Magnesium sulphate at 30 to 34 weeks' gestational age: neuroprotection trial (MAGENTA) -study protocol

Extent: 9 p.BACKGROUND: Magnesium sulphate is currently recommended for neuroprotection of preterm infants for women at risk of preterm birth at less than 30 weeks’ gestation, based on high quality evidence of benefit. However there remains uncertainty as to whether these benefits apply at higher gestational ages. The aim of this randomised controlled trial is to assess whether giving magnesium sulphate compared with placebo to women immediately prior to preterm birth between 30 and 34 weeks’ gestation reduces the risk of death or cerebral palsy in their children at two years’ corrected age. METHODS/DESIGN: DESIGN: Randomised, multicentre, placebo controlled trial. INCLUSION CRITERIA: Women, giving informed consent, at risk of preterm birth between 30 to 34 weeks’ gestation, where birth is planned or definitely expected within 24 hours, with a singleton or twin pregnancy and no contraindications to the use of magnesium sulphate. TRIAL ENTRY & RANDOMISATION: Eligible women will be randomly allocated to receive either magnesium sulphate or placebo. TREATMENT GROUPS: Women in the magnesium sulphate group will be administered 50 ml of a 100 ml infusion bag containing 8 g magnesium sulphate heptahydrate [16 mmol magnesium ions]. Women in the placebo group will be administered 50 ml of a 100 ml infusion bag containing isotonic sodium chloride solution (0.9%). Both treatments will be administered through a dedicated IV infusion line over 30 minutes. PRIMARY STUDY OUTCOME: Death or cerebral palsy measured in children at two years’ corrected age. SAMPLE SIZE: 1676 children are required to detect a decrease in the combined outcome of death or cerebral palsy, from 9.6% with placebo to 5.4% with magnesium sulphate (two-sided alpha 0.05, 80% power, 5% loss to follow up, design effect 1.2). DISCUSSION: Given the magnitude of the protective effect in the systematic review, the ongoing uncertainty about benefits at later gestational ages, the serious health and cost consequences of cerebral palsy for the child, family and society, a trial of magnesium sulphate for women at risk of preterm birth between 30 to 34 weeks’ gestation is both important and relevant for clinical practice globally. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry - ACTRN12611000491965Caroline A. Crowther, Philippa F. Middleton, Dominic Wilkinson, Pat Ashwood and Ross Haslam for the MAGENTA Study Grou

Public Understanding and Knowledge of Rip Currents and Beach Safety

Rip currents present a severe hazard for water users on beaches and account for the greatest cause of lifeguard rescues worldwide. The physical dynamics of rip currents are well studied, and more recently, the social and behavioural science research surrounding human interaction of rip currents has been expanding, providing a social perspective and feeding into public education strategies. The aim of this study was to assess levels of public understanding of rip currents and beach safety on UK beaches. A questionnaire was undertaken (N = 407) during the summer of 2012 on four beaches. Beach users had a poor knowledge of rip currents (n = 263), but those who have been caught in a rip have a higher level of knowledge. Conversely, beach users had a good understanding of what the beach safety flags indicated (n = 314), and most people complied with this flag system (n = 339). In addition, people previously educated on rip currents had a higher knowledge, and lifeguards proved to be the most effective form of education. The study presents an insight into UK beach users’ knowledge of rip currents and provides more evidence with which to pilot a rip current education scheme within the UK

Canadian national surveys on pandemic influenza preparations: pre-pandemic and peri-pandemic findings

BACKGROUND: Prior to the 2009 H1N1 Influenza pandemic, public health authorities in Canada and elsewhere prepared for the future outbreak, partly guided by an ethical framework developed within the Canadian Program of Research on Ethics in a Pandemic (CanPREP). We developed a telephone-based survey based on that framework, which was delivered across Canada in late 2008. In June, 2009, the WHO declared pandemic Phase 6 status and from the subsequent October (2009) until May 2010, the CanPREP team fielded a second (revised) survey, collecting another 1,000 opinions from Canadians during a period of pre-pandemic anticipation and peri-pandemic experience. METHODS: Surveys were administered by telephone with random sampling achieved via random digit dialing. Eligible participants were adults, 18 years or older, with per province stratification approximating provincial percentages of national population. Descriptive results were tabulated and logistic regression analyses used to assess whether demographic factors were significantly associated with outcomes, and to identify divergences (between the pre-pandemic and intra-pandemic surveys). RESULTS: N = 1,029 interviews were completed from 1,986 households, yielding a gross response rate of 52% (AAPOR Standard Definition 3). Over 90% of subjects indicated the most important goal of pandemic influenza preparations was saving lives, with 41% indicating that saving lives solely in Canada was the highest priority and 50% indicating saving lives globally was the highest priority. About 90% of respondents supported the obligation of health care workers to report to work and face influenza pandemic risks excepting those with serious health conditions which that increased risks. Strong majorities favoured stocking adequate protective antiviral dosages for all Canadians (92%) and, if effective, influenza vaccinations (95%). Over 70% agreed Canada should provide international assistance to poorer countries for pandemic preparation, even if resources for Canadians were reduced. CONCLUSIONS: Results suggest Canadians trust public health officials to make difficult decisions, providing emphasis is maintained on reciprocity and respect for individual rights. Canadians also support international obligations to help poorer countries and associated efforts to save lives outside the country, even if intra-national efforts are reduced

A randomized, double-blind, placebo-controlled trial of coenzyme Q10 in Huntington disease

Objective: To test the hypothesis that chronic treatment of early-stage Huntington disease (HD) with high-dose coenzyme Q10 (CoQ) will slow the progressive functional decline of HD. Methods: We performed a multicenter randomized, double-blind, placebo-controlled trial. Patients with early-stage HD (n = 609) were enrolled at 48 sites in the United States, Canada, and Australia from 2008 to 2012. Patients were randomized to receive either CoQ 2,400 mg/d or matching placebo, then followed for 60 months. The primary outcome variable was the change from baseline to month 60 in Total Functional Capacity score (for patients who survived) combined with time to death (for patients who died) analyzed using a joint-rank analysis approach. Results: An interim analysis for futility revealed a conditional power of <5% for the primary analysis, prompting premature conclusion in July 2014. No statistically significant differences were seen between treatment groups for the primary or secondary outcome measures. CoQ was generally safe and well-tolerated throughout the study. Conclusions: These data do not justify use of CoQ as a treatment to slow functional decline in HD

Genome-wide association study of endometrial cancer in E2C2

Endometrial cancer (EC), a neoplasm of the uterine epithelial lining, is the most common gynecological malignancy in developed countries and the fourth most common cancer among US women. Women with a family history of EC have an increased risk for the disease, suggesting that inherited genetic factors play a role. We conducted a two-stage genome-wide association study of Type I EC. Stage 1 included 5,472 women (2,695 cases and 2,777 controls) of European ancestry from seven studies. We selected independent single-nucleotide polymorphisms (SNPs) that displayed the most significant associations with EC in Stage 1 for replication among 17,948 women (4,382 cases and 13,566 controls) in a multiethnic population (African America, Asian, Latina, Hawaiian and European ancestry), from nine studies. Although no novel variants reached genome-wide significance, we replicated previously identified associations with genetic markers near the HNF1B locus. Our findings suggest that larger studies with specific tumor classification are necessary to identify novel genetic polymorphisms associated with EC susceptibility. Electronic supplementary material The online version of this article (doi:10.1007/s00439-013-1369-1) contains supplementary material, which is available to authorized users

Charged-to-neutral correlation at forward rapidity in Au+Au collisions at sNN\sqrt{s_{NN}}=200 GeV

Event-by-event fluctuations of the ratio of inclusive charged to photon multiplicities at forward rapidity in Au+Au collision at $\sqrt{s_{NN}}$=200 GeV have been studied. Dominant contribution to such fluctuations is expected to come from correlated production of charged and neutral pions. We search for evidences of dynamical fluctuations of different physical origins. Observables constructed out of moments of multiplicities are used as measures of fluctuations. Mixed events and model calculations are used as baselines. Results are compared to the dynamical net-charge fluctuations measured in the same acceptance. A non-zero statistically significant signal of dynamical fluctuations is observed in excess to the model prediction when charged particles and photons are measured in the same acceptance. We find that, unlike dynamical net-charge fluctuation, charge-neutral fluctuation is not dominated by correlation due to particle decay. Results are compared to the expectations based on the generic production mechanism of pions due to isospin symmetry, for which no significant (<1%) deviation is observed.Comment: 14 pages, 6 figure

The Relative Value of Measures of Omega-3 Index, Perceived Stress, Cortisol and Sleep Time in Identifying Depression Among a Cohort of Australian Adolescents

Objective: To assess the relative prognostic value of 11 variables including, omega-3, perceived stress, cortisol and sleep duration, in predicting adolescent depression. Design, Setting and Participants: A cross-sectional study of 444 healthy adolescents aged 16-18 years, from 10 schools within the Northern Sydney and Central Coast regions of New South Wales, Australia. Participants provided blood and saliva samples and completed questionnaires. Statistical classification methods were used to model the relationships between the predictors and depression. Main Outcome Measures: relative predictive value of each variable in correctly classifying depression. Results: 6% of boys and 9% of girls were categorised as experiencing severe to extremely severe depression. 4% of boys and 10% of girls were categorised as experiencing severe to extremely severe stress. The mean AM:PM cortisol for boys, 22±101, was higher than that of girls, 11±10. The average omega-3 index for boys, 10.5±3.7, was also higher than that of girls, 7.7±2.6. The average sleep duration of 7.8±1.1 hrs showed no gender differences. The best classification model identified perceived stress as the most significant predictor of depression followed by BMI and omega-3 index. Cortisol ratio was a significant discriminator for boys but not girls. When stress was excluded, shorter sleep duration became a significant discriminator in both boys and girls with waist to hip ratio providing further discrimination in girls only. Conclusion: The strongest predictor of depression in adolescents was perceived stress followed by higher BMI and lower omega-3 levels. These findings provide a rational basis for establishing program priorities for the prevention and treatment of adolescent depression