Use of combinations of antipsychotics: McLean Hospital inpatients, 2002

Background The empirical use of combinations of antipsychotic agents appears to be increasing with little research support for the relative efficacy, safety or cost-effectiveness of this practice. Such treatment was evaluated in hospitalized psychiatric patients. Methods Samples of consecutive inpatients treated with > 2 ('polytherapy') vs 1 antipsychotic ('monotherapy') were matched on age, sex, diagnosis and admission clinical ratings, and these groups were compared on total daily chlorpromazine-equivalent doses, days in hospital, and changes in clinical ratings between admission and discharge. Results The study sample included 69 polytherapy and 115 well-matched monotherapy subjects. Despite matching for initial CGI and GAF ratings, polytherapy was associated with high PANSS subscale scores of positive symptoms among affective psychosis, and relatively greater PANSS subscale ratings of excitement-agitation among patients diagnosed with schizophrenia. Estimated clinical improvement during hospitalization was similar among poly- and monotherapy patients, but total daily CPZ-eq doses at discharge averaged twice-greater with polytherapy, and hospitalization lasted 1.5 times longer. Conclusions Antipsychotic polytherapy as well as the types of agents combined may reflect clinician responses to particular symptom patterns. The value of specific combinations of antipsychotic agents and their comparison with monotherapies requires specific, prospective, randomized and well-controlled trials that consider matching on clinical characteristics and truly comparable doses across regimens. Copyright (c) 2005 John Wiley & Sons, Ltd

Pharmacotherapy of Schizophrenic Patients: Preponderance of Off-Label Drug Use

Multiple drug class combinations are often prescribed for the treatment of schizophrenia, although antipsychotic monotherapy reflects FDA labeling and scientific justification for combinations is highly variable. This study was performed to gain current data regarding drug treatment of schizophrenia as practiced in the community and to assess the frequencies of off-label drug class combinations. 200 DSM IV-diagnosed schizophrenic patients recruited from community treatment sources participated in this cross-sectional study of community based schizophrenic patients. Drug class categories include First and Second Generation Antipsychotic drugs (FGA and SGA, respectively), mood stabilizers, antidepressants and anti-anxiety drugs. 25.5% of patients received antipsychotic monotherapy; 70% of patients received an antipsychotic and another drug class. A total of 42.5% of patients received more than one antipsychotic drug. The most common drug class combination was antipsychotic and a mood stabilizer. Stepwise linear discriminant function analysis identified the diagnosis of schizoaffective schizophrenia, history of having physically hurt someone and high scores on the General Portion of the PANSS rating scale predicted the combined use of an antipsychotic drug and a mood stabilizer. “Real world” pharmacotherapy of schizophrenia has developed its own established practice that is predominantly off-label and may have outstripped current data support. The economic implications for public sector payers are substantial as well as for the revenue of the pharmaceutical industry, whose promotion of off-label drug use is an increasingly problematic. These data are consistent with the recognition of the therapeutic limitations of both first and second generation antipsychotic drugs

Alterations to Melanocortinergic, GABAergic and Cannabinoid Neurotransmission Associated with Olanzapine-Induced Weight Gain

Background/Aim: Second generation antipsychotics (SGAs) are used to treat schizophrenia but can cause serious metabolic side-effects, such as obesity and diabetes. This study examined the effects of low to high doses of olanzapine on appetite/ metabolic regulatory signals in the hypothalamus and brainstem to elucidate the mechanisms underlying olanzapineinduced obesity. Methodology/Results: Levels of pro-opiomelanocortin (POMC), neuropeptide Y (NPY) and glutamic acid decarboxylase (GAD65, enzyme for GABA synthesis) mRNA expression, and cannabinoid CB1 receptor (CB1R) binding density (using [ 3 H]SR-141716A) were examined in the arcuate nucleus (Arc) and dorsal vagal complex (DVC) of female Sprague Dawley rats following 0.25, 0.5, 1.0 or 2.0 mg/kg olanzapine or vehicle (36/day, 14-days). Consistent with its weight gain liability, olanzapine significantly decreased anorexigenic POMC and increased orexigenic NPY mRNA expression in a dose-sensitive manner in the Arc. GAD65 mRNA expression increased and CB1R binding density decreased in the Arc and DVC. Alterations to neurotransmission signals in the brain significantly correlated with body weight and adiposity. The minimum dosage threshold required to induce weight gain in the rat was 0.5 mg/kg olanzapine. Conclusions: Olanzapine-induced weight gain is associated with reduced appetite-inhibiting POMC and increased NPY. This study also supports a role for the CB1R and GABA in the mechanisms underlying weight gain side-effects, possibly b

The performance measurement system: the experience of Sicilian municipalities

The reform of public administration, and specifically that of Local Authorities,has meant that the most economically advanced countries have been affected by a modernization processes aimed at the introduction of New Public Management approaches and principles (Hood,1991; Pollitt, 1990; Borgonovi, 1988; etc.). Since the 1990s, a particularly interesting element in this process of change has been the introduction of an internal control system in the Italian Public Administration. Indeed, it has moved the attention of decision makers away from compliance with formal procedures toward efficient resource allocation and, therefore, toward achieving objectives in from a multi-dimensional viewpoint. The underlying assumption is that measures of a quantitative nature, focused on cost, provide little information on longterm performance. For these reasons, this paper focuses on the planning and strategic control system in Sicilian local authorities. In detail the aim of the paper is to check whether the Balanced Scorecard is implemented in local authorities, or if there are at least the beginnings of implementation of the same. In order to verify the propensity of these organizations toward multidimensional performance measurement, a quantitative research methodology was used, based on analysis of data obtained from a multiple choice and open answer questionnaire

Contraction Analysis of Hopfield Neural Networks with Hebbian Learning

Motivated by advances in neuroscience and machine learning, this paper is concerned with the modeling and analysis of Hopfield neural networks with dynamic recurrent connections undergoing Hebbian learning. To capture the synaptic sparsity of neural circuits, we propose a low dimensional formulation for the model and then characterize its key dynamical properties. First, we give a biologically-inspired forward invariance result. Then, we give sufficient conditions for the non-Euclidean contractivity of the model. Our contraction analysis leads to stability and robustness of time-varying trajectories - for networks with both excitatory and inhibitory synapses governed by both Hebbian and anti-Hebbian rules. Our proposed contractivity test is based upon biologically meaningful quantities, e.g., neural and synaptic decay rate, maximum out-degree, and the maximum synaptic strength. Finally, we show that the model satisfies Dale's principle. The effectiveness of our results is illustrated via a numerical example

Ultrasound-guided lung lavage for life-threatening bronchial obstruction due to meconium plug

We present a case of life-threatening airway obstruction caused by meconium aspiration, a condition with significant neonatal mortality and morbidity. Lung ultrasound detected the obstruction and helped in the clinical management allowing to perform a quick and selective bronchoalveolar lavage with diluted surfactant