Five years of denosumab exposure in women with postmenopausal osteoporosis: results from the first two years of the FREEDOM extension.

The 3-year FREEDOM trial assessed the efficacy and safety of 60 mg denosumab every 6 months for the treatment of postmenopausal women with osteoporosis. Participants who completed the FREEDOM trial were eligible to enter an extension to continue the evaluation of denosumab efficacy and safety for up to 10 years. For the extension results presented here, women from the FREEDOM denosumab group had 2 more years of denosumab treatment (long-term group) and those from the FREEDOM placebo group had 2 years of denosumab exposure (cross-over group). We report results for bone turnover markers (BTMs), bone mineral density (BMD), fracture rates, and safety. A total of 4550 women enrolled in the extension (2343 long-term; 2207 cross-over). Reductions in BTMs were maintained (long-term group) or occurred rapidly (cross-over group) following denosumab administration. In the long-term group, lumbar spine and total hip BMD increased further, resulting in 5-year gains of 13.7% and 7.0%, respectively. In the cross-over group, BMD increased at the lumbar spine (7.7%) and total hip (4.0%) during the 2-year denosumab treatment. Yearly fracture incidences for both groups were below rates observed in the FREEDOM placebo group and below rates projected for a "virtual untreated twin" cohort. Adverse events did not increase with long-term denosumab administration. Two adverse events in the cross-over group were adjudicated as consistent with osteonecrosis of the jaw. Five-year denosumab treatment of women with postmenopausal osteoporosis maintained BTM reduction and increased BMD, and was associated with low fracture rates and a favorable risk/benefit profile.

Dix ans de revue de la littérature en médecine interne générale--un premier bilan [Ten years of literature review in general internal medicine--a first assessment].

A group of family physicians in an outpatient clinic in Switzerland prospectively followed scientific literature for ten years. What to remember among the numerous articles retrieved and which paper really changed our practice? If many readings are quickly forgotten, some of them marked our minds and changed our habits. This article is a summary of our efforts to keep the essential tools in clinical practice.

First building of Orange Union High School, Orange, California, now Wilkinson Hall, Chapman University

Orange Union High School, located at 333 N. Glassell Street, Orange, California, 1905. Constructed in 1905 and designed by local architect, C.B. Bradshaw, image shows main building, now called Wilkinson Hall, which moved north prior to 1921. Acquired in 1954 and currently operated by Chapman University; it was renamed Wilkinson Hall in honor of J. E. Wilkinson, a former trustee, chairman of the board, and acting president. View shows front and south elevations across North Glassell Street.

The role of parental investments for cognitive and noncognitive skill formation : evidence for the first 11 years of life. 'El papel de la influencia de los padres en el desarrollo cognitivo y la formación de habilidades cognitivas : evidencias de los primeros 11 años de vida'.

Resumen basado en el de la publicación

The first five years of the EU Impact Assessment system: a risk economics perspective on gaps between rationale and practice

In 2003 the European Commission started using Impact Assessment (IA) as the main empirical basis for its major policy proposals. The aim was to systematically assess ex ante the economic, social and environmental impacts of EU policy proposals. In parallel, research proliferated in search for theoretical grounds for IAs and in an attempt to evaluate empirically the performance of the first sets of IAs produced by the European Commission. This paper combines conceptual and evaluative studies carried out in the first five years of EU IAs. It concludes that the great discrepancy between rationale and practice calls for a different theoretical focus and a higher emphasis on evaluating empirically crucial risk economics aspects of IAs, such as the value of statistical life, price of carbon, the integration of macroeconomic modelling and scenario analysis.

A modest start, but a steady rise in research use : A longitudinal study of nurses during the first five years in professional life

Background: Newly graduated nurses are faced with a challenging work environment that may impede theirability to provide evidence-based practice. However, little is known about the trajectory of registered nurses’ use ofresearch during the first years of professional life. Thus, the aim of the current study was to prospectively examinethe extent of nurses’ use of research during the first five years after undergraduate education and specifically assesschanges over time.Method: Survey data from a prospective cohort of 1,501 Swedish newly graduated nurses within the nationalLANE study (Longitudinal Analyses of Nursing Education and Entry in Worklife) were used to investigate perceiveduse of research over the first five years as a nurse. The dependent variables consisted of three single itemsassessing instrumental, conceptual, and persuasive research use, where the nurses rated their use on a five-pointscale, from ‘never’ (1) to ‘on almost every shift’ (5). These data were collected annually and analyzed bothdescriptively and by longitudinal growth curve analysis.Results: Instrumental use of research was most frequently reported, closely followed by conceptual use, withpersuasive use occurring to a considerably lower extent. The development over time showed a substantial generalupward trend, which was most apparent for conceptual use, increasing from a mean of 2.6 at year one to 3.6 atyear five (unstandardized slope +0.25). However, the descriptive findings indicated that the increase started onlyafter the second year. Instrumental use had a year one mean of 2.8 and a year five mean of 3.5 (unstandardizedslope +0.19), and persuasive use showed a year one mean of 1.7 and a year five mean of 2.0 (unstandardized slope+0.09).Conclusion: There was a clear trend of increasing research use by nurses during their first five years of practice.The level of the initial ratings also indicated the level of research use in subsequent years. However, it took morethan two years of professional development before this increase ‘kicked in.’ These findings support previousresearch claiming that newly graduated nurses go through a ‘transition shock,’ reducing their ability to useresearch findings in clinical work.

Diurnal variation in oral temperature, sleepiness and performance of high school girls

Evaluation of rhythmic fluctuations cf physical and mental variables should be of special significance for the understanding of students' performance and setting the schedules of school activities. The present study investigated the pattern of diurnal variation in oral temperature, sleepiness and performance of a group of adolescents undergoing a daytime school schedule. Eighteen girls (mean age 16 years-old), who attended the same class from 0715h to 1645h, were tested on seven days. They measured their oral temperature, quantified their sleepiness level by means of a visual analogue scale, and completed the following tests: letter cancellation test, addition test, and a simple motor task. One-way ANOVA statistics for repeated measures was used in order to verify the effect of test time on oral temperature,sleepiness and performance. Possible correlations between the level of sleepiness and performance were investigated by means of Spearman rank correlation. The results revealed significant time of day effect cn all variables, except for the number of addition errors. Oral temperature values showed an increase from morning to afternoon. Letter cancellation, motor task and addition scores increased from early morning to late afternoon, showing rapid fluctuations throughout the day. Sleepiness level was negatively correlated with letter cancellation scores during the first three tests of the day. In agreement with other work, the diurnal variation of oral temperature, letter cancellation and addition test showed an improvement as the day progressed. Sleepiness, on the other hand, decreased throughout the day, with the highest level associated with the first test of the day, suggesting a circadian pattern of variation rather than a cumulative effect due to school activities.

Oral live attenuated human rotavirus vaccine (RotarixTM) offers sustained high protection against severe G9P[8] rotavirus gastroenteritis during the first two years of life in Brazilian children

In a large Phase III trial conducted in 10 Latin American countries, the safety and efficacy of the live attenuated monovalent rotavirus vaccine RIX4414 was evaluated in 15,183 healthy infants followed up during the first two years of life. Belém was the only site in Brazil included in this multicentre trial. The study in Belém included a subset of 653 infants who were followed up until 24 months of age for protection against severe rotavirus gastroenteritis. These subjects were randomly assigned in a 1:1 ratio to receive two doses of vaccine (n = 328) or two doses of placebo (n = 325) at approximately two and four months of age. Of the 653 enrolled infants, 23 dropped out during the study period. For the combined two-year period, the efficacy of RIX4414 was 72.3% [95% confidence interval (CI) 37.5-89.1%] against severe rotavirus-related gastroenteritis, reaching a protection rate of 81.8% (95% CI 36.4-96.6%) against circulating wild-type G9 rotavirus strains. It is concluded that two doses of RIX4414 are highly efficacious against severe rotavirus gastroenteritis in Belém during the first two years of life and provide high protection against the worldwide emergence and spread of G9P[8] strains.