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

First anatomical network analysis of fore- and hindlimb musculoskeletal modularity in bonobos, common chimpanzees, and humans

Studies of morphological integration and modularity, and of anatomical complexity in human evolution typically focus on skeletal tissues. Here we provide the first network analysis of the musculoskeletal anatomy of both the fore- and hindlimbs of the two species of chimpanzee and humans. Contra long-accepted ideas, network analysis reveals that the hindlimb displays a pattern opposite to that of the forelimb: Pan big toe is typically seen as more independently mobile, but humans are actually the ones that have a separate module exclusively related to its movements. Different fore- vs hindlimb patterns are also seen for anatomical network complexity (i.e., complexity in the arrangement of bones and muscles). For instance, the human hindlimb is as complex as that of chimpanzees but the human forelimb is less complex than in Pan. Importantly, in contrast to the analysis of morphological integration using morphometric approaches, network analyses do not support the prediction that forelimb and hindlimb are more dissimilar in species with functionally divergent limbs such as bipedal humans

Composite Fermion Metals from Dyon Black Holes and S-Duality

We propose that string theory in the background of dyon black holes in four-dimensional anti-de Sitter spacetime is holographic dual to conformally invariant composite Dirac fermion metal. By utilizing S-duality map, we show that thermodynamic and transport properties of the black hole match with those of composite fermion metal, exhibiting Fermi liquid-like. Built upon Dirac-Schwinger-Zwanziger quantization condition, we argue that turning on magnetic charges to electric black hole along the orbit of Gamma(2) subgroup of SL(2,Z) is equivalent to attaching even unit of statistical flux quanta to constituent fermions. Being at metallic point, the statistical magnetic flux is interlocked to the background magnetic field. We find supporting evidences for proposed holographic duality from study of internal energy of black hole and probe bulk fermion motion in black hole background. They show good agreement with ground-state energy of composite fermion metal in Thomas-Fermi approximation and cyclotron motion of a constituent or composite fermion excitation near Fermi-point.Comment: 30 pages, v2. 1 figure added, minor typos corrected; v3. revised version to be published in JHE

Insulin-like growth factor 1 has multisystem effects on foetal and preterm infant development.

UNLABELLED: Poor postnatal growth after preterm birth does not match the normal rapid growth in utero and is associated with preterm morbidities. Insulin-like growth factor 1 (IGF-1) axis is the major hormonal mediator of growth in utero, and levels of IGF-1 are often very low after preterm birth. We reviewed the role of IGF-1 in foetal development and the corresponding preterm perinatal period to highlight the potential clinical importance of IGF-1 deficiency in preterm morbidities. CONCLUSION: There is a rationale for clinical trials to evaluate the potential benefits of IGF-1 replacement in very preterm infants.This work was supported by a European Commission FP7 project 305485 PREVENT-ROP grant to all of the authors.This is the final version of the article. It first appeared from Wiley via https://doi.org/10.1111/apa.1335

Development, implementation, and pilot study of a sentinel network ("The Watchtowers") for monitoring emergency primary health care activity in Norway

<p>Abstract</p> <p>Background</p> <p>In Norway there is a shortage of valid health activity statistics from the primary care out-of-hours services and the pre-hospital emergency health care system. There is little systematic information available because data registration is lacking or is only recorded periodically, and definitions of variables are not consistent.</p> <p>Method</p> <p>A representative sample of Norwegian municipalities and out-of-hours districts was contracted to establish a sentinel network, "The Watchtowers", and procedures were developed for collecting continuous data from out-of-hours services. All contacts, either per telephone or direct attendance, are recorded during day and night. The variables are registered in a computer program developed by the National Centre for Emergency Primary Health Care, and sent by email in Excel-file format to the Centre on a monthly basis.</p> <p>Results</p> <p>The selection process yielded a group of 18 municipalities, with a fair degree of representativeness for Norwegian municipalities as a whole. The sample has 212,921 inhabitants, which constitutes 4.6% of the total Norwegian population. During a pilot period lasting three months the Watchtowers recorded all individual contacts. The procedures for registration, submitting and checking data worked satisfactorily. There was little data missing, and during the last three months of 2006 a total of 23,346 contacts were registered.</p> <p>Conclusion</p> <p>We have been able to establish a sentinel network with a fair degree of representativeness for Norwegian out-of-hours districts and municipalities. The data collected reflect national activities from casualty clinics in Norway. Such data are useful for both research and system improvements.</p

Involvement in emergency situations by primary care doctors on-call in Norway - a prospective population-based observational study

<p>Abstract</p> <p>Background</p> <p>Primary care doctors on-call in the emergency primary health care services in Norway are, together with the ambulances, the primary resources for handling emergencies outside hospitals. There is a lack of reliable data for Norway on how often the primary care doctors are alerted and on their responses in the most urgent emergency cases. The aim of this study was to investigate how doctors on-call are involved in red responses (highest priority), using three different emergency medical communication centres (EMCC) as catchment area for a prospective population-based study.</p> <p>Methods</p> <p>In the period from October to December 2007 three dispatch centres covering approximately 816 000 inhabitants prospectively recorded all acute emergency cases. Ambulance records, air ambulance records and records from the doctors on-call were collected. NACA score was used to define the severity of the emergencies.</p> <p>Results</p> <p>5 105 cases were classified as red responses during the period. We have complete basic recordings (AMIS forms) from all and resaved ambulance records, air ambulance records and records from doctors on-call in 89% of the cases. Ambulances were alerted in 96% and doctors on-call in 47% of the cases, but there were large differences between the three EMCCs. Doctors on-call responded with call-out in 42% of the alerted cases. 28% of all patients were taken to a casualty clinic, 46% were admitted to hospital by a doctor and 24% were taken directly to hospital by ambulances. In total, primary care doctors on-call took active part in 42% of all red response cases, and together with GPs' daytime activity the primary health care services were involved in 50% of the cases. 29% of the cases were classified as life-threatening. Call-out by doctors on-call were found to be more frequent in life-threatening situations compared with not life-threatening situations.</p> <p>Conclusion</p> <p>Doctors on-call and GPs on daytime were involved in half of all red responses. There were large differences between the EMCCs in the frequency of doctors alerted. The inhabitants in the three EMMCs were thus offered different levels of professional competency in emergency situations outside hospitals.</p

Sentinel monitoring of activity of out-of-hours services in Norway in 2007: an observational study

<p>Abstract</p> <p>Background</p> <p>In Norway, no valid activity statistics from the primary health care out-of-hours services or the pre-hospital emergency health care system have previously been available.</p> <p>Methods</p> <p>The National Centre for Emergency Primary Health Care has initiated an enterprise called "The Watchtowers" which consists of a representative sample of seven casualty clinics covering 18 Norwegian municipalities. The purpose of the project is to provide routine information over several years, which will enable monitoring, evaluation and comparison of the activities in the out-of-hours services. This paper presents data from 2007, the first full calendar year for the Watchtowers, analyzes some differences in user patterns for the seven casualty clinics involved, and estimates national figures for the use of casualty clinics and out-of-hours services in Norway.</p> <p>Results</p> <p>A total of 85 288 contacts were recorded during 2007 [399 per 1 000 inhabitants] of which 64 846 contacts were considered non-urgent [76.6%]. There were 53 467 consultations by a doctor [250 per 1 000], 8 073 telephone consultations by doctor [38 per 1 000], 2 783 home visits and call-outs by doctor [13 per 1000] and 20 502 contacts managed by nurses on their own [96 per 1000]. The most common mode of contact was by telephone. Women, young children and elderly had the highest rates of contact.</p> <p>Conclusion</p> <p>Norway has a high rate of contacts to the out-of-hours services compared with some other countries with available data. Valid national figures and future research of these services are important both for local services and policy makers.</p

Chromatic Illumination Discrimination Ability Reveals that Human Colour Constancy Is Optimised for Blue Daylight Illuminations

The phenomenon of colour constancy in human visual perception keeps surface colours constant, despite changes in their reflected light due to changing illumination. Although colour constancy has evolved under a constrained subset of illuminations, it is unknown whether its underlying mechanisms, thought to involve multiple components from retina to cortex, are optimised for particular environmental variations. Here we demonstrate a new method for investigating colour constancy using illumination matching in real scenes which, unlike previous methods using surface matching and simulated scenes, allows testing of multiple, real illuminations. We use real scenes consisting of solid familiar or unfamiliar objects against uniform or variegated backgrounds and compare discrimination performance for typical illuminations from the daylight chromaticity locus (approximately blue-yellow) and atypical spectra from an orthogonal locus (approximately red-green, at correlated colour temperature 6700 K), all produced in real time by a 10-channel LED illuminator. We find that discrimination of illumination changes is poorer along the daylight locus than the atypical locus, and is poorest particularly for bluer illumination changes, demonstrating conversely that surface colour constancy is best for blue daylight illuminations. Illumination discrimination is also enhanced, and therefore colour constancy diminished, for uniform backgrounds, irrespective of the object type. These results are not explained by statistical properties of the scene signal changes at the retinal level. We conclude that high-level mechanisms of colour constancy are biased for the blue daylight illuminations and variegated backgrounds to which the human visual system has typically been exposed