Clinical guidelines on long-term pharmacotherapy for bipolar disorder in children and adolescents

Bipolar disorder is a severe affective disorder which can present in adolescence, or sometimes earlier, and often requires a pharmacotherapeutic approach. The phenomenology of bipolar disorder in children and adolescents appears to differ from that of adult patients, prompting the need for specific pharmacotherapy guidelines for long-term management in this patient population. Current treatment guidelines were mainly developed based on evidence from studies in adult patients, highlighting the requirement for further research into the pharmacotherapy of children and adolescents with bipolar disorder. This review compares and critically analyzes the available guidelines, discussing the recommended medication classes, their mechanisms of action, side effect profiles and evidence base

Do obsessive compulsive symptoms mediate the relationship between maternal eating psychopathology and restrictive feeding practices?

Objective: Symptoms of maternal eating disorders have been linked with the use of maladaptive restrictive child feeding practices. However, how these symptoms impact upon restriction in child feeding is poorly understood. The aims of this research were to assess whether symptoms of obsessive compulsiveness, which are often comorbid with eating disorder symptoms, mediate the relationships between maternal eating disorder symptoms and the use of restrictive feeding practices. Method: A total of 128 mothers of children aged 2-6 years completed measures of their restrictive feeding practices, symptoms of eating disorders, and obsessive compulsiveness. Results: Maternal restriction was positively correlated with symptoms of drive for thinness, bulimia, and checking and cleaning obsessions and compulsions. Cleaning obsessions and compulsions mediated the relationships between maternal drive for thinness and feeding restriction. Conclusion: Cleaning obsessions and compulsions may help to explain the relationships between some symptoms of maternal eating disorders and the use of restrictive feeding practices. © 2008 by Wiley Periodicals, Inc.

Does cochlear implantation improve speech recognition in children with auditory neuropathy spectrum disorder? A systematic review

OBJECTIVE: Cochlear implantation (CI) is a standard treatment for severe-profound sensorineural hearing loss (SNHL). However, consensus has yet to be reached on its effectiveness for hearing loss caused by auditory neuropathy spectrum disorder (ANSD). This review aims to summarize and synthesize current evidence of the effectiveness of CI in improving speech recognition in children with ANSD. DESIGN: Systematic review. STUDY SAMPLE: A total of 27 studies from an initial selection of 237. RESULTS: All selected studies were observational in design, including case studies, cohort studies, and comparisons between children with ANSD and SNHL. Most children with ANSD achieved open-set speech recognition with their CI. Speech recognition ability was found to be equivalent in CI users (who previously performed poorly with hearing aids) and hearing-aid users. Outcomes following CI generally appeared similar in children with ANSD and SNHL. Assessment of study quality, however, suggested substantial methodological concerns, particularly in relation to issues of bias and confounding, limiting the robustness of any conclusions around effectiveness. CONCLUSIONS: Currently available evidence is compatible with favourable outcomes from CI in children with ANSD. However, this evidence is weak. Stronger evidence is needed to support cost-effective clinical policy and practice in this area.

The psychosocial impact of an activity holiday for young children with severe food allergy:a longitudinal study

Background Food allergy has been shown to severely affect quality of life (QoL) in children and their families. The Anaphylaxis Campaign UK supports families with allergic children and as part of that support ran an activity holiday for those with food allergy. This study investigated the effectiveness of this activity holiday for reducing anxiety and improving QoL and food allergy management for these children. Methods Measures were taken at baseline, at the start of the activity holiday, at the end of the holiday, at 3 and 6 months follow-up. Children (n = 24) completed a paediatric food allergy–specific QoL questionnaire (PFA-QL), a generic QoL questionnaire (PedsQL™), the Spence Children's Anxiety Scale (SCAS) and the Children's Health Locus of Control (CHLC) scale at all stages of the study. Results There were significant improvements in social QoL, food allergy–specific QoL, total CHLC and internal locus of control scores over time (p > 0.05). There were significant decreases in powerful others locus of control, total anxiety and obsessive compulsive disorder scores (p < 0.05). Greater anxiety significantly correlated with poorer QoL at all time points; no correlations with locus of control were significant at the 3- and 6-month follow-up. Conclusions The activity holiday was of significant benefit to the children who took part, providing support for the need for activity holidays such as this for children with severe food allergy. Ways in which adaptive locus of control and improved quality of life can be facilitated need to be further explored.

Efficacy and safety of second-generation antipsychotic long-acting injections (SGA LAIs) in maintenance treatment of bipolar disorder:protocol for a systematic review and meta-analysis

INTRODUCTION: Bipolar disorder requires long-term treatment but non-adherence is a common problem. Antipsychotic long-acting injections (LAIs) have been suggested to improve adherence but none are licensed in the UK for bipolar. However, the use of second-generation antipsychotics (SGA) LAIs in bipolar is not uncommon albeit there is a lack of systematic review in this area. This study aims to systematically review safety and efficacy of SGA LAIs in the maintenance treatment of bipolar disorder. METHODS AND ANALYSIS: The protocol is based on Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and will include only randomised controlled trials comparing SGA LAIs in bipolar. PubMed, EMBASE, CINAHL, Cochrane Library (CENTRAL), PsychINFO, LiLACS, http://www.clinicaltrials.gov will be searched, with no language restriction, from 2000 to January 2016 as first SGA LAIs came to the market after 2000. Manufacturers of SGA LAIs will also be contacted. Primary efficacy outcome is relapse rate or delayed time to relapse or reduction in hospitalisation and primary safety outcomes are drop-out rates, all-cause discontinuation and discontinuation due to adverse events. Qualitative reporting of evidence will be based on 21 items listed on standards for reporting qualitative research (SRQR) focusing on study quality (assessed using the Jadad score, allocation concealment and data analysis), risk of bias and effect size. Publication bias will be assessed using funnel plots. If sufficient data are available meta-analysis will be performed with primary effect size as relative risk presented with 95% CI. Sensitivity analysis, conditional on number of studies and sample size, will be carried out on manic versus depressive symptoms and monotherapy versus adjunctive therapy.

Adherence to treatment in children and adolescents with cystic fibrosis:a cross-sectional, multi-method study investigating the influence of beliefs about treatment and parental depressive symptoms

Background: Adherence to treatment is often reported to be low in children with cystic fibrosis. Adherence in cystic fibrosis is an important research area and more research is needed to better understand family barriers to adherence in order for clinicians to provide appropriate intervention. The aim of this study was to evaluate adherence to enzyme supplements, vitamins and chest physiotherapy in children with cystic fibrosis and to determine if any modifiable risk factors are associated with adherence. Methods: A sample of 100 children (≤18 years) with cystic fibrosis (44 male; median [range] 10.1 [0.2-18.6] years) and their parents were recruited to the study from the Northern Ireland Paediatric Cystic Fibrosis Centre. Adherence to enzyme supplements, vitamins and chest physiotherapy was assessed using a multi-method approach including; Medication Adherence Report Scale, pharmacy prescription refill data and general practitioner prescription issue data. Beliefs about treatments were assessed using refined versions of the Beliefs about Medicines Questionnaire-specific. Parental depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale. Results: Using the multi-method approach 72% of children were classified as low-adherers to enzyme supplements, 59% low-adherers to vitamins and 49% low-adherers to chest physiotherapy. Variations in adherence were observed between measurement methods, treatments and respondents. Parental necessity beliefs and child age were significant independent predictors of child adherence to enzyme supplements and chest physiotherapy, but parental depressive symptoms were not found to be predictive of adherence. Conclusions: Child age and parental beliefs about treatments should be taken into account by clinicians when addressing adherence at routine clinic appointments. Low adherence is more likely to occur in older children, whereas, better adherence to cystic fibrosis therapies is more likely in children whose parents strongly believe the treatments are necessary. The necessity of treatments should be reinforced regularly to both parents and children.

Liposomes as carriers for polymyxins in the treatment of cystic fibrosis lung infections

Cystic fibrosis (CF) is the most common autosomal recessive disorder affecting Caucasian populations. The pathophysiology of this disorder predisposes the lungs of affected patients to chronic infection, typically by Pseudomonas aeruginosa, which is the main cause of morbidity and mortality. Recently, attention has focused on aerosolised polymyxins, which are given prophylactically in an effort to limit infection and subsequent lung damage. This class of antimicrobial compounds is highly active against P. aeruginosa and possess the advantage that resistance rarely develops. However, the rapid lung clearance of antibiotics is a well documented phenomenon and it was postulated that polymyxin treatment could be further improved by liposomal encapsulation. As part of the development of liposomal polymyxin B, analytical methodology (radiolabelling, HPLC and protein assay) applicable to liposomal formulations was established. Liposomes were prepared by the dehydration-rehydration method and encapsulation efficiencies were determined for a number of phospholipid compositions. Vesicles were characterised with respect to size, zeta potential, morphology and release characteristics. The surface hydrophobicity of vesicles was quantified by hydrophobic interaction chromatography and it was found that this method produced comparable results to techniques conventionally used to assess this property. In vivo testing of liposomal polymyxins demonstrated that encapsulation successfully prevented the rapid pulmonary clearance of PXB. Antimicrobial activity of liposomal formulations was quantified and found to be dependent on both the vesicle surface characteristics and their release profile. Investigation of the interaction of PXB with lipopolysaccharide was undertaken and results demonstrated that PXB caused significant structural distortion of the lipid A region. This may be sufficient to abrogate the potentiating action of LPS in the inflammatory cascade.

The effectiveness of lamotrigine in the treatment of photosensitive epilepsy

Photosensitive epilepsy and associated pattern sensitivity are more prevalent in females and are usually treated with sodium valproate. Sodium valproate has an adverse effect profile, which particularly affects females, including teratogenicity, association with the polycystic ovary syndrome and weight gain. It would be useful therefore if an alternative treatment for photosensitive epilepsy could be found. The principle aim of this study was to investigate the effectiveness of lamotrigine in the treatment of photosensitive epilepsy in adults and children. Patients were either drug-naive, commencing lamotrigine therapy or were transferring from other antiepileptic drugs to lamotrigine (primarily sodium valproate) due to lack of response, adverse effects or desired pregnancy. The photoparoxsymal response in the electroencephalograph was used as the primary measure of photo and pattern sensitivity. In addition the effects of lamotrigine on occipital spikes and normal responses in the EEG to visual stimuli were investigated. Secondary measures also included the resting EEG, seizures, body mass index, menstrual function, mood and cognitive function. The results suggest that in adult patients lamotrigine is efficacious in the treatment of photosensitive epilepsy, although it appears inferior to sodium valproate. Lamotrigine does however have a more favourable adverse effect profile than valproate. The results indicate that lamotrigine therapy is suitable for photosensitive epilepsy in women of childbearing age or in patients experiencing unacceptable adverse effects with valproate therapy. Patients are more likely to respond to lamotrigine treatment if they present with sensitivity to a limited number of frequencies. Lamotrigine does not seem to be as efficacious in the treatment of children, although against it may be considered a second line drug if the child does not respond to or will not tolerate sodium valproate.

A novel dried blood spot-LCMS method for the quantification of methotrexate polyglutamates as a potential marker for methotrexate use in children

Objective: Development and validation of a selective and sensitive LCMS method for the determination of methotrexate polyglutamates in dried blood spots (DBS). Methods: DBS samples [spiked or patient samples] were prepared by applying blood to Guthrie cards which was then dried at room temperature. The method utilised 6-mm disks punched from the DBS samples (equivalent to approximately 12 μl of whole blood). The simple treatment procedure was based on protein precipitation using perchloric acid followed by solid phase extraction using MAX cartridges. The extracted sample was chromatographed using a reversed phase system involving an Atlantis T3-C18 column (3 μm, 2.1x150 mm) preceded by Atlantis guard column of matching chemistry. Analytes were subjected to LCMS analysis using positive electrospray ionization. Key Results: The method was linear over the range 5-400 nmol/L. The limits of detection and quantification were 1.6 and 5 nmol/L for individual polyglutamates and 1.5 and 4.5 nmol/L for total polyglutamates, respectively. The method has been applied successfully to the determination of DBS finger-prick samples from 47 paediatric patients and results confirmed with concentrations measured in matched RBC samples using conventional HPLC-UV technique. Conclusions and Clinical Relevance: The methodology has a potential for application in a range of clinical studies (e.g. pharmacokinetic evaluations or medication adherence assessment) since it is minimally invasive and easy to perform, potentially allowing parents to take blood samples at home. The feasibility of using DBS sampling can be of major value for future clinical trials or clinical care in paediatric rheumatology. © 2014 Hawwa et al.

Adherence to antiepileptic medicines in children:a multiple-methods assessment involving dried blood spot sampling

Purpose - To evaluate adherence to prescribed antiepileptic drugs (AEDs) in children with epilepsy using a combination of adherence-assessment methods. Methods - A total of 100 children with epilepsy (≤17 years old) were recruited. Medication adherence was determined via parental and child self-reporting (≥9 years old), medication refill data from general practitioner (GP) prescribing records, and via AED concentrations in dried blood spot (DBS) samples obtained from children at the clinic and via self- or parental-led sampling in children's own homes. The latter were assessed using population pharmacokinetic modeling. Patients were deemed nonadherent if any of these measures were indicative of nonadherence with the prescribed treatment. In addition, beliefs about medicines, parental confidence in seizure management, and the presence of depressed mood in parents were evaluated to examine their association with nonadherence in the participating children. Key Findings - The overall rate of nonadherence in children with epilepsy was 33%. Logistic regression analysis indicated that children with generalized epilepsy (vs. focal epilepsy) were more likely (odds ratio [OR] 4.7, 95% confidence interval [CI] 1.37–15.81) to be classified as nonadherent as were children whose parents have depressed mood (OR 3.6, 95% CI 1.16–11.41). Significance - This is the first study to apply the novel methodology of determining adherence via AED concentrations in clinic and home DBS samples. The present findings show that the latter, with further development, could be a useful approach to adherence assessment when combined with other measures including parent and child self-reporting. Seizure type and parental depressed mood were strongly predictive of nonadherence.

Ambulatory electroencephalogram in children:a prospective clinical audit of 100 cases

Ambulatory electroencephalogram has been used for differentiating epileptic from nonepileptic events, recording seizure frequency and classification of seizure type. We studied 100 consecutive children prospectively aged 11 days to 16 years that were referred for an ambulatory electroencephalogram to a regional children's hospital. Ambulatory electroencephalogram was clinically useful in contributing to a clinical diagnosis in 71% of children who were referred with a range of clinical questions. A diagnosis of epileptic disorder was confirmed by obtaining an ictal record in 26% and this included 11 children that had previously normal awake and or sleep electroencephalogram. We recommend making a telephone check of the current target event frequency and prioritising those with typical events on most days in order to improve the frequency of recording a typical attack.

The use of antidepressants to treat attention deficit hyperactivity disorder in adults

There is increasing evidence that children continue to experience attention deficit hyperactivity disorder (ADHD) symptoms into adult life. The two main treatments for ADHD are antidepressants and stimulants. Here, the effectiveness data relating to the use of antidepressants in adults with ADHD are reviewed. Four controlled and six open studies were identified. Although, there is only limited data currently available, antidepressants may offer an effective therapy for adult ADHD. Controlled trials have studied desipramine, atomoxetine and bupropion, with most evidence supporting the efficacy of desipramine. The initial data indicate that atomoxetine is less effective than desipramine. The efficacy of bupropion is unclear. Initial published open data suggest a response rate of 50-78% with venlafaxine. Controlled studies are required to confirm this efficacy. Most of the present data are short-term, therefore long-term effectiveness data are required.

Effects of recombinant human DNase and hypertonic saline on airway inflammation in children with cystic fibrosis

Recombinant human DNase (rhDNase) is an established treatment in cystic fibrosis (CF), but it may liberate cationic mediators bound to DNA in the airways. An alternative mucolytic therapy is hypertonic saline (HS); however, HS may potentiate neutrophilic inflammation. We compared the effect of rhDNase and HS on cationic proinflammatory mediators in CF sputum. In a randomized, crossover trial, 48 children with CF were allocated consecutively to 12 weeks of once-daily 2.5 mg rhDNase, alternate-day 2.5 mg rhDNase, and twice-daily 7% HS. Sputum levels of total interleukin-8 (IL-8), free IL-8, myeloperoxidase, eosinophil cationic protein, and neutrophil elastase (NE) activity were measured before and after each treatment. The change in mediator levels from baseline with daily rhDNase and HS was not significant; however, with alternate-day rhDNase, there was an increase in free IL-8. When changes in mediator levels with daily rhDNase were compared with alternate-day rhDNase and HS, no significant differences were detected. Only changes in NE activity were associated with changes in lung function. In summary, we were unable to show that rhDNase or HS promote airway inflammation in CF.

Priming moral self-ambivalence heightens deliberative behaviour in self-ambivalent individuals

Background: Recent work on cognitive-behavioural models of obsessive-compulsive disorder has focused on the roles played by various aspects of self-perception. In particular, moral self-ambivalence has been found to be associated with obsessive-compulsive phenomena. Aims: In this study we used an experimental task to investigate whether artificially priming moral self-ambivalence would increase participants' deliberation on ethical problems, an index that might be analogous to obsessive-compulsive behaviour. Method: Non-clinical participants completed two online tasks designed to prime either moral self-ambivalence, general uncertainty, or neither. All participants then completed a task requiring them to consider solutions to moral dilemmas. We recorded the time participants took to respond to the dilemmas and the length of their responses; we then combined these variables to create a measure of deliberation. Results: Priming moral self-ambivalence led to increases in deliberation, but this was only significant among those participants who scored highly on a baseline measure of moral self-ambivalence. Priming general uncertainty had no significant effect upon deliberation. Conclusions: The results suggest that moral self-ambivalence may play a role in the maintenance of obsessive-compulsive behaviour. We propose that individuals who are morally self-ambivalent might respond to situations in which this ambivalence is made salient by exhibiting behaviour with obsessive-compulsive characteristics. These findings have implications for the incorporation of ideas about self-concept into theories of obsessive-compulsive disorder.

Solid oral forms availability in children:a cost saving investigation

AIM: To assess the suitability and potential cost savings, from both the hospital and community perspective, of prescribed oral liquid medicine substitution with acceptable solid forms for children over 2 years. METHOD: Oral liquid medicines dispensed from a paediatric hospital (UK) in 1 week were assessed by screening for existence of the solid form alternative and evaluating the acceptability of the available solid form, firstly related to the prescribed dose and secondly to acceptable size depending on the child's age. Costs were calculated based on providing treatment for 28 days or prescribed duration for short term treatments. RESULTS: Over 90% (440/476) of liquid formulations were available as a marketed solid form. Considering dosage acceptability (maximum of 10% deviation from prescribed dosage or 0% for narrow therapeutic range drugs, maximum tablet divisions into quarters) 80% of liquids could be substituted with a solid form. The main limitation for liquid substitution would be solid form size. However, two-thirds of prescribed liquids could have been substituted with a suitable solid form for dosage and size, with estimated savings being of 5K and 8K in 1 week, respectively based on hospital and community costs, corresponding to a projected annual saving of 238K and 410K (single institution). CONCLUSION: Whilst not all children over 2 years will be able to swallow tablets, drug cost savings if oral liquid formulations were substituted with suitable solid dosage forms would be considerable. Given the numerous advantages of solid forms compared with liquids, this study may provide a theoretical basis for investing in supporting children to swallow tablets/capsules.