Psychiatrists' judgments about antipsychotic benefit and risk outcomes and formulation in schizophrenia treatment.

OBJECTIVE: The objectives were to quantify psychiatrists' judgments of the benefits and risks of antipsychotic treatments of patients with schizophrenia and to evaluate how patient adherence history affects these judgments. METHODS: Weights assigned by respondents to risks, benefits, and alternative drug formulations in the treatment of schizophrenia were assessed via a Web-based survey by using a discrete-choice experiment. Respondents in the United States and the United Kingdom chose among alternative scenarios characterized by various levels of improvement in positive symptoms, negative symptoms, social functioning, weight gain, extrapyramidal symptoms (EPS), hyperprolactinemia, and hyperglycemia and by formulation. The effect of patient adherence history on respondents' judgments was also assessed. Random-parameters logit and bivariate probit models were estimated. RESULTS: The sample included 394 psychiatrists. Improvement in positive symptoms from "no improvement" to "very much improved" was the most preferred outcome over the range of improvements included and was assigned a relative importance score of 10. Other outcomes, in decreasing order of importance, were improvement in negative symptoms from "no improvement" to "very much improved" (5.2; 95% confidence interval [CI]=4.2-6.2), social functioning from "severe problems" to "mild problems" (4.6, CI=3.8-5.4), no hyperglycemia (1.9, CI=1.5-2.4), <15% weight gain (1.5, CI=.9-2.0), no hyperprolactinemia (1.3, CI=.8-1.6), and no EPS (1.1, CI=.7-1.5). As adherence decreased, formulation became more important than modest efficacy changes and injections were preferred to daily pills (p<.05). CONCLUSIONS: Psychiatrists favored treatments that primarily improve positive symptoms. Choice of formulation became more important as likely adherence declined.

Nanoporous organosilicas as preconcentration materials for the electrochemical detection of trinitrotoluene.

We describe the use of nanoporous organosilicas for rapid preconcentration and extraction of trinitrotoluene (TNT) for electrochemical analysis and demonstrate the effect of template-directed molecular imprinting on TNT adsorption. The relative effects of the benzene (BENZ)- and diethylbenzene (DEB)-bridged organic-inorganic polymers, having narrow or broad pore size distributions, respectively, on electrochemical response and desorption behavior were examined. Sample volumes of 0.5-10 mL containing 5-1000 ppb TNT in a phosphate-buffered saline buffer were preconcentrated in-line before the detector using a microcolumn containing 10 mg of imprinted BENZ or DEB. Square-wave voltammetry was used to detect the first reduction peak of TNT in an electrochemical flow cell using a carbon working electrode and a Ag/AgCl reference electrode. Imprinted BENZ released TNT faster than imprinted DEB with considerably less peak tailing and displayed enhanced sensitivity and an improvement in the limit of detection (LOD) owing to more rapid elution of TNT from that material with increasing signal amplitude. For imprinted BENZ, the slope of signal versus concentration scaled linearly with increasing preconcentration volume, and for preconcentrating 10 mL of sample, the LOD for TNT was estimated to be 5 ppb. Template-directed molecularly imprinted DEB (TDMI-DEB) was 7-fold more efficient in adsorption of TNT from aqueous contaminated soil extract than nonimprinted DEB.

Detection of organics using porphyrin embedded nanoporous organosilicas.

Molecularly imprinted polymers and silica have been studied as receptor binding site mimics for use in a wide range of separation, catalysis, and detection applications employing transduction mechanisms including conductometric, amperometric, and capacitance. Porphyrins are also well known as sensor components due to the extreme sensitivity of their spectrophotometric characteristics to changes in their immediate environment. We have developed periodic mesoporous organosilicas (PMO) which incorporate a porphyrin into the material for use as an optical indicator of target binding. This material combines the stability, selectivity, and high density of binding sites characteristic of the molecularly imprinted PMO with the sensitivity and selectivity of the porphyrin. We demonstrate binding of p-nitrophenol, p-cresol, 2,4,6-trinitrotoluene, and RDX by the porphyrin-embedded PMOs with selective adsorption of TNT over the other analytes. In addition, the binding of each of the organics by the PMO results in unique changes in the spectrophotometric characteristics of the incorporated porphyrin. These changes can be observed by visual inspection or through the use of fluorescence spectra collected in 96-well format.

Investigation of surface interactions in molecular recognition of phosphonate imprinted organosilicates and the role of water.

Surface interactions in molecular recognition of phosphonate imprinted organosilicates and the role of water have been studied. NMR and calorimetry studies have shown the changing nature of the surface water structure on silicate surfaces due to template directed molecular imprinting. Results indicate the interaction of an organophosphonate compound with the functionalized silica surfaces to be through surrounding water molecules. However, with nonfunctionalized surfaces, additional higher energy interactions were possible. Further, our results support the possible templating effect of water during the imprint process.

Organosilica copolymers for the adsorption and separation of multiple pollutants.

Benzene, diethylbenzene, and ethylenediamine-bridged bistrialkoxy precursors were used in the synthesis of multifunctional PMO copolymers for the adsorption of phenols and metal ions. Polyoxyethylene(10) stearyl ether (Brij 76) was used as the structure director with the surfactant template approach in the synthesis. The resulting PMO copolymers with two or more bridging groups have been characterized by nitrogen gas adsorption, powder X-ray diffraction, and 13C and 29Si solid-state NMR. These organosilicas exhibit large surface areas, narrow pore size distributions, large total pore volumes, and pore ordering consistent with well ordered, hexagonally packed p6mm structures. Minimal competitive effects were observed on the adsorption of p-chlorophenol to the copolymers in the presence of copper ions in solution. Similarly, the presence of p-chlorophenol in solution or adsorbed onto the copolymers did not interfere with copper adsorption. Replacement of a small portion of the benzene bridge in the 90:10 BENZ:EDA copolymer with diethylbenzene produced a copolymer 2.5-fold more efficient for p-chlorophenol adsorption. ICP analysis revealed that greater than 98% of adsorbed copper was removed during extraction with HCl, and this extraction process can be repeated with no difference in copper adsorption after regeneration.

Porous polysilsesquioxanes for the adsorption of phenols.

Arylene- and ethylene-bridged polysilsesquioxane materials have been synthesized by the hydrolysis and condensation of alkoxysilyl precursors under basic conditions. Cetyltrimethylammonium chloride was used to increase the porosity and surface areas of these materials via the surfactanttemplate approach. Structural characterization of these materials was carried out by nitrogen gas sorption and X-ray diffraction. The adsorption of three phenolic compounds (4-nitrophenol, 4-chlorophenol, 4-methylphenol) has been investigated by both batch and column testing. The arylene-bridged material exhibited a much greater affinity for all three phenols. The efficient removal of adsorbed phenols by a simple ethanol wash led to sorbent regeneration and separation of the aromatic species.