Publications (14) View all
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Article: Anticholinergic Drug Use, Serum Anticholinergic Activity, and Adverse Drug Events Among Older People: A Population-Based Study.
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ABSTRACT: BACKGROUND: The serum anticholinergic activity (SAA) assay has been used to quantify patients' anticholinergic load. In addition, several ranked lists of anticholinergic drugs have been developed to assess anticholinergic drug burden. OBJECTIVE: This study investigated whether SAA assay results and scores from three ranked lists of anticholinergic drugs (Carnahan's Anticholinergic Drug Scale, Rudolph's Anticholinergic Risk Scale, and Chew's list) are associated with anticholinergic adverse drug events (ADEs) in older people. METHODS: We analyzed data from participants in the population-based Geriatric Multidisciplinary Good Care of the Elderly Study in Kuopio, Finland (n = 621). Demographic, diagnostic, and drug use data were collected during standardized interviews and verified from medical records. Vision, functional capacity, cognition, and mood were assessed using validated techniques. The SAA was measured from blood samples. RESULTS: The SAA was not associated with anticholinergic ADEs. Anticholinergic drug burden computed using each of the three lists was inversely associated with short-distance vision (p < 0.01), activities of daily living (p < 0.05), and instrumental activities of daily living (p < 0.05) in persons with and without dementia. Furthermore, poorer Mini Mental State Examination and poorer Geriatric Depression Scale scores were associated with the anticholinergic drug burden in persons without dementia (p < 0.05-p < 0.001). The association between anticholinergic drug burden and ADEs was strongest when using the lists developed by Carnahan and Chew. CONCLUSIONS: Scores obtained from ranked lists of anticholinergic drugs were associated with clinically significant anticholinergic ADEs but the SAA was not. This finding supports the usefulness of these lists to help identify patients at risk of anticholinergic ADEs in clinical practice.Drugs & Aging 03/2013; · 2.67 Impact Factor -
Article: Comprehensive geriatric assessment decreases prevalence of orthostatic hypotension in older persons.
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ABSTRACT: Background: Orthostatic hypotension (OH) is associated with significant morbidity and mortality among older people. We have studied whether its prevalence can be reduced by a Comprehensive Geriatric Assessment (CGA). Study design and setting: 1000 randomly-selected persons aged ≥75 years were divided into intervention (n = 500) and control groups (n = 500). We focused on those subjects in whom an orthostatic blood pressure test had been performed at least once during the study period (2004-2007) (n = 365 and 332 for intervention and control groups, respectively). A CGA, including evaluation of the adequacy of the medication, was performed annually in the intervention group but not in the control group. We conducted Markov models to study change in the OH profiles and the effect of CGA on it. Competing risk of mortality was modeled as an absorbing state to avoid attrition bias. Results: Over 3 years, the prevalence of OH decreased (35.0% → 28.0%) in the intervention group, whereas its prevalence increased in the control group (32.8% → 40.8%). By Markov models it was shown that CGA had a statistically significant effect on recovering from OH. In addition, CGA was shown to protect from developing OH. Conclusions: Repeated CGA performed annually can reduce the prevalence of OH.Scandinavian Journal of Public Health 02/2013; · 1.39 Impact Factor -
Article: Effects of medication assessment as part of a comprehensive geriatric assessment on drug use over a 1-year period: a population-based intervention study.
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ABSTRACT: High drug consumption among the elderly and inappropriate prescribing practices increase the risk of adverse drug effects in this population. This risk may be decreased by conducting, for example, a medication review alone or as part of a comprehensive geriatric assessment (CGA); however, little is known about the fate of the changes in medication made as a result of the CGA or medication review. To study the performance of the CGA with regards to medication changes and to determine the persistence of these changes over a 1-year period. This study was a population-based intervention study. A random sample of 1000 elderly (age > or =75 years) was randomized either to a CGA group or to a control group. Home-dwelling patients from these groups (n = 331 and n = 313 for intervention and control groups, respectively) were analysed in this study. Study nurses collected information on medication at study entry and 1 year later in both groups; in the intervention group, study physicians assessed, and changed when appropriate, the medication at study entry. The medication changes and their persistence over 1 year were then evaluated. Medication changes were more frequent in the intervention group than in the control group. Regular medication was changed during follow-up in 277 (83.7%) and in 228 (72.8%) [odds ratio (OR) 1.9; 95% CI 1.3, 2.8] patients in the intervention and control groups, respectively. In the intervention group, study physicians were responsible for 35.4% of all new prescriptions and for 15.6% of all drug terminations. Changes took place particularly in the prescription of CNS drugs. About 58% of the drugs initiated by study physicians were still in use 1 year later, and 25.5% of those terminated by study physicians had been reintroduced. Drug intervention as part of a CGA can be used to rationalize the drug therapy of a patient. However, its effectiveness is subsequently partly counteracted by other physicians working in the healthcare system.Drugs & Aging 06/2010; 27(6):507-21. · 2.67 Impact Factor -
Article: The role of PEI structure and size in the PEI/liposome-mediated synergism of gene transfection.
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ABSTRACT: Polyethylenimines (PEIs) and cationic liposomes are widely used for nonviral gene delivery. When PEIs have been used alone, the transfection efficiency has been higher for larger or linear than smaller or branched PEIs. We have reported previously that a combination of small PEIs and liposomes results in a potentiation of transfection efficiency in vitro. Here, the role of PEI size and structure in this synergism has been clarified further. Therefore, two structurally different high MW PEIs, i.e. the linear PEI22K and branched PEI25K, were studied in the SMC cells. We found that both linear PEI22K and branched PEI25K resulted in a similar synergism and comparable transfection efficiencies. However, the potentiation for larger PEIs found in the present study was weaker than that for smaller PEIs obtained in our previous studies. In conclusion, our present and previous results demonstrate that the increment of PEI/liposome-mediated gene transfection by different types of PEIs in vitro is a common attribute that is rather associated with their size than the structure. Interestingly, the effect of PEI size seems to be opposite when combined with liposome or given alone, i.e. the small PEIs are more effective when combined and less effective when alone than the larger ones.Plasmid 10/2008; 61(1):15-21. · 1.52 Impact Factor -
Article: Different viabilities and toxicity types after 6-OHDA and Ara-C exposure evaluated by four assays in five cell lines.
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ABSTRACT: Cell viability studies are useful when screening novel drugs for the diseases that are related to either increased cell death or enhanced cell survival. There are numerous assays but the results that they produce are rarely unanimous. Here we compared the performance of (1) morphological microscopic assay with double DNA staining, (2) propidium iodide-digitonin assay, (3) MTT-assay, and (4) ATP-assay in human neuroblastoma (SH-SY5Y), rat glioma (C6), rabbit smooth muscle (SMC), Chinese hamster ovary (CHO) and monkey fibroblast cells (CV1-P) exposed to cytosine arabinoside (Ara-C) and 6-hydroxydopamine (6-OHDA). We found that neuronal SH-SY5Y cells were most sensitive to both toxins and the results in all viability tests correlated well. All the other cell lines were much more resistant, particularly to Ara-C but also to 6-OHDA. Toxicity of the compounds was best revealed by MTT and ATP assays, measuring the metabolic activity of the cells, and only occasionally by morphological observations or with the propidium iodide-digitonin assay which is based on the cell membrane integrity. In this research, Ara-C induced pure apoptosis whereas the toxicity type of 6-OHDA was dose-dependent. The use of several viability tests and cell lines is recommended when studying cell death, particularly apoptosis, and performance of antiapoptotic compounds.Toxicology in Vitro 03/2008; 22(1):182-9. · 2.78 Impact Factor
