incidence modelled data using the methods reported in the GBD 2017 Study. All estimates were presented as counts and age-standardised rates per 100 000 population, with uncertainty intervals (UIs).ResultsGlobally, the age-standardised point prevalence and annual incidence rate of OA in 2017 were 3754.2 (95% UI 3389.4 to 4187.6) and 181.2 (95% UI 162.6 to 202.4) per 100 000, an increase of 9.3% (95% UI 8% to 10.7%) and 8.2% (95% UI 7.1% to 9.4%) from 1990, respectively. In addition, global age-standardised YLD rate in 2017 was 118.8 (95% UI 59.5 to 236.2), an increase of 9.6% (95% UI 8.3% to 11.1%) from 1990. The global prevalence was higher in women and increased with age, peaking at the >95 age group among women and men in 2017. Generally, a positive association was found between the age-standardised YLD rate and SDI at the regional and national levels. Age-standardised prevalence of OA in 2017 ranged from 2090.3 to 6128.1 cases per 100 000 population. United States (6128.1 (95% UI 5729.3 to 6582.9)), American Samoa (5281 (95% UI 4688 to 5965.9)) and Kuwait (5234.6 (95% UI 4643.2 to 5953.6)) had the three highest levels of age-standardised prevalence. Oman (29.6% (95% UI 24.8% to 34.9%)), Equatorial Guinea (28.6% (95% UI 24.4% to 33.7%)) and the United States 23.2% (95% UI 16.4% to 30.5%)) showed the highest increase in the age-standardised prevalence during 1990–2017.ConclusionsOA is a major public health challenge. While there is remarkable international variation in the prevalence, incidence and YLDs due to OA, the burden is increasing in most countries. It is expected to continue with increased life expectancy and ageing of the global population. Improving population and policy maker awareness of risk factors, including overweight and injury, and the importance and benefits of management of OA, together with providing health services for an increasing number of people living with OA, are recommended for management of the future burden of this condition.

Significance Earth system’s response to major perturbations is of paramount interest. On the basis of multiple isotope compositions for pyrite, carbonate-associated sulfate, carbonates, and organics within, we inferred that the much-debated, enigmatic, extremely 13 C-depleted calcite cements in the ∼635-Ma cap carbonates in South China preserve geochemical evidence for marine microbial sulfate reduction coupled to anaerobic oxidation of methane. This interpretation implies the existence of a brief interval of modern-level marine sulfate. We determined that this interval coincides with the earliest Ediacaran 17 O-depletion episode, and both likely occurred within ∼50 ky since the onset of the 635-Ma meltdown, revealing an astonishing pace of transformation of the Earth system in the aftermath of Earth’s latest snowball glaciation.

Background Cangrelor, an intravenous, reversible P2Y12 antagonist, is approved for use in patients undergoing percutaneous coronary intervention (PCI). Objectives This study sought to evaluate the efficacy and safety of cangrelor compared with clopidogrel in subgroups that did and did not receive glycoprotein IIb/IIIa inhibitors (GPIs). Methods This pooled, patient-level analysis of the 3 CHAMPION (Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition) trials analyzed all randomized patients who underwent PCI and received the study drug (n = 24,902). Only bailout/rescue GPI use was permitted, except in CHAMPION PCI, in which routine or bailout/rescue GPI use was at the site investigator’s discretion. The primary efficacy endpoint was the composite of all-cause mortality, myocardial infarction, ischemia-driven revascularization, or stent thrombosis at 48 h after randomization. Results Overall, 3,173 patients (12.7%) received a GPI, most commonly eptifibatide (69.4%). Despite variation in indications for GPIs, baseline characteristics were well balanced between the cangrelor and clopidogrel arms in subsets receiving and not receiving GPIs. Rates of the primary composite endpoint were lower with cangrelor compared with clopidogrel in patients who did (4.9% vs. 6.5%; odds ratio [OR]: 0.74; 95% confidence interval [CI]: 0.55 to 1.01) or did not receive a GPI (3.6% vs. 4.4%; OR: 0.82; 95% CI: 0.72 to 0.94; Pint = 0.55). Cangrelor did not increase the primary safety endpoint, GUSTO-defined severe/life-threatening bleeding, in patients who did (0.4% vs. 0.5%; OR: 0.71; 95% CI: 0.25 to 1.99) or did not receive GPIs (0.2% vs. 0.1%; OR: 1.56; 95% CI: 0.80 to 3.04; Pint = 0.21). GPI use was associated with increased risk of bleeding in both treatment arms. Conclusions Cangrelor’s efficacy in reducing ischemic complications in patients undergoing PCI was maintained irrespective of GPI administration. GPI use was associated with substantially higher bleeding rates, regardless of the randomization to cangrelor or clopidogrel. (A Clinical Trial to Demonstrate the Efficacy of Cangrelor [PCI]: NCT00305162 ; Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition [PLATFORM]: NCT00385138 ; A Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention [PCI] [CHAMPION PHOENIX] [CHAMPION]: NCT01156571 )

The Idikan adult mortality study is designed to explore the usefulness of the verbal autopsy methodology in the determination of cause-specific adult mortality. Such data have been largely unavailable in developing countries. Members of a stable urban community (4333 adults) were registered in their family units and followed up every 3 months to ascertain deaths, exits and new entries to the study population. Deaths were investigated by means of a verbal autopsy, which was administered by a trained interviewer to the relative closest to the decedent. Two physicians independently studied the results and assigned a cause of death, and these were then confirmed or resolved by a senior physician colleague. Hospitals where deaths occurred were visited and assignable cause of death was obtained where available and compared with the cause assigned by verbal autopsy. Only 8 of the 60 investigated deaths were confirmed to have occurred in a hospital in the first 2 years of the study. The cause of death assigned by verbal autopsy agreed moderately both between the independent coders as well as with the hospital assigned cause of death using the Kappa statistics for agreement beyond chance. We therefore concluded that verbal autopsies appear moderately useful for adult death statistics (Kappa = 0.23 to 0.1). Accumulation of more hospital deaths is needed, however, to make more definite conclusions about the validity of the technique.

Studies of migrants and comparisons of rural versus urban communities are potentially informative study designs because they allow examination of genetically similar population subgroups exposed to diverse environmental conditions. These designs have been underused in Africa, where recent urbanization has created many situations in which nearby communities of common ethnicity and culture live under different social and economic circumstances. The International Study of Hypertension in Blacks (ICSHIB) conducted several overlapping surveys in Nigeria starting in 1993. These surveys were based primarily in the rural village of Idere and the urban community of Idikan, both inhabited by people defined ethnically as Oyo Yoruba and sharing a common language and culture. Survey teams collected standardized blood pressure and anthropometric measurements, and some study participants provided 24-hr urine samples and questionnaire data on psychosocial stress and social integration. Rural and urban groups differed substantially in blood pressure and related characteristics. Age-adjusted prevalence of hypertension (blood pressureor = 140/90 mm Hg) for participants aged 25 years and older was 7-8% in Idere and 24-27% in Idikan. The distributions of overweight, sodium/potassium ratio, perceived stress, and social integration scores all contributed to lower hypertension risk in Idere. The effects and interactions of these identified risk factors remain poorly understood, even among people who share a common genetic background, similar diet, and many other lifestyle features. Nonetheless, the rural-urban distinction is sufficiently salient to engender a nearly threefold difference in hypertension prevalence. This disparity in disease prevalence demonstrates the sensitivity of human beings to the environmental determinants of disease and provides a sobering example of the difficulty in identifying subtle genetic effects, which can be easily overwhelmed by small differences in environmental exposures.

Information on cause of death among adults in sub-Saharan Africa is essentially nonexistent. Published sources provide statistics on both cause-specific and overall rates of mortality, but closer examination reveals that these data consist mostly of extrapolations and outright guesses. In the absence of accurate and comprehensive registries of vital events for the majority of the region's inhabitants, longitudinal studies of defined population-based cohorts represent the only realistic strategy to fill this void in basic public health information. The advantage of longitudinal studies is particularly clear for chronic diseases, the category for which the least is known. Noncommunicable diseases account for a significant portion of adult deaths in sub-Saharan Africa, yet the empirical bases for public health policies and interventions are essentially absent. Verbal autopsy has great potential to contribute to understanding about the cause of death among African adults. This method is discussed in the present article, and practical considerations for longitudinal studies using this methodology are reviewed.This article reviews the major weaknesses contained in estimates of mortality in Africa south of the Sahara. The need for adult mortality data from developing countries has led researchers to propose estimates derived from model-based extrapolations of questionable sources such as outdated studies, nonrepresentative samples, and studies of insufficient size. Although longitudinal, community-based studies provide the best option for obtaining vital statistics in Africa, virtually all such studies have emphasized infectious diseases and childhood morbidity and mortality. Information about chronic diseases and trauma is especially limited despite the fact that they cause a sizable portion of adult deaths in the region. Reliance on longitudinal surveys requires use of verbal autopsy as a means of determining cause of death. This method assumes that it is possible to classify deaths into useful categories based on analysis of retrospective interviews and is associated with considerable difficulties. To assess the feasibility of a potential methodology for collecting cause-specific adult mortality data, the derived estimates must be generalizable; the technical requirements must be reasonable; and the responding community must be large enough (5000-10,000 adults), must cooperate with the survey process and be stable enough to provide long-term data (3-5 years). Intelligent and productive health interventions in the region will depend upon development of the adequate data base that can be collected with appropriate effort.

The technique of verbal autopsy is being used to investigate the causes of adult deaths in part of Ibadan, Nigeria. The problems encountered in the first year of the study and the measures taken to overcome them are described below.

Ventricular septal defects are one of the most common congenital heart defects that either exist alone or coexist with other complex congenital heart diseases. With 3-dimensional echocardiography, exact 3-dimensional shape, size, location, and course of any ventricular septal defects can be evaluated very thoroughly. We are reporting a comprehensive assessment of a complex ventricular septal defect using 3-dimensional echocardiography and longitudinal strain analysis.

The success of genome-wide association studies has paralleled the development of efficient genotyping technologies. We describe the development of a next-generation microarray based on the new highly-efficient Affymetrix Axiom genotyping technology that we are using to genotype individuals of European ancestry from the Kaiser Permanente Research Program on Genes, Environment and Health (RPGEH). The array contains 674,517 SNPs, and provides excellent genome-wide as well as gene-based and candidate-SNP coverage. Coverage was calculated using an approach based on imputation and cross validation. Preliminary results for the first 80,301 saliva-derived DNA samples from the RPGEH demonstrate very high quality genotypes, with sample success rates above 94% and over 98% of successful samples having SNP call rates exceeding 98%. At steady state, we have produced 462 million genotypes per week for each Axiom system. The new array provides a valuable addition to the repertoire of tools for large scale genome-wide association studies.

The amounts of creatinine, protein, carbohydrate and sialic acid in the urine of 19 patients with cystic fibrosis (CF), 12 normal controls and 11 pathological controls with chronic lung disease have been determined. The mean creatinine excretion levels of the total CF group as well as the CF subgroups are significantly decreased when compared to normal controls but comparable to pathological controls. Mean urinary protein levels appear to be increased in patients with CF compared to normal controls and pathological controls but the increased levels resulted from factors (e.g., presence of diabetes mellitus) other than CF. No significant differences were found in amounts of total carbohydrate and sialic acid in urine and fractionated urinary preparations for the total group of nondiabetic patients with CF when compared to both normal and pathological controls. HPLC fractionation of low Mr (less than 10,000 Daltons) urinary preparations indicated the presence of an unknown peak in all of the antibiotic-treated CF patients, 43% of CF patients on low or no medication, 17% of the normal controls and 9% of the pathological controls. The present results illustrate the importance of including appropriate pathological controls and dividing patients with CF into subgroups according to clinical factors and types of therapy employed.

Reliable and accurate data remain scarce on the cause and rates of mortality among adults in sub-Saharan Africa. The Idikan Adult Mortality Study, a prospective community-based study was initiated in order to obtain the overall as well as cause-specific mortality data for a community of adults (15 years and above). Standardised verbal autopsy questionnaire was used to investigate and assign the mode and cause of death. There were 232 reported deaths in the baseline population of 4127 adults over 5 years, giving an unadjusted death rate of 11.2 per 1000 per year. Thirty-nine (16.8% ) of these death occurred suddenly. The commonest known cause of death was due to cardiovascular disease, which was responsible for 43 (18.5% ) of all deaths. It was also the commonest known cause of sudden death accounting for 30.8% of such deaths. Infection was responsible for 28 (12.1% ) deaths while injury accounted for 7 (2.6% ) deaths. Subjects, 50 years and above were more likely to die and also die suddenly than were the younger subject (p0.0001, p0.0001) and significantly more death occurred in males than females (6.9% versus 4.7% ) (P0.01). Deaths were also more likely to have occurred at home and outside the hospital, increasing the probability of these deaths being underreported. Following multivariate logistic regression analysis, respondents between the age of 20 -49 years had significantly reduced risk of dying (p=0.029), while cigarette smoking significantly increased the risk of dying (p=0.012). In the absence of the urgently needed vital statistics, use of verbal autopsies is a potentially useful investigative method for identifying and assigning cause of adult deaths in a community.

Population-based studies of hypertension in Brazil were reviewed. Nineteen studies were identified, all employing cross-sectional study designs. The majority of these studies were conducted in the south and southeast regions of the country, although increasing mortality from cardiovascular diseases is now a nationwide problem in Brazil. Except for Amazonian Indians, age and blood pressure were positively correlated in the studies reviewed. Men generally had higher blood pressures than women up to age 50; studies consistently reported that blacks, or groups combining blacks and mulattoes, had higher blood pressures than whites. Methodological problems that characterize many of these studies were noted, and some suggestions for future research were offered.

The goal of this paper has been to summarize the existing data on the epidemiology of hypertension in Africa and to provide the basis for designating important known risk factors. We hope that this document will serve as the basis for a comprehensive evaluation of the disease burden from hypertension on the continent and the potential for prevention to reduce the health risk from this condition. Given the difficulty in maintaining long-term drug therapy in the African setting, and the increasing scientific basis for primary prevention, the time has clearly come to organize community campaigns to control the causal risk factors for hypertension.

Within the framework of an international collaborative network, we measured the prevalence of diabetes mellitus in a traditional Yoruba community in the city of Ibadan, Nigeria. Using a random sampling technique we enrolled a community sample of 247 men and women. Fasting blood glucose (FBG) was measured at the community clinic from a fingerstick using the Companion2 Medisense blood glucose meter. The mean FBG was 4.7 mmol/L and 4.9 mmol/L for men and women, respectively. Using the 1985 WHO criteria, the prevalence of diabetes was 2.8%. There was no significant rise in FBG with age. Compared to the lowest quartile of the body mass index (BMI), there was about a 1.5 fold increased risk of developing elevated FBG. The test of trend between FBG and BMI was however not statistically significant. Despite a modest hypertension rate (22.3%), there was no significant difference in the FBG for hypertensives compared to normotensives. The findings of this study show that the prevalence of diabetes mellitus in this West African community remains low compared to nations in Western societies. However, in comparison to previous estimates from sub-Saharan Africa, the prevalence of adult onset diabetes seems to be on the increase.