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Hägg, Staffan
Publications (10 of 86) Show all publications
Skoglund, K., Richter, J., Olsson-Stromberg, U., Bergquist, J., Aluthgedara, W., Ubhayasekera, S. J., . . . Green, H. (2016). In Vivo Cytochrome P450 3A Isoenzyme Activity and Pharmacokinetics of Imatinib in Relation to Therapeutic Outcome in Patients With Chronic Myeloid Leukemia. Therapeutic Drug Monitoring, 38(2), 230-238
Open this publication in new window or tab >>In Vivo Cytochrome P450 3A Isoenzyme Activity and Pharmacokinetics of Imatinib in Relation to Therapeutic Outcome in Patients With Chronic Myeloid Leukemia
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2016 (English)In: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 38, no 2, p. 230-238Article in journal (Refereed) Published
Abstract [en]

Background: Cytochrome P450 3A (CYP3A) isoenzyme metabolic activity varies between individuals and is therefore a possible candidate of influence on the therapeutic outcome of the tyrosine kinase inhibitor imatinib in patients with chronic myeloid leukemia (CML). The aim of this study was to investigate the influence of CYP3A metabolic activity on the plasma concentration and outcome of imatinib in patients with CML. Methods: Forty-three patients with CML were phenotyped for CYP3A activity using quinine as a probe drug and evaluated for clinical response parameters. Plasma concentrations of imatinib and its main metabolite, CGP74588, were determined using liquid chromatography-mass spectrometry. Results: Patients with optimal response to imatinib after 12 months of therapy did not differ in CYP3A activity compared to nonoptimal responders (quinine metabolic ratio of 14.69 and 14.70, respectively; P = 0.966). Neither the imatinib plasma concentration nor the CGP74588/imatinib ratio was significantly associated with CYP3A activity. Conclusions: The CYP3A activity does not influence imatinib plasma concentrations or the therapeutic outcome. These results indicate that although imatinib is metabolized by CYP3A enzymes, this activity is not the rate-limiting step in imatinib metabolism and excretion. Future studies should focus on other pharmacokinetic processes so as to identify the major contributor to patient variability in imatinib plasma concentrations.

Place, publisher, year, edition, pages
LIPPINCOTT WILLIAMS & WILKINS, 2016
Keywords
pharmacokinetics; chronic myeloid leukemia; imatinib; CGP74588; CYP3A
National Category
Pharmaceutical Sciences
Identifiers
urn:nbn:se:liu:diva-129678 (URN)10.1097/FTD.0000000000000268 (DOI)000376938000006 ()26693810 (PubMedID)
Note

Funding Agencies|Swedish Research Council; Swedish Cancer Society; Medical Research Council of Southeast Sweden; Novartis

Available from: 2016-06-27 Created: 2016-06-23 Last updated: 2018-01-10
Tjäderborn, M., Jönsson, A. K., Zverkova Sandstrom, T., Ahlner, J. & Hägg, S. (2016). Non-prescribed use of psychoactive prescription drugs among drug-impaired drivers in Sweden. Drug And Alcohol Dependence, 161, 77-85
Open this publication in new window or tab >>Non-prescribed use of psychoactive prescription drugs among drug-impaired drivers in Sweden
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2016 (English)In: Drug And Alcohol Dependence, ISSN 0376-8716, E-ISSN 1879-0046, Vol. 161, p. 77-85Article in journal (Refereed) Published
Abstract [en]

Aims: To determine the prevalence of non-prescribed drug use among subjects suspected of drug impaired driving with a psychoactive prescription drug, and to identify associated factors. Methods: Subjects investigated for drug-impaired driving in Sweden during 2006-2009 with a confirmed intake of diazepam, flunitrazepam, tramadol, zolpidem or zopiclone were identified using the Swedish Forensic Toxicology Database. Information on dispensed prescription drugs was retrieved from the Swedish Prescribed Drug Register. Non-prescribed use was our outcome, defined as a psychoactive prescription drug intake confirmed by toxicological analysis in a subject by whom it was not dispensed in the 12 months preceding the sampling. Prevalence proportions were calculated for each drug and logistic regression was used to identify associated factors. Results: In total, 2225 subjects were included. The median age (range) was 34 (15-80) years and 1864 (83.8%) subjects were male. Non-prescribed use was found in 1513 subjects (58.7%); for flunitrazepam 103 (76.3%), diazepam 1098 (74.1%), tramadol 192 (40.3%), zopiclone 60 (29.7%), and zolpidem 60 (21.2%) subjects, respectively. Younger age and multiple-substance use were associated with non-prescribed use, whereas ongoing treatment with other psychoactive drugs was negatively associated with non prescribed use. Conclusions: Non-prescribed use of psychoactive prescription drugs was common in subjects suspected of drug-impaired driving and was more frequent for benzodiazepines and tramadol compared to zolpidem and zopiclone. The young and multi-substance users were more likely, whereas subjects with ongoing prescribed treatment with other psychoactive drugs were less likely, to use non-prescribed drugs.

Place, publisher, year, edition, pages
ELSEVIER IRELAND LTD, 2016
Keywords
Prescription drug diversion; Non-prescribed use; Drug-impaired driving; Drug dispensing; Pharmacoepidemiology
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-127559 (URN)10.1016/j.drugalcdep.2016.01.031 (DOI)000373419100011 ()26875672 (PubMedID)
Note

Funding Agencies|County Council of Ostergotland, Sweden [LIO-131751]; Forensic Science Centre, Sweden [CFV 121218]; Linkoping University, Sweden [LIU 2009-01356]

Available from: 2016-05-04 Created: 2016-05-03 Last updated: 2017-04-24
Khedidja, H., Hakkarainen, K. M., Gyllensten, H., Jönsson, A. K., Andersson Sundell, K., Petzold, M. & Hägg, S. (2015). Adherence to Antihypertensive Therapy and Elevated Blood Pressure: Should We Consider the Use of Multiple Medications?. PLoS ONE, 10(9), Article ID e0137451.
Open this publication in new window or tab >>Adherence to Antihypertensive Therapy and Elevated Blood Pressure: Should We Consider the Use of Multiple Medications?
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2015 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 9, article id e0137451Article in journal (Refereed) Published
Abstract [en]

Background

Although a majority of patients with hypertension require a multidrug therapy, this is rarely considered when measuring adherence from refill data. Moreover, investigating the association between refill non-adherence to antihypertensive therapy (AHT) and elevated blood pressure (BP) has been advocated.

Objective

Identify factors associated with non-adherence to AHT, considering the multidrug therapy, and investigate the association between non-adherence to AHT and elevated BP.

Methods

A retrospective cohort study including patients with hypertension, identified from a random sample of 5025 Swedish adults. Two measures of adherence were estimated by the proportion of days covered method (PDC≥80%): (1) Adherence to any antihypertensive medication and, (2) adherence to the full AHT regimen. Multiple logistic regressions were performed to investigate the association between sociodemographic factors (age, sex, education, income), clinical factors (user profile, number of antihypertensive medications, healthcare use, cardiovascular comorbidities) and non-adherence. Moreover, the association between non-adherence (long-term and a month prior to BP measurement) and elevated BP was investigated.

Results

Non-adherence to any antihypertensive medication was higher among persons < 65 years (Odds Ratio, OR 2.75 [95% CI, 1.18–6.43]) and with the lowest income (OR 2.05 [95% CI, 1.01–4.16]). Non-adherence to the full AHT regimen was higher among new users (OR 2.04 [95% CI, 1.32–3.15]), persons using specialized healthcare (OR 1.63, [95% CI, 1.14–2.32]), and having multiple antihypertensive medications (OR 1.85 [95% CI, 1.25–2.75] and OR 5.22 [95% CI, 3.48–7.83], for 2 and ≥3 antihypertensive medications, respectively). Non-adherence to any antihypertensive medication a month prior to healthcare visit was associated with elevated BP.

Conclusion

Sociodemographic factors were associated with non-adherence to any antihypertensive medication while clinical factors with non-adherence to the full AHT regimen. These differing findings support considering the use of multiple antihypertensive medications when measuring refill adherence. Monitoring patients' refill adherence prior to healthcare visit may facilitate interpreting elevated BP.

Place, publisher, year, edition, pages
´PLoS, 2015
National Category
Social and Clinical Pharmacy
Identifiers
urn:nbn:se:liu:diva-121822 (URN)10.1371/journal.pone.0137451 (DOI)000361043100040 ()26359861 (PubMedID)
Available from: 2015-10-08 Created: 2015-10-08 Last updated: 2018-01-11
Zetterqvist, A., Aronsson, P., Hägg, S., Kjellgren, K., Reis, M., Tobin, G. & Booth, S. (2015). On the pedagogy of pharmacological communication: a study of final semester health science students. BMC Medical Education, 15
Open this publication in new window or tab >>On the pedagogy of pharmacological communication: a study of final semester health science students
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2015 (English)In: BMC Medical Education, ISSN 1472-6920, E-ISSN 1472-6920, Vol. 15Article in journal (Refereed) Published
Abstract [en]

Background: There is a need to improve design in educational programmes for the health sciences in general and in pharmacology specifically. The objective of this study was to investigate and problematize pharmacological communication in educational programmes for the health sciences. Methods: An interview study was carried out where final semester students from programmes for the medical, nursing and specialist nursing in primary health care professions were asked to discuss the pharmacological aspects of two written case descriptions of the kind they would meet in their everyday work. The study focused on the communication they envisaged taking place on the concerns the patients were voicing, in terms of two features: how communication would take place and what would be the content of the communication. A phenomenographic research approach was used. Results: The results are presented as outcome spaces, sets of categories that describe the variation of ways in which the students voiced their understanding of communication in the two case descriptions and showed the qualitatively distinct ways in which the features of communication were experienced. Conclusions: The results offer a base of understanding the students perspectives on communication that they will take with them into their professional lives. We indicate that there is room for strengthening communication skills in the field of pharmacology, integrating them into programmes of education, by more widely implementing a problem-based, a case-oriented or role-playing pedagogy where final year students work across specialisations and there is a deliberate effort to evoke and assess advanced conceptions and skills.

Place, publisher, year, edition, pages
BIOMED CENTRAL LTD, 2015
Keywords
Pharmacology; Education; Communication; Phenomenography; Case description
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-122654 (URN)10.1186/s12909-015-0467-2 (DOI)000363449600003 ()26502921 (PubMedID)
Note

Funding Agencies|Department of Pedagogical; County Council Ostergotland [LIO-198671]; Mellon Foundation at the Faculty of Humanities, University of the Witwatersrand, South Africa

Available from: 2015-11-16 Created: 2015-11-13 Last updated: 2017-12-01
Khedidja, H., Hakkarainen, K. M., Gyllensten, H., Jönsson, A. K., Petzold, M. & Hägg, S. (2015). Potentially inappropriate prescribing and adverse drug reactions in the elderly: a population-based study. European Journal of Clinical Pharmacology, 71(12), 1525-1533
Open this publication in new window or tab >>Potentially inappropriate prescribing and adverse drug reactions in the elderly: a population-based study
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2015 (English)In: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 71, no 12, p. 1525-1533Article in journal (Refereed) Published
Abstract [en]

Purpose

Potentially inappropriate prescriptions (PIPs) criteria are widely used for evaluating the quality of prescribing in elderly. However, there is limited evidence on their association with adverse drug reactions (ADRs) across healthcare settings. The study aimed to determine the prevalence of PIPs, defined by the Screening Tool of Older Persons’ potentially inappropriate Prescriptions (STOPP) criteria, in the Swedish elderly general population and to investigate the association between PIPs and occurrence of ADRs.

Method

Persons ≥65 years old were identified from a random sample of 5025 adults drawn from the Swedish Total Population Register. A retrospective cohort study was conducted among 813 elderly with healthcare encounters in primary and specialised healthcare settings during a 3-month period in 2008. PIPs were identified from the Swedish Prescribed Drug Register, medical records and health administrative data. ADRs were independently identified by expert reviewers in a stepwise manner using the Howard criteria. Multivariable logistic regression examined the association between PIPs and ADRs.

Results

Overall, 374 (46.0 %) persons had ≥1 PIPs and 159 (19.5 %) experienced ≥1 ADRs during the study period. In total, 29.8 % of all ADRs was considered caused by PIPs. Persons prescribed with PIPs had more than twofold increased odds of experiencing ADRs (OR 2.47; 95 % CI 1.65–3.69). PIPs were considered the cause of 60 % of ADRs affecting the vascular system, 50 % of ADRs affecting the nervous system and 62.5 % of ADRs resulting in falls.

Conclusion

PIPs are common among the Swedish elderly and are associated with increased odds of experiencing ADRs. Thus, interventions to decrease PIPs may contribute to preventing ADRs, in particular ADRs associated with nervous and vascular disorders and falls.

Place, publisher, year, edition, pages
Springer, 2015
Keywords
Inappropriate prescribing – Elderly – Adverse drug reactions – Retrospective study – Medical records – Registries
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:liu:diva-121823 (URN)10.1007/s00228-015-1950-8 (DOI)000365179600013 ()26407684 (PubMedID)
Available from: 2015-10-08 Created: 2015-10-08 Last updated: 2017-12-01Bibliographically approved
Karlsson, S. A., Jacobsson, I., Danell Boman, M., Hakkarainen, K. M., Lövborg, H., Hägg, S. & Jönsson, A. K. (2015). The impact of a changed legislation on reporting of adverse drug reactions in Sweden, with focus on nurses reporting. European Journal of Clinical Pharmacology, 71(5), 631-636
Open this publication in new window or tab >>The impact of a changed legislation on reporting of adverse drug reactions in Sweden, with focus on nurses reporting
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2015 (English)In: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 71, no 5, p. 631-636Article in journal (Refereed) Published
Abstract [en]

In March 2007, a legislative amendment was issued in Sweden compelling nurses to report all suspected adverse drug reactions (ADRs) to the national pharmacovigilance system. The aims of this study were to describe the status of ADR reporting, before and after the implementation of the legislative changes, and to describe the general characteristics of suspected ADRs reported by nurses. The Swedish pharmacovigilance system during the study period constituted six regional centres responsible for the handling of all spontaneous ADR reports within their region. In this study, we identified all individual ADR reports from 2005 and 2010, analysed in depth the ADR reports from two regional centres and collated information about the reporter and the nature of the reported ADR. From the two regional centres, a total of 898 and 1074 reports were submitted in 2005 and 2010 respectively. Nurses submitted 31 % (275 reports) of the reports in 2005 and 24 % (260 reports) in 2010. Nurses reporting of serious ADRs was 3 % (seven reports) in 2005 and 7 % (17 reports) in 2010 with reporting of unlabelled ADRs at 4 % (11 reports) in 2005 and 17 % (45 reports) in 2010. Most of the serious and/or unlabelled reactions were related to vaccine administration (14 reports in 2005 and 36 reports in 2010). The overall ADR reporting by nurses did not appear to increase after the change in reporting legislation. The proportion of serious and/or unlabelled ADRs reported by nurses did however appear to increase during the same period. Taken together, our data suggests that further pro-active measures should be considered in order to involve nurses in the reporting of suspected ADRs.

Place, publisher, year, edition, pages
Springer Verlag (Germany), 2015
Keywords
Adverse drug reaction; Spontaneous reporting; Pharmacovigilance; Nurses
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-118037 (URN)10.1007/s00228-015-1839-6 (DOI)000353059900013 ()25845655 (PubMedID)
Available from: 2015-05-21 Created: 2015-05-20 Last updated: 2017-12-04
Aronsson, P., Booth, S., Hägg, S., Kjellgren, K., Zetterqvist, A., Tobin, G. & Reis, M. (2015). The understanding of core pharmacological concepts among health care students in their final semester. BMC Medical Education, 15(1), Article ID 235.
Open this publication in new window or tab >>The understanding of core pharmacological concepts among health care students in their final semester
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2015 (English)In: BMC Medical Education, ISSN 1472-6920, E-ISSN 1472-6920, Vol. 15, no 1, article id 235Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
BioMed Central, 2015
National Category
Nursing
Identifiers
urn:nbn:se:liu:diva-123977 (URN)10.1186/s12909-015-0522-z (DOI)000367434000001 ()26715297 (PubMedID)
Funder
Östergötland County Council, LIO-198671
Note

Also funded by Sahlgrenska Academy, (V 2011/437)

Available from: 2016-01-15 Created: 2016-01-15 Last updated: 2017-11-30Bibliographically approved
Adolfsson, P. I., Bloth, B., Hägg, S. & Svensson, S. P. (2015). Zinc Induces a Bell-shaped Proliferative Dose-response Effect in Cultured Smooth Muscle Cells From Benign Prostatic Hyperplasia.. Urology, 85(3), 704.e15-704.e19
Open this publication in new window or tab >>Zinc Induces a Bell-shaped Proliferative Dose-response Effect in Cultured Smooth Muscle Cells From Benign Prostatic Hyperplasia.
2015 (English)In: Urology, ISSN 0090-4295, E-ISSN 1527-9995, Vol. 85, no 3, p. 704.e15-704.e19Article in journal (Refereed) Published
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.

National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-115751 (URN)10.1016/j.urology.2014.11.026 (DOI)000351942400059 ()25733304 (PubMedID)
Available from: 2015-03-18 Created: 2015-03-18 Last updated: 2018-01-11
Hägg, S. (2014). Combined Citalopram and Ramipril treatment - Hyponatraemia. WHO Pharmaceuticals Newsletter, 3(2), 13-16
Open this publication in new window or tab >>Combined Citalopram and Ramipril treatment - Hyponatraemia
2014 (English)In: WHO Pharmaceuticals Newsletter, Vol. 3, no 2, p. 13-16Article in journal (Other academic) Published
Place, publisher, year, edition, pages
World Health Organization, 2014
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-116531 (URN)
Available from: 2015-03-27 Created: 2015-03-27 Last updated: 2017-10-17
Hägg, S. (2014). Combined Ibuprofen and Metamizole treatment - Acute renal failure. WHO Pharmaceuticals Newsletter, 3(2), 10-13
Open this publication in new window or tab >>Combined Ibuprofen and Metamizole treatment - Acute renal failure
2014 (English)In: WHO Pharmaceuticals Newsletter, Vol. 3, no 2, p. 10-13Article in journal (Other academic) Published
Place, publisher, year, edition, pages
World Health Organization, 2014
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-116500 (URN)
Available from: 2015-03-27 Created: 2015-03-27 Last updated: 2017-10-17
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