Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials

Objective: To assess the effects of selective cyclo-oxygenase-2 (COX 2) inhibitors and traditional non-steroidal anti-inflammatory drugs (NSAIDs) on the risk of vascular events. Design: Meta-analysis of published and unpublished tabular data from randomised trials, with indirect estimation of the effects of traditional NSAIDs. Data sources: Medline and Embase (January 1966 to April 2005); Food and Drug Administration records; and data on file from Novartis, Pfizer, and Merck. Review methods: Eligible studies were randomised trials that included a comparison of a selective COX 2 inhibitor versus placebo or a selective COX 2 inhibitor versus a traditional NSAID, of at least four weeks' duration, with information on serious vascular events (defined as myocardial infarction, stroke, or vascular death). Individual investigators and manufacturers provided information on the number of patients randomised, numbers of vascular events, and the person time of follow-up for each randomised group. Results: In placebo comparisons, allocation to a selective COX 2 inhibitor was associated with a 42% relative increase in the incidence of serious vascular events (1.2%/year v 0.9%/year; rate ratio 1.42, 95% confidence interval 1.13 to 1.78; P = 0.003), with no significant heterogeneity among the different selective COX 2 inhibitors. This was chiefly attributable to an increased risk of myocardial infarction (0.6%/year v 0.3%/year; 1.86, 1.33 to 2.59; P = 0.0003), with little apparent difference in other vascular outcomes. Among trials of at least one year's duration (mean 2.7 years), the rate ratio for vascular events was 1.45 (1.12 to 1.89; P = 0.005). Overall, the incidence of serious vascular events was similar between a selective COX 2 inhibitor and any traditional NSAID (1.0%/year v 0.9/%year; 1.16, 0.97 to 1.38; P = 0.1). However, statistical heterogeneity (P = 0.001) was found between trials of a selective COX 2 inhibitor versus naproxen (1.57, 1.21 to 2.03) and of a selective COX 2 inhibitor versus non-naproxen NSAIDs (0.88, 0.69 to 1.12). The summary rate ratio for vascular events, compared with placebo, was 0.92 (0.67 to 1.26) for naproxen, 1.51 (0.96 to 2.37) for ibuprofen, and 1.63 (1.12 to 2.37) for diclofenac. Conclusions: Selective COX 2 inhibitors are associated with a moderate increase in the risk of vascular events, as are high dose regimens of ibuprofen and diclofenac, but high dose naproxen is not associated with such an excess

Estimating on-road vehicle fuel economy in Africa:A Case Study Based on an Urban Transport Survey in Nairobi, Kenya

In African cities, like Nairobi, policies to improve vehicle fuel economy help to reduce greenhouse gas emissions and improve air quality, but lack of data is a major challenge. We present a methodology for estimating fuel economy in such cities. Vehicle characteristics and activity data, for both the formal fleet (private cars, motorcycles, light and heavy trucks) and informal fleet (minibuses (matatus), three-wheelers (tuktuks), goods vehicles (AskforTransport) and two-wheelers (bodabodas)), were collected and used to estimate fuel economy. Using two empirical models, general linear modelling (GLM) and artificial neural network (ANN) models, relationship between vehicle characteristics for this fleet was for the first time analyzed. Fuel economy for bodabodas (4.6±0.4 L/100 km), tuktuks (8.7±4.6 L/100 km), passenger cars (22.8±3.0 L/100 km), and matatus (33.1±2.5 L/100 km) was found to be 2-3 times worse than in the countries these vehicles are imported from. The GLM model provided the better estimate of predicted fuel economy based on vehicle characteristics. The analysis of the survey data with large informal urban fleet helps meet the challenge of a lack of availability of vehicle data for emissions inventories. This may be useful to policy makers as emissions inventories underpin policy development to reduce emissions

Effectiveness and reach of a directed-population approach to improving dental health and reducing inequalities: a cross sectional study

Background Childsmile School adopts a directed-population approach to target fluoride varnish applications to 20% of the primary one (P1) population in priority schools selected on the basis of the proportion of enrolled children considered to be at increased-risk of developing dental caries. The study sought to compare the effectiveness of four different methods for identifying individuals most in need when a directed-population approach is taken. <p></p> Methods The 2008 Basic National Dental Inspection Programme (BNDIP) cross-sectional P1 Scottish epidemiological survey dataset was used to model four methods and test three definitions of increased-risk. Effectiveness was determined by the positive predictive value (PPV) and explored in relation to 1-sensitivity and 1-specificity. <p></p> Results Complete data was available on 43470 children (87% of the survey). At the Scotland level, at least half (50%) of the children targeted were at increased-risk irrespective of the method used to target or the definition of increased-risk. There was no one method across all definitions of <i>increased-risk</i> that maximised PPV. Instead, PPV was highest when the targeting method complimented the definition of <i>increased-risk</i>. There was a higher percentage of children at <i>increased-risk</i> who were not targeted (1-sensitivity) when caries experience (rather than deprivation) was used to define <i>increased-risk</i>, irrespective of the method used for targeting. Over all three definitions of <i>increased-risk</i>, there was no one method that minimised (1-sensitivity) although this was lowest when the method and definition of <i>increased-risk</i> were complimentary. The false positive rate (1-specificity) for all methods and all definitions of <i>increased-risk</i> was consistently low (<20%), again being lowest when the method and definition of <i>increased-risk</i> were complimentary. <p></p> Conclusion Developing a method to reach all (or even the vast majority) of individuals at <i>increased-risk</i> defined by either caries experience or deprivation is difficult using a directed-population approach at a group level. There is a need for a wider debate between politicians and public health experts to decide how best to reach those most at need of intervention to improve health and reduce inequalities. <p></p&gt

Randomized multicentre pilot study of sacubitril/valsartan versus irbesartan in patients with chronic kidney disease: United Kingdom Heart and Renal Protection (HARP)- III—rationale, trial design and baseline data

BACKGROUND: Patients with chronic kidney disease (CKD) are at risk of progression to end-stage renal disease and cardiovascular disease. Data from other populations and animal experiments suggest that neprilysin inhibition (which augments the natriuretic peptide system) may reduce these risks, but clinical trials among patients with CKD are required to test this hypothesis. METHODS: UK Heart and Renal Protection III (HARP-III) is a multicentre, double-blind, randomized controlled trial comparing sacubitril/valsartan 97/103 mg two times daily (an angiotensin receptor-neprilysin inhibitor) with irbesartan 300 mg one time daily among 414 patients with CKD. Patients ≥18 years of age with an estimated glomerular filtration rate (eGFR) of ≥45 but <60 mL/min/1.73 m2 and urine albumin:creatinine ratio (uACR) >20 mg/mmol or eGFR ≥20 but <45 mL/min/1.73 m2 (regardless of uACR) were invited to be screened. Following a 4- to 7-week pre-randomization single-blind placebo run-in phase (during which any current renin-angiotensin system inhibitors were stopped), willing and eligible participants were randomly assigned either sacubitril/valsartan or irbesartan and followed-up for 12 months. The primary aim was to compare the effects of sacubitril/valsartan and irbesartan on measured GFR after 12 months of therapy. Important secondary outcomes include effects on albuminuria, change in eGFR over time and the safety and tolerability of sacubitril/valsartan in CKD. RESULTS: Between November 2014 and January 2016, 620 patients attended a screening visit and 566 (91%) entered the pre-randomization run-in phase. Of these, 414 (73%) participants were randomized (mean age 63 years; 72% male). The mean eGFR was 34.0 mL/min/1.73 m2 and the median uACR was 58.5 mg/mmol. CONCLUSIONS: UK HARP-III will provide important information on the short-term effects of sacubitril/valsartan on renal function, tolerability and safety among patients with CKD

Effects of alteplase for acute stroke according to criteria defining the European Union and United States marketing authorizations: individual-patient-data meta-analysis of randomized trials

Background: The recommended maximum age and time window for intravenous alteplase treatment of acute ischemic stroke differs between the Europe Union and United States. Aims: We compared the effects of alteplase in cohorts defined by the current Europe Union or United States marketing approval labels, and by hypothetical revisions of the labels that would remove the Europe Union upper age limit or extend the United States treatment time window to 4.5 h. Methods: We assessed outcomes in an individual-patient-data meta-analysis of eight randomized trials of intravenous alteplase (0.9 mg/kg) versus control for acute ischemic stroke. Outcomes included: excellent outcome (modified Rankin score 0–1) at 3–6 months, the distribution of modified Rankin score, symptomatic intracerebral hemorrhage, and 90-day mortality. Results: Alteplase increased the odds of modified Rankin score 0–1 among 2449/6136 (40%) patients who met the current European Union label and 3491 (57%) patients who met the age-revised label (odds ratio 1.42, 95% CI 1.21−1.68 and 1.43, 1.23−1.65, respectively), but not in those outside the age-revised label (1.06, 0.90−1.26). By 90 days, there was no increased mortality in the current and age-revised cohorts (hazard ratios 0.98, 95% CI 0.76−1.25 and 1.01, 0.86–1.19, respectively) but mortality remained higher outside the age-revised label (1.19, 0.99–1.42). Similarly, alteplase increased the odds of modified Rankin score 0-1 among 1174/6136 (19%) patients who met the current US approval and 3326 (54%) who met a 4.5-h revised approval (odds ratio 1.55, 1.19−2.01 and 1.37, 1.17−1.59, respectively), but not for those outside the 4.5-h revised approval (1.14, 0.97−1.34). By 90 days, no increased mortality remained for the current and 4.5-h revised label cohorts (hazard ratios 0.99, 0.77−1.26 and 1.02, 0.87–1.20, respectively) but mortality remained higher outside the 4.5-h revised approval (1.17, 0.98–1.41). Conclusions: An age-revised European Union label or 4.5-h-revised United States label would each increase the number of patients deriving net benefit from alteplase by 90 days after acute ischemic stroke, without excess mortality

Boys' and girls' clubs

"Club work is based on sound principles and has come to stay. It is supported by federal and state aid as a definite form of agricultural extension work. Boys and girls on the farm are aided in their work and every possible advantage is extended to flt them, for better living and "to improve country life." It is proper in this connection to mention that club work has received special recognition from the State Superintendent of Public Instruction. On Pages 124-126 of the last Annual School Report will be found a general statement of this movement. On Pages 122 and 124 of the last State Course of Study will b.e found the . details of some of the projects. In the first county campaign which had as an aim to acquaint patrons, pupils and teachers with the nature and purpose of Boys' and Girls' Clubs, the state superintendent took personal part and gave sanction to the work. So far as known no other state has given stronger recognition to club work than Missouri."--Page 3

On Soot Sampling: Considerations when Sampling for TEM Imaging and Differential Mobility Spectrometer

Particulate matter (PM) has been sampled from a compression ignition engine using a differential mobility spectrometer (Cambustion DMS 500) and for imaging in a transmission electron microscope (TEM) with the aim of coupling these two measuring techniques. A known issue when coupling these two methods is that a devise like the DMS samples all PM, and the TEM only soot. To help resolve this issue, a thermal denuder was designed and built to remove all volatile organic compounds (VOC) from the sample prior to entering the DMS. For TEM imaging, soot was either collected directly onto a TEM grid using the thermophoretic effect or collected onto quartz filters with the soot then transferred onto the TEM grids. The direct to grid technique did not work after the denuder due to the gas temperature being too low for the thermophoretic effect; hence the reason to collect some soot using the quartz filters. Soot was removed from the filters using an ethanol wash/sonication technique. Morphology; diameter of gyration, projected area, primary particle size and fractal dimension have been compared between the two TEM sampling techniques, with or without the denuder. Denuder effectiveness has been assessed using TGA analysis of sampled soot. Issues concerning the sampling process itself are outlined. A comparison between the TEM and the DMS results is conducted with the discrepancies between them discussed. Direct and filter sampling gave similar results as long as the sonication process and grid prep is done properly, otherwise the filter wash technique results in a number of clusters of agglomerates which distorts the post processing and morphological data

Successful up-scaled population interventions to reduce risk factors for non-communicable disease in adults: Results from the International Community Interventions for Health (CIH) project in China, India and Mexico

Background: Non-communicable disease (NCD) is increasing rapidly in low and middle-income countries (LMIC), and is associated with tobacco use, unhealthy diet and physical inactivity. There is little evidence for up-scaled interventions at the population level to reduce risk in LMIC. Methods: The Community Interventions for Health (CIH) program was a population-scale community intervention study with comparator population group undertaken in communities in China, India, and Mexico, each with populations between 150,000-250,000. Culturally appropriate interventions were delivered over 18-24 months. Two independent cross-sectional surveys of a stratified sample of adults aged 18-64 years were conducted at baseline and follow-up. Results: A total of 6,194 adults completed surveys at baseline, and 6,022 at follow-up. The proportion meeting physical activity recommendations decreased significantly in the control group (C) (44.1 to 30.2%), but not in the intervention group (I) (38.0 to 36.1%), p<0.001. Those eating ≥5 portions of fruit and vegetables daily decreased significantly in C (19.2 to 17.2%), but did not change in I (20.0 to 19.6%,), p=0.013. The proportion adding salt to food was unchanged in C (24.9 to 25.3%) and decreased in I (25.9 to 19.6%), p<0.001. Prevalence of obesity increased in C (8.3 to 11.2%), with no change in I (8.6 to 9.7%,) p=0.092. Concerning tobacco, for men the difference-in-difference analysis showed that the reduction in use was significantly greater in I compared to C (p=0.014) Conclusions: Up-scaling known health promoting interventions designed to reduce the incidence of NCD in whole communities in LMIC is feasible, and has measurable beneficial outcomes on risk factors for NCD, namely tobacco use, diet, and physical inactivity

Sex-specific relevance of diabetes to occlusive vascular and other mortality : a collaborative meta-analysis of individual data from 980 793 adults from 68 prospective studies

Background: Several studies have shown that diabetes confers a higher relative risk of vascular mortality among women than among men, but whether this increased relative risk in women exists across age groups and within defined levels of other risk factors is uncertain. We aimed to determine whether differences in established risk factors, such as blood pressure, BMI, smoking, and cholesterol, explain the higher relative risks of vascular mortality among women than among men. Methods: In our meta-analysis, we obtained individual participant-level data from studies included in the Prospective Studies Collaboration and the Asia Pacific Cohort Studies Collaboration that had obtained baseline information on age, sex, diabetes, total cholesterol, blood pressure, tobacco use, height, and weight. Data on causes of death were obtained from medical death certificates. We used Cox regression models to assess the relevance of diabetes (any type) to occlusive vascular mortality (ischaemic heart disease, ischaemic stroke, or other atherosclerotic deaths) by age, sex, and other major vascular risk factors, and to assess whether the associations of blood pressure, total cholesterol, and body-mass index (BMI) to occlusive vascular mortality are modified by diabetes. Findings: Individual participant-level data were analysed from 980793 adults. During 9 center dot 8 million person-years of follow-up, among participants aged between 35 and 89 years, 19686 (25 center dot 6%) of 76965 deaths were attributed to occlusive vascular disease. After controlling for major vascular risk factors, diabetes roughly doubled occlusive vascular mortality risk among men (death rate ratio [RR] 2 center dot 10, 95% CI 1 center dot 97-2 center dot 24) and tripled risk among women (3 center dot 00, 2 center dot 71-3 center dot 33; x(2) test for heterogeneity p<0 center dot 0001). For both sexes combined, the occlusive vascular death RRs were higher in younger individuals (aged 35-59 years: 2 center dot 60, 2 center dot 30-2 center dot 94) than in older individuals (aged 70-89 years: 2 center dot 01, 1 center dot 85-2 center dot 19; p=0 center dot 0001 for trend across age groups), and, across age groups, the death RRs were higher among women than among men. Therefore, women aged 35-59 years had the highest death RR across all age and sex groups (5 center dot 55, 4 center dot 15-7 center dot 44). However, since underlying confounder-adjusted occlusive vascular mortality rates at any age were higher in men than in women, the adjusted absolute excess occlusive vascular mortality associated with diabetes was similar for men and women. At ages 35-59 years, the excess absolute risk was 0 center dot 05% (95% CI 0 center dot 03-0 center dot 07) per year in women compared with 0 center dot 08% (0 center dot 05-0 center dot 10) per year in men; the corresponding excess at ages 70-89 years was 1 center dot 08% (0 center dot 84-1 center dot 3 2) per year in women and 0 center dot 91% (0 center dot 77-1 center dot 05) per year in men. Total cholesterol, blood pressure, and BMI each showed continuous log-linear associations with occlusive vascular mortality that were similar among individuals with and without diabetes across both sexes. Interpretation: Independent of other major vascular risk factors, diabetes substantially increased vascular risk in both men and women. Lifestyle changes to reduce smoking and obesity and use of cost-effective drugs that target major vascular risks (eg, statins and antihypertensive drugs) are important in both men and women with diabetes, but might not reduce the relative excess risk of occlusive vascular disease in women with diabetes, which remains unexplained