Utilisation of drugs for the treatment of psychiatric diseases in the pediatric population: focus on off-label use

Psychotropics are increasingly used in pediatrics, often as off-label medicines. The guarantees of safety and efficacy are not always granted in clinical practice compared to adult authorised indications. A retrospective observational study was done to estimate the prevalence of psychotropic use in pediatric subjects of Catalonia (Spain). Anonymised data on dispensation of psychotropics to pediatric patients, demography and other related data were obtained by the local healthcare management for the period 2008-2017. Estimation of off-label use was done through description of drug dispensations with no authorised use related to age range. The prevalence of psychotropics was 40.8-64.2 per 1,000 pediatric inhabitants. Hydroxyzine-only represented two-thirds of dispensations, and when removed, the prevalence dropped to 26.4-32.2 per 1,000 pediatric inhabitants. Adolescents and boys were more likely to receive a psychotropic. Psychostimulants had the highest exposure rate, mainly due to methylphenidate. Off-label use was observed in 12% of subjects, corresponding to 4.6% of all dispensed psychotropics with boys being more exposed. The proportion of off-label use vs. labelled use was higher in younger populations. Aripiprazole had the highest off-label frequency. Our data support the frequent reality of off-label use in pediatrics, despite the potential underestimation related to the selected off-label definition. There is an urgent need to systematically ascertain effectiveness and any potential adverse events in the off-label pediatric setting, and to generate valuable information for risk-benefit assessment in these populations where extrapolation from adults is not reliable

Evidence linking life-form to a major shift in diversification rate in Crassula

Premise Plants have evolved different ecological strategies in response to environmental challenges, and a higher lability of such strategies is more common in plant groups that adapt to various niches. Crassula (Crassulaceae), occurring in varied mesic to xeric habitats, exhibits a remarkable diversity of life-forms. However, whether any particular life-form trait has shaped species diversification in Crassula has remained unexplored. This study aims to investigate diversification patterns within Crassula and identify potential links to its life-form evolution. Methods A phylogenetic tree of 140 Crassula taxa was reconstructed using plastid and nuclear loci and dated based on the nuclear DNA information only. We reconstructed ancestral life-form characters to estimate the evolutionary trends of ecophysiological change, and subsequently estimated net diversification rates. Multiple diversification models were applied to examine the association between certain life-forms and net diversification rates. Results Our findings confirm a radiation within Crassula in the last 10 million years. A configuration of net diversification rate shifts was detected, which coincides with the emergence of a speciose lineage during the late Miocene. The results of ancestral state reconstruction demonstrate a high lability of life-forms in Crassula, and the trait-dependent diversification analyses revealed that the increased diversification is strongly associated with a compact growth form. Conclusions Transitions between life-forms in Crassula seem to have driven adaptation and shaped diversification of this genus across various habitats. The diversification patterns we inferred are similar to those observed in other major succulent lineages, with the most-speciose clades originating in the late Miocene

Dynamic and functional alterations of neuronal networks in vitro upon physical damage: a proof of concept

There is a growing technological interest in combining biological neuronal networks with electronic ones, specifically for biological computation, human-machine interfacing and robotic implants. A major challenge for the development of these technologies is the resilience of the biological networks to physical damage, for instance, when used in harsh environments. To tackle this question, here, we investigated the dynamic and functional alterations of rodent cortical networks grown in vitro that were physically damaged, either by sequentially removing groups of neurons that were central for information flow or by applying an incision that cut the network in half. In both cases, we observed a remarkable capacity of the neuronal cultures to cope with damage, maintaining their activity and even reestablishing lost communication pathways. We also observed¿particularly for the cultures cut in half¿that a reservoir of healthy neurons surrounding the damaged region could boost resilience by providing stimulation and a communication bridge across disconnected areas. Our results show the remarkable capacity of neuronal cultures to sustain and recover from damage, and may be inspirational for the development of future hybrid biological-electronic systems

Impact of the COVID-19 Pandemic on the Incidence of Suicidal Behaviors: A Retrospective Analysis of Integrated Electronic Health Records in a Population of 7.5 Million

The COVID-19 pandemic has caused remarkable psychological overwhelming and an increase in stressors that may trigger suicidal behaviors. However, its impact on the rate of suicidal behaviors has been poorly reported. We conducted a population-based retrospective analysis of all suicidal behaviors attended in healthcare centers of Catalonia (northeast Spain; 7.5 million inhabitants) between January 2017 and June 2022 (secondary use of data routinely reported to central suicide and diagnosis registries). We retrieved data from this period, including an assessment of suicide risk and individuals' socioeconomic as well as clinical characteristics. Data were summarized yearly and for the periods before and after the onset of the COVID-19 pandemic in Spain in March 2020. The analysis included 26,458 episodes of suicidal behavior (21,920 individuals); of these, 16,414 (62.0%) were suicide attempts. The monthly moving average ranged between 300 and 400 episodes until July 2020, and progressively increased to over 600 episodes monthly. In the postpandemic period, suicidal ideation increased at the expense of suicidal attempts. Cases showed a lower suicide risk; the percentage of females and younger individuals increased, whereas the prevalence of classical risk factors, such as living alone, lacking a family network, and a history of psychiatric diagnosis, decreased. In summary, suicidal behaviors have increased during the COVID-19 pandemic, with more episodes of suicidal ideation without attempts in addition to younger and lower risk profiles

Rich dynamics and functional organization on topographically designed neuronal networks in vitro

Neuronal cultures are a prominent experimental tool to understand complex functional organization in neuronal assemblies. However, neurons grown on flat surfaces exhibit a strongly coherent bursting behavior with limited functionality. To approach the functional richness of naturally formed neuronal circuits, here we studied neuronal networks grown on polydimethylsiloxane (PDMS) topographical patterns shaped as either parallel tracks or square valleys.We followed the evolution of spontaneous activity in these cultures along 20 days in vitro using fluorescence calcium imaging. The networks were characterized by rich spatiotemporal activity patterns that comprised from small regions of the culture to its whole extent. Effective connectivity analysis revealed the emergence of spatially compact functional modules that were associated with both the underpinned topographical features and predominant spatiotemporal activity fronts. Our results showthe capacity of spatial constraints tomold activity and functional organization, bringing new opportunities to comprehend the structure-function relationship in living neuronal circuits

Proposta de metodologia a seguir per la presa de decisions davant les diferents alternatives de millora en l'accessibilitat d'una estació

En la presa de decisió d'execució de proj~ctes d'accessibilitat cal que intervinguin, a mes deis aspectes c1assicsde minimització de cost, nous criteris com la maximització del benefici social. Així, aquest article proposa a partir de I'avaluació individual de nivell d'accessibilitat de cada estació, un mecanisme de presa de decisions per tal d'obtenir un millor benefici social amb menys costo Amb aquest sistema es pretén aconseguir una avaluació de les diferents alternatives objectiva i quantitativa en un món de característiques qualitatives, assegurant una correcte relació cost/benefici social.Postprint (published version

Poden els registres d'atenció primària ajudar a detectar el risc de suïcidi? : Un estudi de cas a Barcelona

El suïcidi és un greu problema de salut pública que s'ha vist incrementat en les últimes dècades, la qual cosa ha portat a la creació de diferents programes d'intervenció que tenen com a finalitat identificar i ajudar la persona afectada. En aquest article, un grup d'investigadors de l'àrea de Medicina presenta el resum d'un estudi en el qual intenten trobar a partir de registres electrònics del sistema sanitari, quins factors poden ajudar a identificar pacients amb alt risc de suïcidi. Una de les primeres conclusions és que molts d'ells queden recollits de manera rutinària en aquests registres, la qual cosa suposa un bon punt de partida per elaborar estratègies de prevenció.El suicidio es un grave problema de salud pública que se ha visto incrementado en las últimas décadas, lo que ha llevado a la creación de diferentes programas de intervención que tienen como finalidad identificar y ayudar a la persona afectada. En este artículo, un grupo de investigadores del área de Medicina presenta el resumen de un estudio que han llevado cabo para intentar encontrar a partir de registros electrónicos del sistema sanitario, qué factores pueden ayudar a identificar pacientes con alto riesgo de suicidio. Una de Llas primeras conclusiones es que muchos de ellos quedan recogidos de manera rutinaria en estos registros, lo que supone un buen punto de partida para elaborar estrategias de prevención.Suicide is a serious public health problem that has increased in recent decades, and this has led to the creation of different intervention programs that aim to identify and help the affected person. In this article, a group of medical researchers presents the summary of a study they conducted, using electronic records of the health system, to find the factors which could help to identify patients with a high risk of suicide. One of the first conclusions is that many of them are routinely collected in these registries, which is a good starting point for developing prevention strategies

Defining the scope for altering rice leaf anatomy to improve photosynthesis: a modelling approach.

Leaf structure plays an important role in photosynthesis. However, the causal relationship and the quantitative importance of any single structural parameter to the overall photosynthetic performance of a leaf remains open to debate. In this paper, we report on a mechanistic model, eLeaf, which successfully captures rice leaf photosynthetic performance under varying environmental conditions of light and CO2. We developed a 3D reaction-diffusion model for leaf photosynthesis parameterised using a range of imaging data and biochemical measurements from plants grown under ambient and elevated CO2 and then interrogated the model to quantify the importance of these elements. The model successfully captured leaf-level photosynthetic performance in rice. Photosynthetic metabolism underpinned the majority of the increased carbon assimilation rate observed under elevated CO2 levels, with a range of structural elements making positive and negative contributions. Mesophyll porosity could be varied without any major outcome on photosynthetic performance, providing a theoretical underpinning for experimental data. eLeaf allows quantitative analysis of the influence of morphological and biochemical properties on leaf photosynthesis. The analysis highlights a degree of leaf structural plasticity with respect to photosynthesis of significance in the context of attempts to improve crop photosynthesis

Riesgo de suicidio asociado a factores clínicos y farmacológicos : Estudio de Casos y Controles

S'ha realitzat un estudi analític retrospectiu de casos i controls de base poblacional, per identificar i explorar els factors clínics i farmacològics associats a la mort per suïcidi en aquelles persones que han tingut interacció prèvia amb el sistema de salut pública. Els casos es van obtenir a partir dels registres de l'Institut de Medicina Legal i Ciències Forenses de Catalunya per la província de Barcelona durant els anys 2010 a 2015, i els controls es van seleccionar a l'atzar entre la població atesa pels centres d'atenció primària al mateix període, en una raó de 20 a 1 i amb una distribució d'edat, sexe i lloc de residència iguals als casos. Es van vincular dades clíniques de primària i de facturació de medicaments, que es van extreure i anonimitzar per a l'estudi. S'han obtingut paràmetres clínics, assistencials i socials, que s'han analitzat en models univariable i utilitzat per ajustar el model estadístic que va analitzar la relació entre exposicions farmacològiques i risc de suïcidi. S'han estudiat diferents grups de psicofàrmacs, amb èmfasi en els subtipus d'antidepressius, i també hipocolesterolemiants, antihipertensius i altres fàrmacs d'interès. D'un total de 2.109 persones que consten en els registres de morts per suïcidi, 971 van interaccionar prèviament amb el sistema sanitari d'atenció primària, i per a aquestes es van seleccionar 19.420 controls. Entre les 971 persones que van tenir algun contacte assistencial previ, un 33% va morir durant la setmana següent i un 58,5% durant el mes següent a la darrera consulta. Després d'ajustar per altres factors de risc no farmacològics, l'antecedent de qualsevol exposició a fàrmacs dels grups d'antipsicòtics, antidepressius, ansiolítics i hipnosedants, antiepilèptics i opioides s'associa a un increment significatiu de el risc de suïcidi, amb estimadors de risc moderats, entre 1,47 i 2,29. Aquells pacients amb exposicions a antiepilèptics, antipsicótics, opioides i antidepressius sense dispensació d'aquests medicaments en els darrers tres mesos van tenir riscs més elevats. Cap dels grups farmacològics no psiquiàtrics ha mostrat patrons consistents d'increments de risc. En base a aquests resultats s'ha confirmat la hipòtesi que determinats factors clínics, especialment de salut mental i de freqüentació sanitària, i l'exposició a determinats medicaments actius sobre el sistema nerviós, s'associen a un major risc de suïcidi. La disponibilitat de dades en els registres mèdics electrònics d'atenció primària representa una oportunitat per crear eines de detecció de el risc en la història clínica electrònica que permetin indicar accions preventives i un seguiment individualitzat.Se ha realizado un estudio analítico retrospectivo de casos y controles de base poblacional, para identificar y explorar los factores clínicos y farmacológicos asociados a la muerte por suicidio en aquellas personas que han tenido interacción previa con el sistema de salud pública. Los casos se obtuvieron a partir de los registros del Institut de Medicina Legal i Ciències Forenses de Catalunya para la provincia de Barcelona durante los años 2010 a 2015, y los controles se seleccionaron al azar entre la población atendida por los centros de atención primaria en el mismo periodo, en una razón de 20 a 1 y con una distribución de edad, sexo y lugar de residencia iguales a los casos. Se vincularon y extrajeron datos clínicos de primaria y de facturación de medicamentos, anonimizados para el estudio. Se han obtenido parámetros clínicos, asistenciales y sociales, que se han analizado en modelos univariable y utilizado para ajustar el modelo estadístico que analizó la relación entre exposiciones farmacológicas y riesgo de suicidio. Se han estudiado distintos grupos de psicofármacos, con énfasis en los subtipos de antidepresivos, y también hipocolesterolemiantes, antihipertensivos y otros fármacos de interés. Tuvieron interacciones con el sistema sanitario de atención primaria 971 personas de las 2.109 que constaban en los registros de muertes por suicidio. Para estas se seleccionaron 19.420 controles. Entre las 971 personas con algún contacto asistencial previo, un 33% y un 58,5% murieron durante la semana o el el mes siguiente a la consulta, respectivamente. Después de ajustar por otros factores de riesgo no farmacológicos, el antecedente de cualquier exposición a fármacos antipsicóticos, antidepresivos, ansiolíticos e hipnosedantes, antiepilépticos y opioides se asoció a un incremento significativo del riesgo de suicidio, con estimadores de riesgo moderados, entre 1,47 y 2,29. Aquellos pacientes con exposiciones a antiepilépticos, antipsicóticos, opioides y antidepresivos que no tuvieron ninguna dispensación de estos medicamentos en los últimos tres meses tuvieron riesgos más elevados. Ninguno de los fármacos no psiquiátricos analizados ha mostrado patrones consistentes de incrementos de riesgo sustancial. En base a estos resultados se ha confirmado la hipótesis de que determinados factores clínicos, especialmente de salud mental y de frecuentación sanitaria, y la exposición a determinados medicamentos activos sobre el sistema nervioso, se asocian a un mayor riesgo de suicidio. La disponibilidad de datos en los registros médicos electrónicos de atención primaria representa una oportunidad para crear herramientas de detección del riesgo en la historia clínica electrónica que permitan indicar acciones preventivas y un seguimiento individualizado.A retrospective analytical population-based study of cases and controls has been carried out to identify and explore clinical and pharmacological factors associated with death by suicide in those people who have had previous interaction with the public health system. The cases were obtained from the records of the Institut de Medicina Legal i Ciències Forenses de Catalunya for the province of Barcelona during the years 2010 to 2015, and the controls were randomly selected from the population attended by primary care centers in the same period, in a ratio of 20 to 1 and with a distribution of age, sex and place of residence equal to the cases. Data from primary care registries and drug invoicing were linked, extracted and anonimised for the study. Clinical, healthcare and social parameters have been obtained, which have been analyzed in univariate models and used to adjust the statistical model that analyzed the relationship between drug exposures and suicide risk. Different groups of psychotropic drugs have been studied, with an emphasis on antidepressant subtypes, as well as cholesterol-lowering drugs, antihypertensive drugs, and other drugs of interest. 971 people out of 2,109 registered in the suicide death registers had interactions with the primary care health system. For these, 19,420 controls were selected. Among the 971 people with some previous healthcare contact, 33% and 58.5% died during the week or the month following system interaction, respectively. After adjusting for other non-pharmacological risk factors, the antecedent of any exposure to either antipsychotic drugs, antidepressants, anxiolytics and hypnosedatives, antiepileptics or opioids was associated with a significant increase in the risk of suicide, with moderate risk estimators, between 1.47 and 2.29. Those patients with exposures to antiepileptic drugs, antipsychotics, opioids and antidepressants who did not have any dispensation of these drugs in the last three months had higher risks. None of the non-psychiatric drugs analyzed have shown consistent patterns of substantial increases in risk. Based on these results, the hypothesis has been confirmed that certain clinical factors, especially mental health and health frequentation, and the exposure to certain drugs active on the nervous system, are associated with an increased risk of suicide. The availability of data in primary care electronic medical records represents an opportunity to create risk detection tools in the electronic medical record that may allow the indication of preventive actions and individualized follow-up