Defining the clinical and cognitive phenotype of child savants with autism spectrum disorder

Objective: Whilst savant syndrome is most commonly observed in individuals with Autism Spectrum Disorder (ASD), it has historically been associated with intellectual impairment, and little is known about the clinical and cognitive characteristics of intellectually able individuals with ASD and savant skills. Methods: Participants with ASD and validated savant skills were compared with age and intelligence matched non-savants with ASD using a range of diagnostic and standardised tests. Results: Although the analysis of the clinical data revealed few differences between the groups, striking differences emerged during cognitive testing. Children with savant skills exhibited highly superior working memory and their scores on tests of analytic skills were also superior to those of non-savants. Conclusion: We propose that obsessionality, focused attention, superior working memory and analytic skills facilitate veridical mapping and pattern perception abilities characteristic in savant syndrome

Linezolid population pharmacokinetic model in plasma and cerebrospinal fluid among patients with tuberculosis meningitis.

BACKGROUND: Linezolid is evaluated in novel treatment regimens for tuberculous meningitis (TBM). Linezolid pharmacokinetics have not been characterized in this population, particularly in cerebrospinal fluid (CSF) where exposures may be affected by changes in protein concentration. Linezolid co-administration with high-dose rifampicin, has also not been studied. We aimed to characterize linezolid plasma and CSF pharmacokinetics in adults with TBM. METHODS: In LASER-TBM pharmacokinetic-substudy, the intervention groups received high-dose rifampicin (35mg/kg) plus linezolid 1200mg/day for 28days, then reduced to 600mg/day. Plasma sampling was done on day 3 (intensive) and on day 28 (sparse). A lumbar CSF sample was obtained on both visits. RESULTS: 30-participants, median(min-max) age and weight of 40(27-56)years and 58(30-96)kg, contributed 247 plasma and 28 CSF observations. Plasma pharmacokinetics was described by one-compartment model with first-order absorption and saturable elimination. Maximal clearance was 7.25L/h, and Km was 27.2mg/L. Rifampicin co-treatment duration did not affect linezolid pharmacokinetics. CSF-Plasma partitioning correlated with CSF total-protein upto 1.2g/L where the partition-coefficient reached maximal value of 37%. Plasma-CSF equilibration half-life was ∼3.5hours. CONCLUSION: Linezolid was readily detected in CSF despite high-dose rifampicin co-administration. These findings support continued clinical evaluation of linezolid plus high-dose rifampicin for the treatment of TBM in adults

Visual predictive check (VPC) for isoniazid concentration versus time, stratified by NAT2 acetylator status (extensive and intermediate on the left, slow on the right).

<p>The circles represent the original data, the dashed and solid lines are the 5^th, 50^th, and 95^th percentiles of the original data, while the shaded areas are the corresponding 95% confidence intervals for the same percentiles, as predicted by the model.</p

Visual predictive check (VPC) for pyrazinamide concentration versus time, stratified by time on TB treatment.

<p>The circles represent the original data, the dashed and solid lines are the 5^th, 50^th, and 95^th percentiles of the original data, while the shaded areas are the corresponding 95% confidence intervals for the same percentiles, as predicted by the model.</p

Box and whisker plots showing isoniazid exposure vs. time NAT2 acetylator status (grouped as rapid or intermediate together vs. slow).

<p>The left panel displays AUC_0-24 and the right panel C_max. The dots represent individual values. Since for most subjects 2 PK profiles were available, geometric mean was used to summarize the individual values.</p

Baseline characteristics of 100 pulmonary sputum smear positive patients starting TB treatment.

<p>^aData are median (IQR) or n (%).</p><p>^bThe total number of observations was not 100 due to missing values.</p><p>Baseline characteristics of 100 pulmonary sputum smear positive patients starting TB treatment.</p

Flow chart for pulmonary TB-positive patients randomized to receive a nutritional supplement or no supplement and followed for the effects of nutritional supplementation on Isoniazid, Pyrazinamide and Ethambutal exposure at the end of the second month of intensive phase of treatment.

<p>Flow chart for pulmonary TB-positive patients randomized to receive a nutritional supplement or no supplement and followed for the effects of nutritional supplementation on Isoniazid, Pyrazinamide and Ethambutal exposure at the end of the second month of intensive phase of treatment.</p

Box and whisker plots showing pyrazinamide exposure vs. time on TB treatment (approximately less or more than 2 weeks).

<p>The left panel displays AUC_0-24 and the right panel C_max. The dots represent individual values. When 2 PK profiles were available in the same stratum, geometric mean was used to summarize the value.</p

In the left panels, scatter plots showing ethambutol exposure vs. patient age.

<p>In the right small panels, box and whiskers plots summarizing the same values. The top panels refer to AUC_0-24 and the bottom panels to C_max. For all patients for whom 2 PK profiles were available, geometric mean was used to obtain summary values.</p

Nutrients composition of the intervention used in the trial.

<p>^aDuration of intervention 60 days</p><p>Nutrients composition of the intervention used in the trial.</p