Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Daily precipitation statistics in a EURO-CORDEX RCM ensemble: added value of raw and bias-corrected high-resolution simulations

Daily precipitation statistics as simulated by the ERA-Interim-driven EURO-CORDEX regional climate model (RCM) ensemble are evaluated over two distinct regions of the European continent, namely the European Alps and Spain. The potential added value of the high-resolution 12 km experiments with respect to their 50 km resolution counterparts is investigated. The statistics considered consist of wet-day intensity and precipitation frequency as a measure of mean precipitation, and three precipitation-derived indicators (90th percentile on wet days?90pWET, contribution of the very wet days to total precipitation?R95pTOT and number of consecutive dry days?CDD). As reference for model evaluation high resolution gridded observational data over continental Spain (Spain011/044) and the Alpine region (EURO4M-APGD) are used. The assessment and comparison of the two resolutions is accomplished not only on their original horizontal grids (approximately 12 and 50 km), but the high-resolution RCMs are additionally regridded onto the coarse 50 km grid by grid cell aggregation for the direct comparison with the low resolution simulations. The direct application of RCMs e.g. in many impact modelling studies is hampered by model biases. Therefore bias correction (BC) techniques are needed at both resolutions to ensure a better agreement between models and observations. In this work, the added value of the high resolution (before and after the bias correction) is assessed and the suitability of these BC methods is also discussed. Three basic BC methods are applied to isolate the effect of biases in mean precipitation, wet-day intensity and wet-day frequency on the derived indicators. Daily precipitation percentiles are strongly affected by biases in the wet-day intensity, whereas the dry spells are better represented when the simulated precipitation frequency is adjusted to the observed one. This confirms that there is no single optimal way to correct for RCM biases, since correcting some distributional features typically leads to an improvement of some aspects but to a deterioration of others. Regarding mean seasonal biases before the BC, we find only limited evidence for an added value of the higher resolution in the precipitation intensity and frequency or in the derived indicators. Thereby, evaluation results considerably depend on the RCM, season and indicator considered. High resolution simulations better reproduce the indicators? spatial patterns, especially in terms of spatial correlation. However, this improvement is not statistically significant after applying specific BC methods.The authors are grateful to Prof. C. Schär for his helpful comments and E. van Meijgaard for making available the RACMO model data. We acknowledge the observational data providers. Calculations for WRF311F were made using the TGCC super computers under the GENCI time allocation GEN6877. The WRF331A from CRP-GL (now LIST) was funded by the Luxembourg National Research Fund (FNR) through grant FNR C09/SR/16 (CLIMPACT). The KNMI-RACMO2 simulations were supported by the Dutch Ministry of Infrastructure and the Environment. The CCLM and REMO simulations were supported by the Federal Ministry of Education and Research (BMBF) and performed under the Konsortial share at the German Climate Computing Centre (DKRZ). The CCLM simulations were furthermore supported by the Swiss National Supercomputing Centre (CSCS) under project ID s78. Part of the SMHI contribution was carried out in the Swedish Mistra-SWECIA programme founded by Mistra (the Foundation for Strategic Environmental Research). This work is supported by CORWES (CGL2010-22158-C02) and EXTREMBLES (CGL2010-21869) projects funded by the Spanish R&D programme and the European COST ACTION VALUE (ES1102). A. C. thanks the Spanish Ministry of Economy and Competitiveness for the funding provided within the FPI programme (BES-2011-047612 and EEBB-I-13-06354). We also thank two anonymous referees for their useful comments that helped to improve the original manuscript

Prevalence of hallux valgus in the general population: a systematic review and meta-analysis

BACKGROUND: Hallux valgus (HV) is a foot deformity commonly seen in medical practice, often accompanied by significant functional disability and foot pain. Despite frequent mention in a diverse body of literature, a precise estimate of the prevalence of HV is difficult to ascertain. The purpose of this systematic review was to investigate prevalence of HV in the overall population and evaluate the influence of age and gender. METHODS: Electronic databases (Medline, Embase, and CINAHL) and reference lists of included papers were searched to June 2009 for papers on HV prevalence without language restriction. MeSH terms and keywords were used relating to HV or bunions, prevalence and various synonyms. Included studies were surveys reporting original data for prevalence of HV or bunions in healthy populations of any age group. Surveys reporting prevalence data grouped with other foot deformities and in specific disease groups (e.g. rheumatoid arthritis, diabetes) were excluded. Two independent investigators quality rated all included papers on the Epidemiological Appraisal Instrument. Data on raw prevalence, population studied and methodology were extracted. Prevalence proportions and the standard error were calculated, and meta-analysis was performed using a random effects model. RESULTS: A total of 78 papers reporting results of 76 surveys (total 496,957 participants) were included and grouped by study population for meta-analysis. Pooled prevalence estimates for HV were 23% in adults aged 18-65 years (CI: 16.3 to 29.6) and 35.7% in elderly people aged over 65 years (CI: 29.5 to 42.0). Prevalence increased with age and was higher in females [30% (CI: 22 to 38)] compared to males [13% (CI: 9 to 17)]. Potential sources of bias were sampling method, study quality and method of HV diagnosis. CONCLUSIONS: Notwithstanding the wide variation in estimates, it is evident that HV is prevalent; more so in females and with increasing age. Methodological quality issues need to be addressed in interpreting reports in the literature and in future research

Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial

Background Results of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects. Methods FOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762. Findings Between Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839–1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26–6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38–2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months. Interpretation Fluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function. Funding UK Stroke Association and NIHR Health Technology Assessment Programme

Feeding Calcium-Ammonium Nitrate to Lactating Dairy Goats: Milk Quality and Ruminal Fermentation Responses

We aimed to investigate the effects of calcium-ammonium nitrate (CAN) fed to lactating dairy goats on dry matter (DM) intake, digestibility of nutrients, milk properties (composition, antioxidant capacity, fatty acid profile, and nitrate residues), and ruminal fermentation parameters. Twelve lactating Saanen goats averaging 98.5 ± 13.1 days in milk, 53.5 ± 3.3 kg of body weight, and 2.53 ± 0.34 kg of milk/day were randomly assigned in four 3 × 3 Latin squares to receive the following diets: a control group (without CAN) with 7.3 g/kg DM of urea (URE), 10 g/kg DM of CAN (CAN10), and 20 g/kg DM of CAN (CAN20). Each period lasted 21 days, with 14 days for diet adaptation and seven days for data and sample collection. The DM intake, digestibility of nutrients, yields of milk, 3.5% fat-corrected milk, and energy-corrected milk were not affected by treatments. Similarly, there were no treatment effects on the yields and concentrations of milk fat, true protein, and lactose, along with minor effects on milk fatty acid profile. Total antioxidant capacity in milk was unaffected by treatments; however, concentration of conjugated dienes increased, while thiobarbituric acid reactive substances in milk decreased linearly. Nitrate and nitrite residues in milk were elevated by treatments, while the total of volatile fatty acids and ammonia-N concentration in the rumen were unaffected. Collectively, feeding CAN (up to 20 g/kg of DM) to lactating dairy goats did not affect feed intake, nutrient digestibility, and milk composition; however, it may increase milk lipid oxidation, as evidenced by increased conjugated diene concentration