Relationship between polypharmacy and adverse events.

A retrospective data analysis was performed to investigate the association between polypharmacy and adverse events using three different spontaneous adverse event reporting system databases. Multivariate logistic regression analyses were performed to investigate the association between the number of drugs and adverse events, including hepatic disorders, renal disorders, hypersensitivity, and extrapyramidal syndrome. The results showed that the risk of hepatic and renal disorders increased with the number of drugs. Thus, decreasing the number of drugs may reduce the risk of hepatic and renal disorders. Furthermore, attention should be given to specific drugs that may cause hypersensitivity and extrapyramidal syndrome.

Polypharmacy in three different spontaneous adverse drug event databases.

OBJECTIVE: Polypharmacy has become a major problem in medical care worldwide, including in Japan. The purpose of this study was to investigate the current situation of polypharmacy using different spontaneous adverse drug event report databases. MATERIALS AND METHODS: A retrospective data analysis was performed using reports from 2007 to 2015 from three different spontaneous adverse drug event report databases: the Japanese Adverse Drug Event Report (JADER) constructed by the Pharmaceuticals and Medical Devices Agency in Japan, the US Food and Drug Administration (FDA) Adverse Drug Event Reporting System (FAERS) constructed by the FDA in the United States, and the Canada Vigilance Adverse Reaction Online Database (CVARD) constructed by the government of Canada. Polypharmacy trends during the study period were investigated. RESULTS: The mean numbers of drugs per report in the JADER, FAERS, and CVARD databases during the study period were 6.62, 3.76, and 3.44, respectively. The mean number of drugs per report increased with age in all three databases, with a peak at ages 70 - 79 years in all three databases (7.0 drugs for JADER, 4.7 drugs for FAERS, and 4.2 drugs for CVARD). CONCLUSION: Adverse event reports were more likely to develop in the patients treated through polypharmacy. Polypharmacy in Japan should be improved to prevent adverse events. Additionally, the patients aged ≥ 80 years tended to develop adverse events even if the number of prescribed drugs was relatively small. Therefore, polypharmacy should be noted in these patients to prevent adverse events.

Polypharmacy in elderly patients in Japan: Analysis of Japanese real-world databases.

WHAT IS KNOWN AND OBJECTIVE: Polypharmacy is associated with an increased risk of adverse drug reactions (ADRs) and drug interactions, decreased adherence to medication and increased medical cost. Recently, polypharmacy has become a major problem in medical care in Japan as a result of the increase in the ageing population. The purpose of this study was to investigate the current situation of polypharmacy and the association between polypharmacy and adverse events. METHODS: A retrospective data analysis was performed using two different real-world data from 2007 to 2015 in Japan. The Japanese Adverse Drug Event Report (JADER), a public spontaneous adverse drug reaction database constructed by the Pharmaceuticals and Medical Devices Agency (PMDA), and a large prescription database constructed by a database vendor (Japan Medical Information Research Institute, Inc Japan [JMIRI]) were analysed. Trends of polypharmacy during the study period were investigated. RESULTS AND DISCUSSION: The mean number of drugs per report in the JADER database and per prescription in the JMIRI databases during the study period ranged from 4.8 to 5.6 and 3.5 to 3.7, respectively. The mean number of drugs increased with age in both the JADER and JMIRI databases, and the peak of the mean number of drugs was at 80-89 years (5.74 drugs) in the JADER database and at 90-99 years (4.97 drugs) in the JMIRI database. WHAT IS NEW AND CONCLUSIONS: The number of drugs increased until age 90 years or more, even though adverse events are more likely to occur after the age of 80 in Japan. Therefore, polypharmacy in the elderly should be focused on the patients aged ≥80 years rather than patients aged ≥65 years from the viewpoint of the prevention of adverse events.

Synthesis of multiply deuterated 3- and 21-monosulfates of allo-tetrahydrocorticosteroids as internal standards for mass spectrometry.

The accurate analysis of trace components in complex biological matrices requires the use of reliable internal standards. For liquid chromatography/mass spectrometry analysis, the stable isotope-labeled analogues of the analyte molecules are the most appropriate internal standards. In this paper the synthesis of the 3- and 21-monosulfates of allo-tetrahydrocorticosteroids labeled with four or five deuterium atoms is described. The principal reactions used were (1) hydrogen-deuterium exchange reaction of active methylene groups adjacent to 3- and 11-oxo group of 17,20;20,21-bismethylenedioxy derivatives of 5α-3-ketosteroids and/or 5α-11-ketosteroids with NaOD in CH(3)OD followed by reduction with NaBD(4), (2) epimerization of the 3ß-hydroxy group into a 3α configuration, (3) sulfation of hydroxy groups at C-3 or C-21 in the resulting substrates with sulfur trioxide-trimethylamine complex, and (4) removal of 17,20;20,21-bismethylenedioxy groups with hydrogen fluoride in ethanol. Isotopic purity was found to be satisfactory by MS, and NMR properties of the new compounds were tabulated. The labeled compounds can be used as internal standards in liquid chromatography/mass spectrometry assays for clinical and biochemical studies.

Holographic polymer-dispersed liquid crystal memory for optically reconfigurable gate array using subwavelength grating mask.

Holographic polymer-dispersed liquid crystal (HPDLC) memory formed by a subwavelength grating (SWG) mask is presented for new optical information processing. The SWG structure in a photomask is formed on the SiO(2) plate using the anisotropic reactive ion etching technique. The configuration contexts for optically reconfigurable gate arrays (ORGAs) are stored in the HPDLC memory by polarization modulation property based on the form birefringence of the SWG plate. The configuration context pattern in the HPDLC memory is reconstructed to write it for the ORGAs under parallel programmability.

Synthesis of 3- and 21-monosulfates of [2,2,3ß,4,4-²H5]-tetrahydrocorticosteroids in the 5ß-series as internal standards for mass spectrometry.

The 3- and 21-monosulfates of pentadeuterated 5ß-tetrahydrocorticosteroides were synthesized, starting from cortisol and 11-deoxycotisol. The principal reactions used were (1) perdeuteration of the methylene groups adjacent to the 3-oxo group of 17,20:20,21-bismethylendioxy-5ß-3-ketosteroids with NaOD in CH(3)OD followed by stereoselective reduction with NaBD(4), (2) sulfation of hydroxy groups with sulfur trioxide-trimethylamine complex, and (3) removal of the 17,20:20,21-bismethylendioxy group with hydrogen fluoride. The labeled compounds can be used as internal standards in liquid chromatography/mass spectrometry assays for clinical and biochemical studies.

Superimposing acceleration and optimization method of optical reconfiguration speed without any increase of laser power.

This paper proposes a method of superimposing acceleration and optimizing the optical reconfiguration speed while requiring no increase of laser power. Using this technique, the optical reconfiguration speed is increased by superimposing multiple configuration contexts. Simultaneously, optimization of the number of configuration contexts and reconfiguration speed is possible. A full four-context optically reconfigurable gate array system consisting of an optically reconfigurable gate array VLSI, an easily rewritable liquid crystal holographic memory, and four vertical-cavity surface-emitting lasers was constructed to demonstrate this method. This paper clarifies the method's benefits using experimental results obtained from the demonstration system.

Formation of holographic memory for defect tolerance in optically reconfigurable gate arrays.

Holographic polymer-dispersed liquid-crystal (HPDLC) memory using liquid-crystal composites is proposed for new optical information processing. Formation of HPDLC memory using a photomask is discussed for parallel programmability to realize fast reconfiguration of optically reconfigurable gate arrays (ORGAs). The defect tolerance of HPDLC memory is investigated to clarify the defect limitation of holographic configurations using ORGAs. Experimental results show that the noise ratio less than 15% applied to HPDLC memory rarely affects its diffraction pattern or a reconfiguration context.