Comparison of fMRI language laterality with and without sedation in pediatric epilepsy.

Functional MRI is an essential component of presurgical language mapping. In clinical settings, young children may be sedated for the MRI with the functional stimuli presented passively. Research has found that sedation changes language activation in healthy adults and children. However, there is limited research comparing sedated and unsedated functional MRI in pediatric epilepsy patients. We compared language activation patterns in children with epilepsy who received sedation for functional MRI to the ones who did not. We retrospectively identified the patients with focal epilepsy who underwent presurgical functional MRI including Auditory Descriptive Decision Task at Boston Children's Hospital from 2014 to 2022. Patients were divided into sedated and awake groups, based on their sedation status during functional MRI. Auditory Descriptive Decision Task stimuli were presented passively to the sedated group per clinical protocol. We extracted language activation maps contrasted against a control task (reverse speech) in the Frontal and Temporal language regions and calculated separate language laterality indexes for each region. We considered positive laterality indexes as left dominant, negative laterality indexes as right dominant, and absolute laterality indexes <0.2 as bilateral. We defined 2 language patterns: typical (i.e., primarily left-sided) and atypical. Typical pattern required at least one left dominant region (either frontal or temporal) and no right dominant region. We then compared the language patterns between the sedated and awake groups. Seventy patients met the inclusion criteria, 25 sedated, and 45 awake. Using the Auditory Descriptive Decision Task paradigm, when adjusted for age, handedness, gender, and laterality of lesion in a weighted logistic regression model, the odds of the atypical pattern were 13.2 times higher in the sedated group compared to the awake group (Confidence Interval: 2.55-68.41, p-value < 0.01). Sedation may alter language activation patterns in pediatric epilepsy patients. Language patterns on sedated functional MRI with passive tasks may not represent language networks during wakefulness, sedation may differentially suppress some networks, or require a different task or method of analysis to capture the awake language network. Given the critical surgical implication of these findings, additional studies are needed to better understand how sedation impacts the functional MRI blood oxygenation level-dependent signal. Consistent with current practice, sedated functional MRI should be interpreted with greater caution and requires additional validation as well as research on post-surgical language outcomes.

A locally relevant framework for assessing the risk of sea level rise under changing temperature conditions: Application in New Caledonia, Pacific Ocean.

Sea level rise is a key feature in a warmer world and its impact can be seen globally. Assessing climate change-induced sea level rise, therefore, is urgently needed particularly in small island nations, where the threats of sea level rise are immediate, but the level of preparedness is low. Here, we propose a stochastic simulator to link changes in Mean Annual Temperature (MAT) to Mean Annual Sea Level (MASEL) at the local scale. This is through what-if scenarios that are developed based on the association between local temperature and sea level. The model can provide a basis for a bottom-up impact assessment by addressing limitations of applying large-scale projections in small islands and facilitating the accessibility of the impact assessment to stakeholders. For this purpose, we decompose the MAT and MASEL signals into their linear trend and autocorrelation components as well as independent and identically distributed residual terms. We further explore the association between trend and residual terms of MAT and MASEL. If such dependencies exist, scenarios of sea level can be synthesized based on the trend and residual terms of temperature. We use linear regression to link trends of MAT and MASEL, and copulas to formulate dependencies between residuals. This allows stochastic sampling of MASEL conditioned to trend and random variability in MAT. This framework is used for retrospective and prospective simulations of MASEL in Nouméa, the capital city of New Caledonia, the Pacific. We set up six different model configurations for developing the stochastic sampler, each including various parametric options. By selecting the best setup from each configuration, we provide a multi-model stochastic projection of MASEL, assuming the persistence in current long-term trend in MAT and MASEL. We demonstrate how such simulations can be used for a risk-based impact assessments and discuss sources of uncertainty in future projections.

A generic approach to evaluate costs and effectiveness of agricultural Beneficial Management Practices to improve water quality management.

Nutrient export from agricultural areas is among the main contributors to water pollution in various watersheds. Agricultural Beneficial Management Practices (BMPs) are commonly used to reduce excessive nutrient runoff and improve water quality. The successful uptake of BMPs not only depends on their effectiveness but also on their costs of implementation. This study conducts a set of cost-effectiveness analyses to help stakeholders identify their preferred combinations of BMPs in the Qu'Appelle River Basin, a typical watershed in the Canadian Prairies. The considered BMPs are related to cattle and cropping farms and are initially selected by agricultural producers in this region. The analyses use a water quality model to estimate the impact of implementing BMPs on nutrient export, and the cost estimation model to approximate the cost of implementing BMPs at tributary and watershed scales. Our results show that BMPs' effectiveness, total costs of implementation and costs per kilogram of nutrient abatement vary between tributaries. However, wetland conservation is among the optimal practices to improve water quality across the watershed. It is also found that the rates of BMP adoption by stakeholders can influence the effectiveness of practices in a large watershed scale, which highlights the importance of stakeholder engagement in water quality management. This type of analyses can help stakeholders choose single or a combination of BMPs according to their available budget and acceptable levels of reduction in nutrients.

Climate change or irrigated agriculture - what drives the water level decline of Lake Urmia.

Lake Urmia is one of the largest hypersaline lakes on earth with a unique biodiversity. Over the past two decades the lake water level declined dramatically, threatening the functionality of the lake's ecosystems. There is a controversial debate about the reasons for this decline, with either mismanagement of the water resources, or climatic changes assumed to be the main cause. In this study we quantified the water budget components of Lake Urmia and analyzed their temporal evolution and interplay over the last five decades. With this we can show that variations of Lake Urmia's water level during the analyzed period were mainly triggered by climatic changes. However, under the current climatic conditions agricultural water extraction volumes are significant compared to the remaining surface water inflow volumes. Changes in agricultural water withdrawal would have a significant impact on the lake volume and could either stabilize the lake, or lead to its complete collapse.

Incorporating social dimensions in hydrological and water quality modeling to evaluate the effectiveness of agricultural beneficial management practices in a Prairie River Basin.

There is growing interest to develop processes for creating user-informed watershed scale models of hydrology and water quality and to assist in decision-making for balanced policies for managing watersheds. Watershed models can be enhanced with the incorporation of social dimensions of watershed management as brought forward by participants such as the perspectives, values, and norms of people that depend on the land, water, and ecosystems for sustenance, economies, and overall wellbeing. In this work, we explore the value of combining both qualitative and quantitative methods and social science data to enhance salience and legitimacy of watershed models so that end-users are more engaged. We discuss pilot testing and engagement workshops for building and testing a systems dynamics model of the Qu'Appelle Valley to gather insights from local farmers and understand their perceptions of Beneficial Management Practices (BMPs). Mixed-method workshops with agricultural producers in the Qu'Appelle Watershed gathered feedback on the developing model and the incorporation of social determinants affecting decision-making. Analysis of focus groups and factor analysis of Q-sorts were used to identify the desired components of the model, and whether it supported farmers' understanding of the potential effects of BMPs on water quality. We explored farmers' engagement with models testing BMPs and the potential of incorporating their decision processes within the model itself. Finally, we discuss the reception of the process and the practicality of the approach in providing legitimate and credible decision support tools for a community of farmers.

A framework for engaging stakeholders in water quality modeling and management: Application to the Qu'Appelle River Basin, Canada.

Water quality is increasingly at risk due to nutrient pollution entering river systems from cities, industrial zones and agricultural areas. Agricultural activities are typically the largest non-point source of water pollution. The dynamics of agricultural impacts on water quality are complex and stem from the decisions and activities of multiple stakeholders, often with diverse business plans, values, and attitudes towards practices that can improve water quality. This study proposes a framework to understand and incorporate stakeholders' viewpoints into water quality modeling and management. The framework was applied to the Qu'Appelle River Basin, Saskatchewan, Canada. Q-methodology was used to understand viewpoints of stakeholders, namely agricultural producers (annual croppers, cattle producers, mixed farmers) and cottage owners, regarding a range of agricultural Beneficial Management Practices (BMPs) that can improve water quality, and to identify their preferred BMPs. A System Dynamics (SD) approach was employed to develop a transparent and user-friendly water quality model, SD-Qu'Appelle, to simulate nutrient loads in the region before and after implementation of stakeholder identified BMPs. The SD-Qu'Appelle was used in real-time engagement of stakeholders in model simulations to demonstrate and explore the potential effects of different BMPs in mitigating water pollution. Stakeholder perspectives were explored to understand the functionality and value of the SD-Qu'Appelle, preferred policies and potential barriers to BMP implementation on their land. Results show that although there are differences between viewpoints of stakeholders, they identified wetland restoration/retention, flow and erosion control, and relocation of corrals near creeks to sites more distant from waterways as the most effective BMPs for improving water quality. Economics was identified as a primary factor that causes agricultural producers to either accept or refuse the implementation of BMPs. Agricultural producers believe that incentives rather than regulations are the best policies for increasing the adoption of BMPs. Overall, stakeholders indicated the SD-Qu'Appelle had considerable value for water quality management and provided a set of recommendations to improve the model.

Investigating the role of DCE-MRI, over T2 and DWI, in accurate PI-RADS v2 assessment of clinically significant peripheral zone prostate lesions as defined at radical prostatectomy.

PURPOSE: PI-RADS v2 dictates that dynamic contrast-enhanced (DCE) imaging be used to further classify peripheral zone (PZ) cases that receive a diffusion-weighted imaging equivocal score of three (DWI3), a positive DCE resulting in an increase in overall assessment score to a four, indicative of clinically significant prostate cancer (csPCa). However, the accuracy of DCE in predicting csPCa in DWI3 PZ cases is unknown. This study sought to determine the frequency with which DCE changes the PI-RADS v2 DWI3 assessment category, and to determine the overall accuracy of DCE-MRI in equivocal PZ DWI3 lesions. MATERIALS AND METHODS: This is a retrospective study of patients with pathologically proven PCa who underwent prostate mpMRI at 3T and subsequent radical prostatectomy. PI-RADS v2 assessment categories were determined by a radiologist, aware of a diagnosis of PCa, but blinded to final pathology. csPCa was defined as a Gleason score ≥ 7 or extra prostatic extension at pathology review. Performance characteristics and diagnostic accuracy of DCE in assigning a csPCa assessment in PZ lesions were calculated. RESULTS: A total of 271 men with mean age of 59 ± 6 years mean PSA 6.7 ng/mL were included. csPCa was found in 212/271 (78.2%) cases at pathology, 209 of which were localized in the PZ. DCE was necessary to further classify (45/209) of patients who received a score of DWI3. DCE was positive in 29/45 cases, increasing the final PI-RADS v2 assessment category to a category 4, with 16/45 having a negative DCE. When compared with final pathology, DCE was correct in increasing the assessment category in 68.9% ± 7% (31/45) of DWI3 cases. CONCLUSION: DCE increases the accuracy of detection of csPCa in the majority of PZ lesions that receive an equivocal PI-RADS v2 assessment category using DWI.

Predictive role of PI-RADSv2 and ADC parameters in differentiating Gleason pattern 3 + 4 and 4 + 3 prostate cancer.

PURPOSE: To compare the predictive roles of qualitative (PI-RADSv2) and quantitative assessment (ADC metrics), in differentiating Gleason pattern (GP) 3 + 4 from the more aggressive GP 4 + 3 prostate cancer (PCa) using radical prostatectomy (RP) specimen as the reference standard. METHODS: We retrospectively identified treatment-naïve peripheral (PZ) and transitional zone (TZ) Gleason Score 7 PCa patients who underwent multiparametric 3T prostate MRI (DWI with b value of 0,1400 and where unavailable, 0,500) and subsequent RP from 2011 to 2015. For each lesion identified on MRI, a PI-RADSv2 score was assigned by a radiologist blinded to pathology data. A PI-RADSv2 score ≤ 3 was defined as "low risk," a PI-RADSv2 score ≥ 4 as "high risk" for clinically significant PCa. Mean tumor ADC (ADCT), ADC of adjacent normal tissue (ADCN), and ADCratio (ADCT/ADCN) were calculated. Stepwise regression analysis using tumor location, ADCT and ADCratio, b value, low vs. high PI-RADSv2 score was performed to differentiate GP 3 + 4 from 4 + 3. RESULTS: 119 out of 645 cases initially identified met eligibility requirements. 76 lesions were GP 3 + 4, 43 were 4 + 3. ADCratio was significantly different between the two GP groups (p = 0.001). PI-RADSv2 score ("low" vs. "high") was not significantly different between the two GP groups (p = 0.17). Regression analysis selected ADCT (p = 0.03) and ADCratio (p = 0.0007) as best predictors to differentiate GP 4 + 3 from 3 + 4. Estimated sensitivity, specificity, and accuracy of the predictive model in differentiating GP 4 + 3 from 3 + 4 were 37, 82, and 66%, respectively. CONCLUSIONS: ADC metrics could differentiate GP 3 + 4 from 4 + 3 PCa with high specificity and moderate accuracy while PI-RADSv2, did not differentiate between these patterns.

Comparison of quantitative apparent diffusion coefficient parameters with prostate imaging reporting and data system V2 assessment for detection of clinically significant peripheral zone prostate cancer.

PURPOSE: To compare diagnostic performance of PI-RADSv2 with ADC parameters to identify clinically significant prostate cancer (csPC) and to determine the impact of csPC definitions on diagnostic performance of ADC and PI-RADSv2. METHODS: We retrospectively identified treatment-naïve pathology-proven peripheral zone PC patients who underwent 3T prostate MRI, using high b-value diffusion-weighted imaging from 2011 to 2015. Using 3D slicer, areas of suspected tumor (T) and normal tissue (N) on ADC (b = 0, 1400) were outlined volumetrically. Mean ADCT, mean ADCN, ADCratio (ADCT/ADCN) were calculated. PI-RADSv2 was assigned. Three csPC definitions were used: (A) Gleason score (GS) ≥ 4 + 3; (B) GS ≥ 3 + 4; (C) MRI-based tumor volume >0.5 cc. Performances of ADC parameters and PI-RADSv2 in identifying csPC were measured using nonparametric comparison of receiver operating characteristic curves using the area under the curve (AUC). RESULTS: Eighty five cases met eligibility requirements. Diagnostic performances (AUC) in identifying csPC using three definitions were: (A) ADCT (0.83) was higher than PI-RADSv2 (0.65, p = 0.006); (B) ADCT (0.86) was higher than ADCratio (0.68, p < 0.001), and PI-RADSv2 (0.70, p = 0.04); (C) PI-RADSv2 (0.73) performed better than ADCratio (0.56, p = 0.02). ADCT performance was higher when csPC was defined by A or B versus C (p = 0.038 and p = 0.01, respectively). ADCratio performed better when csPC was defined by A versus C (p = 0.01). PI-RADSv2 performance was not affected by csPC definition. CONCLUSIONS: When csPC was defined by GS, ADC parameters provided better csPC discrimination than PI-RADSv2, with ADCT providing best result. When csPC was defined by MRI-calculated volume, PI-RADSv2 provided better discrimination than ADCratio. csPC definition did not affect PI-RADSv2 diagnostic performance.

Prostate imaging reporting and data system version 2 (PI-RADS v2): a pictorial review.

The most recent edition of the prostate imaging reporting and data system (PI-RADS version 2) was developed based on expert consensus of the international working group on prostate cancer. It provides the minimum acceptable technical standards for MR image acquisition and suggests a structured method for multiparametric prostate MRI (mpMRI) reporting. T1-weighted, T2-weighted (T2W), diffusion-weighted (DWI), and dynamic contrast-enhanced (DCE) imaging are the suggested sequences to include in mpMRI. The PI-RADS version 2 scoring system enables the reader to assess and rate all focal lesions detected at mpMRI to determine the likelihood of a clinically significant cancer. According to PI-RADS v2, a lesion with a Gleason score ≥7, volume >0.5 cc, or extraprostatic extension is considered clinically significant. PI-RADS v2 uses the concept of a dominant MR sequence based on zonal location of the lesion rather than summing each component score, as was the case in version 1. The dominant sequence in the peripheral zone is DWI and the corresponding apparent diffusion coefficient (ADC) map, with a secondary role for DCE in equivocal cases (PI-RADS score 3). For lesions in the transition zone, T2W images are the dominant sequence with DWI/ADC images playing a supporting role in the case of an equivocal lesion.

Diffusion-weighted endorectal MR imaging at 3T for prostate cancer: correlation with tumor cell density and percentage Gleason pattern on whole mount pathology.

OBJECTIVE: To determine if tumor cell density and percentage of Gleason pattern within an outlined volumetric tumor region of interest (TROI) on whole-mount pathology (WMP) correlate with apparent diffusion coefficient (ADC) values on corresponding TROIs outlined on pre-operative MRI. METHODS: Men with biopsy-proven prostate adenocarcinoma undergoing multiparametric MRI (mpMRI) prior to prostatectomy were consented to this prospective study. WMP and mpMRI images were viewed using 3D Slicer and each TROI from WMP was contoured on the high b-value ADC maps (b0, 1400). For each TROI outlined on WMP, TCD (tumor cell density) and the percentage of Gleason pattern 3, 4, and 5 were recorded. The ADCmean, ADC10th percentile, ADC90th percentile, and ADCratio were also calculated in each case from the ADC maps using 3D Slicer. RESULTS: Nineteen patients with 21 tumors were included in this study. ADCmean values for TROIs were 944.8 ± 327.4 vs. 1329.9 ± 201.6 mm2/s for adjacent non-neoplastic prostate tissue (p < 0.001). ADCmean, ADC10th percentile, and ADCratio values for higher grade tumors were lower than those of lower grade tumors (mean 809.71 and 1176.34 mm2/s, p = 0.014; 10th percentile 613.83 and 1018.14 mm2/s, p = 0.009; ratio 0.60 and 0.94, p = 0.005). TCD and ADCmean (ρ = -0.61, p = 0.005) and TCD and ADC10th percentile (ρ = -0.56, p = 0.01) were negatively correlated. No correlation was observed between percentage of Gleason pattern and ADC values. CONCLUSION: DWI MRI can characterize focal prostate cancer using ADCratio, ADC10th percentile, and ADCmean, which correlate with pathological tumor cell density.

Segmented diffusion-weighted imaging of the prostate: Application to transperineal in-bore 3T MR image-guided targeted biopsy.

OBJECTIVE: This study aims to evaluate the applicability of using single-shot and multi-shot segmented diffusion-weighted imaging (DWI) techniques to support biopsy target localization in a cohort of targeted MRI-guided prostate biopsy patients. MATERIALS AND METHODS: Single-shot echo-planar diffusion-weighted imaging (SS-DWI) and multi-shot segmented (MS-DWI) were performed intra-procedurally on a 3Tesla system in a total of 35 men, who underwent in-bore prostate biopsy inside the scanner bore. Comparisons between SS-DWI and MS-DWI were performed with (in 16 men) and without (in 19 men) parallel coil acceleration (iPAT) for SS-DWI. Overall image quality and artifacts were scored by a radiologist and scores were compared with the Wilcoxon-Mann-Whitney rank test. Correlation between the presence of air and image quality scores was evaluated with Spearman statistics. To quantify distortion, the anteroposterior prostate dimension was measured in SS and MS b=0 diffusion- and T2-weighted images. Signal-to-noise ratio was estimated in a phantom experiment. Agreement and accuracy of targeting based on retrospective localization of restricted diffusion areas in DWI was evaluated with respect to the targets identified using multi-parametric MRI (mpMRI). RESULTS: Compared to SS-DWI without iPAT, the average image quality score in MS-DWI improved from 2.0 to 3.3 (p<0.005) and the artifact score improved from 2.3 to 1.4 (p<0.005). When iPAT was used in SS-DWI, the average image quality score in MS-DWI improved from 2.6 to 3.3 (p<0.05) and the artifact score improved from 2.1 to 1.4 (p<0.01). Image quality (ρ=-0.74, p<0.0005) and artifact scores (ρ=0.77, p<0.0005) both showed strong correlation with the presence of air in the rectum for the SS-DWI sequence without iPAT. These correlations remained significant when iPAT was enabled (ρ=-0.52, p<0.05 and ρ=0.64, p<0.01). For the comparison MS-DWI vs SS-DWI without iPAT, median differences between diffusion- and T2-weighted image gland measurements were 1.1(0.03-10.4)mm and 4.4(0.5-22.7)mm, respectively. In the SS-DWI-iPAT cohort, median gland dimension differences were 2.7(0.4-5.9)mm and 4.2(0.7-8.9)mm, respectively. Out of the total of 89 targets identified in mpMRI, 20 had corresponding restricted diffusion areas in SS-DWI and 28 in MS-DWI. No statistically significant difference was observed between the distances for the targets in the target-concordant SS- and MS-DWI restricted diffusion areas (5.5mm in SS-DWI vs 4.5mm in MS-DWI, p>0.05). CONCLUSIONS: MS-DWI applied to prostate imaging leads to a significant reduction of image distortion in comparison with SS-DWI. There is no sufficient evidence however to suggest that intra-procedural DWI can serve as a replacement for tracking of the targets identified in mpMRI for the purposes of targeted MRI-guided prostate biopsy.

Key Performance Indicators in Radiology: You Can't Manage What You Can't Measure.

Quality assurance (QA) is a fundamental component of every successful radiology operation. A radiology QA program must be able to efficiently and effectively monitor and respond to quality problems. However, as radiology QA has expanded into the depths of radiology operations, the task of defining and measuring quality has become more difficult. Key performance indicators (KPIs) are highly valuable data points and measurement tools that can be used to monitor and evaluate the quality of services provided by a radiology operation. As such, KPIs empower a radiology QA program to bridge normative understandings of health care quality with on-the-ground quality management. This review introduces the importance of KPIs in health care QA, a framework for structuring KPIs, a method to identify and tailor KPIs, and strategies to analyze and communicate KPI data that would drive process improvement. Adopting a KPI-driven QA program is both good for patient care and allows a radiology operation to demonstrate measurable value to other health care stakeholders.

CT and MRI manifestations of luxatio erecta humeri and a review of the literature.

AIM: We aimed to study luxatio erecta humeri using advanced imaging modalities. METHOD: Patients with luxatio erecta humeri and a subsequent magnetic resonance imaging (MRI) and/or computed tomography (CT) scan were included in this study. RESULTS: Among 10 identified cases, we detected 2 rotator cuff, 4 labral, and 2 inferior glenohumeral ligament tears as well as 2 glenohumeral cartilage defects. We observed six comminuted displaced greater tuberosity fractures, four anterior inferior glenoid fractures, and four impaction fractures of humeral head. CONCLUSION: This study provides detailed radiologic findings associated with luxatio erecta humeri using MRI and CT.

Pioglitazone adjunctive therapy for depressive episode of bipolar disorder: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: The antidepressive effect of pioglitazone has been noted in patients with major depressive disorder in absence of metabolic syndrome. This study was conducted to evaluate the safety and efficacy of pioglitazone in patients with bipolar depression without concomitant metabolic syndrome or diabetes. METHOD: Forty-eight outpatients with the diagnosis of bipolar I disorder and a major depressive episode participated in a parallel, randomized, double-blind, placebo-controlled trial, and 44 patients underwent 6-week treatment with either pioglitazone (30 mg/day) or placebo as an adjunctive treatment to lithium. Therapeutic serum lithium levels of 0.6-0.8 mEq/L were required for two or more consecutive weeks immediately before starting pioglitazone and during the 6-week study. Patients were evaluated using Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS) at baseline and weeks 1, 2, 4, and 6. The primary outcome was to evaluate the efficacy of pioglitazone in improving the depressive symptoms. RESULT: General linear model repeated measures showed significant effect for time × treatment interaction on the HDRS scores [F(2.78, 116.65) = 4.77, P = .005]. Significantly greater reduction was observed in HDRS scores in the pioglitazone group than the placebo group from baseline HDRS score at weeks 2, 4, and 6, P = .003, .006, and .006, respectively. No serious adverse event was observed. CONCLUSION: This study showed that pioglitazone could be a tolerable and effective adjunctive therapy for improving depressive symptoms in bipolar disorder without type 2 diabetes or metabolic syndrome.

Double-blind, placebo-controlled trial of risperidone plus amantadine in children with autism: a 10-week randomized study.

OBJECTIVE: This study aimed to investigate the effect of adding amantadine to risperidone for treatment of autism. METHODS: Forty outpatients aged 4 to12 years, who were diagnosed with autism spectrum disorders based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria, were assigned to this double-blind clinical trial. The subjects were divided randomly into 2 groups. One group received risperidone plus amantadine, and the other group received risperidone plus placebo. The dose of risperidone was titrated between 1 and 2.0 mg/d, and the dose of amantadine was 100 or 150 mg/d for patients less than 30 kg or more than 30 kg, respectively. The patients were assessed using the Aberrant Behavioral Checklist-Community (ABC-C) and adverse effects checklist as well as clinical global impression-improvement (CGI-I) at2 checkpoints of 5-week intervals after the baseline. Informed consentwas obtained from the parents of each participant. RESULTS: Among ABC-C subscales, Hyperactivity and Irritability showed significantly greater reduction in the amantadine group than the placebo group. There was no significant difference in adverse effects between the 2 groups. The CGI-I scores show significant improvement in the amantadine group compared to the placebo group. CONCLUSIONS: The present study suggests that amantadine may be a potential adjunctive treatment strategy for autism and it was generally well tolerated.

Riluzole as an adjunctive therapy to risperidone for the treatment of irritability in children with autistic disorder: a double-blind, placebo-controlled, randomized trial.

BACKGROUND: A hyperglutamatergic state has been shown to play a possible role in the pathophysiology of autistic disorders. Riluzole is a glutamate-modulating agent with neuroprotective properties, which has been shown to have positive effects in many neuropsychiatric disorders. OBJECTIVE: The aim of this study was to assess the efficacy and tolerability of riluzole as an adjunctive to risperidone in the treatment of irritability in autistic children who were not optimally responding to previous medications. STUDY DESIGN: This was a 10-week, randomized, double-blind, parallel-group, placebo-controlled trial. PARTICIPANTS: The study enrolled male and female outpatients aged 5-12 years with a diagnosis of autistic disorder based on the DSM-IV-TR criteria and a score of ≥12 on the Aberrant Behavior Checklist-Community (ABC-C) irritability subscale who had discontinued other medications because of a lack of efficacy. INTERVENTIONS: Subjects received riluzole (titrated to 50 or 100 mg/day based on bodyweight) or placebo in addition to risperidone (titrated up to 2 or 3 mg/day based on bodyweight) for 10 weeks. OUTCOME: Patients were assessed at baseline, week 5, and week 10. The primary outcome measure was the difference in the change in the ABC-C irritability subscale score from baseline to week 10 between the two groups. We also compared changes in other ABC-C subscale scores and Clinical Global Impressions-Improvement (CGI-I) scale scores between the two groups. RESULTS: Forty-nine patients were enrolled in the study, and forty children completed the trial (dropouts: placebo = 4, riluzole = 5). A significantly greater improvement in the study primary outcome (the ABC-C irritability subscale score) was achieved by the riluzole-treated children compared with the placebo group (P = 0.03). Patients in the riluzole group also showed significantly greater improvement on the lethargy/social withdrawal (P = 0.02), stereotypic behavior (P = 0.03), and hyperactivity/non-compliance subscales (P = 0.005), but not on the inappropriate speech subscale (P = 0.20) than patients in the placebo group. Eleven patients in the riluzole group and five patients in the placebo group were classified as responders based on their CGI-I scores [χ(2)(1) = 3.750, P = 0.05]. Children in the riluzole group experienced significantly more increases in their appetite and bodyweight than children in the placebo group by the end of the study. CONCLUSION: Riluzole add-on therapy shows several therapeutic outcomes, particularly for improving irritability, in children with autism. However, its add-on to risperidone also results in significantly increased appetite and weight gain.

Change in frequency of acute and subacute effects of ecstasy in a group of novice users after 6 months of regular use.

BACKGROUND: Recent research trends are to specify the relation between patterns of ecstasy use and side effects, possibility of dependency, tolerance and long term neurocognitive damage. The objective of this study was to assess the impact of regular ecstasy use on its acute and subacute effects. SUBJECTS AND METHODS: At the first stage, we recruited 120 subjects. If participants continued regular use of ecstasy in this period, they were asked to participate in the second stage of the research 6 months later. Thirty-five subjects attended the second stage of the study, 5 of which were excluded because they had less than 5 drug experiences during the last 6 months. At last, we recruited 30 novice ecstasy users by means of the snowball technique in Tehran, Iran. The pattern of use and experienced effects of ecstasy was documented at the beginning and after 6 months of regular consumption with a self administered questionnaire. RESULTS: Little or no change was observed in acute effects. Those subacute effects that had considerable increase in frequency were anxiety, depression, aggression, memory impairment, poor concentration and learning problems. CONCLUSION: Small change in acute effects suggests low possibility of tolerance after at least 6 months of regular use. Our results support long term neurocognitive damage and mood impairment with ecstasy use.