A statistical model to predict the reduction of lichenification in atopic dermatitis

Acute symptoms of atopic dermatitis (AD), such as erythema, oedema/papulations and excoriations, respond quickly to topical corticosteroid treatment. Conversely, lichenification is regarded as a troublesome non-acute symptom of chronic AD which can take months of treatment before any improvement is seen. However, very little data actually support this opinion. Here, we analyse lichenification scores in 3 multicentre, short-term studies of nearly similar design. Two of these studies were active comparator dosage trials administered with either fluticasone propionate cream or ointment once or twice daily, the third study was a placebo control. In each of these 4-weeks studies lichenification was measured weekly. For the evaluation of the lichenification score over time a random-coefficients regression model was used. In all active treatments lichenification significantly improved (p 80% of patients scoring no, very mild or mild lichenification after 4 weeks. We developed a model in which the lichenification score drops off linearly with the square root of time. The resulting convexly-shaped downward time trend of lichenification was significant during all treatments. This effect was significantly stronger during active treatment than with placebo. Fluticasone propionate can improve moderate to severe lichenification in a relative short period of time

Psychosocial sequelae in 29 children with giant congenital melanocytic naevi

Giant congenital melanocytic naevus (GCMN) may be expected to affect psychosocial functioning of children and their parents due to deviant appearance and painful treatment. To obtain insight into clinical aspects and psychosocial functioning of those suffering from GCMN, 29 children diagnosed with GCMN syndrome or single GCMN received a dermatological examination, were interviewed, and their mothers and teachers completed standardized questionnaires on the child's competence and behavioural/emotional problems and their own adjustment. Social problems were reported for 30% of the patients and behavioural/emotional problems for 25.9%. There was no correlation between visibility of the naevus, treatment or child age and psychological problems. Mothers reported considerable psychosocial burden. It is concluded that children with GCMN are at increased risk of social and behavioural/emotional problems, and mothers suffer considerable psychological impact of their child's condition

Value of urinary N-methylhistamine measurements m childhood mastocytosis

Background: Histamine is an indicator of mast cell activation. N- methylhistamine (NMH) is a metabolite of histamine that can be measured in urine. Objective: Our purpose was to assess the usefulness of determining urinary NMH levels for the diagnosis and follow-up of patients with mastocytosis. Methods: Urinary NMH levels were determined in 44 patients and were correlated with disease activity and extension. The control group consisted of 24 children without mastocytosis or any other skin disease. Results: A significant negative correlation was found between NMH and age in patients with active mastocytosis and in the control group. Adjusted for age, NMH values were significantly higher in patients with active mastocytosis. There was a significant difference in NMH values between patients with diffuse cutaneous mastocytosis, patients with active urticaria pigmentosa, and patients with active mastocytomas. However, there was a substantial overlap of NMH values in the different subgroups. Conclusion: Urinary NMH values tend to decrease with age. Urinary NMH values correlated with the extent and the activity of the disease. High NMH values suggest more extensive involvement

Pimecrolimus in atopic dermatitis: Consensus on safety and the need to allow use in infants

Atopic dermatitis (AD) is a distressing dermatological disease, which is highly prevalent during infancy, can persist into later life and requires long-term management with anti-inflammatory compounds. The introduction of the topical calcineurin inhibitors (TCIs), tacrolimus and pimecrolimus, more than 10 yr ago was a major breakthrough for the topical anti-inflammatory treatment of AD. Pimecrolimus 1% is approved for second-line use in children (≥2 yr old) and adults with mild-to-moderate AD. The age restriction was emphasized in a boxed warning added by the FDA in January 2006, which also highlights the lack of long-term safety data and the theoretical risk of skin malignancy and lymphoma. Since then, pimecrolimus has been extensively investigated in short- and long-term studies including over 4000 infants (<2 yr old). These studies showed that pimecrolimus effectively treats AD in infants, with sustained improvement with long-term intermittent use. Unlike topical corticosteroids, long-term TCI use does not carry the risks of skin atrophy, impaired epidermal barrier function or enhanced percutaneous absorption, and so is suitable for AD treatment especially in sensitive skin areas. Most importantly, the studies of pimecrolimus in infants provided no evidence for systemic immunosuppression, and a comprehensive body of evidence from clinical studies, post-marketing surveillance and epidemiological investigations does not support potential safety concerns. In conclusion, the authors consider that the labelling restrictions regarding the use of pimecrolimus in infants are no longer justified and recommend that the validity of the boxed warning for TCIs should be reconsidered

Dopamine and memory dedifferentiation in aging.

The dedifferentiation theory of aging proposes that a reduction in the specificity of neural representations causes declines in complex cognition as people get older, and may reflect a reduction in dopaminergic signaling. The present pharmacological fMRI study investigated episodic memory-related dedifferentiation in young and older adults, and its relation to dopaminergic function, using a randomized placebo-controlled double-blind crossover design with the agonist Bromocriptine (1.25mg) and the antagonist Sulpiride (400mg). We used multi-voxel pattern analysis to measure memory specificity: the degree to which distributed patterns of activity distinguishing two different task contexts during an encoding phase are reinstated during memory retrieval. As predicted, memory specificity was reduced in older adults in prefrontal cortex and in hippocampus, consistent with an impact of neural dedifferentiation on episodic memory representations. There was also a linear age-dependent dopaminergic modulation of memory specificity in hippocampus reflecting a relative boost to memory specificity on Bromocriptine in older adults whose memory was poorer at baseline, and a relative boost on Sulpiride in older better performers, compared to the young. This differed from generalized effects of both agents on task specificity in the encoding phase. The results demonstrate a link between aging, dopaminergic function and dedifferentiation in the hippocampus.This research was funded mainly by a Fellowship to AMM from Research into Ageing, UK, and by an RCUK Academic Fellowship at the University of Edinburgh. Some of the research was conducted by Hunar Abdulrahman as part of a dissertation for the MSc in Neurosciences at the University of Edinburgh. The research was also supported by a Human Brain Project grant from the National Institute of Mental Health and the National Institute of Biomedical Imaging & Bioengineering. PCF was supported by a Wellcome Trust Senior Fellowship in Clinical Science, and by the Bernard Wolfe Health Neuroscience Fund. ETB is a part-time (50%) employee and shareholder of GSK. AMM is a member of the University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross-council Lifelong Health and Wellbeing Initiative, Grant number G0700704/84698.This is the accepted manuscript. The final version is available at http://dx.doi.org/10.1016/j.neuroimage.2015.03.03

Determinants and mediating mechanisms of quality of life and disease-specific symptoms among thyroid cancer patients: the design of the WaTCh study

BACKGROUND: Thyroid cancer (TC) patients are understudied but appear to be at risk for poor physical and psychosocial outcomes. Knowledge of the course and determinants of these deteriorated outcomes is lacking. Furthermore, little is known about mediating biological mechanisms. OBJECTIVES: The WaTCh-study aims to; 1. Examine the course of physical and psychosocial outcomes. 2. Examine the association of demographic, environmental, clinical, physiological, and personality characteristics to those outcomes. In other words, who is at risk? 3. Reveal the association of mediating biological mechanisms (inflammation, kynurenine pathway) with poor physical and psychological outcomes. In other words, why is a person at risk? DESIGN AND METHODS: Newly diagnosed TC patients from 13 Dutch hospitals will be invited. Data collection will take place before treatment, and at 6, 12 and 24 months after diagnosis. Sociodemographic and clinical information is available from the Netherlands Cancer Registry. Patients fill-out validated questionnaires at each time-point to assess quality of life, TC-specific symptoms, physical activity, anxiety, depression, health care use, and employment. Patients are asked to donate blood three times to assess inflammation and kynurenine pathway. Optionally, at each occasion, patients can use a weighing scale with bioelectrical impedance analysis (BIA) system to assess body composition; can register food intake using an online food diary; and can wear an activity tracker to assess physical activity and sleep duration/quality. Representative Dutch normative data on the studied physical and psychosocial outcomes is already available. IMPACT: WaTCh will reveal the course of physical and psychosocial outcomes among TC patients over time and answers the question who is at risk for poor outcomes, and why. This knowledge can be used to provide personalized information, to improve screening, to develop and provide tailored treatment strategies and supportive care, to optimize outcomes, and ultimately increase the number of TC survivors that live in good health

Brain imaging of the cortex in ADHD: a coordinated analysis of large-scale clinical and population-based samples

Objective: Neuroimaging studies show structural alterations of various brain regions in children and adults with attention deficit hyperactivity disorder (ADHD), although nonreplications are frequent. The authors sought to identify cortical characteristics related to ADHD using large-scale studies. Methods: Cortical thickness and surface area (based on the Desikan–Killiany atlas) were compared between case subjects with ADHD (N=2,246) and control subjects (N=1,934) for children, adolescents, and adults separately in ENIGMA-ADHD, a consortium of 36 centers. To assess familial effects on cortical measures, case subjects, unaffected siblings, and control subjects in the NeuroIMAGE study (N=506) were compared. Associations of the attention scale from the Child Behavior Checklist with cortical measures were determined in a pediatric population sample (Generation-R, N=2,707). Results: In the ENIGMA-ADHD sample, lower surface area values were found in children with ADHD, mainly in frontal, cingulate, and temporal regions; the largest significant effect was for total surface area (Cohen’s d=−0.21). Fusiform gyrus and temporal pole cortical thickness was also lower in children with ADHD. Neither surface area nor thickness differences were found in the adolescent or adult groups. Familial effects were seen for surface area in several regions. In an overlapping set of regions, surface area, but not thickness, was associated with attention problems in the Generation-R sample. Conclusions: Subtle differences in cortical surface area are widespread in children but not adolescents and adults with ADHD, confirming involvement of the frontal cortex and highlighting regions deserving further attention. Notably, the alterations behave like endophenotypes in families and are linked to ADHD symptoms in the population, extending evidence that ADHD behaves as a continuous trait in the population. Future longitudinal studies should clarify individual lifespan trajectories that lead to nonsignificant findings in adolescent and adult groups despite the presence of an ADHD diagnosis