EFFICACY AND SAFETY OF MOGUISTEINE IN COMPARISON WITH DEXTROMETHORPHAN IN PATIENTS WITH PERSISTENT COUGH

Cough is a protective mechanism and an important symptom of many respiratory diseases. When coughing is only an annoying reflex and produces no mucus clearance, inducing fatigue or exhaustion for patients and worsening their pathological condition, antitussive drugs may be indicated. In this study we evaluated the efficacy and safety of moguisteine, a new antitussive drug with a peripheral mechanism of action, in a population of 124 adult patients with persistent cough associated with various respiratory disorders. Obstructive chronic bronchitis, reported in about 50% of the study population, was the most frequent underlying diagnosis. We conducted a randomised single-blind short term treatment trial in 7 centres, comparing moguisteine (3 doses of 200mg, over 2 days) to dextromethorphan (3 doses of 30mg, over 2 days). The primary efficacy variable was the percentage reduction in the audio tape-recorded number of coughs during a 6-hour period in the morning after the last dose of the study drug versus a 6-hour recording at baseline. Patients' subjectively assessed visual analogue scale (VAS) scores of cough frequency and cough troublesomeness at night and during the morning were considered as secondary efficacy variables. Safety was assessed by means of routine clinical laboratory tests and adverse event monitoring. The postdrug percentage reduction in the number of coughs approached 30% on either drug. VAS scores of cough frequency and cough troublesomeness showed remarkable reductions in both groups, without any noteworthy difference between treatments. Possible or probable drug-related adverse events were reported in 3 of 61 patients on moguisteine (1 heartburn, 1 gastric pain, 1 diarrhoea) and in 4 of 63 patients on dextromethorphan (1 rhinitis and slight decrease of white blood cell count, 1 syncope, 1 gastric discomfort, 1 diarrhoea). Treatment discontinuation was necessary only for 1 patient, who had a syncope after the first dose of dextromethorphan. Our results indicate that treatment with moguisteine rapidly induces substantial cough relief and that it is well tolerated and as effective as dextromethorphan

Cognitive control neuroimaging measures differentiate between those with and without future recurrence of depression

Background: Major Depressive Disorder (MDD) is a prevalent, disruptive illness. A majority of those with MDD are at high risk for recurrence and increased risk for morbidity and mortality. This study examined whether multimodal baseline (and retest) Cognitive Control performance and neuroimaging markers (task activation and neural connectivity between key brain nodes) could differentiate between those with and without future recurrence of a major depressive (MD) episode within one year. We hypothesized that performance and neuroimaging measures of Cognitive Control would identify markers that differ between these two groups. Methods: A prospective cohort study of young adults (ages 18–23) with history (h) of early-onset MDD (N = 60), now remitted, and healthy young adults (N = 49). Baseline Cognitive Control measures of performance, task fMRI and resting state connectivity (and reliability retest 4–12 weeks later) were used to compare those with future recurrence of MDD (N = 21) relative to those without future recurrence of MDD (N = 34 with resilience). The measures tested were (1) Parametric Go/No-Go (PGNG) performance, and task activation for (2) PGNG Correct Rejections, (3) PGNG Commission errors, and (4 & 5), resting state connectivity analyses of Cognitive Control Network to and from subgenual anterior cingulate. Results: Relative to other groups at baseline, the group with MDD Recurrence had less bilateral middle frontal gyrus activation during commission errors. MDD Recurrence exhibited greater connectivity of right middle frontal gyrus to subgenual anterior cingulate (SGAC). SGAC connectivity was also elevated in this group to numerous regions in the Cognitive Control Network. Moderate to strong ICCs were present from test to retest, and highest for rs-fMRI markers. There were modest, significant correlations between task, connectivity and behavioral markers that distinguished between groups. Conclusion: Markers of Cognitive Control function could identify those with early course MD who are at risk for depression recurrence. Those at high risk for recurrence would benefit from maintenance or preventative treatments. Future studies could test and validate these markers as potential predictors, accounting for sample selection and bias in feature detection

Inhaler mishandling is very common in patients with chronic airflow obstruction and long-term home nebuliser use.

Inhalers and nebulisers are devices used for delivering aerosolised drugs in subjects with Chronic Airflow Obstruction (CAO). This multicentre, cross-sectional observational study was performed in a large population of outpatients with CAO regularly using home aerosol therapy and referring to chest clinics. The aims of the study were to compare the characteristics of the group of subjects with CAO who were using home nebulisers but also experienced with inhalers vs. those only using inhalers and to investigate whether the first group of subjects was particularly prone to inhaler misuse. Information was gained evaluating the responses to a standardised questionnaire on home aerosol therapy and the observations of inhaler technique. We enrolled 1527 patients (58\% males; mean ± SE; aged 61.1 ± 0.4 years; FEV1\% pred 69.9 ± 0.6; 51\% and 44\% respectively suffering from COPD and asthma) who were only inhaler users (OIU group) and 137 (85\% males; aged 67.7 ± 1.3 years; FEV1\% pred 62.3 ± 2.9; 60\% and 23\% respectively suffering from COPD and asthma) who were using both nebulisers and inhalers (NIU group). Nebuliser users were older, had more severe obstruction, related symptoms and health care resources utilisation. Nebulisers users performed more critical inhalers errors than those of the OIU group (49\% vs. 36\%; p = 0.009). We conclude that our patients with CAO and regular nebuliser treatment had advanced age, severe respiratory conditions and common inhaler misuse

Reliability, Convergent Validity and Time Invariance of Default Mode Network Deviations in Early Adult Major Depressive Disorder

There is substantial variability across studies of default mode network (DMN) connectivity in major depressive disorder, and reliability and time-invariance are not reported. This study evaluates whether DMN dysconnectivity in remitted depression (rMDD) is reliable over time and symptom-independent, and explores convergent relationships with cognitive features of depression. A longitudinal study was conducted with 82 young adults free of psychotropic medications (47 rMDD, 35 healthy controls) who completed clinical structured interviews, neuropsychological assessments, and 2 resting-state fMRI scans across 2 study sites. Functional connectivity analyses from bilateral posterior cingulate and anterior hippocampal formation seeds in DMN were conducted at both time points within a repeated-measures analysis of variance to compare groups and evaluate reliability of group-level connectivity findings. Eleven hyper- (from posterior cingulate) and 6 hypo- (from hippocampal formation) connectivity clusters in rMDD were obtained with moderate to adequate reliability in all but one cluster (ICC's range = 0.50 to 0.76 for 16 of 17). The significant clusters were reduced with a principle component analysis (5 components obtained) to explore these connectivity components, and were then correlated with cognitive features (rumination, cognitive control, learning and memory, and explicit emotion identification). At the exploratory level, for convergent validity, components consisting of posterior cingulate with cognitive control network hyperconnectivity in rMDD were related to cognitive control (inverse) and rumination (positive). Components consisting of anterior hippocampal formation with social emotional network and DMN hypoconnectivity were related to memory (inverse) and happy emotion identification (positive). Thus, time-invariant DMN connectivity differences exist early in the lifespan course of depression and are reliable. The nuanced results suggest a ventral within-network hypoconnectivity associated with poor memory and a dorsal cross-network hyperconnectivity linked to poorer cognitive control and elevated rumination. Study of early course remitted depression with attention to reliability and symptom independence could lead to more readily translatable clinical assessment tools for biomarkers