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  • 1.
    Bejhed, Rebecca S.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Physics.
    Kharazmi, Mohammad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Cent Hosp Vasteras, Vasteras, Sweden..
    Hallberg, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Identification of Risk Factors for Bisphosphonate-Associated Atypical Femoral Fractures and Osteonecrosis of the Jaw in a Pharmacovigilance Database2016In: The Annals of Pharmacotherapy, ISSN 1060-0280, E-ISSN 1542-6270, Vol. 50, no 8, p. 616-624Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Atypical femoral fractures (AFs) and osteonecrosis of the jaw (ONJ) are well-known adverse drug reactions (ADRs) associated with bisphosphonates. To prevent these ADRs and to aid in the search for pathogenic mechanisms, knowledge of risk factors can be helpful. Objective: To identify risk factors for bisphosphonate-related ONJ and AF. Methods: In this case-control study of reports of bisphosphonate-related ADRs from February 16, 1984, to October 16, 2013, in the Swedish national database of ADRs, we compared characteristics for cases of ONJ (n = 167) and AF (n = 55) with all other bisphosphonate-related ADRs (n = 565) with regard to demographic variables, clinical characteristics, and concomitant drug treatments. We adjusted for multiple comparisons with Bonferroni correction. Results: Time to onset of ADRs differed statistically significantly between cases of AF and controls (2156 vs 111 days). For ONJ versus controls, differences were statistically significant for time to onset (1240 vs 111 days), intravenous administration (40% vs 20%), dental procedures (49% vs 0.2%) and prostheses (5% vs 0%), cancer disease (44% vs 12%), multiple myeloma (21% vs 1%), rheumatoid arthritis (14% vs 5%), and treatment with antineoplastic agents and oxycodone. Conclusion: These results lend further evidence to previously identified risk factors for ONJthat is, intravenous bisphosphonate administration; invasive dental procedures and dental prostheses; cancer disease, in particular multiple myeloma; and possibly, long-term bisphosphonate treatment. A putative further risk factor is rheumatoid arthritis. Only long-term bisphosphonate treatment was more common among AF cases. The lack of overlap of risk factors between ONJ and AF suggests different pathogenic mechanisms.

  • 2.
    Bingefors, Kerstin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Isacson, D.G.L.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    von Knorring, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Smedby, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Services Research.
    Prescription drug and healthcare use among Swedish patients treated with antidepressants1995In: The Annals of Pharmacotherapy, ISSN 1060-0280, E-ISSN 1542-6270, Vol. 29, no 6, p. 566-72Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    To analyze healthcare and prescription drug use among patients taking and those not taking antidepressant drugs in a Swedish community.

    DESIGN:

    Cross-sectional study.

    SETTING:

    General population of the rural Swedish municipality Tierp of approximately 20,000 inhabitants.

    PARTICIPANTS:

    All residents of Tierp aged 25 years or older during 1988.

    MAIN OUTCOME MEASURES:

    Mean number of ambulatory care visits, hospital bed days, and prescriptions per person; proportion of those taking prescription drugs in different pharmacologic classes.

    RESULTS:

    Patients treated with antidepressant drugs had a significantly (p < 0.05) greater use of ambulatory care, hospital care, and prescription drugs than those who did not take antidepressants in the study population. They also had an increased frequency of use of prescription drugs from virtually all pharmacologic classes. Furthermore, the risk for polypharmacy was high in patients treated with antidepressant medications.

    CONCLUSIONS:

    Those who took antidepressant drugs consumed more health services and prescription drugs than did those not taking an antidepressant. Patients receiving antidepressant treatment may be at serious risk for iatrogenic disease and should be evaluated carefully with respect to concomitant drug use.

  • 3.
    Björkman, Ingeborg
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Services Research.
    Fastbom, Johan
    Schmidt, Ingrid
    Bernsten, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Services Research.
    Drug-drug interactions in the elderly2002In: The Annals of Pharmacotherapy, ISSN 1060-0280, E-ISSN 1542-6270, Vol. 36, no 11, p. 1675-81Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To detect the frequency of potential drug-drug interactions (DDIs) in an outpatient group of elderly people in 6 European countries, as well as to describe differences among countries. DATA SOURCES AND METHODS: Drug use data were collected from 1601 elderly persons living in 6 European countries. The study population participated in a controlled intervention study over 18 months investigating the impact of pharmaceutical care. Potential DDIs were studied using a computerized detection program. RESULTS: The elderly population used on average 7.0 drugs per person; 46% had at least 1 drug combination possibly leading to a DDI. On average, there were 0.83 potential DDIs per person. Almost 10% of the potential DDIs were classified to be avoided according to the Swedish interaction classification system, but nearly one-third of them were to be avoided only for predisposed patients. The risk of subtherapeutic effect as a result of a potential DDI was as common as the risk of adverse reactions. Furthermore, we found differences in the frequency and type of potential DDIs among the countries. CONCLUSIONS: Potential DDIs are common in elderly people using many drugs and are part of a normal drug regimen. Some combinations are likely to have negative effects; more attention must be focused on detecting and monitoring patients using such combinations. As differences in potential DDIs among countries were found, the reasons for this variability need to be explored in further studies.

  • 4. De Fazio, Salvatore
    et al.
    Gallelli, Luca
    De Siena, Antonella
    De Sarro, Giovambattista
    Scordo, Maria Gabriella
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Role of CYP3AS in abnormal clearance of methadone2008In: The Annals of Pharmacotherapy, ISSN 1060-0280, E-ISSN 1542-6270, Vol. 42, no 6, p. 893-897Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To report a case of unusually low concentrations of methadone in a polydrug abuser during maintenance treatment with methadone. CASE SUMMARY: A 25-year-old man (weight 55 kg, height 165 cm) with a 12-year history of polydrug abuse was admitted to an opiates withdrawal methadone program. At the time of our observation, he was using both cannabinoids and heroin; no other medical conditions were discovered. Within the opiates withdrawal methadone program, under medical supervision, the patient started methadone therapy (20 mg/day). Two weeks later, an Abuscreen assay for methadone screening in the urine was negative and, to prevent the development of withdrawal symptoms, the dose of methadone was increased to 60 mg/day. One day later, the patient was asked to collect another urine sample in the presence of a nurse. The Abuscreen for methadone in urine remained negative. Evaluation of urinary samples collected over 24 hours documented low concentrations of methadone and high levels of 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (the primary metabolite of methadone). Evaluation for the presence of the most common polymorphisms in the cytochrome P450 and P-glycoprotein genes showed that the patient was heterozygous for the CYP3A5*1 allele and for 2 single nucleotide polymorphisms in the P-glyooprotein gene (1236C/T and 3435C/T). DISCUSSION: In this patient, poor methadone adherence was ruled out because of the presence of physicians and nurses during both methadone maintenance treatment and Abuscreen screening. Moreover, because the patient reported only heroin and cannabis at the time of evaluation, drug interactions were ruled out as possible causes for the rapid clearance of methadone. CONCLUSIONS: In this case, CYP3A5 polymorphism may have played a role in the rapid methadone metabolism.

  • 5.
    Hallberg, Pär
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Nagy, Julia
    Karawajczyk, Malgorzata
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Nordang, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Islander, Gunilla
    Norling, Pia
    Johansson, Hans-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Kämpe, Mary
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Hugosson, Svante
    Yue, Qun-Ying
    Wadelius, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Comparison of Clinical Factors Between Patients With Angiotensin-Converting Enzyme Inhibitor-Induced Angioedema and Cough2017In: The Annals of Pharmacotherapy, ISSN 1060-0280, E-ISSN 1542-6270, Vol. 51, no 4, p. 293-300Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Angioedema is a rare and serious adverse drug reaction (ADR) to angiotensin-converting enzyme (ACE) inhibitor treatment. Dry cough is a common side effect of ACE inhibitors and has been identified as a possible risk factor for angioedema.

    OBJECTIVE: We compared characteristics between patients with ACE inhibitor-induced angioedema and cough with the aim of identifying risk factors that differ between these adverse events.

    METHODS: Data on patients with angioedema or cough induced by ACE inhibitors were collected from the Swedish database of spontaneously reported ADRs or from collaborating clinicians. Wilcoxon rank sum test, Fisher's exact test, and odds ratios (ORs) with 95% CIs were used to test for between-group differences. The significance threshold was set to P <0.00128 to correct for multiple comparisons.

    RESULTS: Clinical characteristics were compared between 168 patients with angioedema and 121 with cough only. Smoking and concomitant selective calcium channel blocker treatment were more frequent among patients with angioedema than cough: OR = 4.3, 95% CI = 2.1-8.9, P = 2.2 × 10(-5), and OR = 3.7, 95% CI = 2.0-7.0, P = 1.7 × 10(-5). Angioedema cases were seen more often in male patients (OR = 2.2, 95% CI = 1.4-3.6, P = 1.3 × 10(-4)) and had longer time to onset and higher doses than those with cough ( P = 3.2 × 10(-10) and P = 2.6 × 10(-4)). A multiple model containing the variables smoking, concurrent calcium channel blocker treatment, male sex, and time to onset accounted for 26% of the variance between the groups.

    CONCLUSION: Smoking, comedication with selective calcium channel blockers, male sex, and longer treatment time were associated with ACE inhibitor-induced angioedema rather than cough.

  • 6.
    Isacson, Dag
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Johansson, Linnea
    Bingefors, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Nationwide survey of subjectively reported adverse drug reactions in Sweden2008In: The Annals of Pharmacotherapy, ISSN 1060-0280, E-ISSN 1542-6270, Vol. 42, no 3, p. 347-353Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Adverse drug reactions (ADRs) and the safety of drugs continue to be widely discussed. However, information on the prevalence of subjectively experienced ADRs (SADRs) and their subsequent burden in the general population is largely lacking. OBJECTIVE: To analyze, from an epidemiologic perspective, SADRs with respect to occurrence and health status. METHODS: A cross-sectional mail survey to a random national sample in Sweden of inhabitants aged 18-84 years was conducted; 61% (N = 4875) of the sample answered the questionnaire. Self-reported SADRs occurring during a 2-week period of using prescription, over-the-counter (OTC), or herbal drugs were classified according to Meyler's classification of ADRs. Self-perceived health status was assessed with a visual analog scale graded from 0 (worst possible health/death) to 1 (perfect health). RESULTS: SADRs were reported by 6.4% of the total study sample, 10.2% of the 2851 users of prescription drugs, 1.0% of the 2862 users of OTC drugs, and 0.1% of the 1352 users of herbal drugs. Of the total sample, 3.3% reported SADRs of the nervous system, 2.6% of the gastrointestinal system, and 0.6% of the cardiovascular system. Users of prescription drugs with SADRs reported a mean health status score of 0.655, while those who did not report SADRs scored 0.744. Among users of OTC and herbal drugs, the corresponding scores were 0.720 and 0.818, respectively. Those in the population who did not use any drugs rated their health status as 0.846. CONCLUSIONS: Both the prevalence of SADRs and the magnitude of the decrease in subjective health status in respondents experiencing them reflect the importance of individual subjective perceptions for public health. However, in a cross-sectional study like this, causal relationships cannot be firmly established. Further, other factors, such as comorbidity or disappointment with treatment outcomes, could be associated with the decrease in health status.

  • 7. Jorgensen, T
    et al.
    Johansson, Saga
    Kennerfalk, A
    Wallander, Mari-Ann
    Department of Epidemiology, AstraZeneca R&D, Mölndal.
    Svärdsudd, Kurt
    Department of Epidemiology, AstraZeneca R&D, Mölndal.
    Prescription drug use, diagnoses, and healthcare utilization among the elderly2001In: The Annals of Pharmacotherapy, ISSN 1060-0280, E-ISSN 1542-6270, Vol. 35, no 9, p. 1004-1009Article in journal (Refereed)
    Abstract [en]

    BACKGROUND

    More elderly patients affected by severe and chronic diseases are treated in primary care. Reports on the use of prescription drugs by the general elderly population are scarce, and more investigations are needed to optimize pharmaceutical care for these patients.

    OBJECTIVE

    To analyze prescription drug use, diagnoses, and healthcare utilization among noninstitutionalized elderly patients.

    DESIGN

    Retrospective cohort study.

    SETTING AND PATIENTS

    All people > or =65 years old (n = 4642) living in the community of Tierp, Sweden, in 1994 were included. Prescription drug use and healthcare utilization have been registered for all inhabitants of the community since 1972. Information about filled prescriptions and diagnoses were obtained from a computerized research register.

    RESULTS

    Prescription drug use was high among the elderly (78%); the most used pharmacologic groups were cardiovascular, nervous system, and gastrointestinal medications. Women used more prescription drugs than men (average 4.8 vs. 3.8) and had more nonfatal diagnoses. Use of five or more different prescription drugs during 1994 was common (39.0%), and multivariate analysis showed that the greatest number of primary care visits occurred with multiple drug use (> or =5 drugs over 1 y). CONCLUSIONs: This study shows an extensive multiple drug use among elderly people living at home. Whether this multiple drug use per se is harmful to the patients or not could not be evaluated in this study. Further focused investigations are needed to assess the effect of multiple drug use in an elderly population.

  • 8. Kennerfalk, A
    et al.
    Ruigomez, A
    Wallander, Mari-Ann
    Department of Epidemiology, AstraZeneca R&D, S-431 83 Mölndal, Sweden.
    Wilhelmsen, Lars
    Johansson, Saga
    Geriatric drug therapy and healthcare utilization in the United Kingdom2002In: The Annals of Pharmacotherapy, ISSN 1060-0280, E-ISSN 1542-6270, Vol. 36, no 5, p. 797-803Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE

    To describe the use of prescription drug therapy, especially polypharmacy, in an elderly general population; to relate that use to age, gender, and different types of healthcare utilization; and to investigate the influence of selection of different time windows on the result of the quantity as well as the categories of drugs used.

    METHODS

    Data on a sample of 5000 patients aged 65-90 years in 1996 were derived from the General Practice Research Database (GPRD). The population covered by GPRD is broadly representative of the UK population treated in general practice. Drug use was assessed using 2 time windows - current use of individual drugs on a random day (index date) and 1 month following the index date. Healthcare utilization was analyzed by use of information on visits to general practitioners (GPs), hospitalizations, and referrals to specialists.

    RESULTS

    Women used more drugs than men; however, the prevalence of polypharmacy, defined as concomitant use of > or =5 drugs, was similar in both genders. The most frequently used therapeutic groups were cardiovascular, central nervous, and gastrointestinal system drugs. Almost 80% of both women and men visited a GP at least once a year. Overall, women used more ambulatory care services and men were hospitalized more often. Use of random date compared with 1-month period resulted in a significant underestimation of the amount of drugs used for acute conditions and, consequently, the risk of polypharmacy.

    CONCLUSIONS

    The overall results confirm the findings in earlier studies suggesting that the GPRD might be a useful tool in further studies on prescription drug use among elderly persons. More information on the appropriateness of drug use is needed to prevent overuse as well as underuse of medications among the elderly.

  • 9.
    Moen, Janne
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Antonov, Karolina
    Larsson, Charlotte A
    Lindblad, Ulf
    Nilsson, J Lars G
    Råstam, Lennart
    Ring, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Factors associated with multiple medication use in different age groups2009In: The Annals of Pharmacotherapy, ISSN 1060-0280, E-ISSN 1542-6270, Vol. 43, no 12, p. 1978-1985Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Multiple medicine use among elderly persons is likely to be the result of treatment regimens developed over a long period of time. By learning more about how multiple medication use develops, the quality of prescribing may be improved across the adult lifespan. OBJECTIVE: To describe patterns of multiple medicine use in the general Swedish population and its association with sociodemographic, lifestyle, and health status factors. METHODS: Data from a cross-sectional population health survey collected during 2001-2005 from 2816 randomly selected Swedish residents (age 30-75 y; response rate 76%) were analyzed. Multiple medicine use was restricted to prescription drugs and defined as the 75th percentile; that is, the 25% of the study group using the highest number of drugs per individual. RESULTS: Seventy-one percent of the respondents used some kind of drug, 51.5% used one or more prescription drug, 38.4% used one or more over-the-counter (OTC) medication, and 8.3% used one or more herbal preparation. The cutoff amounts defining multiple medicine use were: 2 or more medications for 30- to 49-year-olds, 3 or more for 50- to 64-year-olds, and 5 or more for 65- to 75-year-olds. No association between use of multiple medicines and use of OTC drugs or herbal preparations was found. When drugs were classified into therapeutic subgroups, 76.3% of those aged 30-49 years, 97.9% of those aged 50-64 years, and 100% of those aged 65-75 years were taking a unique combination of drugs. Multivariate analyses showed that diabetes and poor self-rated health were associated with multiple medicine use in all age cohorts. Female sex and hypertension were associated with multiple medicine use among those aged 30-49 and 50-64 years, current smoking among those aged 50-64 years, and obesity among those aged 65-75 years. CONCLUSIONS: Multiple medicine use was associated with morbidity and poor self-rated health across all age groups. The vast majority of users of multiple drugs are taking a unique combination of medications.

  • 10. Schmidt, IK
    et al.
    Claesson, Cecilia B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Westerholm, B
    Nilsson, JLG
    Physician and staff assessments of drug interventions and outcomes in Swedish nursing homes1998In: The Annals of Pharmacotherapy, ISSN 1060-0280, E-ISSN 1542-6270, Vol. 32, no 1, p. 27-32Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To describe the type and frequency of drug-related problems discussed in regular team meetings conducted in 15 Swedish nursing homes and report physician and staff assessments of these interventions and residents' outcomes. DATA SOURCES AND METHODS: The data were collected within the context of a controlled trial with the primary aim of exploring the effects of regular team interventions on drug prescribing practices in Swedish nursing homes. In 15 experimental nursing homes, the residents' drug therapy was discussed regularly by a team consisting of a pharmacist, a physician, nurses, undernurses (similar to licensed practical nurses), and nurse's aides. The pharmacist documented problems, made changes, and observed outcomes. Following the intervention period, a questionnaire was sent to the medical staff that contained items regarding perceived outcomes, the intervention's impact on knowledge of drug therapy in the elderly, and attitudes toward the pharmacist's role. RESULTS: Unclear indication and problematic choice of drugs were the most common drug-related problems discussed. In 19% of the situations, therapy changes were reported to have had a beneficial effect on the residents' clinical status; in 47% of the situations, staff reported no observable outcome from changes, suggesting that the changes had been appropriate. Finally, medical staff claimed in the follow-up survey that their knowledge about drug therapy had increased; they expressed an overall positive attitude toward this interactive collaboration. CONCLUSIONS: Regular intervention conducted by a multidisciplinary team incorporating a pharmacist can effectively improve prescribing practices, increase staff knowledge about appropriate drug therapy in the elderly, and result in improved quality of care for nursing home residents.

  • 11.
    Scordo, Maria Gabriella
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Stjernberg, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Edvardsson, Anne Maria
    Wadelius, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Warfarin-noscapine interaction: a series of four case reports2008In: The Annals of Pharmacotherapy, ISSN 1060-0280, E-ISSN 1542-6270, Vol. 42, no 3, p. 448-450Article in journal (Refereed)
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