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Introduction: Several developmental changes occur in adolescence, particularly in the metarepresentational domain, which allows and promotes adaptive sociality. We explored the possible relationships between theory of mind (ToM) and definitional competence, both metarepresentational, beyond age and gender effects. Methods: To reach our goals, we involved 75 adolescents (age range 14-19 years, M = 15.7, and SD = 1.36). ToM was measured through "The Reading the Mind in the Eyes Test" (RMET), and definitional competence was assessed through a new instrument, namely, the "Co.De. Scale". Attention was paid to check whether results were different when considering mental states vs. non-mental states of the scale and emotional words vs. non-emotional words. Results: T-tests showed that older adolescents (third grade of high school) performed better than younger ones (first grade of high school) in both tasks. Only in the male group, there were no school grade differences in the ToM task. Regression analyses showed that RMET performance predicted the score of non-emotional mental states definitions and, even if marginally, of ToM word definitions. However, RMET was not a predictor of the general performance of the definitional task or emotion definitions. Discussion: Connections with global adolescents' development and possible educational implications are discussed.
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[This corrects the article DOI: 10.3389/fpsyg.2022.960893.].
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This study proposes a psychometric validation of the Italian version of the Child-Parent Relationship Scale (CPRS) developed by Pianta in 1992. Based on attachment theory, the scale assesses parents' relationship perceptions with their own child and comprises three scales: Closeness, Conflict, and Dependency. A sample of 501 parents (188 fathers and 313 mothers) completed 30 items of the Italian version of the Child-Parent Relationship Scale (CPRS-I) online, but only 437 answered 85% of the entire protocol; hence, the analyses only focused on 437 participants. The first analysis of the original theoretical model revealed poor fit, item loadings, and internal consistency. Therefore, a follow-up analysis was conducted. Exploratory and confirmatory analyses with a split sample (EFA = 218; CFA = 219) confirmed the original three-factor structure of the Italian sample, although some items were eliminated. The validity and reliability of the Italian version of the CPRS-I were also verified by correlating the above three factors with measures of adult attachment styles and children's internalizing and externalizing behaviors. The CPRS-I showed significant correlations with all tested constructs, in line with those found by Driscoll and Pianta for the short form of the scale. Our results confirm that the CPRS-I has the same structure as the original scale; therefore, it can be a useful tool for assessing parents' perceptions of their relationship with their children. The implications for educational and clinical settings are also discussed.
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Introduction: Given the vulnerability of children during the COVID-19 pandemic, paying close attention to their wellbeing at the time is warranted. The present protocol-based systematic mixed-studies review examines papers published during 2020-2022, focusing on the impact of the COVID-19 pandemic on children's internalizing/externalizing symptoms and the determinants thereof. Method: PROSPERO: CRD42022385284. Five databases were searched and the PRISMA diagram was applied. The inclusion criteria were: papers published in English in peer-reviewed journals; papers published between January 2020 and October 2022 involving children aged 5-13 years; qualitative, quantitative, and mixed studies. The standardized Mixed Method Appraisal Tool protocol was used to appraise the quality of the studies. Results: Thirty-four studies involving 40,976 participants in total were analyzed. Their principal characteristics were tabulated. The results showed that children's internalizing/externalizing symptoms increased during the pandemic, largely as a result of disengagement from play activities and excessive use of the internet. Girls showed more internalizing symptoms and boys more externalizing symptoms. Distress was the strongest parental factor mediating children's internalizing/externalizing symptoms. The quality of the studies was appraised as low (n = 12), medium (n = 12), and high (n = 10). Conclusion: Gender-based interventions should be designed for children and parents. The studies reviewed were cross-sectional, so long-term patterns and outcomes could not be predicted. Future researchers might consider a longitudinal approach to determine the long-term effects of the pandemic on children's internalizing and externalizing symptoms. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022385284, identifier: CRD42022385284.
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After formal school entry, theory of mind development encounters a blooming period of growth intertwined with social and academic achievements and challenges. Within this framework, in last years researchers have proposed training programs to foster mature ToM skills, but also, to test causal pathways for the role that ToM development may have in broader cognitive and social outcomes. In the current mini-review we examine which training programs have been developed so far to enhance three key aspects of mature ToM skills: second-order false belief reasoning, the ability to put one's own ToM knowledge into use, and the mentalization of thoughts and emotions. We also illustrate effects of these activities on intra- and inter- personal competence. In its conclusion the paper provides considerations of both first achievements of research in this area and gaps to be addressed in future works.
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Multiple Myeloma (MM) typically originates from underlying precursor conditions, known as Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM). Validated risk factors, related to the main features of the clonal plasma cells, are employed in the current prognostic models to assess long-term probabilities of progression to MM. In addition, new prognostic immunologic parameters, measuring protective MM-specific T-cell responses, could help to identify patients with shorter time-to-progression. In this report, we described a novel Multi-antigenic Myeloma-specific (MaMs) T-cell assay, based on ELISpot technology, providing simultaneous evaluation of T-cell responses towards ten different MM-associated antigens. When performed during long-term follow-up (mean 28 months) of 33 patients with either MGUS or SMM, such deca-antigenic myeloma-specific immunoassay allowed to significantly distinguish between stable vs. progressive disease (p < 0.001), independently from the Mayo Clinic risk category. Here, we report the first clinical experience showing that a wide (multi-antigen), standardized (irrespective to patients' HLA), MM-specific T-cell assay may routinely be applied, as a promising prognostic tool, during the follow-up of MGUS/SMM patients. Larger studies are needed to improve the antigenic panel and further explore the prognostic value of MaMs test in the risk assessment of patients with monoclonal gammopathies.
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BACKGROUND: The COVID-19 outbreak caused severe changes in school activities over the past two years. Teachers underwent a re-planning of their teaching approaches, shifting from face-to-face teaching formats to remote ones. These challenges resulted in high levels of burnout. The identification of risk/protective factors contributing to burnout is crucial in order to inform intervention programs. Thus, we hypothesized a mediation role of teachers' mentalizing ability (processing of emotions, a component of mentalized affectivity) on the relationship between depression, anxiety, and depersonalization (burnout dimension). Two reverse models were computed. Job satisfaction, teachers' age and gender, school grade, and length of teaching experience served as covariates. METHODS: 466 (M(sd) = 46.2 (10.4) years) online questionnaires were completed by Italian teachers of primary (n = 204) and middle (n = 242) schools. Measures of burnout, depression, anxiety, and mentalization were administered. RESULTS: The findings corroborated our hypotheses: in all models, processing emotions served as a mediator on the relationship between depression, anxiety, and depersonalization, and on the reciprocal one. Job satisfaction positively impacted processing emotion, and negatively impacted depression and depersonalization; women teachers reported high levels of the anxious trait. CONCLUSIONS: Overall, it can be concluded that the ability to mentalize has a beneficial impact on teachers' well-being. Policymaking, clinical, and research implications were discussed.
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Agotamiento Profesional , COVID-19 , Mentalización , Humanos , Femenino , Depresión/epidemiología , COVID-19/epidemiología , Ansiedad/epidemiología , Agotamiento Profesional/psicología , Maestros/psicologíaRESUMEN
The COVID-19 pandemic and the measures to face it have placed children and their caregivers in front of many challenges that could represent sources of stress. This work aims to explore the point of view of children through drawing, as a spontaneous means of expression, relating it to parents' perceptions of children's difficulties, strengths, and mentalization skills. The sample consists of 18 children (mean age = 8.22, SD = 1.79). Parents were asked to complete: a socio-demographic questionnaire with information on the impact of COVID-19 on the family, the Strengths and Difficulties Questionnaire, and the Everyday Mindreading Scale. Children were asked to draw three moments: "Before" the pandemic, "During" the lockdown, and "After," when the COVID-19 will be passed. The drawings were coded by constructing a content and expressive analysis grid, adapting coding systems found in the literature. Data were collected at the beginning of the summer of 2020, just after the first lockdown period (from March to May 2020 in Italy). The results of the present work are in line with previous studies that reported experiences of wellbeing and tranquility of children in time spent at home with family during the pandemic. From the drawings emerges that children feel sufficiently able to master the situation, as reflected by including themselves in drawings and providing many details of the house in "During" drawings. The literature also reports a feeling of sadness/loneliness caused by the lack of friends, an element that we also find in the tendency to represent friends significantly more in the drawings concerning the future. Some contents of drawings (inclusion of friends, relatives, and parents) appeared associated with emotional, interpersonal, and mentalizing abilities of children, as perceived by parents. Exploring children's representations of a stressful event like the pandemic through drawings allows to focus both on their difficulties and on their resources, with useful implications for the educational support.
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The resorption rate of autologous fat transfer (AFT) is 40-60% of the implanted tissue, requiring new surgical strategies for tissue reconstruction. We previously demonstrated in a rabbit model that AFT may be empowered by adipose-derived mesenchymal stromal/stem cells (AD-MSCs), which improve graft persistence by exerting proangiogenic/anti-inflammatory effects. However, their fate after implantation requires more investigation. We report a xenograft model of adipose tissue engineering in which NOD/SCID mice underwent AFT with/without human autologous AD-MSCs and were monitored for 180 days (d). The effect of AD-MSCs on AFT grafting was also monitored by evaluating the expression of CD31 and F4/80 markers. Green fluorescent protein-positive AD-MSCs (AD-MSC-GFP) were detected in fibroblastoid cells 7 days after transplantation and in mature adipocytes at 60 days, indicating both persistence and differentiation of the implanted cells. This evidence also correlated with the persistence of a higher graft weight in AFT-AD-MSC compared to AFT alone treated mice. An observation up to 180 d revealed a lower resorption rate and reduced lipidic cyst formation in the AFT-AD-MSC group, suggesting a long-term action of AD-MSCs in support of AFT performance and an anti-inflammatory/proangiogenic activity. Together, these data indicate the protective role of adipose progenitors in autologous AFT tissue resorption.
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Tejido Adiposo , Células Madre Mesenquimatosas , Animales , Proteínas Fluorescentes Verdes/metabolismo , Humanos , Células Madre Mesenquimatosas/metabolismo , Ratones , Ratones Endogámicos NOD , Ratones SCID , ConejosRESUMEN
Multiple Myeloma (MM) is a malignant growth of clonal plasma cells, typically arising from asymptomatic precursor conditions, namely monoclonal gammopathy of undetermined significance (MGUS) and smoldering MM (SMM). Profound immunological dysfunctions and cytokine deregulation are known to characterize the evolution of the disease, allowing immune escape and proliferation of neoplastic plasma cells. In the past decades, several studies have shown that the immune system can recognize MGUS and MM clonal cells, suggesting that anti-myeloma T cell immunity could be harnessed for therapeutic purposes. In line with this notion, chimeric antigen receptor T cell (CAR-T) therapy is emerging as a novel treatment in MM, especially in the relapsed/refractory disease setting. In this review, we focus on the pivotal contribution of T cell impairment in the immunopathogenesis of plasma cell dyscrasias and, in particular, in the disease progression from MGUS to SMM and MM, highlighting the potentials of T cell-based immunotherapeutic approaches in these settings.
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Gammopatía Monoclonal de Relevancia Indeterminada , Mieloma Múltiple , Paraproteinemias , Mieloma Múltiple Quiescente , Progresión de la Enfermedad , Humanos , Gammopatía Monoclonal de Relevancia Indeterminada/patología , Mieloma Múltiple/patología , Mieloma Múltiple/terapia , Paraproteinemias/terapia , Linfocitos T/patologíaRESUMEN
Mentalization is a useful ability for social functioning and a crucial aspect of mentalizing is emotion regulation. Literature suggests programmes for children and adults to increase mentalizing abilities useful both for emotional and social competences. For this reason, the issue of how to prompt children's mentalization has started to attract researchers' attention, supporting the importance of the interpersonal dimension for the individual differences in the developmental of mentalization. The TiM (Thoughts in Mind) Project, a training programme based on the explanation of mentalization mechanisms and designed for adults, deals with emotion regulation. Starting from the TiM Project, this study tests the effects of the TiM Child (TiM-C) training programme, over a control training programme, a conversational training designed for the school context, in children attending Year 2 of primary school. We designed a training based on narratives, followed by multiple-choice questions and conversations about mental states. Our results revealed significant improvements over the training period only in the TiM-C Project group for Metacognition, Emotion Regulation Strategies and a Theory of Mind task. As far as the educational implications, our findings suggest that it is possible to enhance mentalization through activities at school by promoting not only the understanding of the relations between mind and emotion, but also metacognitive skills.
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Regulación Emocional , Mentalización , Metacognición , Teoría de la Mente , Adulto , Niño , Humanos , Instituciones Académicas , Teoría de la Mente/fisiologíaRESUMEN
In recent years, the introduction of new drugs targeting Bruton's tyrosine kinase (BTK) has allowed dramatic improvement in the prognosis of patients with chronic lymphocytic leukemia (CLL) and other B-cell neoplasms. Although these small molecules were initially considered less immunosuppressive than chemoimmunotherapy, an increasing number of reports have described the occurrence of unexpected opportunistic fungal infections, in particular invasive aspergillosis (IA). BTK represents a crucial molecule in several signaling pathways depending on different immune receptors. Based on a variety of specific off-target effects on innate immunity, namely on neutrophils, monocytes, pulmonary macrophages, and nurse-like cells, ibrutinib has been proposed as a new host factor for the definition of probable invasive pulmonary mold disease. The role of platelets in the control of fungal growth, through granule-dependent mechanisms, was described in vitro almost two decades ago and is, so far, neglected by experts in the field of clinical management of IA. In the present study, we confirm the antifungal role of platelets, and we show, for the first time, that the exposure to BTK inhibitors impairs several immune functions of platelets in response to Aspergillus fumigatus, i.e., the ability to adhere to conidia, activation (as indicated by reduced expression of P-selectin), and direct killing activity. In conclusion, our experimental data suggest that antiplatelet effects of BTK inhibitors may contribute to an increased risk for IA in CLL patients.
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Aspergilosis , Infecciones Fúngicas Invasoras , Leucemia Linfocítica Crónica de Células B , Agammaglobulinemia Tirosina Quinasa/metabolismo , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Aspergilosis/tratamiento farmacológico , Aspergilosis/metabolismo , Plaquetas/metabolismo , Humanos , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéuticoRESUMEN
In order to explore the psychological impact of the COVID-19 outbreak on the caregiver-child relationship, we investigated the interplay among COVID-19 exposure and children's internalizing/externalizing problems during the Italian lockdown, hypothesizing a mediation effect played by maternal distress. Additionally, we included maternal reflective functioning (i.e., hypermentalization) as a moderator factor among this interplay. A total of 305 Italian mothers of children aged 6-13 years (M = 10.3; SD = 2.4) filled in an online survey. Findings revealed an indirect effect of maternal COVID-19 exposure on children's anxious/depressed (k2 = 0.46) and attention problems (k2 = 0.32) via maternal distress. Hypermentalization moderated the impact of maternal COVID-19 exposure on children's anxious/depressed problems (ß = -1.08, p = 0.04). Hypermentalization moderated both the relation between maternal distress and children's aggressive behaviors (ß = 12.226; p < 0.001) and between maternal distress and children's attention problems (ß = 5.617, p < 0.001). We found pivotal significant effects of maternal hypermentalization on children's anxious/depressed and attention problems, indicating that the higher the mother's hypermentalization was, the higher the children's problems were. Our results broaden what we knew on the role of maternal reflective and emotional functioning on children's emotional/behavioral adjustment during stressful situations.
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COVID-19 , Distrés Psicológico , Control de Enfermedades Transmisibles , Femenino , Humanos , Madres , Pandemias , SARS-CoV-2RESUMEN
[This corrects the article DOI: 10.1371/journal.pone.0249272.].
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BACKGROUND: When COVID-19 was declared as a pandemic, many countries imposed severe lockdowns that changed families' routines and negatively impacted on parents' and children's mental health. Several studies on families with children with autism spectrum disorder (ASD) revealed that lockdown increased the difficulties faced by individuals with ASD, as well as parental distress. No studies have analyzed the interplay between parental distress, children's emotional responses, and adaptive behaviors in children with ASD considering the period of the mandatory lockdown. Furthermore, we compared families with children on the spectrum and families with typically developing (TD) children in terms of their distress, children's emotional responses, and behavioral adaptation. METHODS: In this study, 120 parents of children aged 5-10 years (53 with ASD) participated. RESULTS: In the four tested models, children's positive and negative emotional responses mediated the impact of parental distress on children's playing activities. In the ASD group, parents reported that their children expressed more positive emotions, but fewer playing activities, than TD children. Families with children on the spectrum reported greater behavioral problems during the lockdown and more parental distress. CONCLUSIONS: Our findings inform the interventions designed for parents to reduce distress and to develop coping strategies to better manage the caregiver-child relationship.
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This study proposes a psychometric validation of the Italian version of the Mentalized Affectivity Scale (MAS) developed by Greenberg and colleagues in 2017. The mentalized affectivity construct integrates mentalization ability in the process of emotional regulation. An adult sample (N = 506) completed the 60-items MAS online version. In contrast to the three-factor structure of the original version, the Italian context confirmatory and exploratory factor analyses with splitted sample (CFA = 258; EFA = 248) revealed a five-factor structure. The hierarchically structured MAS factors are: Emotional Processing (being able to process emotion in situations); Expressing Emotions (talking and knowing emotions); Identifying Emotions (awareness of emotions); Control Processing (to control emotional reactions and expression), and Autobiographical Memory (related to childhood experiences). We also verified the convergent validity and reliability of the Italian version of the MAS by correlating the above five factors with measures of emotion regulation and reflective functioning. Moreover, we analyzed the relationships among the factors of the MAS, personality measures and well-being indexes, such as life satisfaction and self-efficacy: The new 35-item MAS scale showed robust correlations with all the tested constructs. Our results confirm that the MAS is a useful measure to assess mentalized affectivity, with the Italian version showing a more complex structure than the original English one, thus enriching the literature about mentalization.
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Psicometría/métodos , Adolescente , Adulto , Anciano , Emociones , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Satisfacción Personal , Personalidad , Reproducibilidad de los Resultados , Autoeficacia , Encuestas y Cuestionarios , Adulto JovenRESUMEN
The present study focused on the psychological impact that the lockdown due to coronavirus disease-19 (COVID-19) had on families in Italy. During the COVID-19 pandemic, the Italian government imposed a strict lockdown for all citizens. People were forced to stay at home, and the length of the lockdown was uncertain. Previous studies analyzed the impact of social distance measures on individuals' mental health, whereas few studies have examined the interplay between the adults' functioning, as parents, during this period and the association with the child's adjustment. The present study tested if maternal distress/coping predicts children's behaviors during the COVID-19 lockdown, hypothesizing a mediation effect via children's emotional experience. Participants were 144 mothers (M age = 39.3, 25-52, SD = 5.6) with children aged 5-10 years (M age = 7.54, SD = 1.6, 82 boys); mothers answered to an online survey. Results indicated that mothers with higher exposure to COVID-19 showed higher levels of distress and higher display of coping attitudes, even if in the structural equation modeling model, the COVID-19 exposure was not a predictor of mothers' distress. Compared with mothers with good coping skills, mothers with higher stress levels were more likely to attribute negative emotions to their children at the expense of their positive emotions. Moreover, children's emotions acted as mediators between maternal distress/coping and children's adaptive/maladaptive behaviors. In conclusion, it is important to support parents during pandemic emergence, by providing them with adequate information to manage the relationship with their children, to reduce their level of distress and to enhance their coping abilities.
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Adaptación Psicológica , COVID-19/psicología , Madres/psicología , Madres/estadística & datos numéricos , Pandemias/estadística & datos numéricos , Estrés Psicológico , Adulto , COVID-19/epidemiología , Niño , Preescolar , Femenino , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , SARS-CoV-2 , Encuestas y CuestionariosRESUMEN
Patients with Alzheimer's disease (AD) and Parkinson's disease (PD) develop a progressive decline of visual function. This condition aggravates overall cognitive and motor abilities, is a risk factor for developing hallucinations, and can have a significant influence on general quality of life. Visual problems are common complaints of patients with PD and AD in the early stages of the disease, but they also occur during normal aging, making it difficult to differentiate between normal and pathological conditions. In this respect, their real incidence has remained largely underestimated, and no rehabilitative approaches have been standardized. With the aim to increase awareness for ocular and visual disorders, we collected the main neurophthalmologic and orthoptic parameters, including optical coherence tomography (OCT), in six patients with a diagnosis of PD, six patients with a diagnosis of early AD, and eight control subjects in an easily assessable outpatient setting. We also evaluated the patient's ability to recognize changes in facial expression. Our study demonstrates that visual problems, including blurred vision, diplopia, reading discomfort, photophobia, and glare, are commonly reported in patients with PD and AD. Moreover, abnormal eye alignment and vergence insufficiency were documented in all patients during examination. Despite the small size of the sample, we demonstrated greater ganglion cell and retinal nerve fibers layer (RNFL) damage and a defect of facial emotion recognition in AD/PD patients with respect to a comparable group of normal elderly persons, with peculiarities depending upon the disease. Ocular defects or visual discomfort could be correctly evaluated in these patients and possibly corrected by means of lens, orthoptic exercises, and visual rehabilitation. Such a practical approach may help to ameliorate motor autonomy, reading ability, and may also reduce the risk of falls, with a positive impact in daily living activities.
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Maintaining social skills such as Theory of Mind (ToM) competences is important to counteract the conversion into dementia in Mild Cognitive Impairment (MCI). Multidimensional nonpharmacological interventions demonstrated their potential in improving cognitive and behavioral abilities; however, little is known about the long-term effect of such interventions on social skills in people with MCI. The aim of this longitudinal study was to monitor ToM competences considering both cognitive and affective domains in an amnestic MCI (aMCI) sample involved in a home-based multistimulation treatment (MST@H). 30 aMCI subjects (M : F = 15 : 15; mean age ± SD = 77.00 ± 4.60) were enrolled, and three steps of evaluation with neuropsychological tests and ToM tasks have been implemented. 21 healthy controls (HC) were also included (M : F = 9 : 12; mean age ± SD = 74.95 ± 3.88) to characterize the aMCI sample regarding differences in ToM performance compared to HC at the baseline evaluation. Our results show that the aMCI group statistically significantly underperformed the HC group only in the advanced ToM tasks, confirming an initial decline of high-level ToM competences in this population. The longitudinal evaluation revealed time changes not only in some subcognitive domains of MoCA (memory and executive functions) but also in cognitive and affective ToM dimensions in aMCI subjects. Our findings suggest that cognitive and affective ToM can be considered useful outcome measures to test the long-term effect of treatment over time.
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Disfunción Cognitiva/fisiopatología , Disfunción Cognitiva/psicología , Teoría de la Mente/fisiología , Anciano , Anciano de 80 o más Años , Cognición/fisiología , Disfunción Cognitiva/metabolismo , Función Ejecutiva/fisiología , Femenino , Humanos , Estudios Longitudinales , Masculino , Pruebas Neuropsicológicas , Cognición SocialRESUMEN
BACKGROUND: Despite its cardiotoxicity doxorubicin is widely used for the treatment of paediatric malignancies. Current treatment regimens appear to be suboptimal as treatment strategies vary and do not follow a clear pharmacological rationale. Standardisation of dosing strategies in particular for infants and younger children is required but is hampered by scarcely defined exposure-response relationships. The aim is to provide a rational dosing concept allowing for a reduction of variability in systemic therapy intensity and subsequently unforeseen side effects. METHODS: Doxorubicin plasma concentrations in paediatric cancer patients were simulated for different treatment schedules using a population pharmacokinetic model which considers age-dependent differences in doxorubicin clearance. Overall drug exposure and peak concentrations were assessed. Simulation results were used to support a three round Delphi consensus procedure with the aim to clarify the pharmacological goals of doxorubicin dosing in young children. A group of 28 experts representing paediatric trial groups and clinical centres were invited to participate in this process. RESULTS: Pharmacokinetic simulations illustrated the substantial differences in therapy intensity associated with current dosing strategies. Consensus among the panel members was obtained on a standardised a priori dose adaptation that individualises doxorubicin doses based on age and body surface area targeting uniform drug exposure across children treated with the same protocol. Further, a reduction of peak concentrations in very young children by prolonged infusion was recommended. CONCLUSIONS: An approach to standardise current dose modification schemes in young children is proposed. The consented concept takes individual pharmacokinetic characteristics into account and involves adaptation of both the dose and the infusion duration potentially improving the safety of doxorubicin administration.