Adverse drug reactions from psychotropic medicines in the paediatric population: analysis of reports to the Danish Medicines Agency over a decade

<p>Abstract</p> <p>Background</p> <p>The prescribing of psychotropic medicines for the paediatric population is rapidly increasing. In attempts to curb the use of psychotropic medicine in the paediatric population, regulatory authorities have issued various warnings about risks associated with use of these products in childhood. Little evidence has been reported about the adverse drug reactions (ADRs) of these medicines in practice. As spontaneous reports are the main source for information about previously unknown ADRs, we analysed data submitted to a national ADR database. The objective was to characterise ADRs reported for psychotropic medicines in the Danish paediatric population over a decade.</p> <p>Findings</p> <p>All spontaneous ADR reports from 1998 to 2007 for children from birth to 17 years of age were included. The unit of analysis was one ADR. We analysed the distribution of ADRs per year, seriousness, age and gender of the child, suspected medicine and type of reported ADR. A total of 429 ADRs were reported for psychotropic medicines and 56% of these were classified as serious. Almost 20% of psychotropic ADRs were reported for children from birth up to 2 years of age and one half of ADRs were reported in adolescents, especially for antidepressants and psychostimulants. Approximately 60% of ADRs were reported for boys. Forty percent of all ADRs were from the category 'nervous and psychiatric disorders'. All but one ADR reported for children below two years were serious and two of these were fatal. A number of serious ADRs reported in children from birth up to 2 years of age were presumably caused by mothers' use of psychotropic medicines during pregnancy.</p> <p>Conclusion</p> <p>The high number of serious ADRs reported for psychotropic medicines in the paediatric population should be a concern for health care professionals and physicians. Considering the higher number of birth defects being reported greater care has to be given while prescribing these drugs for pregnant women.</p

How Small Nations Fare in the Global War on Talent: The Case of Denmark

In light of the looming shortage of skilled professionals, companies are increasingly eager to recruit highly educated and competent employees, regardless of country of origin and nationality, in order to remain globally competitive. This paper seeks to shed light on how nations compete for the same talent pool by presenting the findings of two related studies on whether (a) Chinese students who are studying in Denmark choose to return to work in China; and (b) Danish students in Denmark are willing to work for Chinese companies in Denmark and/or China. Despite its population of 1.3 billion, China has a critical shortage of managerial talent. The vast majority of Chinese students in Denmark do not plan to remain in Denmark upon completion of their education, while many Danish students are receptive to working for Chinese companies, albeit more so in Denmark than in China. The findings of this study have implications on the plight of smaller nations, such as Denmark, in attracting and retaining human talent. These findings also have implications for small-sized companies in their competition with large firms for human talent

Associations between biopsychosocial factors and chronic upper limb pain among slaughterhouse workers:cross sectional study

BACKGROUND: Knowledge of factors associated with chronic pain is necessary for preventive strategies. The present study investigates biopsychosocial differences, with specific focus on rate of force development (RFD) and work ability, between workers with and without chronic upper limb pain. METHODS: Eighty-two male slaughterhouse workers, 49 with chronic upper limb pain and 33 pain-free controls participated in the study. Maximal muscle strength, RFD, and muscle activity was determined from fast and forceful maximal voluntary contractions for the shoulder and hand. Participants filled out a questionnaire on work ability (work ability index), work disability (Work module of DASH questionnaire), fear avoidance, and self-rated health. Additionally, pressure pain threshold (PPT) was measured in muscles of the arm, shoulder and lower leg. RESULTS: Muscle strength and RFD (determined within time intervals of 30, 50, 100, and 200 ms relative to onset of contraction) was 28 % and 58–78 % lower, respectively, in workers with chronic pain compared with pain-free controls, and paralleled by reduced muscle activity (all p < 0.001). Workers with chronic pain had lower PPT of the arm, shoulder and lower leg (p < 0.01), and reported impaired work ability index score and general health along with higher work disability and fear avoidance compared with controls (all p < 0.0001). No differences were observed between the groups in regard to age, BMI, physical activity level, job position and duration of slaughterhouse work (all p > 0.4). CONCLUSIONS: Chronic upper limb pain was paralleled by reduced neuromuscular function of the shoulder and hand along with impaired work ability, work disability and general health. Future studies on chronic pain management at the workplace should carefully consider the biopsychosocial nature of pain when designing and implementing preventive strategies

Physical exercise at the workplace prevents deterioration of work ability among healthcare workers:cluster randomized controlled trial

BACKGROUND: Imbalance between individual resources and work demands can lead to musculoskeletal disorders and reduced work ability. The purpose of this study was to investigate the effect of workplace- versus home-based physical exercise on work ability among healthcare workers. METHODS: Two hundred female healthcare workers (Age: 42.0, BMI: 24.1, work ability index [WAI]: 43.1) from 18 departments at three Danish hospitals participated (Copenhagen, Denmark, Aug 2013—Jan 2014). Participants were randomly allocated at the cluster level to 10 weeks of: 1) workplace physical exercise (WORK) performed during working hours for 5x10 min per week and up to 5 group-based coaching sessions on motivation for regular physical exercise, or 2) home-based physical exercise (HOME) performed during leisure time for 5x10 min per week. Both groups received ergonomic counseling on patient handling and use of lifting aides. The main outcome measure was the change from baseline to 10-week follow-up in WAI. RESULTS: Significant group by time interaction was observed for WAI (p < 0.05). WAI at follow-up was 1.1 (0.3 to 1.8) higher in WORK compared with HOME corresponding to a small effect size (Cohens’d = 0.24). Within-group changes indicated that between-group differences were mainly caused by a reduction in WAI in HOME. Of the seven items of WAI, item 2 (work ability in relation to the demands of the job) and item 5 (sickness absence during the past year) were improved in WORK compared with HOME (P < 0.05). CONCLUSIONS: Performing physical exercise together with colleagues at the workplace prevents deterioration of work ability among female healthcare workers. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT01921764. Registered 10 August 2013

Distributions of nuclear fuel-reprocessing tracers in the Arctic Ocean: Indications of Russian river influence

Radionuclide sampling in 1986 and 1993 in the Canada Basin, and in 1993 in the Amundsen Basin and on the adjacent Laptev shelf, provides new insights into the origin, timing, pathways, and mechanisms for dispersal of non-fallout radioactive tracers in the Arctic Ocean. First, samples from the Beaufort Sea shelf, slope, and adjacent basin show a four-fold increase in 129I concentrations from 1986 to 1993. Second, anthropogenic non-fallout radionuclide concentrations in the Beaufort Sea increase with proximity to slope boundary currents. Third, there is evidence for riverine contributions of anthropogenic radionuclides to surface waters of the Amundsen Basin and the Laptev continental shelf. This evidence includes high surface water burdens of 237Np and 129I, with the maximum in anthropogenic 129I found in the least saline and most 18O-depleted waters, consistent with an origin in high-latitude runoff. Additionally, the 237Np/129I atom ratios in the Laptev Sea and Amundsen Basin in 1993 were significantly lower than observed elsewhere in the Arctic Ocean and can be reasonably explained by 129I added during transit of the Russian shelves. The 240Pu/239Pu ratios in the water column were mostly near 0.18, consistent both with stratospheric bomb fallout and with the discharged-weighted mean Sellafield ratio during 1966-1985. In the least saline water samples collected at the most shallow Laptev shelf station, however, the Pu ratios were lower, consistent with a non-European nuclear fuel reprocessing source. There are clear secondary maxima in 237Np and 129I near 1000 m in the Amundsen Basin, likely associated with the Barents Sea branch of Atlantic water. Finally, the 129I/salinity and 129I/δ18O relationships in the Amundsen and Canada Basins at middepths are indistinguishable, suggesting effective horizontal dispersion

Experimental Zika Virus Infection in the Pregnant Common Marmoset Induces Spontaneous Fetal Loss and Neurodevelopmental Abnormalities.

During its most recent outbreak across the Americas, Zika virus (ZIKV) was surprisingly shown to cause fetal loss and congenital malformations in acutely and chronically infected pregnant women. However, understanding the underlying pathogenesis of ZIKV congenital disease has been hampered by a lack of relevant in vivo experimental models. Here we present a candidate New World monkey model of ZIKV infection in pregnant marmosets that faithfully recapitulates human disease. ZIKV inoculation at the human-equivalent of early gestation caused an asymptomatic seroconversion, induction of type I/II interferon-associated genes and proinflammatory cytokines, and persistent viremia and viruria. Spontaneous pregnancy loss was observed 16-18 days post-infection, with extensive active placental viral replication and fetal neurocellular disorganization similar to that seen in humans. These findings underscore the key role of the placenta as a conduit for fetal infection, and demonstrate the utility of marmosets as a highly relevant model for studying congenital ZIKV disease and pregnancy loss

Multigenic lentiviral vectors for combined and tissue-specific expression of miRNA- and protein-based antiangiogenic factors.

Lentivirus-based gene delivery vectors carrying multiple gene cassettes are powerful tools in gene transfer studies and gene therapy, allowing coexpression of multiple therapeutic factors and, if desired, fluorescent reporters. Current strategies to express transgenes and microRNA (miRNA) clusters from a single vector have certain limitations that affect transgene expression levels and/or vector titers. In this study, we describe a novel vector design that facilitates combined expression of therapeutic RNA- and protein-based antiangiogenic factors as well as a fluorescent reporter from back-to-back RNApolII-driven expression cassettes. This configuration allows effective production of intron-embedded miRNAs that are released upon transduction of target cells. Exploiting such multigenic lentiviral vectors, we demonstrate robust miRNA-directed downregulation of vascular endothelial growth factor (VEGF) expression, leading to reduced angiogenesis, and parallel impairment of angiogenic pathways by codelivering the gene encoding pigment epithelium-derived factor (PEDF). Notably, subretinal injections of lentiviral vectors reveal efficient retinal pigment epithelium-specific gene expression driven by the VMD2 promoter, verifying that multigenic lentiviral vectors can be produced with high titers sufficient for in vivo applications. Altogether, our results suggest the potential applicability of combined miRNA- and protein-encoding lentiviral vectors in antiangiogenic gene therapy, including new combination therapies for amelioration of age-related macular degeneration