Catechol O-methyltransferase (COMT) plays an important role in the metabolism of catecholamines, catecholestrogens and catechol drugs. A common COMT G472A genetic polymorphism (Val108/158Met) that was identified previously is associated with decreased levels of enzyme activity and has been implicated as a possible risk factor for neuropsychiatric disease. We set out to 'resequence' the human COMT gene using DNA samples from 60 African-American and 60 Caucasian-American subjects. A total of 23 single nucleotide polymorphisms (SNPs), including a novel nonsynonymous cSNP present only in DNA from African-American subjects, and one insertion/deletion were observed. The wild type (WT) and two variant allozymes, Thr52 and Met108, were transiently expressed in COS-1 and HEK293 cells. There was no significant change in level of COMT activity for the Thr52 variant allozyme, but there was a 40% decrease in the level of activity in cells transfected with the Met108 construct. Apparent K m values of the WT and variant allozymes for the two reaction cosubstrates differed slightly, but significantly, for 3,4-dihydroxybenzoic acid but not for S-adenosyl-L-methionine. The Met108 allozyme displayed a 70-90% decrease in immunoreactive protein when compared with WT, but there was no significant change in the level of immunoreactive protein for Thr52. A significant decrease in the level of immunoreactive protein was also observed in hepatic biopsy samples from patients homozygous for the allele encoding Met108. These observations represent steps toward an understanding of molecular genetic mechanisms responsible for variation in COMT level and/or properties, variation that may contribute to the pathophysiology of neuropsychiatric disease.

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What is known and objective With the ageing of the population also comes increasing comorbidities and the use of multiple medications and administration methods, along with greater susceptibility to adverse drug reactions. Dosage form modification to facilitate drug administration in older adults can be potentially problematic as altering the original licensed formulation can affect medication safety and efficacy. The reporting of adverse drug reactions and medication incidents is a key strategy in avoiding preventable adverse drug events for aged care residents. This study evaluated the effect of an on‐site clinical pharmacist on reducing inappropriate dosage form modification and staff time spent on medication administration, and optimizing the documentation of drug allergies, adverse drug reactions and medication incidents. Methods A pilot‐controlled trial was performed in a purposive sample of two residential aged care homes. Both homes belonged to the same organization; the study site had 104 beds and the control site had 100 beds. All permanent residents were eligible for inclusion in the study if written consent was provided. A residential care pharmacist position was implemented at the study site for six months, with a focus on performing medication reviews and quality improvement activities. Observational audits of medication rounds were performed, and documentation relating to allergies, adverse drug reactions, and medication incidents was obtained from both sites before and after the pharmacist trial period. Results At the study site, there was a significant reduction over the trial in the proportion of inappropriate dosage form modification (from 24% to 0% of all dosage form modifications; P < 0.01). Mean time spent on medication rounds per resident reduced from 4.8 minutes per resident (SD 1.1) to 3.2 minutes per resident (SD 1.7) per round (P < 0.05). The incidence of previous allergy and adverse drug reaction documentation significantly improved from 77% of residents pre‐study to 100% of residents post‐study (P < 0.01). Mean monthly medication incident reports significantly improved from 13.3 (SD 7.4) pre‐study to 25.7 (SD 10.8) post‐study (P < 0.05). There was no change in these outcomes at the control site. What is new and conclusion Including a pharmacist in a residential aged care home can improve medication administration practices by reducing inappropriate dosage form modification and staff time spent on medication administration rounds, and increasing the documentation of resident allergies, adverse drug reactions and medication incidents. These findings warrant further exploration in a large randomized controlled trial.

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