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  • 1.
    Adolfsson, Per I
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Bloth, Björn
    Department of Clinical Neuroscience, Laboratory of Translational Neuropharmacology, Center of Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Futurum Academy for Health and Care, Jönköping County Council, Sweden.
    Svensson, Samuel P S
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Zinc Induces a Bell-shaped Proliferative Dose-response Effect in Cultured Smooth Muscle Cells From Benign Prostatic Hyperplasia.2015In: Urology, ISSN 0090-4295, E-ISSN 1527-9995, Vol. 85, no 3, p. 704.e15-704.e19Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate the effects of zinc (Zn(2+)) concentrations on cultured benign prostatic hyperplasia (BPH) smooth muscle cell (SMC) proliferation.

    METHODS: The effects of Zn(2+) were studied in primary cultures of human BPH SMC, stimulated with either 10-μM lysophosphatidic acid (LPA) or LPA in combination with 100-nM testosterone. Deoxyribonucleic acid replication and protein synthesis using [(3)H]-thymidine and [(35)S]-methionine incorporation were measured. Furthermore, studies were performed to evaluate if Zn(2+) could potentiate the inhibitory effect of phosphodiesterase-5 blockers, on BPH SMC proliferation.

    RESULTS: Zn(2+) generated a bell-shaped concentration response, both regarding deoxyribonucleic acid replication and protein synthesis in cultured BPH SMC. Below a threshold value (approximately 200 μM), a significant mitogenic effect was seen, whereas higher concentrations inhibited SMC proliferation after stimulation with LPA. This effect was even more pronounced after stimulation of LPA in combination with testosterone. Moreover, phosphodiesterase-5 inhibitors, that is, sildenafil blocked LPA-stimulated BPH SMC proliferation. This antiproliferative effect, was significantly potentiated by coincubation with Zn(2+) in an additative manner.

    CONCLUSION: The bell-shaped concentration response of Zn(2+) on cultured BPH SMC proliferation suggests that changes in prostate Zn(2+) concentrations, during aging, diet, or inflammatory conditions, may be of importance in the pathogenesis of BPH.

  • 2.
    Aronsson, Patrik
    et al.
    Department Pharmacology, Institution of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Booth, Shirley
    Department Pedagogical, Curricular and Professional Studies, Faculty of Education, University of Gothenburg, Gothenburg, Sweden; School of Education, University of the Witwatersrand, Johannesburg, South Africa.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Kjellgren, Karin
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Zetterqvist, Ann
    Department Pedagogical, Curricular and Professional Studies, Faculty of Education, University of Gothenburg, Gothenburg, Sweden.
    Tobin, Gunnar
    Department Pharmacology, Institution of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Reis, Margareta
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    The understanding of core pharmacological concepts among health care students in their final semester2015In: BMC Medical Education, E-ISSN 1472-6920, Vol. 15, no 1, article id 235Article in journal (Refereed)
    Abstract [en]

    Background

    The overall aim of the study was to explore health care students´ understanding of core concepts in pharmacology.

    Method

    An interview study was conducted among twelve students in their final semester of the medical program (n = 4), the nursing program (n = 4), and the specialist nursing program in primary health care (n  = 4) from two Swedish universities. The participants were individually presented with two pharmacological clinically relevant written patient cases, which they were to analyze and propose a solution to. Participants were allowed to use the Swedish national drug formulary. Immediately thereafter the students were interviewed about their assessments. The interviews were audio-recorded and transcribed verbatim. A thematic analysis was used to identify units of meaning in each interview. The units were organized into three clusters: pharmacodynamics, pharmacokinetics, and drug interactions. Subsequent procedure consisted of scoring the quality of students´ understanding of core concepts. Non-parametric statistics were employed.

    Results

    The study participants were in general able to define pharmacological concepts, but showed less ability to discuss the meaning of the concepts in depth and to implement these in a clinical context. The participants found it easier to grasp concepts related to pharmacodynamics than pharmacokinetics and drug interactions.

    Conclusion

    These results indicate that education aiming to prepare future health care professionals for understanding of more complex pharmacological reasoning and decision-making needs to be more focused and effective.

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  • 3. Axelsson Rosén, Stina
    et al.
    Hägg, Staffan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Eriksson, Andreas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Pharmacology.
    Lindahl, Tomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Whiss, Per A
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Pharmacology.
    In vitro effects of antipsychotics on human platelet adhesion and aggregation and plasma coagulation2007In: Clinical and experimental pharmacology & physiology, ISSN 0305-1870, E-ISSN 1440-1681, Vol. 34, no 8, p. 775-780Article in journal (Refereed)
    Abstract [en]

    1. Several studies suggest an association between venous thromboembolism and the use of antipsychotic drugs, especially clozapine, but the biological mechanisms are unknown. It has been suggested that antipsychotic drugs enhance aggregation of platelets and thereby increase the risk of venous thrombosis. The purpose of the present study was to examine the effects of clozapine and its main metabolite, N-desmethyl clozapine, as well as olanzapine, risperidone and haloperidol, on platelet adhesion and aggregation and on plasma coagulation in vitro. 2. Blood was collected from healthy subjects free of medication. Platelet adhesion to different protein surfaces and aggregation were measured in microplates. The coagulation methods of activated partial thromboplastin time (APTT) and prothrombin time were performed in platelet-poor plasma. 3. Clozapine was the only compound that increased platelet adhesion and aggregation and shortened APTT. The effect appeared at therapeutic concentrations and was significant but weak. 4. This weak effect of clozapine on haemostasis may explain, in part, the association of this compound and venous thromboembolism. © 2007 The Authors.

  • 4.
    Boiso, Samuel
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Zackrisson, Anna Lena
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Jakobsen Falk, Ingrid
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Karlsson, Louise
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Carlsson, Björn
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    Tillmar, Andreas
    Natl Board Forens Med, Dept Forens Genet and Forens Toxicol, Linkoping, Sweden .
    Kugelberg, Fredrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    Green, Henrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    ABCB1 gene polymorphisms are associated with suicide in forensic autopsies2013In: Pharmacogenetics & Genomics, ISSN 1744-6872, E-ISSN 1744-6880, Vol. 23, no 9, p. 463-469Article in journal (Refereed)
    Abstract [en]

    Background Polymorphisms in ABCB1 have the ability to affect both the function and the expression of the transporter protein P-glycoprotein and may lead to an altered response for many drugs including some antidepressants and antipsychotics.Objective The aim of this study was to examine the impact of the ABCB1 polymorphisms 1199Gandgt;A, 1236Candgt;T, 2677Gandgt;T/A, and 3435Candgt;T in deaths by suicide.Patients and methods A total of 998 consecutive Swedish forensic autopsies performed in 2008 in individuals 18 years of age or older, where femoral blood was available and a toxicological screening had been performed, were investigated. Genotypes were assessed with pyrosequencing and information on the cause and manner of each death was obtained from the forensic pathology and toxicology databases.Results There was a significantly higher frequency of the T allele at positions 1236, 2677, and 3435 among the suicide cases compared with the nonsuicide cases.Conclusion Our result from forensic cases suggests that ABCB1 polymorphisms are associated with an increased risk for completed suicides. The biological mechanisms involved and the clinical implications for these findings are largely unknown and need to be examined further.

  • 5.
    Bro, Tomas
    et al.
    Hoglandssjukhuset, Sweden; Futurum, Sweden.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Futurum, Sweden.
    Worth changing? Clinical effects of switching treatment in neovascular age-related macular degeneration from intravitreal ranibizumab and aflibercept to bevacizumab in a region in southern Sweden2021In: European Journal of Ophthalmology, ISSN 1120-6721, E-ISSN 1724-6016, Vol. 31, no 1, p. 144-148Article in journal (Refereed)
    Abstract [en]

    Purpose: To examine the clinical effects of switching intravitreal drug treatment from the approved vascular endothelial growth factor inhibitors, ranibizumab and aflibercept, to off label use of bevacizumab in patients with wet age-related macular degeneration. Methods: This retrospective study scrutinized medical records of patients with wet age-related macular degeneration who switched therapy to bevacizumab due to a policy decision. Best corrected visual acuity, central retinal thickness, and number of injections before and 1 year after the switch was compared. The non-inferiority margin of best corrected visual acuity was five Early Treatment Diabetic Retinopathy Study letters. Results: A switch from ranibizumab was evaluable in 93 eyes and from aflibercept in 19 eyes. Neither of the groups had a significant non-inferior visual acuity 16 month after the switch. Mean best corrected visual acuity in Early Treatment Diabetic Retinopathy Study letters was 63.8 (95% confidence interval: 61.3-66.4) before and 62.2 (95% confidence interval: 59.3-65.1) after in the ranibizumab group and 68.2 (95% confidence interval: 63.3-73.1) before and 67.7 (95% confidence interval: 62.8-72.6) after in the aflibercept group. Mean central retinal thickness in micrometers decreased from 254 (95% confidence interval: 247-261) to 250 (95% confidence interval: 225-275) in the ranibizumab group and from 265 (95% confidence interval: 255-276) to 262 (95% confidence interval: 251-273) in the aflibercept group. The treatment was changed again after the switch in 18% of the patients in the ranibizumab group and 19% in the aflibercept group and these subjects were excluded from the analyses. Conclusion: In patients with neovascular age-related macular degeneration, a switch from ranibizumab or aflibercept to bevacizumab seems possible without a significant decrease in visual acuity in most patients.

  • 6.
    Dolores Cherma Yeste, Maria
    et al.
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Reis, Margareta
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Hägg, Staffan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Bengtsson, Finn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Therapeutic Drug Monitoring of Ziprasidone in a Clinical Treatment Setting2008In: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 30, no 6, p. 682-688Article in journal (Refereed)
    Abstract [en]

    There is limited information on the pharmacokinetics of ziprasidone (ZIP) in naturalistic clinical settings. The objective of this study was to investigate the concentrations of ZIP and its active metabolite S-methyl-dihydroziprasidone (SMDZ), and the dose-normalized concentrations, using routine therapeutic drug monitoring (TDM) data. A high-performance liquid chromatographic method for determining serum concentrations of these substances for routine clinical use was established at the TDM Laboratory in Linkoping, Sweden. This analytical service was available to all physicians in Sweden. Between January 2001 and December 2004, 545 analyses, representing samples from 370 patients, were performed. The median daily ZIP dose was 120 mg (range 20-320 mg). In all, 121 steady-state trough specimens with essential clinical information were included in the pharmacokinetic evaluation. The median (25th to 75th percentile) serum concentration of ZIP was 125 nmol/L (82-188 nmol/L). The SMDZ:ZIP ratio decreased with increasing serum concentration of ZIP. The median (25th to 75th percentile) dose-normalized concentrations (nmol L-1 mg(-1) d(-1)) for ZIP and SMDZ were 1.13 (0.74-1.77) and 0.62 (0.45-0.86), respectively, with SMDZ:ZIP ratio of 0.57 (0.42-0.79). The overall coefficients of variation for close-normalized scruin concentrations of ZIP, SMDZ, and SMDZ:ZIP ratio were 62%, 56%, and 57%, respectively (n = 121). Smoking women had lower normalized ZIP concentrations than nonsmoking women. Twenty-eight patients with repeated eligible TDM analyses were studied for intraindividual variance over time. In summary, great interindividual and intraindividual differences in ZIP concentrations were observed. TDM of ZIP maybe used for individual dose adjustments and monitoring medication adherence.

  • 7.
    Ekman, Elisabet
    et al.
    Regional Pharmacovigilance Unit, Clinical Pharmacology, Lund University Hospital, Lund, Sweden.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    Sundström, Anders
    Centre for Pharmacoepidemiology, Karolinska Institute, Stockholm, Sweden.
    Werkström, Viktoria
    Regional Pharmacovigilance Unit, Clinical Pharmacology, Lund University Hospital, Lund, Sweden.
    Antihypertensive drugs and erectile dysfunction as seen in spontaneous reports, with focus on angiotensin II type 1 receptor blockers2010In: Drug, Healthcare and Patient Safety, E-ISSN 1179-1365, Vol. 2, p. 21-25Article in journal (Refereed)
    Abstract [en]

    Aim: To describe spontaneously reported cases of erectile dysfunction (ED) in association with angiotensin II type I blockers (ARB) and other antihypertensive drugs.

    Subjects and methods: All spontaneously reported cases of ED submitted to the Swedish Medical Products Agency (MPA) between 1990 and 2006, where at least one antihypertensive drug was the suspected agent, were scrutinized. Patient demographics, drug treatment and adverse reactions were recorded. Using the Bayesian Confidence Propagation Neural Network (BCPNN) method, the information component (IC) was calculated.

    Results: Among a total of 225 reports of ED, 59 involved antihypertensive drugs including ARB (9 cases) as suspected agents. A positive IC value was found indicating that ED was reported more often in association with antihypertensive drugs classes, except for angiotensin-converting enzyme inhibitors, compared with all other drugs in the database. Positive dechallenge was reported in 43 cases (72%).

    Discussion: All classes of major antihypertensive drugs including ARB were implicated as suspected agents in cases of ED. Few risk factors were identified. The relatively high reporting of ED in association with ARB is in contrast with previous studies, suggesting that ARB have neither a positive nor any effect on ED. This discrepancy suggests that further studies are warrnted on this potential adverse reaction to ARB.

  • 8.
    Ginstman, Charlotte
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Frisk, Jessica
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Carlsson, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Ärlemalm, A.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Futurum, Jönköping, Sweden.
    Brynhildsen, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Plasma concentrations of etonogestrel in women using oral desogestrel before and after Roux-en-Y gastric bypass surgery: a pharmacokinetic study2019In: British Journal of Obstetrics and Gynecology, ISSN 1470-0328, E-ISSN 1471-0528, Vol. 126, no 4, p. 486-492Article in journal (Refereed)
    Abstract [en]

    Objective

    To investigate whether Roux‐en‐Y gastric bypass (RYGB) affects oral desogestrel (etonogestrel) pharmacokinetics.

    Design

    Single centre, open label, phase‐2 pharmacokinetic study.

    Setting

    University hospital of Linköping, Sweden.

    Population

    Fourteen women with planned RYGB surgery were included; nine women aged 18–45 years using 75 micrograms desogestrel completed the study.

    Methods

    Steady‐state etonogestrel pharmacokinetic (PK) parameters were measured on three occasions for each individual (at 8 ± 6 weeks before surgery, and at 12 ± 2 and 52 ± 2 weeks after surgery). Each patient served as her own control. On each occasion, serum samples were collected during a 24‐hour period and etonogestrel concentrations were determined with ultra‐performance liquid chromatography/tandem mass spectrometry.

    Main outcome measures

    Area under the plasma concentration time curve of etonogestrel (AUC0–24 hours).

    Results

    All women had significant postoperative weight loss. There were no significant differences in AUC0–24 hours, terminal half‐lives (t½), time to peak serum concentrations (Tmax), or apparent oral clearances of etonogestrel (CLoral) before and after gastric bypass surgery on any occasion. Peak serum concentrations (Cmax) increased after 52 ± 2 weeks compared with preoperative values (0.817 ng/ml versus 0.590 ng/ml, P = 0.024).

    Conclusion

    To our knowledge, this is the first study to investigate the effects on desogestrel pharmacokinetics after RYGB. This study did not reveal any clinically significant changes in etonogestrel pharmacokinetics, suggesting that oral desogestrel may be used by women after RYGB surgery. The sample size was limited, however, and therefore the results should be interpreted cautiously.

  • 9.
    Gyllensten, H
    et al.
    Nordic School Public Heatlh.
    Hakkarainen, K M
    Nordic School Public Heatlh.
    Jönsson, A K
    Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting.
    Andersson Sundell, K
    Nordic School Public Heatlh.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Pharmacology.
    Rehnberg, C
    Karolinska Institute.
    Carlsten, A
    Nordic School Public Heatlh.
    DRUG-RELATED MORBIDITY - MODELING THE COST-OF-ILLNESS IN SWEDEN USING PHARMACISTS OPINION in VALUE IN HEALTH, vol 14, issue 7, pp A344-A3442011In: VALUE IN HEALTH, Wiley-Blackwell / Elsevier , 2011, Vol. 14, no 7, p. A344-A344Conference paper (Refereed)
    Abstract [en]

    n/a

  • 10.
    Gyllensten, Hanna
    et al.
    Nordic School Public Health NHV, Sweden University of Gothenburg, Sweden .
    Hakkarainen, Katja M.
    Nordic School Public Health NHV, Sweden University of Gothenburg, Sweden .
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    Carlsten, Anders
    Nordic School Public Health NHV, Sweden;Medical Prod Agency, Sweden .
    Petzold, Max
    University of Gothenburg, Sweden .
    Rehnberg, Clas
    Karolinska Institute, Sweden .
    Jönsson, Anna K
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    Economic Impact of Adverse Drug Events - A Retrospective Population-Based Cohort Study of 4970 Adults2014In: PLOS ONE, E-ISSN 1932-6203, Vol. 9, no 3, p. 0092061-Article in journal (Refereed)
    Abstract [en]

    Background: The aim was to estimate the direct costs caused by ADEs, including costs for dispensed drugs, primary care, other outpatient care, and inpatient care, and to relate the direct costs caused by ADEs to the societal COI (direct and indirect costs), for patients with ADEs and for the entire study population. Methods: We conducted a population-based observational retrospective cohort study of ADEs identified from medical records. From a random sample of 5025 adults in a Swedish county council, 4970 were included in the analyses. During a three-month study period in 2008, direct and indirect costs were estimated from resource use identified in the medical records and from register data on costs for resource use. Results: Among 596 patients with ADEs, the average direct costs per patient caused by ADEs were USD 444.9 [95% CI: 264.4 to 625.3], corresponding to USD 21 million per 100 000 adult inhabitants per year. Inpatient care accounted for 53.9% of all direct costs caused by ADEs. For patients with ADEs, the average societal cost of illness was USD 6235.0 [5442.8 to 7027.2], of which direct costs were USD 2830.1 [2260.7 to 3399.4] (45%), and indirect costs USD 3404.9 [2899.3 to 3910.4] (55%). The societal cost of illness was higher for patients with ADEs compared to other patients. ADEs caused 9.5% of all direct healthcare costs in the study population. Conclusions: Healthcare costs for patients with ADEs are substantial across different settings; in primary care, other outpatient care and inpatient care. Hence the economic impact of ADEs will be underestimated in studies focusing on inpatient ADEs alone. Moreover, the high proportion of indirect costs in the societal COI for patients with ADEs suggests that the observed costs caused by ADEs would be even higher if including indirect costs. Additional studies are needed to identify interventions to prevent and manage ADEs.

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  • 11.
    Gyllensten, Hanna
    et al.
    Nordic School Public Health NHV, Sweden .
    Hakkarainen, Katja M.
    Nordic School Public Health NHV, Sweden .
    Jonsson, Anna K.
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Andersson Sundell, Karolina
    Nordic School Public Health NHV, Sweden .
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Pharmacology.
    Rehnberg, Clas
    Karolinska Institute, Sweden .
    Carlsten, Anders
    Nordic School Public Health NHV, Sweden Medical Prod Agency, Sweden .
    Modelling drug-related morbidity in Sweden using an expert panel of pharmacists2012In: INTERNATIONAL JOURNAL OF CLINICAL PHARMACY, ISSN 2210-7703, Vol. 34, no 4, p. 538-546Article in journal (Refereed)
    Abstract [en]

    Background Drug-related morbidity (DRM) is common and to some extent preventable, and associated with considerable costs in patients attending hospital. In outpatients and in the general public corresponding data are limited, but pharmacists expert opinion has suggested high rates of DRM also in US ambulatory care. It is unknown if the results are applicable in Sweden today. Objective To estimate the proportions of patients with DRM and preventable DRM and the cost-of-illness (COI) of DRM in Sweden based on pharmacists expert opinion. Setting Swedish healthcare. Method The study applied a conceptual model of DRM based on a decision tree. An expert panel of pharmacists determined the probabilities of therapeutic outcomes of medication therapy. The COI analysis included direct costs from the healthcare perspective. Sensitivity analyses were performed for variations in probabilities and pathway costs. Main outcome measure DRM included new medical problems (adverse drug reactions, drug dependence and intoxications) and therapeutic failures (insufficient effects of medicines and morbidity due to untreated indication). Results The expert panel estimated that 61 +/- A 14 % (mean +/- A SD) of all patients attending healthcare suffered from DRM, of which 29 +/- A 8 % suffered from new medical problems, 18 +/- A 6 % from therapeutic failures, and 15 +/- A 7 % from a combination of both. The DRM was considered preventable in 45 +/- A 15 % of the patients with DRM. The estimated COI was EUR 997 per patient attending healthcare, corresponding to an annual cost of EUR 6,600 million to the Swedish healthcare system. The COI ranged from EUR 490 to EUR 1,314 when varying the participants probabilities of DRM and clinical outcomes from the first to the third quartile. Of the pathway costs, the COI was most sensitive to variation in the cost of prolonged hospital stay (COI range EUR 953-1,306). Conclusion According to pharmacists expert opinion, a large proportion of patients in Sweden experience DRM and preventable DRM, and the estimated COI of DRM is extensive. Since observational studies have not addressed the burden of DRM to the general public, this study adds the pharmacists perception on DRM. Other healthcare professionals perceptions on DRM need to be investigated in future studies.

  • 12.
    Hakkarainen, K M
    et al.
    Nordic School of Public Health NHV, Gothenburg, Sweden and University of Gothenburg, Sweden.
    Gyllensten, H
    Nordic School of Public Health NHV, Gothenburg, Sweden and University of Gothenburg, Sweden.
    Jönsson, Anna K
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    Andersson Sundell, K
    University of Gothenburg, Sweden.
    Petzold, M
    University of Gothenburg, Sweden.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology. Futurum Academy for Health and Care, Jönköping County, Jönköping County Council, Sweden.
    Prevalence, nature and potential preventability of adverse drug events - A population-based medical record study of 4970 adults2014In: British Journal of Clinical Pharmacology, ISSN 0306-5251, E-ISSN 1365-2125, Vol. 78, no 1, p. 170-183Article in journal (Refereed)
    Abstract [en]

    AIMS: To estimate the 3-month prevalence of adverse drug events (ADEs), categories of ADEs, and preventable ADEs, and the preventability of ADEs among adults in Sweden. Further, to identify drug classes and organ systems associated with ADEs and estimate their seriousness.

    METHODS: A random sample of 5025 adults in Swedish county council in 2008 was drawn from the Total Population Register. All their medical records in 29 inpatient care departments in three hospitals, 110 specialised outpatient clinics, and 51 primary care units were reviewed retrospectively in a stepwise manner, and complemented with register data on dispensed drugs. ADEs, including adverse drug reactions (ADRs), sub-therapeutic effects of drug therapy (STEs), drug dependence and abuse, drug intoxications from overdose, and morbidities due to drug-related untreated indication, were detected during a 3-month study period, and assessed for preventability.

    RESULTS: Among included 4970 individuals, the prevalence of ADEs was 12.0% (95% confidence interval 11.1-12.9%), and preventable ADEs 5.6% (5.0-6.2%). ADRs (6.9%; 6.2-7.6%) and STEs (6.4%; 5.8-7.1%) were more prevalent than the other ADEs. Of the ADEs, 38.8% (35.8-41.9%) was preventable, varying by ADE category and seriousness. ADEs were frequently associated with nervous system and cardiovascular drugs, but the associated drugs and affected organs varied by ADE category.

    CONCLUSIONS: The considerable burden of ADEs and preventable ADEs from commonly used drugs across care settings warrants large-scale efforts to redesign safer, higher quality healthcare systems. The heterogeneous nature of the ADE categories should be considered in research and clinical practice for preventing, detecting and mitigating ADEs.

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  • 13.
    Hakkarainen, Katja M
    et al.
    Nordic School of Public Health NHV, Gothenburg, Sweden.
    Alström, Daniel
    Nordic School of Public Health NHV, Gothenburg, Sweden.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Pharmacology.
    Carlsten, Anders
    Medical Products Agency, Uppsala, Sweden.
    Gyllensten, Hanna
    Nordic School of Public Health NHV, Gothenburg, Sweden.
    Modelling drug-related morbidity in Sweden using an expert panel of physicians2012In: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 68, no 9, p. 1309-1319Article in journal (Refereed)
    Abstract [en]

    PURPOSE: In modelling studies using pharmacists' opinions, drug-related morbidity (DRM) and preventable DRM have been more common than in observational studies, and the resulting costs are extensive. Modelling studies' estimates may vary depending on informants' profession. The purpose of this modelling study was to estimate the proportion of patients with DRM and preventable DRM and the cost of illness (COI) of DRM in Sweden based on physicians' expert opinions. METHOD: A conceptual model of DRM was modified from previous studies. Using a modified Delphi technique, a panel of physicians (n = 19) estimated the probabilities of DRM, preventable DRM, and clinical outcomes of DRM separately for outpatients and inpatients. DRM included new medical problems (adverse drug reactions, drug dependence, and intoxications by overdose) and therapeutic failure (insufficient effects of medicines, and morbidity due to untreated indication). A COI analysis included the direct costs of DRM. RESULTS: Physicians estimated that 51 ± 22% [mean ± standard deviation (SD)] of outpatients experience DRM and 12 ± 8% preventable DRM. Of inpatients, 54 ± 17% was estimated to experience DRM and 16 ± 7% preventable DRM. Of outpatients with DRM, 24 ± 11% was estimated to experience preventable DRM, whereas this proportion for inpatients was 31 ± 15%. The estimated COI was 376 euros per outpatient and 838 euros per inpatient. CONCLUSIONS: Swedish physicians estimated that every other outpatient and inpatient experiences DRM, which is often preventable and costly. As physicians' estimates on the proportion of patients with DRM were higher than in observational studies in restricted subpopulations, DRM may be more common in the general population than observational studies suggest.

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  • 14.
    Hakkarainen, Katja M
    et al.
    Nordic School of Public Health.
    Hedna, Khadidja
    Mediterranean University.
    Petzold, Max
    Nordic School of Public Health.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Pharmacology.
    Frequency of Preventable Adverse Drug Reactions in Outpatients and Inpatients and Their Preventability A Meta-Analysis in PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, vol 20, issue , pp S353-S3532011In: PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, John Wiley and Sons , 2011, Vol. 20, p. S353-S353Conference paper (Refereed)
    Abstract [en]

    n/a

  • 15.
    Hakkarainen, Katja M
    et al.
    Nordic School of Public Health (NHV), Gothenburg, Sweden.
    Hedna, Khadidja
    Université de la Méditerrané, Marseille, France.
    Petzold, Max
    Nordic School of Public Health (NHV), Gothenburg, Sweden, /Centre for Applied Biostatistics, University of Gothenburg, Gothenburg, Sweden .
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    Percentage of patients with preventable adverse drug reactions and preventability of adverse drug reactions - a meta-analysis2012In: PLOS ONE, E-ISSN 1932-6203, Vol. 7, no 3, p. 1-9, article id e33236Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Numerous observational studies suggest that preventable adverse drug reactions are a significant burden in healthcare, but no meta-analysis using a standardised definition for adverse drug reactions exists. The aim of the study was to estimate the percentage of patients with preventable adverse drug reactions and the preventability of adverse drug reactions in adult outpatients and inpatients.

    METHODS: Studies were identified through searching Cochrane, CINAHL, EMBASE, IPA, Medline, PsycINFO and Web of Science in September 2010, and by hand searching the reference lists of identified papers. Original peer-reviewed research articles in English that defined adverse drug reactions according to WHO's or similar definition and assessed preventability were included. Disease or treatment specific studies were excluded. Meta-analysis on the percentage of patients with preventable adverse drug reactions and the preventability of adverse drug reactions was conducted.

    RESULTS: Data were analysed from 16 original studies on outpatients with 48797 emergency visits or hospital admissions and from 8 studies involving 24128 inpatients. No studies in primary care were identified. Among adult outpatients, 2.0% (95% confidence interval (CI): 1.2-3.2%) had preventable adverse drug reactions and 52% (95% CI: 42-62%) of adverse drug reactions were preventable. Among inpatients, 1.6% (95% CI: 0.1-51%) had preventable adverse drug reactions and 45% (95% CI: 33-58%) of adverse drug reactions were preventable.

    CONCLUSIONS: This meta-analysis corroborates that preventable adverse drug reactions are a significant burden to healthcare among adult outpatients. Among both outpatients and inpatients, approximately half of adverse drug reactions are preventable, demonstrating that further evidence on prevention strategies is required. The percentage of patients with preventable adverse drug reactions among inpatients and in primary care is largely unknown and should be investigated in future research.

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  • 16.
    Hakkarainen, Katja Marja
    et al.
    Nordic School of Public Health (NHV), Gothenburg, Sweden.
    Andersson Sundell, Karolina
    Nordic School of Public Health (NHV), Gothenburg, Sweden.
    Petzold, Max
    Nordic School of Public Health (NHV), Gothenburg, Sweden.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    Methods for assessing the preventability of adverse drug events: A systematic review2012In: Drug Safety, ISSN 0114-5916, E-ISSN 1179-1942, Vol. 35, no 2, p. 105-126Article in journal (Refereed)
    Abstract [en]

    Background: Preventable adverse drug events (ADEs) are common in both outpatient and inpatient settings. However, the proportion of preventable ADEs varies considerably in different studies, even when conducted in the same setting, and methods for assessing the preventability of ADEs are diverse. Objective: The aim of this article is to identify and systematically evaluate methods for assessing the preventability of ADEs. Data sources: Seven databases (Cochrane, CINAHL, EMBASE, IPA, MEDLINE, PsycINFO and Web of Science) were searched in September 2010 utilizing the databases' index terms and other common terminology on preventable ADEs. No limits for the years of publication were set. Reference lists of included original articles and relevant review articles were also screened. Study selection: After applying predetermined inclusion and exclusion criteria on 4161 unique citations, 142 (3.4%) original research articles were included in the review. One additional article was included from reference lists. Outcome measures of included studies had to include the frequency of ADEs and the assessment of their preventability. Studies were excluded if they focused on individuals with one specific type of treatment, medical condition, medical procedure or ADE. Data extraction: Measurement instruments for determining the preventability of ADEs in each article were extracted and unique instruments were compared. The process of assessing the preventability of ADEs was described based on reported actions taken to standardize and conduct the assessment, and on information about the reliability and validity of the assessment. Data synthesis: Eighteen unique instruments for determining the preventability of ADEs were identified. They fell under the following four groups: (i) instruments using a definition of preventability only (n = 3); (ii) instruments with a definition of preventability and an assessment scale for determining preventability (n = 5); (iii) instruments with specific criteria for each preventability category (n = 3); and (iv) instruments with an algorithm for determining preventability (n = 7). Of actions to standardize the assessment process, performing a pilot study was reported in 21 (15%), and use of a standardized protocol was reported in 18 (13%), of the included 143 articles. Preventability was assessed by physicians in 86 (60%) articles and by pharmacists in 41 (29%) articles. In 29 (20%) articles, persons conducting the assessment were described as trained for or experienced in preventability assessment. In 94 (66%) articles, more than one person assessed the preventability of each case. Among these 94 articles, assessment was done independently in 73 (51%) articles. Procedures for managing conflicting assessments were diverse. The reliability of the preventability assessment was tested in 39 (27%) articles, and 16 (11%) articles referred to a previous reliability assessment. Reliability ranged from poor to excellent (kappa 0.19-0.98; overall agreement 26-97%). Four (3%) articles mentioned assessing validity, but no sensitivity or specificity analyses or negative or positive predictive values were presented. Conclusions: Instruments for assessing the preventability of ADEs vary from implicit instruments to explicit algorithms. There is limited evidence for the validity of the identified instruments, and instrument reliability varied significantly. The process of assessing the preventability of ADEs is also commonly imprecisely described, which hinders the interpretation and comparison of studies. For measuring the preventability of ADEs more accurately and precisely in future, we believe that existing instruments should be further studied and developed, or that one or more new instruments should be developed, and the validity and reliability of the existing and new instruments be established.

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  • 17.
    Hakkarainen, Katja Marja
    et al.
    Nordic School of Public Health NHV, Gothenburg.
    Andersson Sundell, Karolina
    Nordic School of Public Health NHV, Gothenburg. Department of Public Health and Community Medicine, University of Gothenburg.
    Petzold, Max
    Nordic School of Public Health NHV, Gothenburg. Centre fo Applied Biostatistics, Sahlgrenska Academy, University of Gothenburg.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    Prevalence and perceived preventability of self-reported adverse drug events - a population-based survey of 7099 adults2013In: PLOS ONE, E-ISSN 1932-6203, Vol. 8, no 9, p. e73166-Article in journal (Refereed)
    Abstract [en]

    Purpose

    Adverse drug events (ADEs) are common and often preventable among inpatients, but self-reported ADEs have not been investigated in a representative sample of the general public. The objectives of this study were to estimate the 1-month prevalence of self-reported ADEs among the adult general public, and the perceived preventability of 2 ADE categories: adverse drug reactions (ADRs) and sub-therapeutic effects (STEs).

    Methods

    In this cross-sectional study, a postal survey was sent in October 2010 to a random sample of 13 931 Swedish residents aged ≥18 years. Self-reported ADEs experienced during the past month included ADRs, STEs, drug dependence, drug intoxications and morbidity due to drug-related untreated indication. ADEs could be associated with prescription, non-prescription or herbal drugs. The respondents estimated whether ADRs and STEs could have been prevented. ADE prevalences in age groups (18–44, 45–64, or ≥65 years) were compared.

    Results

    Of 7099 respondents (response rate 51.0%), ADEs were reported by 19.4% (95% confidence interval, 18.5–20.3%), and the prevalence did not differ by age group (p>0.05). The prevalences of self-reported ADRs, STEs, and morbidities due to drug-related untreated indications were 7.8% (7.2–8.4%), 7.6% (7.0–8.2%) and 8.1% (7.5–8.7%), respectively. The prevalence of self-reported drug dependence was 2.2% (1.9–2.6%), and drug intoxications 0.2% (0.1–0.3%). The respondents considered 19.2% (14.8–23.6%) of ADRs and STEs preventable. Although reported drugs varied between ADE categories, most ADEs were attributable to commonly dispensed drugs. Drugs reported for all and preventable events were similar.

    Conclusions

    One-fifth of the adult general public across age groups reported ADEs during the past month, indicating a need for prevention strategies beyond hospitalised patients. For this, the underlying causes of ADEs should increasingly be investigated. The high burden of ADEs and preventable ADEs from widely used drugs across care settings supports redesigning a safer healthcare system to adequately tackle the problem.

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  • 18.
    Hakkarinen, Katja
    et al.
    Nordic School of Public Health NHV, Sweden .
    Olsson, Sten
    Uppsala Monitoring Centre, WHO Collaborating Centre for International Drug Monitoring Sweden.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    Comments: Patient safety in developing countries: retrospective estimation of scale and nature of harm to patients in hospital (volume 344, article number e832, 2012)2012In: The BMJ, E-ISSN 1756-1833, Vol. 344, article id 10.1136/bmj.e832Article in journal (Other academic)
    Abstract [en]

    We commend Wilson and colleagues1 for their excellent study providing valuable evidence on the frequency and nature of adverse events in hospitals in transitional economies. Wilson and colleagues defined an adverse event as “an unintended injury that resulted in temporary or permanent disability or death (including increased length of stay or readmission) and that was associated with healthcare management rather than the underlying disease”, and found that 8.2% of the 15 548 reviewed records included at least one adverse event. The most common adverse events were therapeutic errors (34% of all adverse events), diagnostic events (19%), and operation-related events (18%). Drug-related adverse events represented only 4% of all adverse events, and were present in 0.3% of all records. Thus, drug-related events were markedly less frequent than in western studies,2 as the authors acknowledge. Wilson and colleagues imply that less frequent use of medicines in transitional economies may contribute to fewer drug-related events, and argue that improvements are needed in the diagnostic and therapeutic steps in the care of patients.

  • 19.
    Hallbäck, Ida
    et al.
    Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology. Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    Eriksson, Andreas
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Whiss, Per
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    In vitro effects of serotonin and noradrenaline reuptake inhibitors on human platelet adhesion and coagulation2012In: Pharmacological Reports, ISSN 1734-1140, Vol. 64, no 4, p. 979-983Article in journal (Refereed)
    Abstract [en]

    Background: Although several studies show that there is an increased risk of bleeding events during antidepressant treatment with selective serotonin reuptake inhibitors (SSRIs), few studies show direct effects in vitro of SSRIs on hemostasis. less thanbrgreater than less thanbrgreater thanMethods: This study was undertaken to investigate the effects on platelet adhesion and plasma coagulation (APTT and PT) of two common SSRIs, citalopram and sertraline, the selective noradrenaline reuptake inhibitor reboxetine, and the serotonin and noradrenaline reuptake inhibitor venlafaxine. less thanbrgreater than less thanbrgreater thanResults: None of the compounds affected plasma coagulation significantly but all compounds except for venlafaxine inhibited platelet adhesion by approximately 50% or more at the highest concentration (100 mu g/l, p andlt; 0.01). The potency of respective compound to inhibit platelet adhesion to both collagen and fibrinogen surfaces was in the following order; citalopram andgt; sertraline andgt; reboxetine. In contrast, venlafaxine caused a weak but statistically significant increased platelet adhesion to fibrinogen. less thanbrgreater than less thanbrgreater thanConclusion: This study showed that sertraline, citalopram and reboxetine direct and acutely decrease platelet adhesion to both collagen and fibrinogen in vitro. These results also indicate that increased risk for bleeding complications in antidepressant users may not only be explained by depletion of serotonin in platelets.

  • 20.
    Hedna, Khadidja
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Univ Gothenburg, Sweden.
    Andersson, Marine L.
    Karolinska Inst, Sweden.
    Gyllensten, Hanna
    Karolinska Inst, Sweden; Univ Gothenburg, Sweden; Univ Gothenburg, Sweden.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Futurum, Sweden.
    Böttiger, Ylva
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Clinical relevance of alerts from a decision support system, PHARAO, for drug safety assessment in the older adults2019In: BMC Geriatrics, ISSN 1471-2318, E-ISSN 1471-2318, Vol. 19, article id 164Article in journal (Refereed)
    Abstract [en]

    BackgroundPHARAO is a decision support system developed to evaluate the risk for a set of either common or serious side-effects resulting from a combination of pharmacodynamic effects from a patients medications. The objective of this study was to investigate the validity of the risk scores for the common side-effects generated by PHARAO in older patients.MethodsSide-effects included were sedation, constipation, orthostatic symptoms, anticholinergic and serotonergic effects. The alerts generated by PHARAO were tested in 745 persons 65years old. Dispensed prescriptions retrieved from the Swedish prescribed drug register were used to generate the pharmacological risk scores of patients medications. Symptoms possibly related to side-effects were extracted from medical records data.ResultsThe PHARAO system generated 776 alerts, most often for the risk of anticholinergic symptoms. The total specificity estimates of the PHARAO system were 0.95, 0.89 and 0.78 for high, intermediate and low risk alerts, respectively. The corresponding sensitivity estimates were between 0.12 and 0.37. The negative predictive value was 0.90 and the positive predictive value ranged between 0.20-0.25.ConclusionsThe PHARAO system had a high specificity and negative predictive value to detect symptoms possibly associated with the of patients medications, while the sensitivity and positive predictive value were low. The PHARAO system has the potential to minimise the risk of over-alerts in combination with a drug-drug interaction alert system, but should be used in connection with a medical evaluation of the patient.

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  • 21.
    Hedna, Khedidja
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Nordic School of Public Health NHV, Gothenburg, Sweden.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Andersson Sundell, Karolina
    Unit of Social Medicine, University of Gothenburg, Sweden.
    Petzold, Max
    Centre for Applied Biostatistics, University of Gothenburg, Sweden.
    Hakkarainen, Katja M
    Nordic School of Public Health NHV, Gothenburg, Sweden.
    Refill adherence and self-reported adverse drug reactions and sub-therapeutic effects: a population-based study2013In: Pharmacoepidemiology and Drug Safety, ISSN 1053-8569, E-ISSN 1099-1557, Vol. 22, no 12, p. 1317-1325Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To assess refill adherence to dispensed oral long-term medications among the adult population and to investigate whether the percentages of self-reported adverse drug reactions (ADRs) and sub-therapeutic effects (STEs) differed for medications with adequate refill adherence, oversupply, and undersupply.

    METHOD: Survey responses on self-reported ADRs and STEs were linked to the Swedish Prescribed Drug Register in a cross-sectional population-based study. Refill adherence to antihypertensive, lipid-lowering, and oral anti-diabetic medications was measured using the continuous measure of medication acquisition (CMA). The percentages of self-reported ADRs and STEs were compared between medications with adequate refill adherence (CMA 0.8-1.2), oversupply (CMA > 1.2), and undersupply (CMA < 0.8).

    RESULTS: The study included 1827 persons, and the refill adherence was measured for 3014 antihypertensive, 839 lipid lowering, and 253 oral anti-diabetic medications. Overall, 65.7% of the medications had adequate refill adherence, 21.9% oversupply, and 12.4% undersupply. The percentages of self-reported ADRs and STEs were respectively 2.6%, 2.7%, and 2.1% (p > 0.5) for ADRs and 1.1%, 1.6%, and 1.5% (p > 0.5) for STEs.

    CONCLUSIONS: Adequate refill adherence was found in two thirds of the medication therapies. ADRs and STEs were unexpectedly equally commonly reported for medications with adequate refill adherence, oversupply, and undersupply. These results suggest that a better understanding of patients' refill behaviors and their perceived medication adverse outcomes is needed and should be considered in improving medication management. The impact of individual and healthcare factors that may influence the association between refill adherence and reported medication adverse outcomes should be investigated in future studies. Copyright © 2013 John Wiley & Sons, Ltd.

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  • 22.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Combined Citalopram and Ramipril treatment - Hyponatraemia2014In: WHO Pharmaceuticals Newsletter, Vol. 3, no 2, p. 13-16Article in journal (Other academic)
  • 23.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    Combined Ibuprofen and Metamizole treatment - Acute renal failure2014In: WHO Pharmaceuticals Newsletter, Vol. 3, no 2, p. 10-13Article in journal (Other academic)
  • 24.
    Hägg, Staffan
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Bate, Andrew
    Uppsala.
    Stahl, Malin
    Uppsala.
    Spigset, Olav
    Trondheim Norge.
    Associations between venous thromboembolism and antipsychotics: A study of the WHO database of adverse drug reactions2008In: Drug Safety, ISSN 0114-5916, E-ISSN 1179-1942, Vol. 31, no 8, p. 685-694Article in journal (Refereed)
    Abstract [en]

    Background: Concern has been raised about the occurrence of venous thromboembolism (VTE) during treatment with antipsychotics. However, to date, clozapine is the only antipsychotic agent for which recurring evidence supports an association with VTE. Therefore, the aim of this study was to investigate the association between antipsychotic drugs, including clozapine and VTE. Study design and methods: Data mining of the WHO database of adverse drug reactions (ADRs) using Bayesian statistics is in routine use for early alerting to possible ADRs. An information component measure was used to investigate the association between antipsychotic drugs and VTE reactions in the database. Results: A total of 754 suspected cases of VTE related to treatment with antipsychotics had been reported. After excluding cases related to clozapine, 379 cases remained. A robust association was found for the second-generation antipsychotics group but not for the high-potency, first-generation antipsychotics group or the low-potency first-generation antipsychotics group. The individual compounds with statistically significant associations were olanzapine, sertindole and zuclopenthixol. A time-dependent analysis showed that the associations were positive for these drugs in 2002, 2001 and 2003, respectively. Case analyses were undertaken after excluding ten suspected duplicate reports. Of the remaining 369 cases, 91 cases were associated with olanzapine, 9 with zuclopenthixol and 6 with sertindole. Conclusions: VTE was more often reported with the antipsychotic drugs olanzapine, sertindole and zuclopenthixol than with other drugs in the WHO database. Further studies are warranted to explain this disproportional reporting. Since the associations found were based on incomplete clinical data, the results should be considered as preliminary and interpreted cautiously. © 2008 Adis Data Information BV. All rights reserved.

  • 25.
    Hägg, Staffan
    et al.
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    Jönsson, Anna K
    Nordic School of Public Health, Gothenburg, Sweden.
    Spigset, Olav
    St Olav University Hospital, Department of Clinical Pharmacology, Trondheim, Norway.
    Risk of venous thromboembolism due to antipsychotic drug therapy.2009In: Expert opinion on drug safety, ISSN 1744-764X, Vol. 8, no 5, p. 537-47Article in journal (Refereed)
    Abstract [en]

    An increasing number of reports suggest a link between venous thromboembolism (VTE) and the use of antipsychotics. To better understand this association the available body of evidence has been critically scrutinised. Relevant articles were identified in the databases Scopus and PubMed. Several observational studies using different methodologies show an increased risk of VTE in psychiatric patients. This elevated risk seems to be related to the use of antipsychotic medication and in particular to the use of clozapine and low-potency first-generation drugs. Many studies investigating the association have, however, methodological limitations. The biological mechanisms involved in the pathogenesis of this possible adverse reaction are largely unknown but several hypotheses have been suggested such as drug-induced sedation, obesity, increased levels of antiphospholipid antibodies, enhanced platelet aggregation, hyperhomocysteinemia and hyperprolactinemia. The association may also be related to underlying risk factors present in psychotic patients. Physicians need to be aware of this possible adverse drug reaction. Although supporting evidence has not been published they should consider discontinuing or switching the antipsychotic treatment in patients experiencing VTE. In addition, although data is lacking, the threshold for considering prophylactic antithrombotic treatment should be low when risk situations for VTE arise, such as immobilisation, surgery and so on.

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  • 26.
    Hägg, Staffan
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Lindblom, Y
    Umeå.
    Mjörndal, Tom
    Umeå.
    Adolfsson, R
    Umeå.
    High prevalence of the metabolic syndrome among a Swedish cohort of patients with schizophrenia2006In: International Clinical Psychopharmacology, ISSN 0268-1315, E-ISSN 1473-5857, Vol. 21, no 2, p. 93-98Article in journal (Refereed)
    Abstract [en]

    Several cardiovascular risk factors have been linked to antipsychotic treatment and cardiovascular mortality is increased in these patients compared to the general population. The full metabolic syndrome (or its components) is associated with an increased risk of cardiovascular disorders. The prevalence of the metabolic syndrome was investigated using a cross-sectional study design in a cohort of 269 patients, aged 20-69 years, with schizophrenia living in Northern Sweden, and was defined according to the criteria of the National Cholesterol Education program. The prevalence of the metabolic syndrome was 34.6% (95% CI = 28.8-40.3) and highest (43%, 95% CI = 32-53) for participants aged 40-49 years. Clozapine treated subjects reached the highest prevalence of the metabolic syndrome (48%, 95% CI = 34-62). The prevalence was similar for men (32.8%, 95% CI = 25.8-39.8) and women (38.0%, 95% CI = 27.9-48.2). Men had a high prevalence of hypertension (49.2%, 95% CI = 41.7-56.6) and women had high prevalence of low high-density lipoprotein cholesterol (40.2%, 95% CI = 30.0-50.4) and abdominal obesity (75.0%, 95% CI = 66.0-84.0). Subjects with the metabolic syndrome had significantly higher mean body mass index (BMI) (P < 0.001), HbA1c (P = 0.002), and fasting serum insulin (P < 0.001) compared to non-metabolic syndrome subject. Subjects with the metabolic syndrome had also significantly more often a positive history of cardiovascular diseases compared to non-metabolic syndrome subjects (25.8% versus 12.5%, P = 0.01). Of all study subjects 36.8% were obese (BMI > 30). These results clearly show that the metabolic syndrome and its components are highly prevalent in patients with schizophrenia. Physicians treating patients with schizophrenia are recommended to monitor the components included in the metabolic syndrome. © 2006 Lippincott Williams & Wilkins.

  • 27.
    Jacobsson, Ingela
    et al.
    Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Danell Boman, M
    Div of Clinical Pharmacology, Umeå.
    Jönsson, Anna
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Pharmacology.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Pharmacology.
    Who Reports Suspected Adverse Drug Reactions to the Spontaneous Reporting System in Sweden?2008Conference paper (Refereed)
  • 28.
    Jacobsson, Ingela
    et al.
    Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Jönsson, Anna
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    Gerdén, Barbro
    Läkemedelsverket, Uppsala.
    Axling, Cecilia
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    Spontaneously Reported Suspected Adverse Drug Reactions in Association with Complementary and Alternative Medicine Products2007In: Pharmacoepidemiology and Drug Safety, Wiley , 2007, p. 196-197Conference paper (Refereed)
  • 29.
    Jacobsson, Ingela
    et al.
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences.
    Jönsson, Anna K
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences.
    Gerdén, Barbro
    Department of Communication, Medical Products Agency, Uppsala, Sweden.
    Hägg, Staffan
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences.
    Spontaneously reported adverse reactions in association with complementary and alternative medicine substances in Sweden.2009In: Pharmacoepidemiology and drug safety, ISSN 1099-1557Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Although the safety information is limited, use of complementary and alternative medicine (CAM) products is not without risks. Spontaneous reporting systems may be used in the surveillance of these products. We describe the pattern of spontaneously reported CAM related adverse reactions submitted to the Swedish Medical Products Agency (MPA) and highlight areas of safety concern. METHODS: All adverse reactions spontaneously reported to MPA between 1987 and 2006, where at least one CAM substance was a suspected agent, were scrutinised. From each report information about the patient, adverse reaction/s, drug treatment/s, dosage, time relationship and outcome was retrieved. RESULTS: Among a total of 64 493 reports, 778 reports concerned 967 suspected adverse reactions related to 175 different CAM products. The main distribution of suspected adverse reactions was: urticaria (8.3%), exanthema (7.4%) and contact dermatitis (5.7%). The most reported CAM substances were purple coneflower (Echinacea purpurea) (8.1%), purple coneflower + siberian ginseng (Eleutherococcus senticosus) + malabar nut (Adhatoda vasica) (7.3%) and ginkgo leaf (Ginkgo biloba) (6.7%). In 221 reports, at least one reaction was categorised as serious, the most frequent being pulmonary embolism (1.7%), mixed liver reaction (2.8%), and anaphylactic reaction (2.0%). Eleven of the serious adverse reactions had a fatal outcome. CONCLUSIONS: CAM substances were associated with a variety of adverse reactions. Some of these have previously been unrecognised or poorly documented and suggest further investigations. By stimulating the reporting of adverse reactions of CAM products, the signal detection power of the spontaneous reporting system may increase further.

  • 30.
    Johansson, Marie-Louise
    et al.
    Sahlgrens University Hospital.
    Brunlof, Gertrud
    Sahlgrens University Hospital.
    Hägg, Staffan
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Wallerstedt, Susanna M
    Sahlgrens University Hospital.
    Effects of a One Page ADR Information Letter on the Reporting Rate and the Information Value of ADR Reports2009In: in PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, vol 18, 2009, Vol. 18, p. S251-S252Conference paper (Refereed)
    Abstract [en]

    n/a

  • 31.
    Johansson, Marie-Louise
    et al.
    Sahlgrenska University Hospital.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    Wallerstedt, Susanna M
    Sahlgrenska University Hospital.
    Impact of information letters on the reporting rate of adverse drug reactions and the quality of the reports: a randomized controlled study2011In: BMC clinical pharmacology, ISSN 1472-6904, Vol. 11, no 14Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Spontaneous reporting of adverse drug reactions (ADRs) is an important method for pharmacovigilance, but under-reporting and poor quality of reports are major limitations. The aim of this study was to evaluate if repeated one-page ADR information letters affect (i) the reporting rate of ADRs and (ii) the quality of the ADR reports.

    METHODS: All 151 primary healthcare units in the Region Västra Götaland, Sweden, were randomly allocated (1:1) to an intervention (n = 77) or a control group (n = 74). The intervention consisted of one-page ADR information letters administered at three occasions during 2008 to all physicians and nurses in the intervention units. The number of ADR reports received from the 151 units was registered, as was the quality of the reports, which was defined as high if the ADR was to be reported according to Swedish regulations, that is, if the ADR was (i) serious, (ii) unexpected, and/or (iii) related to the use of new drugs and not labelled as common in the Summary of Product Characteristics. A questionnaire was administered to evaluate if the ADR information letter had reached the intended recipient.

    RESULTS: Before the intervention, no significant differences in reporting rate or number of high quality reports could be detected between the randomization groups. In 2008, 79 reports were sent from 37 intervention units and 52 reports from 30 control units (mean number of reports per unit ± standard deviation: 1.0 ± 2.5 vs. 0.7 ± 1.2, P = 0.34). The number of high quality reports was higher in intervention units than in control units (37 vs. 15 reports, 0.5 ± 0.9 vs. 0.2 ± 0.6, P = 0.048). According to the returned questionnaires (n = 1,292, response rate 57%), more persons in the intervention than in the control group had received (29% vs. 19%, P < 0.0001) and read (31% vs. 26%, P < 0.0001) an ADR information letter.

    CONCLUSIONS: This study suggests that repeated ADR information letters to physicians and nurses do not increase the ADR reporting rate, but may increase the number of high quality reports.

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  • 32.
    Jonsson, Anna
    et al.
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences.
    Spigset, Olav
    Division of Clinical Pharmacology and Department of Laboratory Medicine and Women’s Health, Trondheim, Norway.
    Tjäderborn, Micaela
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences.
    Druid, Henrik
    Department of Forensic Medicine, Karolinska Institute.
    Hägg, Staffan
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Fatal drug poisonings in a Swedish general population.2009In: BMC clinical pharmacology, ISSN 1472-6904, Vol. 9, no 7, p. 1-5Article in journal (Refereed)
    Abstract [en]

    ABSTRACT: BACKGROUND: Pharmaceutical drug poisonings have previously been reported using single sources of information, either hospital data or forensic data, which might not reveal the true incidence. We therefore aimed to estimate the incidence of suspected fatal drug poisonings, defined as poisonings by pharmaceutical agents, by using all relevant case records from various sources in a Swedish population. METHODS: Every seventh randomly selected deceased in three counties in southeastern Sweden during a one-year period was identified in the Cause of Death Register. Relevant case records (death certificates, files from hospitals and/or primary care centres and medico-legal files) were reviewed for all study subjects. RESULTS: Of 1574 deceased study subjects, 12 cases were classified as pharmaceutical drug poisonings according to the death certificates and 10 according to the medico-legal files. When reviewing all available data sources, 9 subjects (0.57%; 95% confidence interval: 0.20-0.94%) were classified as drug poisonings, corresponding to an incidence of 6.5 (95% confidence interval: 2.3-10.7) per 100 000 person-years in the general population. The drug groups most often implicated were benzodiazepines (33%), antihistamines (33%) and analgesics (22%). CONCLUSIONS: Fatal drug poisonings is a relatively common cause of death in Sweden. By using multiple sources of information when investigating the proportion of fatal poisonings in a population, more accurate estimates may be obtained.

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  • 33.
    Jönsson, Anna
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Andersson, Mats
    Neurologiska kliniken Neurocentrum.
    Jacobsson, Ingela
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Hägg, Staffan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Large underreporting of cerebral haemorrhage during warfarin treatment in Sweden2005In: 7th Congress of European association for clinical pharmacology,2005, 2005Conference paper (Other academic)
  • 34.
    Jönsson, Anna
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Andersson, Mats
    Neurologiska kliniken Neurocentrum.
    Jacobsson, Ingela
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Hägg, Staffan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Stor underrapportering av hjärnblödningar under warfarinbehandling2005In: Läkarsällskapets Riksstämma,2005, 2005Conference paper (Other academic)
  • 35.
    Jönsson, Anna
    et al.
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Brudin, Lars
    Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Linköping University, Faculty of Health Sciences.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Hedenmalm, Karin
    Uppsala University, Sweden.
    Eriksson, Anders
    Umeå, University, Sweden.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Antipsychotics associated with pulmonary embolism in a Swedish medicolegal autopsy series2008In: International Clinical Psychopharmacology, ISSN 0268-1315, E-ISSN 1473-5857, Vol. 23, no 5, p. 263-268Article in journal (Refereed)
    Abstract [en]

    To determine the association between fatal pulmonary embolism and use of antipsychotic drugs in a Swedish medicolegal autopsy series. Persons aged 18-65 years and subjected to a medicolegal autopsy in 1992-2005 were selected. On the basis of external cause of death, determined by the forensic pathologist, unnatural deaths (including fatal intoxications) were excluded and participants in whom pulmonary embolism was the cause of death were identified. Use of antipsychotics was based on the results of the postmortem analyses and categorized as use of high-potency first-generation antipsychotics, low-potency first-generation antipsychotics, second-generation antipsychotics or no use of antipsychotics. Logistic regression analyses were performed. Use of antipsychotics was verified in 538 of the 14,439 included participants. Pulmonary embolism was recorded as the cause of death in 279 participants and 33 of these used antipsychotics. Use of low-potency first-generation antipsychotics and second-generation antipsychotics was significantly associated with fatal pulmonary embolism (adjusted odds ratio: 2.39, 95% confidence interval: 1.46-3.92 and 6.91, 95% confidence interval: 3.95-12.10, respectively). Out of 26 participants classified as high-potency first-generation antipsychotic drug users, none had pulmonary embolism as the cause of death. Pulmonary embolism was overrepresented among medicolegal autopsy cases identified as users of low-potency first-generation and second-generation antipsychotics.

  • 36.
    Jönsson, Anna
    et al.
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Pharmacology.
    Brudin, Lars
    Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Linköping University, Faculty of Health Sciences.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Hedenmalm, Karin
    Dpt of Clinical Pharmacology, Uppsala universitet. Clinical Trial Unit, Medical Products Agency, Uppsala.
    Eriksson, Anders
    Section of Forensic Medicine, Umeå universitet.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Pharmacology.
    Antispychotics Associated with Pulmonary Emboi in a Swedish Medico-Legal Autopsy Series2007Conference paper (Refereed)
  • 37.
    Jönsson, Anna
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Brundin, Lars
    Ahlner, Johan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Hedenmalm, Karin
    Eriksson, Anders
    Hägg, Staffan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Low-potency and atypical antipsychotics were associated with pulmonary embolism among Swedish autopsy cases2006In: International conference on Pharmacoepidemiology Therapeutic risk management,2006, 2006Conference paper (Other academic)
  • 38.
    Jönsson, Anna
    et al.
    Nordiska högskolan för folkhälsovetenskap, Göteborg.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    Många läkemedelsorsakade dödsfall kan förhindras2010In: Läkartidningen, ISSN 0023-7205, Vol. 107, no 11, p. 745-Article in journal (Other academic)
    Abstract [en]

    Flera studier visar att läkemedelsbiverkningar som leder till döden är relativt vanliga. Dock saknas kunskap om hur stor andel som är möjlig att förebygga. Syftet med denna studie var att beskriva andelen undvikbara letala läkemedelsbiverkningar och förgiftningar i en svensk population.

    I en tidigare studie identifierades läkemedelsbiverkningar och förgiftningar bland 1 574 slumpmässigt utvalda personen som avlidit i den sydöstra sjukvårdsregionen under 2001. Detta gjordes genom att granska dödsbevis, sjukhus- och vårdcentralsjournaler och resultat av genomförda rättsmedicins­ka obduktioner. Man fann då 49 fall (3 procent) av läkemedelsbiverkningar och 9 fall (0,6 procent) av förgiftningar hos 57 personer.

    I den aktuella studien värderades om de identifierade letala läkemedelsbiverkningarna och förgiftningarna hade kunnat förhindras. Detta gjordes stegvis av kliniska experter (klinisk farmakologi, rättsmedicin, farmaci) med hjälp av fördefinierade väletablerade kriterier för prevention.

    Av de 49 läkemedelsbiverkningarna var 14 procent (sju fall) säkert eller möjligt undvikbara. Fyra av dessa berodde på att läkemedlet var kontraindicerat för dessa patienter. Alla nio förgiftningsdödsfall bedömdes vara möjliga att förebygga. Hos en person bidrog både en läkemedelsbiverkan och en förgiftning till dödsfallet, därför bedömdes totalt 15 personer (26 procent) ha en förebyggbar läkemedelsbiverkan eller förgiftning.

    Detta innebär att cirka 1 procent av alla dödsfall i Sverige beror på misstänkta läkemedelsbiverkningar eller förgiftningar som skulle kunna förebyggas. Att arbeta mer aktivt för att reducera antalet biverkningar som går att förebygga bedöms angeläget. Det är dock fortfarande oklart vilka interventioner som har bäst möjlighet att förhindra biverkningar.

  • 39.
    Jönsson, Anna
    et al.
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    Jacobsson, Ingela
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    Andersson, Karolina
    Nordic School of Public Health, Göteborg.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    Sundström, Anders
    Centre of Pharmacoepidemiology, KI, Stockholm. , Dpt of Drug Safety, Medical Products Agency, Uppsala .
    Factors Predisposing an Abstract To Be Accepted for Oral Presentation2008In: Pharmacoepidemiology and drug safety, Wiley-Blackwell , 2008, p. 190-191Conference paper (Refereed)
  • 40.
    Jönsson, Anna
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Jacobsson, Ingela
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Andersson, Mats
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurology. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Hägg, Staffan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Stor underrapportering av hjärnblödning som läkemedelsbiverkning2006In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 103, p. 3456-3458Article in journal (Refereed)
    Abstract [sv]

         

  • 41.
    Jönsson, Anna K.
    et al.
    Nordic School of Public Health, Gothenburg, Sweden.
    Hakkarainen, Katja M.
    Nordic School of Public Health, Gothenburg, Sweden.
    Spigset, Olav
    Department of Laboratory medicine, Children´s and Women´s Health, Norwegian University of Science and Technology, Trondheim, Norway. Division of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway.
    Druid, Henrik
    Division of Forensic Medicine, Department of Oncology-pathology, Karolinska institute Stockholm, Sweden.
    Hiselius, Anne
    Jönköping County Council, Jönköping, Sweden.
    Hägg, Staffan
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Pharmacology.
    Preventable drug related mortality in a Swedish population2010In: Pharmacoepidemiology and Drug Safety, ISSN 1053-8569, E-ISSN 1099-1557, Vol. 19, no 2, p. 211-215Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Several studies indicate that the medical burden of fatal adverse drug reactions (FADRs) is significant, but the preventability of FADRs in the general population is largely unknown. The aim of this study was to determine the proportion of preventable FADRs and preventable fatal drug poisonings (FDPs) in a Swedish population. METHODS: Previously, a population-based sample of 1574 deceased subjects was scrutinised for FADRs and FDPs using relevant case records, including death certificates, medical charts and medico-legal files. Forty-nine cases (3%) of FADRs and nine cases (0.6%) of FDPs were identified in 57 subjects. In this study, the preventability of all these identified FADRs and FDPs was evaluated by clinical experts in a stepwise manner, applying a set of predefined and well established preventability criteria. Only cases for which consensus was achieved were included in the study. RESULTS: Of 49 FADRs, 14% (seven fatalities) was considered definitely or possibly preventable and four of these were due to the presence of a contraindication for the drug. All nine FDPs were considered possibly preventable. As one subject had a combination of an FADR and an FDP, a total of 15 persons (26%) were considered having a definitely or possibly preventable FADR or FDP, corresponding to 0.95% of all deceased subjects in Sweden. CONCLUSIONS: The results of this study indicate that approximately one fourth of FADRs and FDPs could be prevented. Therefore, an increased awareness of the possibility to reduce the risk of fatal events due to pharmaceutical drugs is warranted.

  • 42.
    Jönsson, Anna K.
    et al.
    Nordic School of Public Health, Gothenburg, Sweden.
    Horváth-Puhó, Erzsebet
    Aarhus Danmark.
    Hägg, Staffan
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Pedersen, Lars
    Aarhus Danmark.
    Sörensen, Henrik T
    Aarhus Danmark.
    Antipsychotics and risk for venous thromboembolism: A population based case-control study2009In: Clinical Epidemiology, ISSN 1179-1349, Vol. 1, p. 19-26Article in journal (Refereed)
    Abstract [en]

    During the last decade, the risk of venous thromboembolism (VTE) has been reported in users of antipsychotic drugs. However, the reports have been inconclusive. This study aimed to determine the relative risk of VTE in antipsychotic drug users. Using data from medical databases in North Jutland and Aarhus Counties, Denmark, and the Danish Civil Registration System, we identified 5,999 cases with a first-time diagnosis of VTE and, based on risk set sampling, 59,990 sex- and age-matched population controls during 1997–2005. Users of antipsychotic drugs were identified from population-based prescription databases and categorized based on filled prescriptions prior to admission date for VTE or index date for controls as current (at least one prescription within 90 days), recent (at least one prescription within 91–180 days), former (at least one prescription within 181–365 days) or nonusers (no recorded prescription within 365 days). Compared with nonusers, current users of any antipsychotic drugs had an increased risk of VTE (adjusted relative risk [ARR]: 1.99, 95% confidence interval [CI]: 1.69–2.34). Former users of any antipsychotic drugs had a nonsignificant elevated risk of VTE compared with nonusers (ARR: 1.54, 95% CI: 0.99–2.40, p-value: 0.056). In conclusion, users of antipsychotic drugs have an increased risk of VTE, compared with nonusers, which might be due to the treatment itself, to lifestyle factors, to the underlying disease, or to residual confounding.

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  • 43.
    Jönsson, Anna K.
    et al.
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    Spigset, Olav
    Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    Venous Thromboembolism in Recipients of Antipsychotics: Incidence, Mechanisms and Management2012In: CNS Drugs, ISSN 1172-7047, E-ISSN 1179-1934, Vol. 26, no 8, p. 649-662Article, review/survey (Refereed)
    Abstract [en]

    Since chlorpromazine was introduced to the market in the early 1950s, theuse of antipsychotic drugs has been associated with venous thromboembolism(VTE) in a number of reports. During the last decade the evidence hasbeen strengthened with large epidemiological studies. Whether all antipsychoticsincrease the risk for VTE or the risk is confined to certain drugs is stillunclear. The aim of this article is to present an updated critical reviewfocusing on the incidence, mechanisms and management of VTE in users ofantipsychotics. After searching the databases PubMed and Scopus for relevantarticles we identified 12 observational studies, all of which were publishedafter the year 2000. In most of these studies an elevated risk of VTE wasobserved for antipsychotic drugs, with the highest risk for clozapine, olanzapineand low-potency first-generation antipsychotics. The risk seems to becorrelated with dose. The elderly, who mainly use lower doses, do not showan increased risk of VTE to the same extent as younger subjects.The underlying biological mechanisms explaining the association betweenantipsychotic medication and VTE are to a large extent unknown. Severalhypotheses have been proposed, such as body weight gain, sedation, enhancedplatelet aggregation, increased levels of antiphospholipid antibodies,hyperprolactinaemia and hyperhomocysteinaemia. The risk of VTE in schizophreniaand other psychotic disorders may also be related to the underlyingdisease rather than the medication.Very limited evidence exists to guide how cases of VTE in subjects usingantipsychotics should be handled. An attempt to compile an algorithm wherethe patients’ individual risk of VTE is assessed and preventive clinical measuresare suggested has been published recently. Strong consideration shouldbe given to discontinuation of the offending antipsychotic drug in patientsexperiencing a VTE, and another antipsychotic drug with a presumably lowerrisk should be chosen if antipsychotic drug treatment is still indicated. It isessential that physicians and patients are aware that VTE may be an adversedrug reaction to the antipsychotic treatment so the condition is identifiedearly and treated appropriately.

  • 44.
    Jönsson, Anna K.
    et al.
    Linköping University, Department of Medicine and Care, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Spigset, Olav
    Department of Clinical Pharmacology, St. Olav University Hospital; and Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway.
    Jacobsson, Ingela
    Linköping University, Department of Medicine and Care, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Hägg, Staffan
    Linköping University, Department of Medicine and Care, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Cerebral haemorrhage induced by warfarin - the influence of drug-drug interactions2007In: Pharmacoepidemiology and Drug Safety, ISSN 1053-8569, E-ISSN 1099-1557, ISSN 1, Vol. 16, no 3, p. 309-315Article in journal (Refereed)
    Abstract [en]

    Purpose: To evaluate the frequency, severity and preventability of warfarin-induced cerebral haemorrhages due to warfarin and warfarin-drug interactions in patients living in the county of Östergötland, Sweden.

    Methods: All patients with a diagnosed cerebral haemorrhage at three hospitals during the period 2000-2002 were identified. Medical records were studied retrospectively to evaluate whether warfarin and warfarin-drug interactions could have caused the cerebral haemorrhage. The proportion of possibly avoidable cases due to drug interactions was estimated.

    Results: Among 593 patients with cerebral haemorrhage, 59 (10%) were assessed as related to warfarin treatment. This imply an incidence of 1.7/100 000 treatment years. Of the 59 cases, 26 (44%) had a fatal outcome, compared to 136 (25%) among the non-warfarin patients (p < 0.01). A warfarin-drug interaction could have contributed to the haemorrhage in 24 (41%) of the warfarin patients and in 7 of these (12%) the bleeding complication was considered being possible to avoid.

    Conclusions: Warfarin-induced cerebral haemorrhages are a major clinical problem with a high fatality rate. Almost half of the cases was related to a warfarin-drug interaction. A significant proportion of warfarin-related cerebral haemorrhages might have been prevented if greater caution had been taken when prescribing drugs known to interact with warfarin.

  • 45.
    Jönsson, Anna
    et al.
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    Sörensen, Henrik
    Dpt of Clinical Epidemiology, Aalborg University Hospital, Denmark.
    Horváth-Puhó, Erzébet
    Dpt of Human Genetics and Teratology, National Center for Epidemiology, Budapest, Hungary.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Association between Venous Thromboembolism and Antipsychotics: A Population Based Case-Control Study2007In: Pharmacoepidemiology and Drug Safety, Wiley , 2007, p. 256-256Conference paper (Refereed)
  • 46.
    Karimi, Ghazaleh
    et al.
    Uppsala Monitoring Centre, Sweden .
    Star, Kristina
    Uppsala Monitoring Centre, Sweden .
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Pharmacology.
    Noren, Niklas G.
    Uppsala Monitoring Centre, Sweden .
    Letter: Time-to-onset in spontaneous reports: the possibility to detect the unexpected2013In: Pharmacoepidemiology and Drug Safety, ISSN 1053-8569, E-ISSN 1099-1557, Vol. 22, no 5, p. 556-557Article in journal (Other academic)
    Abstract [en]

    n/a

  • 47.
    Karimi, Ghazaleh
    et al.
    WHO Collaborating Centre Int Drug Monitoring, Sweden.
    Star, Kristina
    WHO Collaborating Centre Int Drug Monitoring, Sweden.
    Noren, Niklas G.
    WHO Collaborating Centre Int Drug Monitoring, Sweden.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    The Impact of Duration of Treatment on Reported Time-to-Onset in Spontaneous Reporting Systems for Pharmacovigilance2013In: PLOS ONE, E-ISSN 1932-6203, Vol. 8, no 7Article in journal (Refereed)
    Abstract [en]

    Within pharmacovigilance, knowledge of time-to-onset (time from start of drug administration to onset of reaction) is important in causality assessment of drugs and suspected adverse drug reactions (ADRs) and may indicate pharmacological mechanisms involved. It has been suggested that time-to-onset from individual case reports can be used for detection of safety signals. However, some ADRs only occur during treatment, while those that do occur later are less likely to be reported. The aim of this study was to investigate the impact of treatment duration on the reported time-to-onset. Case reports from the WHO Global ICSR database, VigiBase, up until February 5th 2010 were the basis of this study. To examine the effect of duration of treatment on reported time-to-onset, angioedema and hepatitis were selected to represent short and long latency ADRs, respectively. The reported time-to-onset for each of these ADRs was contrasted for a set of drugs expected to be used short- or long-term, respectively. The study included 2,980 unique reports for angioedema and 1,159 for hepatitis. Median reported time-to-onset for angioedema in short-term treatments ranged 0-1 days (median 0.5), for angioedema in long-term treatments 0-26 days (median 8), for hepatitis in short-term treatments 4-12 days (median 7.5) and for hepatitis in long term treatments 19-73 days (median 28). Short-term treatments presented significantly shorter reported time-to-onset than long-term treatments. Of note is that reported time-to-onset for angioedema for long-term treatments (median value of medians being 8 days) was very similar to that of hepatitis for short-term treatments (median value of medians equal 7.5 days). The expected duration of treatment needs to be considered in the interpretation of reported time-to-onset and should be accounted for in signal detection method development and case evaluation.

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  • 48.
    Karlsson, John
    et al.
    Sektionen för klinisk farmakologi, Sahlgrenska universitetssjukhuset, Göteborg.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Pharmacology.
    Star, Kristina
    WHO Collaborating Centre for International Drug Monitoring, Uppsala.
    Wallerstedt, Susanna M
    Sektionen för klinisk farmakologi, Sahlgrenska universitetssjukhuset, Göteborg.
    Plötslig död och behandling med andra generationens antispykotika: Data från WHO:s Biverkningsdatabas (Vigibase)2008Conference paper (Refereed)
  • 49.
    Karlsson, John
    et al.
    Dpt of Clinical Pharmacology, Sahlgrenska university Hospital, Göteborg.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    Star, Kristina
    WHO Collaborating Centre for International Drug Monitoring, Uppsala.
    Wallerstedt, Susanna M
    Dpt of Clinical Pharmacology, Sahlgrenska university Hospital, Göteborg.
    Sudden Death and Treatmet with New Generation Antipsychotics: Data from the WHO Database of Adverse Drug Reactions (Vigibase)2008In: Pharmacoepidemiology and drug safety, Wiley-Blackwell , 2008Conference paper (Refereed)
  • 50.
    Karlsson, John
    et al.
    Sahlgrens University Hospital.
    Wallerstedt, Susanna M
    Sahlgrens University Hospital.
    Star, Kristina
    Uppsala Monitoring Centre.
    Bate, Andrew
    Uppsala Monitoring Centre.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Letter: Sudden Cardiac Death in Users of Second-Generation Antipsychotics2009In: Journal of Clinical Psychiatry, ISSN 0160-6689, E-ISSN 1555-2101, Vol. 70, no 12, p. 1725-1726Article in journal (Other academic)
    Abstract [en]

    n/a

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