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  • 1.
    Brännström, Jon
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Boström, Gustaf
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Rosendahl, Erik
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Nordström, Peter
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Littbrand, Håkan
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Lövheim, Hugo
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Gustafson, Yngve
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Psychotropic drug use and mortality in old people with dementia: investigating sex differences2017In: BMC Pharmacology & Toxicology, E-ISSN 2050-6511, Vol. 18, article id 36Article in journal (Refereed)
    Abstract [en]

    Background: Psychotropic drugs are common among old people with dementia, and have been associated with increased mortality. Previous studies have not investigated sex differences in this risk. This study was conducted to analyse associations between the use of antipsychotics, antidepressants, and benzodiazepines and 2-year mortality in old people with dementia, and to investigate sex differences therein.

    Methods: In total, 1037 participants (74% women; mean age, 89 years) with dementia were included from four cohort studies and followed for 2 years. Data were collected through home visits and medical records. Cox proportional hazard regression models were used to analyse associations between ongoing baseline drug use and mortality. Multiple possible confounders were evaluated and adjusted for.

    Results: In fully adjusted models including data from the whole population, no association between baseline psychotropic drug use and increased 2-year mortality was seen. Significant sex differences were found in mortality associated with antidepressant use, which was protective in men, but not in women (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.40–0.92 and HR 1.09, 95% CI 0.87–1.38, respectively). The interaction term for sex was significant in analyses of benzodiazepine use, with a higher mortality risk among men than among women.

    Conclusions: Among old people with dementia, ongoing psychotropic drug use at baseline was not associated with increased mortality in analyses adjusted for multiple confounders. Sex differences in mortality risk associated with antidepressant and benzodiazepine use were seen, highlighting the need for further investigation of the impact of sex.

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  • 2.
    Gustafsson, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Karlsson, Stig
    Umeå University, Faculty of Medicine, Department of Nursing.
    Gustafson, Yngve
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Lövheim, Hugo
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Psychotropic drug use among people with dementia - a six-month follow-up study2013In: BMC Pharmacology & Toxicology, E-ISSN 2050-6511, Vol. 14, article id 56Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Psychotropic drugs are widely used among old people with dementia but few studies have described long-term treatment in this group of patients. The purpose of this study was to explore the long-term use of psychotropic drugs in old people with dementia.

    METHODS: Data on psychotropic drug use, functioning in the activities of daily living (ADL), cognitive function and behavioral and psychological symptoms were collected at baseline and six months later, using the Multi-Dimensional Dementia Assessment Scale (MDDAS). The data were collected in 2005-2006. Detailed data about the prescribing of psychotropic drugs were collected from prescription records. This study was conducted in 40 specialized care units in northern Sweden, with a study population of 278 people with dementia.

    RESULTS: At the start of the study, 229 of the participants (82%) were prescribed at least one psychotropic drug; 150 (54%) used antidepressants, 43 (16%) used anxiolytics, 107 (38%) used hypnotics and sedatives, and 111 (40%) used antipsychotics. Among the baseline users of antidepressants, anxiolytics, hypnotics and sedatives and antipsychotics, 67%, 44%, 57% and 57% respectively, still used the same dose of the same psychotropic drug after six months. Associations were found between behavioral and psychological symptoms and different psychotropic drugs.

    CONCLUSION: Psychotropic drug use was high among people with dementia living in specialized care units and in many cases the drugs were used for extended periods. It is very important to monitor the effects and adverse effects of the prescribed drug in this frail group of people.

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  • 3.
    Pfister, Bettina
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Jonsson, Jeanette
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Gustafsson, Maria
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Drug-related problems and medicationreviews among old people with dementia2017In: BMC Pharmacology & Toxicology, E-ISSN 2050-6511, Vol. 18, article id 52Article, review/survey (Refereed)
    Abstract [en]

    Background: Drug-related problems, including medication errors and adverse drug events, are common among old people. Due to, for example, greater susceptibility to side effects, people with dementia are even more at risk of drug-related problems. The objectives of this study were to assess the occurrence and character of drug-related problems found among old people with dementia or cognitive impairment. Methods: Data from a randomized controlled clinical trial exploring the effects of a pharmacist intervention as part of a hospital ward team in patients 65 years and older with dementia or cognitive impairment were used. The study was conducted between 2012 and 2014 in the orthopedic and medicine wards in two hospitals located in Northern Sweden. Drug-related problems identified in this patient group were classified and described, and associations with different factors were investigated. Results: Clinical pharmacists identified at least one DRP in 66% (140/212) of participants in the intervention group, for a total of 310 DRPs. Ineffective drug/inappropriate drug and unnecessary drug therapy were the most common drug-related problems. Discontinuation of drug therapy was the most common action carried out. Drug-related problems were more common among people prescribed a larger number of drugs and among people with an earlier stroke. Conclusions: Drug-related problems are common among people with dementia and cognitive impairment. Comprehensive medication reviews conducted by clinical pharmacists as part of a health care team might be important to prevent, identify and solve these problems.

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  • 4.
    Popova, Dina
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Karlsson, Jessica
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Jacobsson, Stig O. P.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Comparison of neurons derived from mouse P19, rat PC12 and human SH-SY5Y cells in the assessment of chemical- and toxin-induced neurotoxicity2017In: BMC Pharmacology & Toxicology, E-ISSN 2050-6511, Vol. 18, article id 42Article in journal (Refereed)
    Abstract [en]

    Background: Exposure to chemicals might be toxic to the developing brain. There is a need for simple and robust in vitro cellular models for evaluation of chemical-induced neurotoxicity as a complement to traditional studies on animals. In this study, neuronally differentiated mouse embryonal carcinoma P19 cells (P19 neurons) were compared with human neuroblastoma SH-SY5Y cells and rat adrenal pheochromocytoma PC12 cells for their ability to detect toxicity of methylmercury (MeHg), okadaic acid and acrylamide. Methods: Retinoic acid-treated P19 and SH-SY5Y cells and nerve growth factor-stimulated PC12 cells, allowed to differentiate for 6 days, were exposed to MeHg, okadaic acid and acrylamide for 48 h. Cell survival and neurite outgrowth were assessed with the calcein-AM assay and fluorescence detection of antibodies against the cytoskeletal neuron-specific protein beta III-tubulin, respectively. The effects of glutathione (GSH) and the potent inhibitor of GSH synthesis buthionine sulfoximine (BSO) on the MeHg induced-toxicity were assessed using the PrestoBlue (TM) cell viability assay and the TMRE mitochondrial membrane potential assay. Results: Differentiated P19 cells developed the most extensive neuronal network among the three cell models and were the most sensitive neuronal model to detect neurotoxic effects of the test compounds. MeHg produced a concentration-dependent toxicity in differentiated P19 cells and SH-SY5Y cells, with statistically significant effects at concentrations from 0.1 mu M in the P19 neurons and 1 mu M in the SH-SY5Y cells. MeHg induced a decrease in the cellular metabolic activity and mitochondrial membrane potential (Delta Psi m) in the differentiated P19 cells and SH-SY5Y cells, that were attenuated by GSH. Okadaic acid and acrylamide also showed statistically significant toxicity in the P19 neurons, but not in the SH-SY5Y cells or the P12 cells. Conclusions: P19 neurons are more sensitive to detect cytotoxicity of MeHg, okadaic acid and acrylamide than retinoic acid-differentiated SH-SY5Y cells and nerve growth factor-treated PC12 cells. P19 neurons are at least as sensitive as differentiated SH-SY5Y cells to detect the loss of mitochondrial membrane potential produced by MeHg and the protective effects of extracellular GSH on MeHg toxicity. P19 neurons may be a useful model to study neurotoxic effects of chemicals.

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