Applying results from clinical trials: tranexamic acid in trauma patients.

This paper considers how results from clinical trials should be applied in the care of patients, using the results of the Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage (CRASH-2) trial of tranexamic acid in bleeding trauma patients as a case study. We explain why an understanding of the mechanisms of action of the trial treatment, and insight into the factors that might be relevant to this mechanism, is critical in order to properly apply (generalise) trial results and why it is not necessary that the trial population is representative of the population in which the medicine will be used. We explain why cause (mechanism)-specific mortality is more generalizable than all-cause mortality and why the risk ratio is the generalizable measure of the effect of the treatment. Overall, we argue that a biological insight into how the treatment works is more relevant when applying research results to patient care than the application of statistical reasoning

Mechanism of action of tranexamic acid in bleeding trauma patients: an exploratory analysis of data from the CRASH-2 trial.

INTRODUCTION: To investigate the mechanism of action of tranexamic acid (TXA) in bleeding trauma patients, we examined the timing of its effect on mortality. We hypothesised that if TXA reduces mortality by decreasing blood loss, its effect should be greatest on the day of the injury when bleeding is most profuse. However, if TXA reduces mortality via an anti-inflammatory mechanism its effect should be greater over the subsequent days. METHODS: Exploratory analysis, including per-protocol analyses, of data from the CRASH-2 trial, a randomised placebo controlled trial of the effect of TXA on mortality in 20,211 trauma patients with, or at risk of, significant bleeding. We examined hazard ratios (HR) and 95% confidence intervals for all-cause mortality, deaths due to bleeding and non-bleeding deaths, according to the day since injury. The CRASH-2 trial is registered as ISRCTN86750102 and ClinicalTrials.gov NCT00375258. RESULTS: The effect of TXA on mortality is greatest for deaths occurring on the day of the injury (HR all-cause mortality = 0.83, 0.73 to 0.93). This survival benefit is only evident in patients in whom treatment is initiated within 3 hours of their injury (HR ≤ 3 hours = 0.78, 0.68 to 0.90; HR > 3 hours = 1.02, 0.76 to 1.36). Initiation of TXA treatment within 3 hours of injury reduced the hazard of death due to bleeding on the day of the injury by 28% (HR = 0.72, 0.60 to 0.86). TXA treatment initiated beyond 3 hours of injury appeared to increase the hazard of death due to bleeding, although the estimates were imprecise. CONCLUSIONS: Early administration of tranexamic acid appears to reduce mortality primarily by preventing exsanguination on the day of the injury

Identifying signals of potentially harmful medications in pregnancy: use of the double false discovery rate method to adjust for multiple testing.

AIMS: Surveillance of medication use in pregnancy is essential to identify associations between first trimester medications and congenital anomalies (CAs). Medications in the same Anatomical Therapeutic Chemical classes may have similar effects. We aimed to use this information to improve the detection of potential teratogens in CA surveillance data. METHODS: Data on 15 058 malformed fetuses with first trimester medication exposures from 1995-2011 were available from EUROmediCAT, a network of European CA registries. For each medication-CA combination, the proportion of the CA in fetuses with the medication was compared to the proportion of the CA in all other fetuses in the dataset. The Australian classification system was used to identify high-risk medications in order to compare two methods of controlling the false discovery rate (FDR): a single FDR applied across all combinations, and a double FDR incorporating groupings of medications. RESULTS: There were 28 765 potential combinations (523 medications × 55 CAs) for analysis. An FDR cut-off of 50% resulted in a reasonable effective workload, for which single FDR gave rise to eight medication signals (three high-risk medications) and double FDR 50% identified 16 signals (six high-risk). Over a range of FDR cut-offs, double FDR identified more high-risk medications as signals, for comparable effective workloads. CONCLUSIONS: The double FDR method appears to improve the detection of potential teratogens in comparison to the single FDR, while maintaining a low risk of false positives. Use of double FDR is recommended in routine signal detection analyses of CA data

Differences in stroke and ischemic heart disease mortality by occupation and industry among Japanese working-aged men

Occupation- and industry-based risks for stroke and ischemic heart disease may vary among Japanese working-aged men. We examined the differences in mortality rates between stroke and ischemic heart disease by occupation and industry among employed Japanese men aged 25–59 years. In 2010, we obtained occupation- and industry-specific vital statistics data from the Japanese Ministry of Health, Labour, and Welfare dataset. We analyzed data for Japanese men who were aged 25–59 years in 2010, grouped in 5-year age intervals. We estimated the mortality rates of stroke and ischemic heart disease in each age group for occupation and industry categories as defined in the national census. We did not have detailed individual-level variables. We used the number of employees in 2010 as the denominator and the number of events as the numerator, assuming a Poisson distribution. We conducted separate regression models to estimate the incident relative risk for stroke and ischemic heart disease for each category compared with the reference categories “sales” (occupation) and “wholesale and retail” (industry). When compared with the reference groups, we found that occupations and industries with a relatively higher risk of stroke and ischemic heart disease were: service, administrative and managerial, agriculture and fisheries, construction and mining, electricity and gas, transport, and professional and engineering. This suggests there are occupation- and industry-based mortality risk differences of stroke and ischemic heart disease for Japanese working-aged men. These differences in risk might be explained to factors associated with specific occupations or industries, such as lifestyles or work styles, which should be explored in further research. The mortality risk differences of stroke and ischemic heart disease shown in the present study may reflect an excessive risk of Karoshi (death from overwork)

El fomento de la creatividad a través del teatro de luz negra y el teatro de sombras en educación infantil

El presente Trabajo Fin de Grado tiene como principal objetivo aportar dos propuestas de carácter innovador y motivador, como son el teatro de luz negra y el teatro de sombras, para favorecer el desarrollo de la creatividad en los niños y niñas de Educación Infantil. Para ello, resulta necesario ofrecer al alumnado un ambiente y unos estímulos que propicien la experimentación directa con su cuerpo y otros materiales, el juego y la expresión. Asimismo, este trabajo parte de una experiencia desarrollada tanto a nivel teórico como práctico, con alumnos de edades comprendidas entre tres y seis años.Grado en Educación Infanti

Effect of changes in moderate or vigorous physical activity on changes in health-related quality of life of elderly British women over seven years.

PURPOSE: This study investigates the effect of changes in moderate or vigorous physical activity (MVPA) on trajectories in health-related quality of life (HR-QoL) over 7 years in British elderly women. METHODS: A total of 1,926 women from the British Women's Heart and Health Study with information on MVPA and HR-QoL [measured using Euro quality of life 5 dimension (EQ-5D)] at baseline and at 7 years of follow-up were included in the analysis. Baseline and 7-year follow-up MVPA values were categorised into 3 groups, generating 9 categories of change in MVPA. Logistic regression was used to obtain odds ratios (ORs) of maintaining or improving HR-QoL according to different patterns of change in MVPA level. RESULTS: Women who remained inactive over the 7 years of follow-up had the largest reduction in their EQ-5D scores. Compared to these women, women that increased their MPVA level from "inactive" to "low" or to "moderate-high" were more likely to maintain or improve their HR-QoL over 7 years (ORs 1.65 or 2.70, respectively, p value for trend <0.001). After adjustment for baseline EQ-5D score and a wide range of potential confounders, results remained largely unchanged, though precision of the estimates generally decreased. CONCLUSIONS: Our findings suggest that relatively regular MVPA, even taken up later in life, can help older women prevent a decline in HR-QoL and even improve their enjoyment of life

Detection of the technical-tactical pattern of the scoring actions in judo in the men’s category of -73 kg

The scoring actions determine the judoka winner in a combat. The scientific community has studied them, but these studies are especially descriptive. To this end, the purpose of this study is to discover and analyse the technical-tactical patterns of the scoring actions in judo combat. Ninety-one scoring actions were analysed (−73 kg males, Judo World Championship 2017) using different commonly used analysis techniques within the observational methodology: traditional statistical analysis, T-Patterns detection, sequential analysis delays and polar coordinates analysis. The tendency of scoring with leg and arm projections prevails (seoi-otoshi, ouchi-gari, tai-otoshi and uchi-mata). The more efficient technique on the ground was yoko-shiho-gatame. The waza-ari is three times more frequent than the ippon. The actions score mainly during the final stages of combat. The judokas with favourable scores score more points through immobilisations, with scores equal to leg techniques and with scores against sacrificial techniques. It is important to conduct the combat’s initiative because in most the actions, the judoka that scores has no penalties and the one who does not score does. A common pattern is achieving a waza-ari with a direct leg attack technique or a static arm technique

The access to broadband services as a strategy to retain population in the depopulated countryside in Spain

The aim of this paper is to analyze at what extent the connectivity of small localities is a determinant of their demography. Specifically, we pay attention to three factors: the evolution of the population; the distance, measured both in kilometres and travel time, to the province capital, the usual city where the largest set of services is available; and finally, the coverage of different kinds of broadband services (from ADSL or 3.5 G to the fastest ones FTTH) in rural areas. An econometric model was estimated where the dependent variable captures the increase of inhabitants along 2017–2020 of the 5955 Spanish municipalities with a population between 101 and 10,000 inhabitants (73.3 % of all municipalities). The results point out to the following facts: digital connectivity of small localities is a determinant of their demography, whatever the technology used, but physical distance remains being a significant factor on the population growth (both if it is measured of physical distance or travelling time) to explain the population growth of each locality

Effect of changes in moderate or vigorous physical activity on changes in health-related quality of life of elderly British women over seven years.

PURPOSE: This study investigates the effect of changes in moderate or vigorous physical activity (MVPA) on trajectories in health-related quality of life (HR-QoL) over 7 years in British elderly women. METHODS: A total of 1,926 women from the British Women's Heart and Health Study with information on MVPA and HR-QoL [measured using Euro quality of life 5 dimension (EQ-5D)] at baseline and at 7 years of follow-up were included in the analysis. Baseline and 7-year follow-up MVPA values were categorised into 3 groups, generating 9 categories of change in MVPA. Logistic regression was used to obtain odds ratios (ORs) of maintaining or improving HR-QoL according to different patterns of change in MVPA level. RESULTS: Women who remained inactive over the 7 years of follow-up had the largest reduction in their EQ-5D scores. Compared to these women, women that increased their MPVA level from "inactive" to "low" or to "moderate-high" were more likely to maintain or improve their HR-QoL over 7 years (ORs 1.65 or 2.70, respectively, p value for trend <0.001). After adjustment for baseline EQ-5D score and a wide range of potential confounders, results remained largely unchanged, though precision of the estimates generally decreased. CONCLUSIONS: Our findings suggest that relatively regular MVPA, even taken up later in life, can help older women prevent a decline in HR-QoL and even improve their enjoyment of life

Práctica de los negocios correspondientes a la sala de Hijos-Dalgo de la Real Chancillería de Valladolid ...

Copia digital. Valladolid : Junta de Castilla y León. Consejería de Cultura y Turismo, 2009-201