Assessment of cognitive safety in clinical drug development.

Cognitive impairment is increasingly recognised as an important potential adverse effect of medication. However, many drug development programmes do not incorporate sensitive cognitive measurements. Here, we review the rationale for cognitive safety assessment, and explain several basic methodological principles for measuring cognition during clinical drug development, including study design and statistical analysis, from Phase I through to postmarketing. The crucial issue of how cognition should be assessed is emphasized, especially the sensitivity of measurement. We also consider how best to interpret the magnitude of any identified effects, including comparison with benchmarks. We conclude by discussing strategies for the effective communication of cognitive risks.

Improving some selected properties of dental polyacid-modified composite resins.

OBJECTIVES: Polyacid-modified composite resins (compomers) are restorative dental materials that exhibit certain features of traditional dental composites and glass-ionomer cements. The aim of this paper was to develop experimental compomers with enhanced properties, based on adhesive monomers vinyl phosphonic acid and pyromellitic dianhydride glycerol dimethacrylate, and to compare their properties to those of commercially available products. METHODS: Factorial experimental design was employed to optimize both chemical and physical properties. Properties such as biaxial flexural strength (BFS), wear resistance (WR), water uptake (WU), and adhesion using shear bond strength (SBS) as well as fluoride release (FR) were evaluated and compared with those of commercial products. RESULTS: Results were subjected to one-way ANOVA (p<0.05); significant differences were observed in properties of materials such as WR, BFS and SBS but not in WU and FR compared to commercial products. Experimental materials exhibited significantly higher WR, BFS and SBS values than commercial materials. Properties of materials were affected by their respective storage media with time. SIGNIFICANCE: Based on the results of this study, higher amounts of vinyl phosphonic acid (VPA), pyromellitic dianhydride glycerol dimethacrylate (PMGDM) and reactive glasses render the material with enhanced fluoride release and adhesion with properties similar to glass-ionomers whereas their decrease gives properties similar to conventional dental composite resins with improved properties such as strength and wear resistance.

Effects of storage media on physical properties of selected tooth coloured restorative materials.

It is known that storage media can affect the physical properties of some restorative dental materials. The purpose of this laboratory study was to investigate the possible effects of storage media on physical properties of a conventional glass-ionomer, a resin modified glass ionomer and a compomer. Specimens of the restorative materials in the study (FujiII LC, FujiIX and Dyract EXTRA) were prepared. The specimens were stored in either water or artificial saliva with or without exposure to Listerine. The compressive and diametral tensile strength and Vickers hardness of these materials were tested at 24 hours, 1 week, 4 weeks and 12 weeks. Compressive and diametral tensile strength for FujiII LC and Fuji IX had increased at 12 weeks. A decrease was observed for Dyract EXTRA in the same period. No significant differences were observed between the storage media (P > 0.01). Vickers hardness values fluctuated during the testing period, with a pattern being consistent for each material. Storage of materials investigated for the period in this study resulted in superior compressive and diametral tensile strength for Fuji II LC and FujiIX. The opposite was true for Dyract EXTRA. Effects of time were found to be more pronounced than the media (P < 0.01).

A clinical assessment of the performance of a sensor to detect crystalline biofilm formation on indwelling bladder catheters.

OBJECTIVES: To test the ability of a sensor developed to signal infection by the organisms that generate the crystalline biofilms that encrust catheters, to give an early warning that encrustation was occurring on patients' catheters, as the care of many patients undergoing long-term bladder catheterization is complicated by the encrustation and blockage of their catheters. PATIENTS AND METHODS: Twenty patients were followed prospectively for the lifetime of one of their catheters. Sensors based on cellulose acetate/bromothymol blue were placed in the urine-collection bags, which were changed as usual at weekly intervals. The bacteriology was assessed and pH determined weekly on urine samples. Photographic records were made of the sensors twice weekly. On removal, each catheter was examined for encrustation and blockage. RESULTS: Proteus mirabilis was not isolated from five patients and in these cases the sensor colour remained golden-yellow to brown. The catheters drained for the scheduled period and showed no signs of encrustation. By contrast, the sensors turned dark blue/black in the urine of all 15 patients infected with P. mirabilis. All these patients' catheters were encrusted and in 12 the catheters blocked. The mean interval between the sensor signalling and the catheter blocking was 12 days. CONCLUSION: The cellulose acetate/bromothymol blue sensors placed in the urine collection bags are capable of signalling infection by P. mirabilis. They also signal the early stages of catheter encrustation and allow catheter replacement in ample time to avoid the clinical crises and emergency referrals caused by catheter blockage.

A preliminary study of experimental polyacid-modified composite resins ('compomers') containing vinyl phosphonic acid.

OBJECTIVES: The aim of this investigation was to determine the properties of two novel compomers formulated with the monomer vinyl phosphonic acid (VPA). The setting properties, mechanical strength, wear characteristics and fluoride release of two experimental unshaded compomers containing VPA were determined, and compared with the commercial compomer Dyract A (shade C3). METHODS: Two novel compomers were prepared, containing, respectively, 0.24% (A) and 2.31% (B) by mass of VPA, and an appropriate amount of reactive glass filler. Their properties were compared with those of Dyract AP (shade A3). Depth of cure was determined according to the method of ISO 4049. Polymerization of model mixtures of bisGMA, TEGDMA and VPA was studied using FT Raman spectroscopy, by comparing the absorption at 1608cm(-1) (aromatic C-C bond) with that at 1313cm(-1) (CC aliphatic). Compressive and biaxial flexure strengths were determined for sets of 6 specimens stored either wet or dry. Wear was determined using a toothbrushing machine and an abrasive slurry, and fluoride release was determined following up to 6 weeks storage in aqueous media, using a fluoride-selective electrode. RESULTS: Of the model monomer mixtures, the one with the greater quantities of VPA showed lowest degrees of polymerization after irradiation for 40s. Compomer A had an acceptable depth of cure, and similar properties to Dyract AP in terms of compressive and biaxial flexure strength, and also fluoride release. Resistance to toothbrush abrasion of both of the experimental compomers was superior to that of Dyract AP. SIGNIFICANCE: These studies demonstrate that VPA can be used as the active monomer in experimental compomers, and is capable of yielding materials with properties equivalent to a commercial material, but with improved resistance to toothpaste abrasion. The level of VPA in the formulation is critical, because this monomer inhibits addition polymerization, hence must be used only in small amounts.

The role of the ionomer glass component in polyacid-modified composite resin dental restorative materials.

In order to model the processes that occur within polyacid-modified composite resin ("compomer") dental restoratives, a series of experiments has been carried out with silanated and silane-free ionomer glass G338, and silanated and silane-free unreactive glass (Raysorb T-4000). In an acid-base reaction with dental grade aqueous maleic acid-acrylic acid copolymer solution, the setting time of the silanted G338 was found to be 9 min, compared with 5 min for the silane-free glass. Inclusion of each glass in an experimental composite resin system showed that the formulations which contained G338 absorbed more water than the formulations which contained Raysorb T-4000, regardless of whether or not the glass was silanted. Biaxial flexure strength was superior for experimental composites containing Raysorb T-4000, with highest results being obtained with the silanated glass. Overall these results demonstrate that silanation of the filler is essential for optimal physical properties but that, for the ionomer glass, it inhibits the acid-base reaction. The presence of ionomer glass led to an increase in water uptake compared with the unreactive glass, regardless of the presence of silane.