METHODS: We did a network meta-analysis based on a systematic review of randomised controlled trials comparing fibrinolytic drugs in patients with STEMI. Several databases were searched from inception up to Feb 28, 2017. We included only randomised controlled trials that compared fibrinolytic agents as a reperfusion therapy in adult patients with STEMI, whether given alone or in combination with adjunctive antithrombotic therapy, against other fibrinolytic agents, a placebo, or no treatment. Only trials investigating agents with an approved indication of reperfusion therapy in STEMI (streptokinase, tenecteplase, alteplase, and reteplase) were included. The primary efficacy outcome was all-cause mortality within 30-35 days and the primary safety outcome was major bleeding. This study is registered with PROSPERO (CRD42016042131).

FINDINGS: A total of 40 eligible studies involving 128 071 patients treated with 12 different fibrinolytic regimens were assessed. Compared with accelerated infusion of alteplase with parenteral anticoagulants as background therapy, streptokinase and non-accelerated infusion of alteplase were significantly associated with an increased risk of all-cause mortality (risk ratio [RR] 1·14 [95% CI 1·05-1·24] for streptokinase plus parenteral anticoagulants; RR 1·26 [1·10-1·45] for non-accelerated alteplase plus parenteral anticoagulants). No significant difference in mortality risk was recorded between accelerated infusion of alteplase, tenecteplase, and reteplase with parenteral anticoagulants as background therapy. For major bleeding, a tenecteplase-based regimen tended to be associated with lower risk of bleeding compared with other regimens (RR 0·79 [95% CI 0·63-1·00]). The addition of glycoprotein IIb or IIIa inhibitors to fibrinolytic therapy increased the risk of major bleeding by 1·27-8·82-times compared with accelerated infusion alteplase plus parenteral anticoagulants (RR 1·47 [95% CI 1·10-1·98] for tenecteplase plus parenteral anticoagulants plus glycoprotein inhibitors; RR 1·88 [1·24-2·86] for reteplase plus parenteral anticoagulants plus glycoprotein inhibitors).

INTERPRETATION: Significant differences exist among various fibrinolytic regimens as reperfusion therapy in STEMI and alteplase (accelerated infusion), tenecteplase, and reteplase should be considered over streptokinase and non-accelerated infusion of alteplase. The addition of glycoprotein IIb or IIIa inhibitors to fibrinolytic therapy should be discouraged.

METHODS: The Prospective Urban Rural Epidemiology (PURE) study is a large, epidemiological cohort study of individuals aged 35-70 years (enrolled between Jan 1, 2003, and March 31, 2013) in 18 countries with a median follow-up of 7·4 years (IQR 5·3-9·3). Dietary intake of 135 335 individuals was recorded using validated food frequency questionnaires. The primary outcomes were total mortality and major cardiovascular events (fatal cardiovascular disease, non-fatal myocardial infarction, stroke, and heart failure). Secondary outcomes were all myocardial infarctions, stroke, cardiovascular disease mortality, and non-cardiovascular disease mortality. Participants were categorised into quintiles of nutrient intake (carbohydrate, fats, and protein) based on percentage of energy provided by nutrients. We assessed the associations between consumption of carbohydrate, total fat, and each type of fat with cardiovascular disease and total mortality. We calculated hazard ratios (HRs) using a multivariable Cox frailty model with random intercepts to account for centre clustering.

FINDINGS: During follow-up, we documented 5796 deaths and 4784 major cardiovascular disease events. Higher carbohydrate intake was associated with an increased risk of total mortality (highest [quintile 5] vs lowest quintile [quintile 1] category, HR 1·28 [95% CI 1·12-1·46], ptrend=0·0001) but not with the risk of cardiovascular disease or cardiovascular disease mortality. Intake of total fat and each type of fat was associated with lower risk of total mortality (quintile 5 vs quintile 1, total fat: HR 0·77 [95% CI 0·67-0·87], ptrend<0·0001; saturated fat, HR 0·86 [0·76-0·99], ptrend=0·0088; monounsaturated fat: HR 0·81 [0·71-0·92], ptrend<0·0001; and polyunsaturated fat: HR 0·80 [0·71-0·89], ptrend<0·0001). Higher saturated fat intake was associated with lower risk of stroke (quintile 5 vs quintile 1, HR 0·79 [95% CI 0·64-0·98], ptrend=0·0498). Total fat and saturated and unsaturated fats were not significantly associated with risk of myocardial infarction or cardiovascular disease mortality.

INTERPRETATION: High carbohydrate intake was associated with higher risk of total mortality, whereas total fat and individual types of fat were related to lower total mortality. Total fat and types of fat were not associated with cardiovascular disease, myocardial infarction, or cardiovascular disease mortality, whereas saturated fat had an inverse association with stroke. Global dietary guidelines should be reconsidered in light of these findings.

METHODS: We did a prospective cohort study (Prospective Urban Rural Epidemiology [PURE] in 135 335 individuals aged 35 to 70 years without cardiovascular disease from 613 communities in 18 low-income, middle-income, and high-income countries in seven geographical regions: North America and Europe, South America, the Middle East, south Asia, China, southeast Asia, and Africa. We documented their diet using country-specific food frequency questionnaires at baseline. Standardised questionnaires were used to collect information about demographic factors, socioeconomic status (education, income, and employment), lifestyle (smoking, physical activity, and alcohol intake), health history and medication use, and family history of cardiovascular disease. The follow-up period varied based on the date when recruitment began at each site or country. The main clinical outcomes were major cardiovascular disease (defined as death from cardiovascular causes and non-fatal myocardial infarction, stroke, and heart failure), fatal and non-fatal myocardial infarction, fatal and non-fatal strokes, cardiovascular mortality, non-cardiovascular mortality, and total mortality. Cox frailty models with random effects were used to assess associations between fruit, vegetable, and legume consumption with risk of cardiovascular disease events and mortality.

FINDINGS: Participants were enrolled into the study between Jan 1, 2003, and March 31, 2013. For the current analysis, we included all unrefuted outcome events in the PURE study database through March 31, 2017. Overall, combined mean fruit, vegetable and legume intake was 3·91 (SD 2·77) servings per day. During a median 7·4 years (5·5-9·3) of follow-up, 4784 major cardiovascular disease events, 1649 cardiovascular deaths, and 5796 total deaths were documented. Higher total fruit, vegetable, and legume intake was inversely associated with major cardiovascular disease, myocardial infarction, cardiovascular mortality, non-cardiovascular mortality, and total mortality in the models adjusted for age, sex, and centre (random effect). The estimates were substantially attenuated in the multivariable adjusted models for major cardiovascular disease (hazard ratio [HR] 0·90, 95% CI 0·74-1·10, ptrend=0·1301), myocardial infarction (0·99, 0·74-1·31; ptrend=0·2033), stroke (0·92, 0·67-1·25; ptrend=0·7092), cardiovascular mortality (0·73, 0·53-1·02; ptrend=0·0568), non-cardiovascular mortality (0·84, 0·68-1·04; ptrend =0·0038), and total mortality (0·81, 0·68-0·96; ptrend<0·0001). The HR for total mortality was lowest for three to four servings per day (0·78, 95% CI 0·69-0·88) compared with the reference group, with no further apparent decrease in HR with higher consumption. When examined separately, fruit intake was associated with lower risk of cardiovascular, non-cardiovascular, and total mortality, while legume intake was inversely associated with non-cardiovascular death and total mortality (in fully adjusted models). For vegetables, raw vegetable intake was strongly associated with a lower risk of total mortality, whereas cooked vegetable intake showed a modest benefit against mortality.

INTERPRETATION: Higher fruit, vegetable, and legume consumption was associated with a lower risk of non-cardiovascular, and total mortality. Benefits appear to be maximum for both non-cardiovascular mortality and total mortality at three to four servings per day (equivalent to 375-500 g/day).

METHODS: We estimated mortality using natural history models for acute hepatitis infections and GBD's cause-of-death ensemble model for cirrhosis and liver cancer. We used meta-regression to estimate total cirrhosis and total liver cancer prevalence, as well as the proportion of cirrhosis and liver cancer attributable to each cause. We then estimated cause-specific prevalence as the product of the total prevalence and the proportion attributable to a specific cause. Disability-adjusted life-years (DALYs) were calculated as the sum of years of life lost (YLLs) and years lived with disability (YLDs).

FINDINGS: Between 1990 and 2013, global viral hepatitis deaths increased from 0·89 million (95% uncertainty interval [UI] 0·86-0·94) to 1·45 million (1·38-1·54); YLLs from 31·0 million (29·6-32·6) to 41·6 million (39·1-44·7); YLDs from 0·65 million (0·45-0·89) to 0·87 million (0·61-1·18); and DALYs from 31·7 million (30·2-33·3) to 42·5 million (39·9-45·6). In 2013, viral hepatitis was the seventh (95% UI seventh to eighth) leading cause of death worldwide, compared with tenth (tenth to 12th) in 1990.

INTERPRETATION: Viral hepatitis is a leading cause of death and disability worldwide. Unlike most communicable diseases, the absolute burden and relative rank of viral hepatitis increased between 1990 and 2013. The enormous health loss attributable to viral hepatitis, and the availability of effective vaccines and treatments, suggests an important opportunity to improve public health.