Simeprevir added to peginterferon and ribavirin lessens time with fatigue,depressive symptoms and functional limitations in patients with chronic hepatitis C compared with peginterferon and ribavirin: results from 1161 patients in the QUEST‐1, QUEST‐2 and PROMISE studies

The value of adding simeprevir (SMV) vs placebo (PBO) to peginterferon and ribavirin (PR) for treatment of chronic hepatitis C virus infection was examined using patient‐reported outcomes (PROs); further, concordance of PROs with virology endpoints and adverse events (AEs) was explored. Patients (n = 768 SMV/PR, n = 393 PBO/PR) rated fatigue (FSS), depressive symptoms (CES‐D) and functional impairment (WPAI: Hepatitis C Productivity, Daily Activity and Absenteeism) at baseline and throughout treatment in three randomised, double‐blind trials comparing the addition of SMV or PBO during initial 12 weeks of PR. PR was administered for 48 weeks (PBO group) and 24/48 weeks (SMV group) using a response‐guided therapy (RGT) approach. Mean PRO scores (except Absenteeism) worsened from baseline to Week 4 to the same extent in both groups but reverted after Week 24 for SMV/PR and only after Week 48 for PBO/PR. Accordingly, there was a significantly lower area under the curve (baseline–Week 60, AUC₆₀) and fewer weeks with clinically important worsening of scores in the SMV/PR group at any time point. Incidences of patients with fatigue and anaemia AEs were similar in both groups, but FSS scores showed that clinically important increases in fatigue lasted a mean of 6.9 weeks longer with PBO/PR (P < 0.001). PRO score subgroup analysis indicated better outcomes for patients who met the criteria for RGT or achieved sustained virological response 12 weeks post‐treatment (SVR12); differences in mean PRO scores associated with fibrosis level were only observed with PBO/PR. Greater efficacy of SMV/PR enabled reduced treatment duration and reduced time with PR‐related AEs without adding to AE severity.     

Does stroke impair academic achievement in children? The role of metacognition in math and spelling outcomes following pediatric stroke

Introduction: Current research suggests that pediatric stroke is associated with a reduction in intellectual functioning. However, less is known about academic achievement and the contribution of specific executive functions to math and literacy in this population. The current study investigates behavioral ratings of executive functioning and their relationship to math and spelling performance in children with a history of unilateral arterial ischemic stroke.

Method: Thirty-two pediatric patients with stroke (M_age = 9.5 ± 2.7 years) and 32 demographically equivalent, healthy controls were tested on standardized measures of arithmetic, spelling, and intelligence. Executive functioning data were collected via standardized parent questionnaire.

Results: Relative to controls, stroke participants demonstrated significantly poorer functioning in math, spelling, metacognition, and behavioral-regulation. Pencil and paper arithmetic was particularly challenging for the stroke group, with 40% of patients reaching levels of clinical impairment. Hierarchical regression in stroke participants further revealed that metacognition was a robust predictor of academic deficits. Stroke occurring in later childhood and affecting cortical and subcortical brain regions also presented as potential clinical risk factors.

Conclusions: Children with stroke were especially vulnerable to math achievement deficits. Metacognition made a substantial contribution to academic achievement abilities among stroke patients, and results underscore the importance of early metacognitive skills in the completion of schoolwork. Results also emphasize that pediatric stroke patients are a heterogeneous group with regard to functioning and that there is value in examining standard score distributions of clinical participant samples.     

Caudate nucleus volume and cognitive performance: Are they related in childhood psychopathology?

BACKGROUND: Impaired neuropsychological test performance, especially on tests of executive function and attention, is often seen in children diagnosed with autism spectrum disorders (ASD). Structures involved in fronto-striatal circuitry, such as the caudate nucleus, may support these cognitive abilities. However, few studies have examined caudate volumes specifically in children with ASD, or correlated caudate volumes to cognitive ability. METHODS: Neuropsychological test scores and caudate volumes of children with ASD were compared to those of children with bipolar disorder (BD) and of typically developing (TD) children. The relationship between test performance and caudate volumes was analyzed. RESULTS: The ASD group displayed larger right and left caudate volumes, and modest executive deficits, compared to TD controls. While caudate volume inversely predicted performance on the Wisconsin Card Sorting Test in all participants, it differentially predicted performance on measures of attention across the ASD, BD and TD groups. CONCLUSIONS: Larger caudate volumes were related to impaired problem solving. On a test of attention, larger left caudate volumes predicted increased impulsivity and more omission errors in the ASD group as compared to the TD group, however smaller volume predicted poorer discriminant responding as compared to the BD group.     

Effect of short daily home haemodialysis on quality of life, cognitive functioning and the electroencephalogram.

BACKGROUND: End-stage renal disease patients have a poor quality of life (QoL), suffer from impaired cognitive functioning, and their electroencephalogram (EEG) shows abnormalities. Conventional haemodialysis (CHD) only partially restores these disorders. Short daily haemodialysis (SDHD) has been reported to improve QoL, but effects on cognitive functioning and EEG have yet to be described. METHODS: Of the 13 patients (11 male, 2 female, age 45.5 +/- 8.1 years), 11 completed the Kidney Disease Quality of Life and Affect Balance Scale questionnaires, 10 underwent neuropsychological testing, and all 13 underwent EEG examination. For the neuropsychological assessments, nine patients (six male, three female, age 45.4 +/- 12.6) who remained on the CHD schedule, served as controls. The dialysis schedule of thrice-a-week for 4 h was changed in the experimental group to six times a week for 2 h (SDHD) over a period of 6 months and back to thrice a week for 4 h. RESULTS: When on SDHD, patients rated several dimensions of health-related QoL as being improved. After resuming CHD, one of these dimensions again decreased and several others worsened even lower than baseline. Cognitive functioning did not change when compared with control data. On the EEG, alpha peak frequency increased slightly when on SDHD but decreased significantly after resuming CHD. CONCLUSIONS: SDHD improves health-related QoL, but has no clear effects on cognitive functioning and EEG. Resumption of CHD after SDHD decreases aspects of QoL and EEG alpha peak frequency but has no effect on cognitive functioning.     

Family Functioning and Social Support in the Adaptation of Caregivers of Children With Sickle Cell Syndromes

Objective: To examine moderating effects of family functioningand social support on the relationship of child-related stressorsto caregivers' psychological adaptation in a sample of caregiversof children with a chronic illness. Method: Participants were 67 caregivers of children and adolescentswith sickle cell syndromes. We conducted MANOVAs and subsequenteffect size calculations to determine if family functioningwould buffer the effects of caring for difficult-to-manage childrenwith this illness. Results: Findings supported a moderator effect of family functioningon the association of children's externalizing behavioral problemsto caregivers symptoms of hostility. Greater levels of cohesiveand adaptive family functioning buffered the potential detrimentaleffects of caring for children perceived as hard to manage.No significant associations were obtained between measures ofcaregivers' psychological adaptation and the severity of theirchildren's disease. Conclusions: We make recommendations for family systems interventions,particularly for caregivers of children with behavior problems.     

Executive cognitive deficits in primary dystonia.

Primary dystonia is a disorder of movement for which no consistent pathophysiology has been identified; in the absence of evidence to the contrary, it is assumed to be cognitively benign. We have studied a clinically heterogeneous group of 14 patients with primary dystonia on a battery of neuropsychological tests. Despite well-preserved speed of information processing, language, spatial, memory and general intellectual skills relative to normal controls, we have identified a constellation of attentional-executive cognitive deficits on the Cambridge Neuropsychological Test Automated Battery (CANTAB). Specifically, patients demonstrated significant difficulties negotiating the extra-dimensional set-shifting phase of the IED task. The implications of these findings for the pathophysiology of primary dystonia are discussed. This is, to the best of our knowledge, the first report of a significant cognitive deficit in patients with primary dystonia.     

Effects of haloperidol on motor and cognitive functioning in aged mice

The effects of haloperidol on motor and functioning and cognitive functioning were studied in young (3-5 months old) and aged (20-22 months old) male mice by examining haloperidol-induced catalepsy and haloperidol-induced decrements in performance on a radial arm maze. The aged mice were much more sensitive to these adverse effects of haloperidol than were the young mice. Studies of the distribution of radioactivity from [3H]haloperidol to the brain indicated that the differences in sensitivity to this drug were not due to pharmacokinetic differences. The results demonstrate that mice are suitable for studies of aging-induced changes in the behavioral effects of neuroleptic agents.     

Sensorimotor gating deficits in adults with autism.

BACKGROUND: Prepulse inhibition (PPI) is an operational measure of sensorimotor gating and is impaired in a family of neuropsychiatric disorders characterized by abnormalities of inhibitory function. Adults with autistic disorder (AD) exhibit clinical features of inhibitory deficits, such as restrictive and repetitive behaviors, that may be explained by deficits in sensorimotor gating. METHODS: Acoustic startle reactivity, habituation, and PPI (30-, 60-, 120-msec interstimulus intervals) were assessed in 14 adult men diagnosed with AD and 16 typically developing normal comparison (NC) participants. All participants were administered measures of intelligence and frontal-executive functioning. RESULTS: Adults with AD exhibited significantly less PPI in the 60-msec condition than NC participants, which was correlated with increased ratings of restricted and repetitive behaviors. The groups did not differ on measures of startle amplitude or overall habituation. There was, however, a significant group-by-block habituation effect. Furthermore, PPI was not related to intelligence but was moderately associated with performance on a measure of frontal-executive functioning. CONCLUSIONS: Adults with AD have sensorimotor gating deficits similar to other neurodevelopmental disorders, implicating a failure of normal inhibitory regulation of sensory, motor, and attentional mechanisms. Thus, PPI deficits may be indirectly linked to one of the hallmark features of AD.     

Return of sexual functioning following penile replant surgery

The penis, scrotum, and testicles of a 31-year-old man were cut off in a fight. Fourteen hours later the penis and one testicle were reattached, but the testicle later had to be removed. By 3 weeks normal urinary function returned but the penis was misshapen. The patient had suicidal intentions. His partner was sexually supportive but afraid to touch the penis. By 10 weeks penile swelling occurred in response to a movie with frank sexual content. By 12 weeks the penile swelling was sufficient for entry but the partner was acutely afraid that her vaginal contractions would tear the scars. The man was concerned because he experienced only mild sexual tensions. Physical examination reassured both, and they gained hope for recovery. At 16 weeks erections were still not full but active intercourse was attempted and he experienced seminal seepage and mild orgasmic sensations; she was relaxed enough to have orgasm. Testosterone was administered at regular intervals from the 19th week on, with immediate improvement of erection. By 32 weeks full erection, ejaculation, and orgasmic functions returned and the couple resumed their normal sexual practices.     

Brief report: cognitive functioning in children with Tourette's syndrome with and without comorbid ADHD

OBJECTIVE: To examine whether patients with Tourette's syndrome (TS) with and without comorbid attention deficit and hyperactivity disorder (ADHD) differ in cognitive functioning and whether a higher level of cognitive functioning is associated with severity of TS symptoms and psychosocial functioning. METHODS: Cognitive functioning, symptom severity, and psychosocial functioning were examined in 40 patients (33 boys, 7 girls; age range 6-18 years) with TS, of whom 17 had the comorbid diagnosis of ADHD. RESULTS: Patients with a comorbid ADHD diagnosis evidenced poorer performance than those with TS alone with respect to severity of TS symptoms, psychosocial functioning, verbal and performance intelligence, and word fluency, but not on tests of cognitive flexibility. Psychosocial functioning was predicted by symptom severity, but not by intelligence or fluency. CONCLUSIONS: Results confirm prior findings that comorbid ADHD is associated with more TS symptoms and worse psychosocial and cognitive functioning, and motivate whether cognitive flexibility plays a role in moderating the deleterious psychosocial effects of Tourette's syndrome and ADHD.