Search

Aim: Since parental stress and family empowerment were shown to influence children's and adolescents' outcome, especially in the case of psychotherapeutic treatments, the present study aims to deeply explore factors that are likely to impact on stress and empowerment in parents of children with a psychiatric diagnosis., Methods: Parenting stress and empowerment have been compared between 45 parents of children with a psychiatric disorder and 96 parents of children without psychiatric disorders., Results: Parenting stress appeared to be higher in patients' parents and it varied according to disorder severity, while socio-demographic variables seemed to influence the stress levels only to a slight extent. Moreover parental stress and empowerment influenced each other within the parental couple., Conclusions: Developing interventions aimed to support parenting and to involve fathers in the parent-child relationship, focused on increasing parents empowerment and self-efficacy, could contribute to decrease stress and positively influence children's psychopathology.

The study, conducted on Italian preadolscents aged 11 to 13 belonging to the general population, aims to investigate the relationship between the emotional functioning, namely, alexithymia, and the risk of developing behavioral and emotional problems measured using the Strength and Difficulty Questionnaire. The latent class analysis approach allowed to identify two latent variables, accounting for the internalizing (emotional symptoms and difficulties in emotional awareness) and for the externalizing problems (conduct problems and hyperactivity, problematic relationships with peers, poor prosocial behaviors and externally oriented thinking). The two latent variables featured two latent classes: the difficulty in dealing with problems and the strength to face problems that was representative of most of the healthy participants with specific gender differences. Along with the analysis of psychopathological behaviors, the study of resilience and strengths can prove to be a key step in order to develop valuable preventive approaches to tackle psychiatric disorders., (© 2016 Scandinavian Psychological Associations and John Wiley & Sons Ltd.)

Introduction: Nonsuicidal self-injury (NSSI) is a multifaceted phenomenon and a major health issue among adolescents. A better understanding of self-injury comorbidities is crucial to improve our ability to assess, treat, and prevent NSSI., Purpose: This study aimed at analyzing some of the psychobehavioral correlates of NSSI: psychological problems, alexithymia, impulsiveness, and sociorelational aspects., Patients and Methods: This was a case-control study. The clinical sample (n=33) included adolescents attending our unit for NSSI and other issues; the controls (n=79) were high-school students. Data were collected using six questionnaires: Youth Self-Report, Barratt's Impulsiveness Scale, Toronto Alexithymia Scale, Children's Depression Inventory, Symptom Checklist-90-R, and Child Behavior Checklist., Results: Cases scored significantly higher in all questionnaires. Habitual self-injurers scored higher on impulsiveness and alexithymia. The gesture's repetition seems relevant to the global clinical picture: habitual self-injurers appear more likely to seek help from the sociosanitary services. We found a difference between the self-injurers' and their parents' awareness of the disorder., Conclusion: Habitual self-injurers show signs of having difficulty with assessing the consequences of their actions (nonplanning impulsiveness) and the inability to manage their feelings. Given the significantly higher scores found for cases than for controls on all the psychopathological scales, NSSI can be seen as a cross-category psychiatric disorder, supporting the Diagnostic and Statistical Manual of Mental Disorders decision to include it as a pathological entity in its own right.

Study Objectives: To investigate behavioral aspects and quality of life in children and adolescents with type 1 narcolepsy (NT1)., Methods: We performed a case-control study comparing 29 patients with NT1 versus sex- and age-matched patients with idiopathic epilepsy (n = 39) and healthy controls (n = 39). Behavior and quality of life were evaluated by self-administered questionnaires (Child Behavior Checklist, Pediatric Quality of Life Inventory). Patient groups were contrasted and scale results were correlated with clinical and polysomnographic parameters, and cerebrospinal fluid hypocretin-1 levels., Results: Young patients with NT1 showed increased internalizing problems associated with aggressive behavior. Emotional profile in patients with NT1 positively correlated with age at onset, diagnostic delay, and subjective sleepiness, whereas treatment and disease duration were associated with fewer behavioral problems (attention problems, aggressive behavior, and attention deficit/hyperactivity disorder). Psychosocial health domains of pediatric NT1 were worse than in healthy controls, whereas the physical health domains were comparable., Conclusions: Young NT1 patients show a discrete pattern of altered behavioral, thought, and mood profile in comparison with healthy controls and with idiopathic epilepsy patients thus suggesting a direct link with sleepiness. Further studies investigating behavior in patients with idiopathic hypersomnia or type 2 narcolepsy are needed to disentangle the role of REM sleep dysfunction and hypocretin deficiency in psychiatric disorders. Symptoms of withdrawal, depression, somatic complaints, thought problems, and aggressiveness were common, NT1 children perceived lower school competencies than healthy children, and their parents also reported worse psychosocial health. Our data suggest that early effective treatment and disease self-awareness should be promoted in NT1 children for their positive effect on behavior and psychosocial health., (© 2016 Associated Professional Sleep Societies, LLC.)

Background: This study aims to estimate the alcohol consumption in a large student population in Veneto (North Italy) and to identify possible psychosocial factors associated, with particular attention to the relationship between alcohol consumption and psychopathological vulnerability., Methods: Two semi-structured questionnaires were administered: the Questionnaire for Adolescents' Saturday evening, ad hoc designed for the study, which investigates the habits and alcohol consumption patterns, and the Youth Self Report which assesses the possible presence of psychic and behavioral problems. We recruited 10,465 students attending secondary and high schools in two Venetian provinces (age range 11-19 years). Frequency and amount of alcohol consumption were analyzed in relation to socio-demographic characteristics, habits, and vulnerability to psycho-behavioral problems., Results: Data confirmed the high occurrence of alcohol consumption among young people (36.5%), with a higher prevalence among males (58,0%); the frequency of consumption and the amount of alcohol in taking increase with age, in greater measure after the transition to higher education level (10.4% in secondary school, 36,% in first year till 50% in third year of high school). Alcohol misuse was associated with: pubs and clubs attendance, coming back home late, a greater availability of money and externalizing behavioral problems., Conclusions: Results from this study confirmed the worrying data about the prevalence of alcohol misuse among young people, pointing out some protective and risk factors to be taken into account in planning of preventive interventions.

Background: There is a need to improve the quality of communication between clinicians and parents of young patients with atopic eczema (AE)., Objective: To create a tool to measure the suffering that caregivers experience in association with their child's AE (Caregiver Pictorial Representation of Illness and Self-Measure, Caregiver-PRISM), assess the validity and reliability, and identify factors associated with caregiver suffering., Methods: Caregiver-PRISM was administered to 45 parents of patients from an AE outpatient service (Padua, Italy)., Results: Caregiver-PRISM had a good test-retest reliability (r = 0.85; t7 = 4.13; p < 0.05), content validity and construct validity when used in parents of AE children. Parents with a less positive family affective climate, higher education, or with children following a diet experienced higher suffering associated with their child's AE, demonstrated by lower Caregiver-PRISM scores (p < 0.05)., Conclusion: Our results support the use of Caregiver-PRISM in parents of AE patients to assess suffering associated with patients' illness., (© 2016 S. Karger AG, Basel.)

High-density accumulation of voltage-gated sodium (Nav) channels at nodes of Ranvier ensures rapid saltatory conduction along myelinated axons. To gain insight into mechanisms of node assembly in the CNS, we focused on early steps of nodal protein clustering. We show in hippocampal cultures that prenodes (i.e., clusters of Nav channels colocalizing with the scaffold protein ankyrinG and nodal cell adhesion molecules) are detected before myelin deposition along axons. These clusters can be induced on purified neurons by addition of oligodendroglial-secreted factor(s), whereas ankyrinG silencing prevents their formation. The Nav isoforms Nav1.1, Nav1.2, and Nav1.6 are detected at prenodes, with Nav1.6 progressively replacing Nav1.2 over time in hippocampal neurons cultured with oligodendrocytes and astrocytes. However, the oligodendrocyte-secreted factor(s) can induce the clustering of Nav1.1 and Nav1.2 but not of Nav1.6 on purified neurons. We observed that prenodes are restricted to GABAergic neurons, whereas clustering of nodal proteins only occurs concomitantly with myelin ensheathment on pyramidal neurons, implying separate mechanisms of assembly among different neuronal subpopulations. To address the functional significance of these early clusters, we used single-axon electrophysiological recordings in vitro and showed that prenode formation is sufficient to accelerate the speed of axonal conduction before myelination. Finally, we provide evidence that prenodal clusters are also detected in vivo before myelination, further strengthening their physiological relevance.

Background: Alexithymia is a personality construct characterized by difficulties in verbal emotional expression and a limited ability to use one's imagination. Evidence of alexithymic characteristics was found in adults suffering from headache, while little is known about children. The aim of this study was to establish the prevalence of alexithymia in two different subgroups of children and adolescents suffering from primary headache. We also looked for correlation between alexithymia in children and in their mothers., Methods: This study involved 89 participants: 47 (11 males, 36 females, aged 8 to 17 years) suffering from tension-type headache (TTH), and 42 (18 males, 24 females, aged 8 to 17 years) suffering from migraine (M), based on the International Classification of Headache Disorders (ICHD 2013). A control group of 32 headache-free subjects (26 females and 6 males, aged 8 to 17 years) was also considered. Two questionnaires were administered to measure alexithymia: the Alexithymia Questionnaire for Children to young patients and controls, and the Toronto Alexithymia Scale (TAS-20) to the mothers., Results: Higher rates of alexithymia emerged in the TTH group compared to the M group. In particular, TTH sufferers had difficulty identifying their feelings. The mothers of children with headaches didn't score higher in alexithymia compared to other mothers. In the M and in the control group, there was a significant correlation between the rates of alexithymia in young people and in their mothers., Conclusions: To date no other study has investigated alexithymia in subgroups of primary headaches in developmental age. Our results suggest that patients suffering from TTH are more alexithymic than M patients. This pave the way to etiopathogenetic and clinical considerations, calling for a comprehensive and multidisciplinary approach to tackle the problem of headache.

Background: Headache is the most common symptom of Chiari 1 malformation, a condition characterized by the herniation of cerebellar tonsils through the foramen magnum. However, the headache pattern of cases with Chiari 1 malformations is not well defined in the literature, especially in children., Objective: The aim of this retrospective chart review was to evaluate the frequency and the characteristics of headache in children with Chiari 1 malformation at initial evaluation and during follow up., Methods: Forty-five cases with tonsillar ectopia were selected among 9947 cases under 18 years of age who underwent neuroimaging between 2002 and 2010. A semistructured clinical interview (mean follow-up: 5.2 years) was conducted. Headache was classified according to the second edition of the International Classification of Headache Disorders., Results: Possible associations between clinical picture, in particular headache pattern, but also other signs and symptoms attributable to Chiari 1 malformation, and the extent of tonsillar ectopia were found for 3 different groups: those with borderline (<5 mm, N = 12), mild (5-9 mm, N = 27), and severe tonsillar ectopia (≥10 mm, N = 6), respectively. Twenty-four out of 33 (73%) cases with Chiari 1 malformation complained of headache, and 9/33 (27%) of those patients (5 with mild and 4 with severe tonsillar ectopia) reported headache attributed to Chiari 1 malformation., Conclusions: In our studied pediatric population, the most common symptom for cases diagnosed with Chiari 1 malformation was headache, and headache attributed to Chiari 1 malformation was the most common headache pattern in patients with Chiari 1 malformation. The presence of headache attributed to Chiari 1 malformation along with 3 other signs or symptoms of Chiari 1 malformation were highly predictive of severe tonsillar ectopia., (© 2014 American Headache Society.)

Introduction: Pharmacokinetic variability in critically ill patients is the result of the overlapping of multiple pathophysiological and clinical factors. Unpredictable exposure from standard dosage regimens may influence the outcome of treatment. Therefore, strategies for dosage individualisation are recommended in this setting., Areas Covered: The authors focus on several approaches for dosage individualisation that have been developed, ranging from the well-established therapeutic drug monitoring (TDM) up to the innovative application of pharmacogenomics criteria. Furthermore, the authors summarise the specific population pharmacokinetic models for different drugs developed for critically ill patients to improve the initial dosage selection and the Bayesian forecasting of serum concentrations. The authors also consider the use of Monte Carlo simulation for the selection of dosage strategies., Expert Opinion: Pharmacokinetic/pharmacodynamics (PK/PD) modelling and dosage individualisation methods based on mathematical and statistical criteria will contribute in improving pharmacologic treatment in critically ill patients. Moreover, substantial effort will be necessary to integrate pharmacogenomics criteria into critical care practice. The lack of availability of target biomarkers for dosage adjustment emphasizes the value of TDM which allows a large part of treatment outcome variability to be controlled.

Headache is one of the most common neurological symptom reported in childhood and adolescence, leading to high levels of school absences and being associated with several comorbid conditions, particularly in neurological, psychiatric and cardiovascular systems. Neurological and psychiatric disorders, that are associated with migraine, are mainly depression, anxiety disorders, epilepsy and sleep disorders, ADHD and Tourette syndrome. It also has been shown an association with atopic disease and cardiovascular disease, especially ischemic stroke and patent foramen ovale (PFO).

Background: Short lasting headaches related to activity or cough are rare, particularly in childhood, and can be difficult to diagnose, especially in young children who are not able to describe their symptoms. In the literature there are few data on this topic in adults and the paediatric cases reported are even more rare., Findings: We present the clinical history of a 7-year-old child and a 3-year-old child both diagnosed as having activity-related headaches, characterized by sudden onset of short lasting (few seconds) attacks, that were triggered by cough or exercise. There were no accompanying symptoms and the neurological examination was normal in both cases. Brain magnetic resonance imaging showed, in the first case, a cerebellar pilocytic astrocytoma and, in the second case, a Chiari 1 malformation. Both cases received an early diagnosis, were surgically treated and had a good prognosis at follow-up., Conclusions: When headache has a recent onset, it presents suddenly, and it is triggered by strain, even with normal neurological examination, neuroimaging is mandatory in order to exclude secondary headaches, especially in children.

Background: Osmophobia is frequent in children with migraine (20-35%) but can also occur in up to 14% of cases with tension-type headache (TTH). So far, the prognostic role of this symptom in children with primary headaches has never been evaluated., Methods: A longitudinal prospective study was conducted on 90 young patients with TTH (37 with osmophobia, 53 without osmophobia). We evaluated whether osmophobia could predict the diagnosis transformation from TTH to migraine after a 3-year follow-up., Results and Discussion: In our cases the rate of diagnosis change was significantly greater in cases with osmophobia (62%) than in those without (23%). Osmophobia persisted at a 3-year follow-up in the majority of our cases (85%) and it was found to be one of the major predictors for the development of migraine; other predictors of evolution to migraine were phonophobia, a probable rather than certain diagnosis of TTH and olfactory triggers (p < 0.05)., Conclusion: Our data confirm that osmophobia has an important diagnostic and prognostic role in children with primary headaches and should be systematically investigated at diagnosis and during follow-up.

Polymicrogyria (involving or not the sylvian scissure) with cerebellar cortical dysplasia or vermis hypoplasia has been reported in few cases. In addition, the association between ectopic neurohypophysis and other cortical malformations, including bilateral perisylvian polymicrogyria, has been documented. We describe a girl affected by focal epilepsy since the age of 2 years. Magnetic resonance imaging (MRI) at 11 and 22 years of age showed bilateral perisylvian polymicrogyria, dysplasia of the left cerebellar hemisphere, and ectopic neurohypophysis. Genetic tests, including fluorescent in situ hybridization 22q11.2 and array-comparative genomic hybridization, and pituitary hormones (at the age of 20 years) were normal. The patient is now 22 years old, and she is seizure free under therapy with lamotrigine and levetiracetam. To the best of our knowledge, this is the first description of this complex cerebral malformation. This finding confirms that bilateral perisylvian polymicrogyria can be associated with other cerebral malformations; cerebellum and neurohypophysis must be carefully evaluated in patients with polymicrogyria.

Starting in the 1990s, there has been accumulating evidence of alexithymic characteristics in adult patients with primary headache. Little research has been conducted, however, on the relationship between alexithymia and primary headache in developmental age. In their research on alexithymia in the formative years, the authors identified one of the most promising prospects for research, as discussed here. The aim of this study was to verify whether there is: (a) a link between tension-type headache and alexithymia in childhood and early adolescence; and (b) a correlation between alexithymia in children/preadolescents and their mothers. This study was based on an experimental group of 32 patients (26 females and 6 males, aged from 8 to 15 years, mean 11.2 ± 2.0) suffering from tension-type headache and 32 control subjects (26 females and 6 males, aged from 8 to 15 years, mean 11.8 ± 1.6). Tension-type headache was diagnosed by applying the International Headache Classification (ICHD-II, 2004). The alexithymic construct was measured using an Italian version of the Alexithymia Questionnaire for Children in the case of the juvenile patients and the Toronto Alexithymia Scale (TAS-20) for their mothers. Higher rates of alexithymia were observed in the children/preadolescents in the experimental group (EG) than in the control group; in the EG there was no significant correlation between the alexithymia rates in the children/preadolescents and in their mothers.

Glucose transporter type 1 deficiency syndrome is an inborn error of glucose transport across the blood-brain barrier with hypoglychorrachia. Patients usually present developmental delay, movement disorders, seizures, and acquired microcephaly, variously associated and leading to different phenotypes. We report a 3-year-old girl affected by glucose transporter type 1 deficiency syndrome with carbohydrate responsiveness. Her history was characterized by worsening of ataxia with an increasing interval to the last food intake, occurrence of seizures in the morning before breakfast, slowing of electroencephalogram (EEG) background activity with the appearance of epileptiform discharges during preprandial recordings, and improvement of the electroclinical picture after food intake. By adding a new case to the pertinent literature, we stress the role of pre- and postprandial EEG recordings for the identification of individuals potentially affected by glucose transporter type 1 deficiency syndrome. We also provide a possible physiopathological interpretation of EEG changes related to food intake.

The aim of this study was to show the benefits of combining therapeutic drug monitoring (TDM) and pharmacogenetic analyses to optimize efavirenz (EFV) therapy. Patients were selected to minimize nongenetic differences between patients: 32 HIV adherent patients without drug interactions treated with an EFV nonindividualized dose over at least 1 year and included in a TDM program were genotyped according to minimum steady-state concentrations (C ss min). The EFV plasma concentrations (n = 158) were quantified by high-performance liquid chromatography-ultraviolet, and genetic polymorphisms were analyzed using the PHARMAchip. Central nervous system side effects were assessed systematically. Genetic polymorphisms were detected in 79.2% of patients with EFV Css min outside the therapeutic range (1-4 mg/L), showing the high diagnostic efficacy of combining TDM with pharmacogenetic testing. CYP2B6 (516 G>T) polymorphisms were associated with a significant decrease in EFV plasma clearance in 80% of the poor metabolizer patients (G/T, T/T). All homozygous patients had C ss min greater than 4 mg/L, 75% of them showing central nervous system side effects. For such patients, pharmacogenetic testing with TDM could be advantageous because the polymorphism is a determinant of these circumstances and TDM would allow reductions in dose to be specified without assuming an equal dose for any given genotype. In fact, poor metabolizer patients required less than a 600 mg standard starting dose, implying that if CYP2B6 screening were available, EFV therapy could be started at 400 mg and later TDM-individualized. The results of this study clarify the genotype versus phenotype debate for optimizing drug therapy. Pharmacogenetic testing together with TDM links genotype to phenotypic differences in drug concentrations and adverse events, providing additional support for dosage adjustment and a more efficient use of both approaches. As genotype screens become cheaper, and in combination with TDM, adjusting dosages in the light of genetic polymorphisms will become a reality.

In the literature it has been stressed how important it is during consultation interviews to evaluate an adolescent's insight with a view to starting psychotherapeutic work. Motivated adolescents bring to the therapeutic effort a real, interiorized request for help and can start moving towards a change. The aim of this study is to assess the insight of adolescents with mental disorders during the diagnostic process and to analyze how this relates to further therapeutic compliance and clinical evolution. The study included 55 adolescents, 35 males and 20 females aged between 11 and 19 years, who were advised to receive psychotherapeutic treatment after a diagnostic procedure. Patient insight was assessed at the beginning and end of the diagnostic process. Then, six months later, a clinical interview assessed their therapeutic compliance and clinical evolution. The findings suggest that insight is important when working with adolescents because it influences both therapeutic compliance and clinical outcome.

The aim of the study is to analyze the clinician's alliance with parents during the diagnostic process in relation to therapeutic compliance and clinical evolution of individuals aged 0-11 years. The sample was formed by 84 individuals aged 0 to 11 years (18 < 6 years, 66 aged 6 to 11 years; 62 males and 22 females) who came to the Neuropsychiatric Unit for Children and Adolescents for a consultation regarding psychorelational and behavioral problems. Neuropsychiatric consultation took place in five diagnostic interviews with child and parents, separately. The last session was devoted to communication of psychiatric diagnosis (according to ICD 10) and therapeutic suggestions, if any. The clinician's relationship with parents and patients' participation were evaluated in terms of collaboration and quality of interaction, on the basis of pre-established criteria. Data about patients' therapeutic compliance and clinical outcome were collected during a follow-up visit eight months after the last session. Results suggest that the better the alliance between parents and clinician, the higher the therapeutic compliance and the likelihood of a positive outcome for patients. Our data suggest that good communication with parents benefits child patients, both in terms of response to the parents' need to report their children's worrying behavior and as a response to the discomfort expressed by children when they come in for consultation.

This study determines vancomycin (VAN) population pharmacokinetics (PK) in adult patients with hematological malignancies. VAN serum concentration data (n = 1,004) from therapeutic drug monitoring were collected retrospectively from 215 patients. A one-compartment PK model was selected. VAN pharmacokinetics population parameters were generated using the NONMEM program. A graphic approach and stepwise generalized additive modeling were used to elucidate the preliminary relationships between PK parameters and clinical covariates analyzed. Covariate selection revealed that total body weight (TBW) affected V, whereas renal function, estimated by creatinine clearance, and a diagnosis of acute myeloblastic leukemia (AML) influenced VAN clearance. We propose one general and two AML-specific models. The former was defined by CL (liters/h) = 1.08 x CL(CR(Cockcroft and Gault)) (liters/h); CV(CL) = 28.16% and V (liters) = 0.98 x TBW; CV(V) =37.15%. AML models confirmed this structure but with a higher clearance coefficient (1.17). The a priori performance of the models was evaluated in another 59 patients, and clinical suitability was confirmed. The models were fairly accurate, with more than 33% of the measured concentrations being within +/-20% of the predicted value. This therapeutic precision is twofold higher than that of a non-customized population model (16.1%). The corresponding standardized prediction errors included zero and a standard deviation close to unity. The models could be used to estimate appropriate VAN dosage guidelines, which are not clearly defined for this high-risk population. Their simple structure should allow easy implementation in clinical software and application in dosage individualization using the Bayesian approach.

A new ion exclusion HPLC procedure accomplished with a pulsed electrochemical detection for the determination of several common aliphatic acids is described. A triple-step waveform of the applied potentials, based on the formation/inhibition of PtOH species on the electrode surface, is successfully used for sensitive detection of several aliphatic acids in flowing systems avoiding pre- or postcolumn derivatization and/or cleanup procedures. Under optimal chromatographic conditions (i.e., 50 mM HClO(4)) the proposed method allowed detection limits between 0.5 and 7 microM for all investigated acids, and the dynamic linear range spanned generally over 1 or 2 orders of magnitude. Determination of citric, malic, tartaric, lactic, formic, and acetic acids in several foods and beverages was performed, in approximately 15 min, without the necessity of any sample pretreatment.

Immunosuppressive therapy in paediatric transplant recipients is changing as a consequence of the increasing number of available immunosuppressive agents. Generic and other new formulations are now emerging onto the market, clinical experience is growing, and it is expected that clinicians should tailor immunosuppressive protocols to individual patients by optimising dosages and drugs according to the maturation and clinical status of the child. Most information about the clinical pharmacokinetics of immunosuppressive drugs in paediatrics is centred on cyclosporin, tacrolimus and mycophenolate mofetil in renal and liver transplant recipients; data regarding other immunosuppressants and transplant types are limited. Although the clinical pharmacokinetics of these drugs in paediatric transplant recipients are still under investigation, it is evident that the pharmacokinetic parameters observed in adults may not be applicable to children, especially in younger age groups. In general, patients younger than 5 years old show higher clearance rates irrespective of the organ transplanted or drug used. Another important factor that frequently affects clearance in this patient population is the post-transplant time. In accordance with these findings, and in contrast with the usual under-dosage in children, the need for higher dosages in younger recipients and during the early post-transplant period seems evident. To achieve the best compromise between prevention of rejection and toxicity, dosage individualisation is required and this can be achieved through therapeutic drug monitoring (TDM). This approach is particularly useful to ensure the cost-effective management of paediatric transplant recipients in whom the pharmacokinetic behaviour, target concentrations for clinical use and optimal dosage strategies of a particular drug may not yet be well defined. Although TDM may be a tool for improving immunosuppressive therapy, there is little information concerning its positive contribution to clinical events, including outcomes, for paediatric patients. Substantial information to support the use of TDM exists for cyclosporin and, to a lesser extent, for tacrolimus, but a diversity of options affects their implementation in the clinical setting. The role of TDM in therapy with mycophenolate mofetil and sirolimus has yet to be defined regarding both methods and clinical indications. Pharmacodynamic monitoring appears more suited to other immunosuppressants such as azathioprine, corticosteroids and monoclonal or polyclonal antibodies. If coupled with pharmacokinetic measurements, such monitoring would allow earlier and more precise optimisation of therapy. Very few population pharmacokinetic studies have been carried out in paediatric transplant patients. This type of study is needed so that techniques such as Bayesian forecasting can be applied to optimise immunosuppressive therapy in paediatric transplant patients.

A chemically modified electrode composed of nickel oxyhydroxide film deposited on noble metals (i.e., gold or platinum) was characterized in an alkaline medium by cyclic voltammetry and XPS (X-ray photoelectron spectroscopy) techniques. The nickel was deposited on the gold substrate in an alkaline medium by various strategies: cycling the potential between -0.1 and 0.65 V vs SCE, in potentiostatic conditions at potentials comprised between 0.0 and 0.55 V and by simple immersion of the electrode in non-deaerated 0.2 M NaOH solutions containing 3 mM K2Ni(CN)4. The effects of several experimental parameters such as applied potentials, pH, tetracyanonickelate concentration, electrode substrate, etc., on the nickel film formation and growth were evaluated. The electroactivity of the resulting composite gold-nickel electrode was investigated in an alkaline medium toward the oxidation of carbohydrates using arabinose as a model compound.

Objective: To characterize the population pharmacokinetics of amikacin in intensive care unit (ICU) patients and to analyse whether these patients show different kinetic behaviour on the basis of their clinical diagnoses., Method: The patient population comprised 104 medical ICU patients on amikacin treatment for several presumed or documented Gram-negative infections. Four study groups were defined according to patients' clinical diagnosis: sepsis group (n = 39), trauma group (n = 20), pneumonia group (n = 21) and 'other diagnosis' group (n = 24). The pharmacokinetic parameters for amikacin in these patients were then compared., Results: The ICU patients were found to have increased values for the amikacin volume of distribution (0.52 +/- 0.21 litres/kg), whereas total amikacin clearance expressed as a linear function of creatinine clearance was Cl (ml/min/kg) = 0.13 +/- 0.86 ClCR, which is not significantly different from other estimations reported in the literature. However, this relationship revealed statistically significant differences among the four groups of ICU patients. Moreover, the septic and trauma patients showed higher (but not statistically significant) values for the amikacin volume of distribution., Conclusion: The amikacin pharmacokinetic parameters obtained should allow Bayesian individualization of amikacin doses in patients admitted to medical ICUs, on the basis of their clinical diagnoses.

Bayesian forecasting offers several important advantages for dosage individualisation in children, although, unlike for adults, its use in this population is much lower. Indeed, currently Bayesian methods are underused in this patient population. The paucity of paediatric population pharmacokinetic parameters, and the unavailability of specific clinical pharmacokinetic software for the whole paediatric population, are the main limitations to the application of Bayesian methods in these patients. When these problems have been overcome, this approach will allow clinicians to achieve therapeutic concentrations more readily, faster and more precisely, thus making the methodology highly attractive in the paediatric setting.

Objective: This study evaluates the cost-effectiveness of vancomycin serum concentration monitoring in patients with hematologic malignancies., Methods: The study was designed as a prospective randomized study. Seventy immunocompromised febrile patients with hematologic malignancies were randomly assigned to either a vancomycin therapeutic drug monitoring group (TDM group; n = 37) or to a control group (n = 33). Intervention in the TDM group involved patient follow-up by a clinical pharmacist to obtain and pharmacokinetically interpret serum vancomycin concentrations for dosage individualization., Results: Evaluation of all patients included global clinical response and nephrotoxicity, as well as the economic costs and effectiveness derived from the vancomycin monitoring program. There were no significant differences between the TDM and control groups in the outcome measures, except for the incidence of nephrotoxicity: the rates of minor nephrotoxicity were 33.3% and 13.5% in the control and TDM groups, respectively. The corresponding figures for moderate nephrotoxicity were 9.1% and 0%. Logistic regression analysis confirmed that TDM independently reduced the incidence of nephrotoxicity in this patient population. On the basis of this reduced nephrotoxicity, a incremental cost of $435 per case of nephrotoxicity prevented was found for vancomycin serum concentration monitoring., Conclusions: A decreased incidence of nephrotoxicity provides evidence of a real clinical benefit to patient management in patients with hematologic malignancies. The TDM for vancomycin therapy in this high-risk population has been shown to be a cost-effective procedure.

We evaluated the predictive performance of two commercial computer programs (Abbott and Simkin) for pharmacokinetic dosing of vancomycin in 50 critically ill patients, 40 with hematologic malignancies and 10 in intensive care. Predictive performance was assessed for both pharmacokinetics and forecasting vancomycin serum levels by using a set of peak and trough drug levels per patient. The effect of renal function and serum sampling (steady state, nonsteady state) on predictive performance of both programs was also analyzed. No statistically significant differences were found between the programs for predicting either pharmacokinetics or serum levels, regardless of a patient's renal function or serum sampling. The Abbott and Simkin programs were similar for individualizing vancomycin dosage regimens.

1. The aim of this study has been to evaluate the response to imipramine treatment in enuretic children through the use of a series of clinical and pharmacological variables and by applying a multivariate (principal components) analysis technique. 2. The study was carried out on 146 children whose ages ranged from 5 to 14 years, and who received variable doses of imipramine (12.5 to 100 mg day-1). 3. The quantitative variables analyzed were: drug dosage, serum levels of imipramine and its metabolite desipramine, the relationship between them both, the duration of treatment, age and weight. 4. The qualitative variables were: compliance, presence of side-effects, enuretic and/or psychiatric antecedents, intelligence quotient (I.Q.), the existence (or absence) of related pathologies, sex, and the type of enuresis. 5. The response to treatment was quantified by means of the percentage of decrease in frequency of enuresis as compared with the initial frequency. 6. The results obtained show that the variables which are most associated with the reduction of enuresis are, in decreasing order: the dosage of imipramine administered, the duration of treatment, compliance and the level/dose ratio for the sum of the drug and metabolite levels.

Photosensitizing activity of haematoporphyrin (Hp) on Candida albicans cells is mainly promoted by unbound dye molecules in the bulk aqueous medium. Moreover, the death of photosensitized cells is dependent on the dye concentration, irradiation time, irradiation temperature, and the composition of the growth media. Morphological and biochemical studies indicate that the photoprocess involves an initial limited alteration of the cytoplasmic membrane, which allows the penetration of the dye into the cell with consequent photodamage of intracellular targets. In this respect, the Hp-sensitized photoinactivation of eukaryotic microbial cells differs from that in prokaryotic cells.

The incidence of potentially toxic serum levels (greater than or equal to 400 ng/ml) was analyzed in a group of 196 monitored patients on a standard dosage regimen (75-225 mg/day) of several antidepressants: imipramine, amitriptyline, nortriptyline, maprotiline and clomipramine. Mean incidence was 12%. The maximum antidepressants serum levels in these patients ranged from 403 to 1,776 ng/ml. The drug/metabolite ratio was 1.5 +/- 0.7. Only in 23% of the cases did the clinical symptoms allow us to suspect the presence of potentially toxic serum levels. The factors that may contribute to the appearance of high serum levels were analyzed; these are: association of neuroleptic agents to the antidepressant therapy, advanced age and administration of doses above 2.5 mg/kg/day. In 64% of the patients, the clinical criteria suggested the need for a reduction in the dose, with a mean value of 42%.

The aim of this study was to establish the performance of pharmacokinetic methods employing little data on serum drug concentrations obtained in routine therapeutic drug monitoring of imipramine. Forty-three and 123 serum levels were obtained in 8 adult depressive patients (aged 57-80 y) and 34 enuretic children (aged 5-13 y), respectively. Forecasting of the serum concentrations was performed based on mean population pharmacokinetic parameters (method A), with knowledge of one steady-state serum concentration (method B), and from two or more steady-state serum concentrations (method C). The accuracy and precision of each method were evaluated from the mean prediction error (ME) and from the root mean squared prediction error (RMSE), respectively. The values of ME and RMSE of methods B and C proved to be significantly lower than those found using method A. Method C was the most precise and accurate in both populations. Method A underestimates the serum concentrations observed in adults (ME greater than 0) but overestimates them in children (ME less than 0), although to a lesser extent. The study shows that it is possible to obtain a good estimation of individual dosage needs from one or more serum concentrations obtained at steady state. Clinical application of these methods (B and C) yields an increase in the efficiency and safety of the treatment, particularly in special populations such as geriatric and pediatric patients.