Physiologic Effects of Housing Rats in Metabolic Cages.

Currently, metabolic cages (MC) are the only way to achieve serial sampling of urine and feces in rodents. However, the use of this caging creates a dramatic change from an animal's usual microenvironment. Here we sought to examine the effect of MC on physiologic parameters that are stress-responsive in rats. We surgically implanted 8 male Wistar rats (weight, 150 to 175 g) with telemetric transmitters and allowed them to recover for at least 2 wk. At the beginning of the study, the rats were moved to conventional open-top cages, and telemetry recording was initiated. After 24 h, the rats were moved to MC or to another conventional cage and the recording continued for another 24 h. Finally, the rats were returned to their home cages, and telemetry recording was performed for a final 24 h. After 10 days, this process was then repeated, with MC and conventional assignments switched. During the 78-h monitoring period, we recorded heart rate, arterial blood pressure, locomotor activity, body weight, and food and water consumption. Heart rate and arterial blood pressure showed transient but significant changes. Locomotor activity during the dark phase was greatly decreased in MC compared with conventional cages, perhaps due to space constraints. In addition, when the rats were housed in MC, they showed a small but significant weight loss. Food consumption did not differ between housing environments, but water consumption was lower when rats were in MC. In conclusion, the housing of rats in MC for 24 h can elicit mild and reversible cardiovascular changes. This finding is consistent with European Directive 2010/63/EU, which considers short-term (less than 24 h) restraint in MC a procedure of mild severity.

Health care and societal costs of the management of children and adolescents with attention-deficit/hyperactivity disorder in Spain: a descriptive analysis.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition in childhood (5.3% to 7.1% worldwide prevalence), with substantial overall financial burden to children/adolescents, their families, and society. The aims of this study were to describe the clinical characteristics of children and adolescents with ADHD in Spain, estimate the associated direct/indirect costs of the disorder, and assess whether the characteristics and financial costs differed between children/adolescents adequately responding to currently available pharmacotherapies compared with children/adolescents for whom pharmacotherapies failed. METHODS: This was a multicenter, cross-sectional, descriptive analysis conducted in 15 health units representative of the overall Spanish population. Data on demographic characteristics, socio-occupational status, social relationships, clinical variables of the disease, and pharmacological and non-pharmacological treatments received were collected in 321 children and adolescents with ADHD. Direct and indirect costs were estimated over one year from both a health care system and a societal perspective. RESULTS: The estimated average cost of ADHD per year per child/adolescent was €5733 in 2012 prices; direct costs accounted for 60.2% of the total costs (€3450). Support from a psychologist/educational psychologist represented 45.2% of direct costs and 27.2% of total costs. Pharmacotherapy accounted for 25.8% of direct costs and 15.5% of total costs. Among indirect costs (€2283), 65.2% was due to caregiver expenses. The total annual costs were significantly higher for children/adolescents who responded poorly to pharmacological treatment (€7654 versus €5517; P = 0.024), the difference being mainly due to significantly higher direct costs, particularly with larger expenses for non-pharmacological treatment (P = 0.012). CONCLUSIONS: ADHD has a significant personal, familial, and financial impact on the Spanish health system and society. Successful pharmacological intervention was associated with lower overall expenses in the management of the disorder.

Consenso del GEITDAH sobre los trastornos de conducta en niños y adolescentes / GEITDAH consensus on conduct disorders in children and adolescents

El Grupo de Especial Interés en el Trastorno por Déficit de Atención/Hiperactividad (GEITDAH) presenta en este artículo un consenso de expertos de toda España sobre los trastornos de conducta en niños y adolescentes. A partir del trabajo inicial del equipo de la Unidad de Paidopsiquiatría del Hospital Quirón-Teknon de Barcelona, se han consensuado aspectos básicos que podrían ser el punto de partida para futuros consensos. Ha sido también objetivo prioritario del trabajo actualizar en los trastornos de conducta en niños y adolescentes los criterios del Manual diagnóstico y estadístico de los trastornos mentales, quinta edición, y su comorbilidad con el trastorno por déficit de atención/hiperactividad (AU)

In this paper, the Special Interest Group on Attention Deficit Hyperactivity Disorder (GEITDAH, from its name in Spanish) presents a consensus reached by experts from all over Spain on conduct disorders in children and adolescents. Following the initial work by the team at the Pedopsychiatry Unit at the Quirón-Teknon Hospital in Barcelona, agreements have been reached on a number of basic aspects that could be the starting point for future consensuses. A top priority aim of the work was also to update the criteria in the Diagnostic and statistical manual of mental disorders, fifth edition, for conduct disorders in children and adolescents, together with their comorbidity with attention deficit hyperactivity disorder (AU)

[GEITDAH consensus on conduct disorders in children and adolescents]. / Consenso del GEITDAH sobre los trastornos de conducta en niños y adolescentes.

In this paper, the Special Interest Group on Attention Deficit Hyperactivity Disorder (GEITDAH, from its name in Spanish) presents a consensus reached by experts from all over Spain on conduct disorders in children and adolescents. Following the initial work by the team at the Pedopsychiatry Unit at the Quiron-Teknon Hospital in Barcelona, agreements have been reached on a number of basic aspects that could be the starting point for future consensuses. A top priority aim of the work was also to update the criteria in the Diagnostic and statistical manual of mental disorders, fifth edition, for conduct disorders in children and adolescents, together with their comorbidity with attention deficit hyperactivity disorder.

TITLE: Consenso del GEITDAH sobre los trastornos de conducta en niños y adolescentes.El Grupo de Especial Interes en el Trastorno por Deficit de Atencion/Hiperactividad (GEITDAH) presenta en este articulo un consenso de expertos de toda España sobre los trastornos de conducta en niños y adolescentes. A partir del trabajo inicial del equipo de la Unidad de Paidopsiquiatria del Hospital Quiron-Teknon de Barcelona, se han consensuado aspectos basicos que podrian ser el punto de partida para futuros consensos. Ha sido tambien objetivo prioritario del trabajo actualizar en los trastornos de conducta en niños y adolescentes los criterios del Manual diagnostico y estadistico de los trastornos mentales, quinta edicion, y su comorbilidad con el trastorno por deficit de atencion/hiperactividad.

Effects of Changing to Individually Ventilated Caging on Guinea Pigs (Cavia porcellus).

The goal of this study was to evaluate the effect of changing to IVC housing on guinea pigs by recording several physiologic parameters in guinea pigs housed sequentially in open-top cages (OTC) and IVC. To register heart rate and locomotor activity, 10 male Dunkin-Hartley guinea pigs implanted with telemetric transmitters were moved from OTC to new, freshly prepared OTC or IVC and subsequently monitored by telemetry during the 4 d after the first cage change. Body weight and food consumption were measured twice during the study. Comparison of data from OTC- and IVC-housed guinea pigs showed no relevant differences in heart rate (mean ± 1 SD; 213 ± 10 bpm and 207 ± 9 bpm, respectively) at any time point. In contrast, locomotor activity varied: whereas activity during the first 4 h after the change of cage type was greater in IVC-housed animals, that during the following 24 h was greater in OTC but was similar between groups thereafter. Animals housed in OTC consumed more food than did those in IVC and, under both conditions, consumption was statistically related to body weight changes. Together, these results show that a change to IVC housing induced only transient increases in locomotor activity in guinea pigs without a marked increase in heart rate but with a decrease in food consumption. Because decreased food consumption was the only stress-associated sign during the 4-d observation, longer studies are needed to ascertain the importance of this finding.

Recomendaciones del GEITDAH en el tratamiento nutricional del déficit de atención con y sin hiperactividad (TDAH) / Recommendations on the nutritional treatment of attention deficit hyperactivity disorder (ADHD)

El grupo GEITDAH (Grupo de Especial Interés en el Trastorno por Déficit de Atención/Hiperactividad) presenta en este artículo un consenso de expertos de toda España sobre el tratamiento nutricional del TDAH. El tratamiento del trastorno por déficit de atención con o sin hiperactividad (TDAH) debe ser multimodal. El tratamiento nutricional es suplementario y comienza a haber pruebas científicas de su eficacia. Las intervenciones dietéticas pueden tener pequeños efectos beneficiosos en los síntomas del TDAH. La controvertida eliminación de aditivos artificiales, conservantes, colorantes y azúcares ha sido bien estudiada, y no tiene suficiente soporte científico por el momento para su recomendación generalizada como tratamiento eficaz del TDAH. Tampoco el empleo adicional de Acetil-L Carnitina con metilfenidato. Los suplementos de hierro o zinc deben suministrarse en los pacientes con TDAH con deficiencias conocidas. En este momento los hallazgos de los ensayos controlados aleatorizados son demasiado limitados y no apoyan de forma definitiva hasta la fecha el uso habitual en la práctica clínica de los ácidos grasos esenciales (omega-3 y 6) como tratamiento primario o suplementario en los niños con TDAH. Aunque, parecen aliviar síntomas relacionados con el TDAH, al menos en algunos niños, y los beneficios son mayores en el colegio que en casa

In this article, the GEITDAH -the Spanish abbreviation of the Special Interest Group on Attention Deficit Hyper-activity Disorder (ADHD)- presents a consensus about nutritional treatment for ADHD reached by experts in the management of ADHD from all over Spain. The ADHD treatment should be multimodal.Nutritional treatment is supplementary and there is some begining evidence of modest efficacy. Dietary interventions can have little beneficial effects in ADHD symptomatology. The controversial restricted elimination of food additives, preservatives, artificial food colours and refined sugar from diet is good studied. Present findings do not support to date the positive recommendation of its use as an appropriate treatment in ADHD. Neither do they support Acetyl-L Carnitine supplementation to augment methylphenidate. Iron and zinc should be supplemented in selected patients with know deficiencies. Current findings from randomized trials are limited and have not consistently supported the generalized clinical use of PUFA supplements (omega-3 fatty acids) as a primary or supplementary treatment for children with ADHD

Evaluating Internet information on attention-deficit/hyperactivity disorder (ADHD) treatment: parent and expert perspectives.

BACKGROUND: The Internet is increasingly used as a source of health-related information. The objective of this study was to assess the quality of web-based information on treatments for attention-deficit/hyperactivity disorder (ADHD). METHODS: Sixteen expert health professionals in ADHD and 35 parents of paediatric patients with a recent diagnosis of ADHD assessed the information contained in the 10 highest ranked websites in Spanish, using the Spanish version of the DISCERN tool - a validated questionnaire designed to assess the quality and reliability of web-based information on treatment choices (rating scores from 15 to 75). RESULTS: DISCERN scores given by parents and experts were low (total mean scores [standard deviation]: 35.9 [13.1] and 43.4 [13.7], respectively) and inter-rater agreement was poor/moderate (weighted kappa for the global assessment between -0.69 and +0.93, average = 0.29). There was a significant change on the ADHD-knowledge and motivation for treatment (ADHD-KMT) basic knowledge sub-scale score after the assessment of the different websites by parents (total mean scores [standard deviation]: 49.09 [9.46] and 63.21 [9.45]). CONCLUSIONS: Despite a poor/moderate inter-rater agreement between parent and expert opinions, all agreed that the quality of the web-based information on treatment choices for ADHD is generally poor.

Beneficios y riesgos de la discontinuación del tratamiento durante las vacaciones de verano en niños de edad escolar con trastorno por déficit de atención con hiperactividad / Benefits and risks of treatment discontinuation during summer holidays in school-aged children with attention deficit/hyperactivity disorder

En este estudio retrospectivo se evaluaron los beneficios y riesgos de la discontinuación del tratamiento farmacológico durante las vacaciones de verano (≥ 30 días) en 802 niños con trastorno por déficit de atención con hiperactividad (TDAH). En 440 de los pacientes (55%) se retiró el tratamiento durante el verano. El riesgo de mala adherencia (≤ 85%) fue más alto en los pacientes con vacaciones de tratamiento (odds ratio: 5,82). Comparados con los pacientes que recibieron tratamiento, los pacientes que no lo recibieron durante el verano tenían cuatro veces mayor probabilidad de empeorar o de no mejorar en la Escala de Impresión Clínica Global de Gravedad del TDAH (ICG-G-TDAH) (odds ratio 4,20, P < 0,0001). Además, los pacientes del grupo de vacaciones de tratamiento tenían tres veces mayor probabilidad de tener una puntuación > 1,67 en la escala de valoración SNAP-IV (odds ratio 2,60, P < 0,0001), y era más probable que sufrieran lesiones accidentales (odds ratio 1,49, P < 0,01), con un mayor número de lesiones por paciente (1,24 [DE = 3,67] frente a 0,8 [DE = 2,9], P = 0,05). Este análisis sugiere que las vacaciones del tratamiento en niños con TDAH pueden asociarse con resultados clínicos adversos

This retrospective study assessed the benefits and risks of discontinuation of pharmacological treatment during summer holidays (≥ 30 days) in 802 school-aged children with attention deficit/hyperactivity disorder (ADHD). A total of 440 patients (55%) discontinued medical treatment during the summertime. The risk of poor adherence (≤ 85%) was higher for patients with drug holidays (odds ratio 5.82). As compared with children treated pharmacologically during the summertime, patients in the drug holiday group were four times more likely to have worsening or no improvement of their symptoms in the Clinical Global Impression ADHD Severity (GCIADHD- S) scale (odds ratio 4.20, P < 0.0001). Moreover, patients in the drug holiday group as compared with patients treated pharmacologically were almost three times more likely to score > 1.67 in the ADHD SNAP-IV rating scale (odds ratio 2.60, P < 0.0001), and more likely to suffer from accidental injuries (odds ratio 1.49, P < 0.01), with a higher mean number of injuries per patient (1.24 [SD = 3.67] vs. 0.8 [SD = 2.9], P = 0.05). This retrospective cohort analyses suggest that drug holidays during the summertime in children with ADHD may be associated with adverse clinical outcomes

Algoritmos de derivación del TDAH: Consenso Geitadh / ADHD Algorithms for clinical pathways: GEITDAH consensus

El grupo de especial interés en TDAH (GEITADH) expone en este artículo su consenso sobre algoritmos de derivación en la asistencia para el paciente afecto de TDAH. Es un diseño sencillo realizado por un amplio número de profesionales de toda España con el objetivo de poder ser adaptado a necesidades asistenciales locales. Se revisan también otros algoritmos con influencia nacional

The Spanish Especial Interest Group on ADHD (GEITDAH) presents in this article its consensus on pathways for attending ADHD patients. This is a clear and simple consensus in order to facilitate the development of local algoritms inspired on it. Some ADHD algorithms used in the Spanish Health Services are reviewed

Effects of wire-bottom caging on heart rate, activity and body temperature in telemetry-implanted rats.

Some experimental procedures are associated with placement of animals in wire-bottom cages. The goal of this study was to evaluate stress-related physiological parameters (heart rate [HR], body temperature [BT], locomotor activity [LA], body weight [BW] and food consumption) in rats under two housing conditions, namely in wire-bottom cages and in bedding-bottom cages. Telemetry devices were surgically implanted in male Sprague-Dawley rats. HR, BT and LA were recorded at 5 min intervals. Analysis under each housing condition was performed from 16:00 to 08:00 h of the following day (4 h light, 12 h dark). During almost all of the light phase, the HR of rats housed in wire-bottom cages remained high (371 ± 35 bpm; mean ± SD; n = 6) and was significantly different from that of rats housed in bedding-bottom cages (340 ± 29 bpm; n = 6; P < 0.001; Student's t-test). In general, BT was similar under the two housing conditions. However, when rats were in wire-bottom cages, BT tended to fluctuate more widely during the dark phase. LA decreased when animals were housed in wire-bottom cages, in particular during the dark phase. Moreover, there was a significant difference with respect to the gain in BW: BW of rats housed in bedding-bottom cages increased 12 ± 2 g, whereas that of rats in wire-bottom cages decreased by 2 ± 3 g (P < 0.001). Our results demonstrate that housing rats in wire-bottom cages overnight leads to immediate alterations of HR, BW and LA, which might be related to a stress response.

Consenso del GEITDAH sobre el trastorno por déficit de atención/hiperactividad / GEITDAH consensus on attention deficit hyperactivity disorder

El GEITDAH, Grupo de Especial Interés en el Trastorno por Déficit de Atención/Hiperactividad (TDAH), presenta en este artículo un consenso de expertos de toda España sobre el manejo del TDAH. Se han consensuado aspectos básicos que deberían ser el punto de partida para futuros consensos locales o regionales. Es también un objetivo de este consenso disminuir la variabilidad en la asistencia que se da en nuestro país al TDAH y servir de estímulo para fines docentes. Su reducida extensión permitirá una mayor difusión a fin de lograr todos estos fines de forma más efectiva. Las conclusiones del consenso se han articulado en torno a una introducción sobre aspectos básicos y recomendaciones para: diagnóstico, tratamiento (farmacológico y psicoterapéutico), flujo de pacientes y aspectos organizativos (AU)

In this article, the GEITDAH –the Spanish abbreviation of the Special Interest Group on Attention Deficit Hyperactivity Disorder (ADHD)– presents a consensus reached by experts in the management of ADHD from all over Spain. The consensus concerns fundamental aspects that should be the starting point for future local or regional consensus guides. Another aim of this consensus is also to reduce the amount of variability that occurs in the health care offered to patients with ADHD in our country, as well as to act as a stimulus in educational matters. That fact that it is not very long will make it more popular among greater numbers of people and this will allow these goals to be reached more effectively. The conclusions in the consensus guide have been constructed around an introduction dealing with basic aspects and recommendations for diagnosis, treatment (both pharmacological and psychotherapeutic), patient flow and organisational aspects (AU)

UR-1505, a new salicylate, blocks T cell activation through nuclear factor of activated T cells.

2-Hydroxy-4(-2,2,3,3,3-pentafluoropropoxy)-benzoic acid (UR-1505), a new molecule chemically related to salicylic acid, has immunomodulator properties and is currently under clinical development for treatment of atopic dermatitis. The present work describes the immunomodulatory profile of UR-1505. UR-1505 targets T cells, inhibiting their proliferation and cytokine production by blocking nuclear factor of activated T cells (NF-AT) DNA-binding activity. The effects of UR-1505 (100-300 microM) on T cell proliferation seems to be dependent on the stimulus, because UR-1505 inhibited CD3/CD28-induced T-cell proliferation, increased p27(KIP) levels, and induced G1/S cell arrest but, interestingly, did not inhibit the Janus tyrosine kinase/signal transducer and activator of transcription-induced T-cell proliferation. These data suggest that UR-1505 acts by means of a specific mechanism inhibiting T cell activation depending on T cell receptor signaling pathway. Furthermore, the antiproliferative effects of UR-1505 are not a consequence of decreased cell viability. In addition to the inhibition of T-cell proliferation, UR-1505 decreased, in a dose-dependent manner, the production of interleukin (IL)-5 and interferon (IFN)-gamma in activated T cells, and this effect was produced at the transcriptional level. Because T-cell proliferation and cytokine production were regulated through NF-AT, we examined the effect of UR-1505 on this transcription factor. According to its effect on IL-5 and IFN-gamma mRNA expression, UR-1505 specifically inhibited NF-AT DNA binding without effect on nuclear factor-kappaB and activator protein-1 activities. The effect of UR-1505 on NF-AT is not attributable to a blockade of nuclear import. In conclusion, UR-1505 is a new immunomodulator agent that specifically inhibits NF-AT activation. Because NF-AT regulates the transcription of most genes involved in lymphocyte activation, its selective inactivation results in both decreased T-cell proliferation and cytokine production.