Characteristics of placebo response during long-term treatment of panic disorder

Mixed-panic disorder patients (16/60, 27%) randomly assigned to receive blind placebo during a 40-week treatment study were defined as placebo responders based on combined criteria of Hamilton Anxiety Scale score percentage decreases below the median point (-42%), moderate to marked improvement on both clinician and patient Clinical Global Impressions scores, and panic-free at final treatment visit. These criteria applied separately also resulted in a similar clinical grouping and pattern of response. Differential patterns of response between responders and nonresponders occurred across most clinical measures of panic/anxiety. Responders experienced early improvement within the first week of double-blind treatment. This response progressed during treatment and tended to persist during taper and at followup 1 month later. Post-hoc analysis of demographic and clinical features at entrance into the study failed to characterize this stringently defined group of placebo responders.     

Distributional Properties and Criterion Validity of a Shortened Version of the Social Responsiveness Scale: Results from the ECHO Program and Implications for Social Communication Research

Prior work proposed a shortened version of the Social Responsiveness Scale (SRS), a commonly used quantitative measure of social communication traits. We used data from 3031 participants (including 190 ASD cases) from the Environmental Influences on Child Health Outcomes (ECHO) Program to compare distributional properties and criterion validity of 16-item “short” to 65-item “full” SRS scores. Results demonstrated highly overlapping distributions of short and full scores. Both scores separated case from non-case individuals by approximately two standard deviations. ASD prediction was nearly identical for short and full scores (area under the curve values of 0.87, 0.86 respectively). Findings support comparability of shortened and full scores, suggesting opportunities to increase efficiency. Future work should confirm additional psychometric properties of short scores.

     

Behavioral,cognitive, and adaptive development in infants with autism spectrum disorder in the first 2?years of life

Background

To delineate the early progression of autism spectrum disorder (ASD) symptoms, this study investigated developmental characteristics of infants at high familial risk for ASD (HR), and infants at low risk (LR).

Methods

Participants included 210 HR and 98 LR infants across 4 sites with comparable behavioral data at age 6, 12, and 24 months assessed in the domains of cognitive development (Mullen Scales of Early Learning), adaptive skills (Vineland Adaptive Behavioral Scales), and early behavioral features of ASD (Autism Observation Scale for Infants). Participants evaluated according to the DSM-IV-TR criteria at 24 months and categorized as ASD-positive or ASD-negative were further stratified by empirically derived cutoff scores using the Autism Diagnostic Observation Schedule yielding four groups: HR-ASD-High, HR-ASD-Moderate (HR-ASD-Mod), HR-ASD-Negative (HR-Neg), and LR-ASD-Negative (LR-Neg).

Results

The four groups demonstrated different developmental trajectories that became increasingly distinct from 6 to 24 months across all domains. At 6 months, the HR-ASD-High group demonstrated less advanced Gross Motor and Visual Reception skills compared with the LR-Neg group. By 12 months, the HR-ASD-High group demonstrated increased behavioral features of ASD and decreased cognitive and adaptive functioning compared to the HR-Neg and LR-Neg groups. By 24 months, both the HR-ASD-High and HR-ASD-Moderate groups demonstrated differences from the LR- and HR-Neg groups in all domains.

Conclusions

These findings reveal atypical sensorimotor development at 6 months of age which is associated with ASD at 24 months in the most severely affected group of infants. Sensorimotor differences precede the unfolding of cognitive and adaptive deficits and behavioral features of autism across the 6- to 24-month interval. The less severely affected group demonstrates later symptom onset, in the second year of life, with initial differences in the social-communication domain.

Electronic supplementary material

The online version of this article (doi:10.1186/s11689-015-9117-6) contains supplementary material, which is available to authorized users.     

Clinical outcome following Transcatheter Aortic Valve Implantation in patients with impaired left ventricular systolic function

Objectives: To determine the prevalence of impaired left ventricular (LV) systolic function and its impact on the in‐hospital and long‐term outcome in patients who underwent Transcatheter Aortic Valve Implantation (TAVI). Background: Although impaired LV function may be considered a contra‐indication for aortic valve replacement, the hemodynamic characteristics of transcatheter valves may offer procedural and long‐term clinical benefit in such patients. Methods: 230 consecutive patients underwent TAVI with the Medtronic‐CoreValve System. Impaired LV function was defined by a Left Ventricular Ejection Fraction (LVEF) ≤ 35% (European Multicenter Study on Operative Risk Stratification and Long‐term Outcome in patients with Low‐Flow/Low‐Gradient Aortic Stenosis). Study endpoints were selected and defined according to the Valve Academic Research Consortium recommendations. Results: Compared with patients with a LVEF > 35% (n = 197), those with LVEF ≤ 35% (n = 33) were more often male (78.8 % vs. 46.7%, P < 0.001), more symptomatic (NYHA class III or IV, 97.0% vs. 77.2%, P = 0.008) and had a higher prevalence of prior coronary artery disease (63.6% vs. 43.1%, P = 0.029). The Logistic EuroSCORE was 14.8% and 22.8, respectively (P = 0.012). No difference was observed between the two groups in in‐hospital or 30‐day mortality (3.0% vs. 9.6%, P = 0.21), the Combined Safety Endpoint at 30 days (24.2% and 24.4%, P = 0.99) and survival free from readmission at one year (69.2% and 69.7%, P = 0.85). After adjustment, LVEF ≤ 35% was not associated with an increased risk of 30‐day mortality, in‐hospital complications and survival free from readmission at follow‐up. Conclusion: The immediate and long‐term outcome after TAVI did not differ between patients with an impaired and preserved LVEF. LVEF ≤ 35% did not predict adverse immediate and long‐term outcome. These findings suggest that TAVI should not be withheld in selected patients with impaired LV function. © 2011 Wiley Periodicals, Inc.     

Reproducibility of proton MR spectroscopic imaging (PEPSI): comparison of dyslexic and normal-reading children and effects of treatment on brain lactate levels during language tasks

BACKGROUND AND PURPOSE: We repeated a proton echo-planar spectroscopic imaging (PEPSI) study to test the hypothesis that children with dyslexia and good readers differ in brain lactate activation during a phonologic judgment task before but not after instructional treatment. METHODS: We measured PEPSI brain lactate activation (TR/TE, 4000/144; 1.5 T) at two points 1-2 months apart during two language tasks (phonologic and lexical) and a control task (passive listening). Dyslexic participants (n = 10) and control participants (n = 8) (boys and girls aged 9-12 years) were matched in age, verbal intelligence quotients, and valid PEPSI voxels. In contrast to patients in past studies who received combined treatment, our patients were randomly assigned to either phonologic or morphologic (meaning-based) intervention between the scanning sessions. RESULTS: Before treatment, the patients showed significantly greater lactate elevation in the left frontal regions (including the inferior frontal gyrus) during the phonologic task. Both patients and control subjects differed significantly in the right parietal and occipital regions during both tasks. After treatment, the two groups did not significantly differ in any brain region during either task, but individuals given morphologic treatment were significantly more likely to have reduced left frontal lactate activation during the phonologic task. CONCLUSION: The previous finding of greater left frontal lactate elevation in children with dyslexia during a phonologic judgment task was replicated, and brain activation changed as a result of treatment. However, the treatment effect was due to the morphologic component rather than the phonologic component.     

Ximelagatran: an oral direct thrombin inhibitor

OBJECTIVE: To present the chemistry, pharmacology, and pharmacokinetics of ximelagatran, an oral direct thrombin inhibitor (DTI), and to review available comparative clinical trial data evaluating its efficacy and safety relative to other antithrombotic agents in the prevention and treatment of thromboembolism. DATA SOURCES: A search of the PubMed and Cochrane databases (1995-August 2004), supplemented by a manual search of article bibliographies, conference abstracts, and data on file from the manufacturer, was conducted. Key search terms were ximelagatran, melagatran, H376/95, and direct thrombin inhibitors. STUDY SELECTION AND DATA EXTRACTION: Pertinent information from available clinical trials, including study design, patient demographics, dosing regimens, anticoagulant comparators, methods for evaluating effectiveness, treatment outcomes, adverse events, and pharmacokinetic and pharmacodynamic evaluations, was extracted. DATA SYNTHESIS: Ximelagatran is an orally administered DTI under development for use in the treatment of venous thromboembolism (VTE), long-term prevention of a second VTE event, stroke secondary to atrial fibrillation, prevention of VTE after orthopedic procedures, and recurrent ischemic events after acute myocardial infarction. CONCLUSIONS: Ximelagatran, in twice-daily doses of 24 or 36 mg, is an alternative to low-molecular-weight heparins or warfarin in thromboprophylaxis following orthopedic knee replacement, atrial fibrillation, or initial treatment of VTE. Improved outcomes versus placebo were seen in the long-term prevention of VTE in patients who completed an initial 6 months of treatment. Liver-related effects need further clarification.     

Low-field magnetic stimulation in bipolar depression using an MRI-based stimulator

OBJECTIVE: Anecdotal reports have suggested mood improvement in patients with bipolar disorder immediately after they underwent an echo-planar magnetic resonance spectroscopic imaging (EP-MRSI) procedure that can be performed within clinical MR system limits. This study evaluated possible mood improvement associated with this procedure. METHOD: The mood states of subjects in an ongoing EP-MRSI study of bipolar disorder were assessed by using the Brief Affect Scale, a structured mood rating scale, immediately before and after an EP-MRSI session. Sham EP-MRSI was administered to a comparison group of subjects with bipolar disorder, and actual EP-MRSI was administered to a comparison group of healthy subjects. The characteristics of the electric fields generated by the EP-MRSI scan were analyzed. RESULTS: Mood improvement was reported by 23 of 30 bipolar disorder subjects who received the actual EP-MRSI examination, by three of 10 bipolar disorder subjects who received sham EP-MRSI, and by four of 14 healthy comparison subjects who received actual EP-MRSI. Significant differences in mood improvement were found between the bipolar disorder subjects who received actual EP-MRSI and those who received sham EP-MRSI, and, among subjects who received actual EP-MRSI, between the healthy subjects and the bipolar disorder subjects and to a lesser extent between the unmedicated bipolar disorder subjects and the bipolar disorder subjects who were taking medication. The electric fields generated by the EP-MRSI scan were smaller (0.7 V/m) than fields used in repetitive transcranial magnetic stimulation (rTMS) treatment of depression (1-500 V/m) and also extended uniformly throughout the head, unlike the highly nonuniform fields used in rTMS. The EP-MRSI waveform, a 1-kHz train of monophasic trapezoidal gradient pulses, differed from that used in rTMS. CONCLUSIONS: These preliminary data suggest that the EP-MRSI scan induces electric fields that are associated with reported mood improvement in subjects with bipolar disorder. The findings are similar to those for rTMS depression treatments, although the waveform used in EP-MRSI differs from that used in rTMS. Further investigation of the mechanism of EP-MRSI is warranted.     

Bright light treatment of winter depression: morning versus evening light

In a randomized crossover design, 7 patients with winter depression were treated with 7 d of bright morning light (0600 to 0800) and 7 d of evening light (2000 to 2200). Bright lights in the morning significantly reduced the Hamilton Rating Scale for Depression (HRSD) score (18.4 to 5.0); the bright light in the evening moderately decreased the HRSD score (19.4 to 15.1). The improvement in the HRSD score was significantly greater with morning light than with evening light.