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  • 1. Burman, Matthew
    et al.
    Nikolayenskyy, Vladyslav
    Kontsevaya, Irina
    Molina-Moya, Barbara
    Rzhepishevska, Olena
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Guglielmetti, Lorenzo
    Tackling the MDR-TB epidemic in Ukraine: every little helps … and much more needed2017In: Journal of Public Health, ISSN 2198-1833, E-ISSN 1613-2238Article in journal (Refereed)
  • 2.
    Carlberg, Bo
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Samuelsson, Ola
    Lindholm, Lars H
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Finns möjligen hela bilden om atenolol hos Kent Forsén?2005In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 102, no 3, p. 151-152Article in journal (Other academic)
  • 3. Cisneros, Jose Antonio
    et al.
    Vandevoorde, Severine
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Ortega-Gutierrez, Silvia
    Paris, Clement
    Fowler, Christopher J
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Lopez-Rodriguez, Maria L
    Structure-activity relationship of a series of inhibitors of monoacylglycerol hydrolysis-comparison with effects upon fatty acid amide hydrolase2007In: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 50, no 20, p. 5012-5023Article in journal (Refereed)
    Abstract [en]

    A series of 32 heterocyclic analogues based on the structure of 2-arachidonoylglycerol (2-AG) were synthesized and tested for their ability to inhibit monoacylglycerol lipase and fatty acid an-tide hydrolase activities. The designed compounds feature a hydrophobic moiety and different heterocyclic subunits that mimic the glycerol fragment. This series has allowed us to carry out the first systematic structure activity relationship study on inhibition of 2-AG hydrolysis. The most promising compounds were oxiran-2-ylmethyl (5Z,8Z,l 11Z,14Z)-icosa-5,8,11,14-tetraenoate (1) and tetrahydro-2H-pyran-2-ylmethyl (5Z,8Z,11Z,14z)-icosa5,8,11,14-tetraenoate (5). They inhibited cytosolic 2-oleoylglycerol (2-OG) hydrolysis completely (IC50 values of 4.5 and 5.6 mu M, respectively). They also blocked, albeit less potently, 2-OG hydrolysis in membrane fractions (IC50 values of 19 and 26,mu M, respectively) and anandamide hydrolysis (IC50 values of 12 and 51 mu M, respectively). These compounds will be useful in delineating the importance of the cytosolic hydrolytic activity in the regulation of 2-AG levels and, hence, its potential as a target for drug development.

  • 4.
    Elobeid, Adila
    et al.
    Uppsala, Sweden.
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Cesarini, Kristina Giuliana
    Uppsala, Sweden.
    Alafuzoff, Irina
    Uppsala, Sweden.
    Correlations Between Mini-Mental State Examination Score, Cerebrospinal Fluid Biomarkers, and Pathology Observed in Brain Biopsies of Patients With Normal-Pressure Hydrocephalus2015In: Journal of Neuropathology and Experimental Neurology, ISSN 0022-3069, E-ISSN 1554-6578, Vol. 74, no 5, p. 470-479Article in journal (Refereed)
    Abstract [en]

    Alzheimer disease (AD)-related pathology was assessed in cortical biopsy samples of 111 patients with idiopathic normal-pressure hydrocephalus. Alzheimer disease hallmark lesions-beta-amyloid (A beta) and hyperphosphorylated tau (HPtau)-were observed in 47% of subjects, a percentage consistent with that for whole-brain assessment reported postmortem in unselected cohorts. Higher-immunostained area fraction of AD pathology corresponded with lower preoperative mini-mental state examination scores. Concomitant A beta and HPtau pathology, reminiscent of that observed in patients with AD, was observed in 22% of study subjects. There was a significant correlation between A beta-immunostained area fraction in tissue and A beta 42 (42-amino-acid form of A beta) in cerebrospinal fluid (CSF). Levels of A beta 42 were significantly lower in CSF in subjects with concomitant A beta and HPtau pathology compared with subjects lacking pathology. Moreover, a significant correlation between HPtau-immunostained area fraction and HPtau in CSF was noted. Both HPtau and total tau were significantly higher in CSF in subjects with concomitant A beta and HPtau pathology compared with subjects lacking pathology. The 42-amino-acid form of A beta (A beta 42) and HPtau in CSF were the most significant predictors of the presence of AD pathology in cortical biopsies. Long-term follow-up studies are warranted to assess whether all patients with idiopathic normal-pressure hydrocephalus with AD pathology progress to AD and to determine the pathologic substrate of idiopathic normal-pressure hydrocephalus.

  • 5.
    Glader, Eva-Lotta
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Sjölander, Maria
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Pharmacology.
    Eriksson, Marie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lundberg, Michael
    Persistent use of secondary preventive drugs declines rapidly during the first 2 years after stroke.2010In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 41, no 2, p. 397-401Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: To prevent new cardiovascular events after stroke, prescribed preventive drugs should be used continuously. This study measures persistent use of preventive drugs after stroke and identifies factors associated with persistence.

    METHODS: A 1-year cohort (21,077 survivors) from Riks-Stroke, the Swedish Stroke Register, was linked to the Swedish Prescribed Drug Register.

    RESULTS: The proportion of patients who were persistent users of drugs prescribed at discharge from hospital declined progressively over the first 2 years to reach 74.2% for antihypertensive drugs, 56.1% for statins, 63.7% for antiplatelet drugs, and 45.0% for warfarin. For most drugs, advanced age, comorbidity, good self-perceived health, absence of low mood, acute treatment in a stroke unit, and institutional living at follow-up were independently associated with persistent medication use.

    CONCLUSIONS: Persistent secondary prevention treatment declines rapidly during the first 2 years after stroke, particularly for statins and warfarin. Effective interventions to improve persistent secondary prevention after stroke need to be developed.

  • 6.
    Gustafsson, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Sjölander, Maria
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Gallego, Gisselle
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience. School of Medicine, The University of Notre Dame, Australia, Darlinghurst, Australia.
    Where there is no pharmacist: doctors' and nurses' expectations on the implementation of clinical pharmacy services in rural Sweden2017In: International Journal of Clinical Pharmacy, ISSN 2210-7703, E-ISSN 2210-7711, Vol. 39, no 1, p. 216-216, article id HP-PC011Article in journal (Refereed)
  • 7.
    Gustafsson, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Sjölander, Maria
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Pfister, Bettina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Jonsson, Jeanette
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Schneede, Jörn
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Lövheim, Hugo
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Pharmacist participation in hospital ward teams and hospital readmission rates among people with dementia: a randomized controlled trial2017In: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 7, no 73, p. 827-835Article in journal (Refereed)
    Abstract [en]

    Purpose: To assess whether comprehensive medication reviews conducted by clinical pharmacists as part of a healthcare team reduce drug-related hospital readmission rates among people with dementia or cognitive impairment.

    Methods: This randomized controlled trial was carried out between January 9, 2012, and December 2, 2014. Patients aged ≥65 years with dementia or cognitive impairment admitted to three wards at two hospitals located in Northern Sweden were included.

    Results: Of the 473 deemed eligible for participation, 230 were randomized to intervention and 230 to control group by block randomization. The primary outcome, risk of drug-related hospital readmissions, was assessed at 180 days of follow-up by intention-to-treat analysis.

    During the 180 days of follow-up, 18.9% (40/212) of patients in the intervention group and 23.0% (50/217) of those in the control group were readmitted for drug-related reasons (HR = 0.80, 95% CI = 0.53–1.21, p = 0.28, univariable Cox regression). Heart failure was significantly more common in the intervention group. After adjustment for heart failure as a potential confounder and an interaction term, multiple Cox regression analysis indicated that pharmacist participation significantly reduced the risk of drug-related readmissions (HR = 0.49, 95% CI = 0.27–0.90, p = 0.02). A post-hoc analysis showed a significantly reduced risk of 30-day readmissions due to drug-related problems in the total sample (without adjustment for heart failure).

    Conclusion: Participation of clinical pharmacists in healthcare team conducting comprehensive medication reviews did not significantly reduce the risk of drug-related readmissions in patients with dementia or cognitive impairment; however, post-hoc and subgroup analyses indicated significant effects favoring the intervention. More research is needed.

    Trial registration: Clinical trials NCT01504672.

  • 8.
    Huber, Daniel
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Henriksson, Robin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Jakobsson, Stina
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Mooe, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Nurse-led telephone-based follow-up of secondary prevention after acute coronary syndrome: One-year results from the randomized controlled NAILED-ACS trial2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 9, article id e0183963Article in journal (Refereed)
    Abstract [en]

    Background. Secondary prevention after acute coronary syndrome (ACS) could reduce morbidity and mortality, but guideline targets are seldom reached. We hypothesized that nurse-led telephone- based intervention would increase adherence.

    Methods. The NAILED ACS trial is a prospective, controlled, randomized trial. Patients admitted for ACS at Ostersund hospital, Sweden, were randomized to usual follow-up by a general practitioner or a nurse-led intervention. The intervention comprised telephone follow-up after 1 month and then yearly with lifestyle counselling and titration of medications until reaching target values for LDL-C (< 2.5 mmol/L) and blood pressure (BP; < 140/90 mmHg) or set targets were deemed unachievable. This is a 12-month exploratory analysis of the intervention.

    Results. A total of 768 patients (396 intervention, 372 control) completed the 12-month follow-up. After titration at the 1-month follow-up, mean LDL-C was 0.38 mmol/L (95% CI 0.28 to 0.48, p< 0.05), mean systolic BP 7 mmHg (95% CI 4.5 to 9.2, p< 0.05), and mean diastolic BP 4 mmHg (95% CI 2.4 to 4.1, p< 0.05) lower in the intervention group. Target values for LDL-C and systolic BP were met by 94.1% and 91.9% of intervention patients and 68.4% and 65.6% of controls (p< 0.05). At 12 months, mean LDL was 0.3 mmol/L (95% CI 0.1 to 0.4, p < 0.05), systolic BP 1.5 mmHg (95% CI -1.0 to 4.1, p = 0.24), and mean diastolic BP 2.1 mmHg (95% CI 0.6 to 3.6, p < 0.05) lower in the intervention group. Target values for LDL-C and systolic BP were met in 77.7% and 68.9% of intervention patients and 63.2% and 63.7% of controls (p< 0.05 and p = 0.125).

    Conclusion. Nurse-led telephone-based secondary prevention was significantly more efficient at improving LDL-C and diastolic BP levels than usual care. The effect of the intervention declined between 1 and 12 months. Further evaluation of the persistence to the intervention is needed.

  • 9.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Central venkateter och malign sjukdom: värdet av trombosprofylax ifrågasätts nu2005In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 102, no 26-27, p. 1984-1985Article in journal (Other academic)
    Abstract [sv]

    Kateterrelaterad trombos är vanligt hos patienter med malign sjukdom och central venkateter, och konsekvenserna för patienten kan bli betydande. Nyare studier ifrågasätter nyttan med lågdos warfarin och lågmolekylärt heparin som profylax mot kateterrelaterade tromboser hos dessa patienter.

  • 10.
    Kling, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Pharmacology.
    Danell-Boman, Marit
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Pharmacology.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Dahlqvist, Rune
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Pharmacology.
    Association between the use of serotonin receptor 2A-blocking antidepressants and joint disorders2009In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 61, no 10, p. 1322-1327Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: There are case reports about antidepressants causing arthritis and arthralgia, and the majority of these reports deal with atypical antidepressants, which are serotonin receptor 2A (5-HT(2A))-blocking substances. The aim of this study was to examine a possible association between joint disorders and the use of 5-HT(2A)-blocking atypical antidepressants.

    METHODS: We performed a retrospective study using reports of adverse drug reactions (ADRs) of 5-HT(2A)-blocking atypical antidepressant substances concerning joint disorders reported to the Swedish Adverse Drug Reactions Committee and the World Health Organization (WHO) Adverse Reactions Database during the period January 1, 1990 to December 31, 2006. The reports of joint disorders were related to sales figures measured as defined daily doses and to the total number of ADR reports.

    RESULTS: In the Swedish material, the 5-HT(2A) antagonists were 45 times more often reported to give joint ADRs when related to sales figures and compared with the selective serotonin reuptake inhibitors (SSRIs; P < 0.001). Joint disorders constituted 6.6% of the total number of reports of possible ADRs for the three 5-HT(2A)-blocking substances mianserin, mirtazapine, and nefazodone compared with 0.5% for the SSRIs (P < 0.001). In the WHO material, the joint disorders constituted 1.3% of all ADRs for the 5-HT(2A)-blocking antidepressants and 0.6% for the SSRIs (P < 0.001).

    CONCLUSION: In this study, joint disorders were considerably more frequently reported ADRs of 5-HT(2A)-blocking antidepressants than of other comparable drugs, suggesting a possible association between the use of 5-HT(2A)-blocking antidepressants and joint disorders.

  • 11.
    Kling, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Pharmacology.
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Mjörndal, Tom
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Pharmacology.
    Decreased density of serotonin 5-HT2A receptors in rheumatoid arthritis2006In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 65, no 6, p. 816-819Article in journal (Refereed)
    Abstract [en]

    Background: Animal studies have indicated that 5-HT2A receptors could play a role in arthritic diseases.                             

    Objective: To analyse the binding properties of 5-HT2A receptors in patients with rheumatoid arthritis.                             

    Methods: Using a radioactive binding assay, 43 patients with rheumatoid arthritis were compared with 49 sex and age matched controls for density and affinity (measured as Bmax and Kd) of 5-HT2A serotonin receptors. Genotyping, using polymerase chain reaction, was undertaken to exclude the possibility that differences in the genetic polymorphism T102C for the 5-HT2A receptor determine differences in receptor density.                             

    Results: Mean of Bmax of 5-HT2A receptors in rheumatoid patients was significantly lower than in controls, at 45.3 v 57.4 fmol/mg protein (p = 0.004), but there was no significant difference in Kd. The T102C receptor polymorphism genotypes showed a skewed distribution between the two groups. Even when adjusted for this, there was a significant difference in Bmax between the groups.                             

    Conclusions: The density of 5-HT2A serotonin receptors in patients with rheumatoid arthritis is markedly reduced. This could either reflect a difference involved in the susceptibility to the disease or be a secondary effect of the disease.                             

  • 12.
    Kling, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Pharmacology.
    Seddighzadeh, M
    Arlestig, Lisbeth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Alfredsson, L
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Padyukov, L
    Genetic variations in the serotonin 5-HT2A receptor gene (HTR2A) are associated with rheumatoid arthritis2008In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 67, no 8, p. 1111-1115Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To analyse the association between the genetic polymorphisms within the HTR2A gene for the serotonin receptor and rheumatoid arthritis (RA).

    METHODS: HTR2A gene polymorphisms were analysed in patients with RA and controls from two study populations using PCR based restriction endonuclease mapping or TaqMan allelic discrimination with more than 4000 individuals included in the current study.

    RESULTS: At the discovery stage we detected significant differences in frequency of rs6313 (T102C polymorphism) between the patients with RA and controls (p = 0.006). Following validation with an extended set of single nucleotide polymorphisms (SNPs) and number of DNA samples, a trend in associations in allelic model for SNPs rs6314, rs1328674, rs6313 and rs6311 (p = 0.006, 0.002, 0.006, 0.009) was seen, although it was lost after correction for multi-comparison for all but rs1328674 (empirical p value = 0.021). However, haplotype frequency analysis based on these four SNPs showed significantly low representation of TCTT combination in patients with RA in comparison with controls (3.6% and 5.6%, p<0.001 on chi(2) test, empirical p = 0.004 after 100 000 permutations) and a significantly higher frequency of CTCC combination in patients with RA in comparison with controls (3.6% and 2.2%, p = 0.002 on chi(2) test, empirical p = 0.022 after 100 000 permutations).

    CONCLUSIONS: In our study, genetic polymorphisms at the HTR2A gene are associated with susceptibility for RA, suggesting possible links between the serotonergic system and development of the disease.

  • 13. Langworth, Sven
    et al.
    Bodlund, Owe
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Ågren, Hans
    Efficacy and tolerability of reboxetine compared with citalopram: a double-blind study in patients with major depressive disorder2006In: Journal of Clinical Psychopharmacology, ISSN 0271-0749, E-ISSN 1533-712X, Vol. 26, no 2, p. 121-127Article in journal (Refereed)
    Abstract [en]

    The objective of this study was to compare efficacy and tolerability of the selective noradrenalin reuptake inhibitor reboxetine with the selective serotonin reuptake inhibitor citalopram, in the treatment of major depressive disorder (MDD). In total, 357 outpatients with MDD were randomized to treatment with reboxetine 8-10 mg or citalopram 20-40 mg per day during 24 weeks. Primary end-point was change from baseline in the Hamilton Depression Rating Scale (HAM-D, 21 items). Sexual function/dysfunction was measured by the Sexual Function scale (SF). Observed case analysis showed that both treatments yielded a gradual reduction of HAM-D scores: reboxetine with -21.4 and citalopram with -22.1 points (NS). LOCF analysis showed a greater reduction of the HAM-D scores with citaloprarn compared with reboxetine (- 19.6 vs. - 17.8; P = 0.034). The response rate was 90.3% for reboxetine and 92.7% for citalopram (NS). The most common side effect in the reboxetine group was dry mouth, and in the citalopram group sexual dysfunction. At week 24, anorgasmia was reported by 5.9% of the sexually active women in the reboxetine group vs 39% in the citalopram group. The dropout number was 91 in the reboxetine group, and 54 in the citaloprarn group. To summarize, both treatments gave a satisfactory antidepressant effect. The side effect profile differed between the groups, with a notably high prevalence of sexual dysfunctions in the citalopram group. The high number of dropouts in the reboxetine group, is considered as a result of the non-titration starting dose of 8 mg reboxetine per day, which gave a high incidence of early side-effects.

  • 14.
    Lennestål, Roland
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Pharmacology.
    Otterblad Olausson, Petra
    Källén, Bengt
    Maternal use of antihypertensive drugs in early pregnancy and delivery outcome, notably the presence of congenital heart defects in the infants2009In: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 65, no 6, p. 615-625Article in journal (Refereed)
    Abstract [en]

    Purpose To investigate the association between maternal use of antihypertensives in early pregnancy and delivery outcome, notably infant congenital malformations.

    Methods A cohort study of 1,418 women who had used antihypertensive drugs in early pregnancy but had no diabetes diagnosis were identified from the Swedish Medical Birth Register.

    Results There was an excess risk for placental abruption, caesarean section, delivery induction, and post-delivery hemorrhage in women taking hypertensives. Infants were more often than expected born preterm, were small for gestational age, and had an excess of various neonatal symptoms. Cardiovascular defects occurred with an adjusted odds ratio of 2.59 (95% CI 1.92-3.51). The results were similar when the woman had used ACE inhibitors or other antihypertensives, notably beta blockers. Stillbirth rate was increased (risk ratio 1.87, 95% CI 1.02-3.02), again without any clear drug specificity.

    Conclusions There seems to be little drug specificity in the association between maternal use of antihypertensives and an increased risk for infant cardiovascular defects.

  • 15. Miletic, Hrvoje
    et al.
    Niclou, Simone P
    Johansson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. NorLux Neuro-Oncology Laboratory, CRP-Santé, Luxembourg.
    Bjerkvig, Rolf
    Anti-VEGF therapies for malignant glioma: treatment effects and escape mechanisms2009In: Expert opinion on therapeutic targets, ISSN 1472-8222, E-ISSN 1744-7631, Vol. 13, no 4, p. 455-468Article, review/survey (Refereed)
    Abstract [en]

    Background: Glioblastoma multiforme (GBM) has a very poor prognosis and novel treatment strategies are urgently needed. GBM appears to be an optimal target for anti-angiogenic therapy as the tumour shows a high degree of endothelial cell proliferation and pro-angiogenic growth factor expression. Objective: To examine the role of angiogenic factors (particularly VEGF) in glioma and whether inhibition of these factors can be used as a treatment.

    Methods: A review of relevant literature.

    Results/conclusions: Anti-angiogenic therapy has fulfilled the proof of concept in glioma animal models. In glioma patients, the efficacy of anti-angiogenic mono-therapies initially has been disappointing. However recent clinical trials combining bevacizumab, an anti-VEGF antibody, with chemotherapy reported very encouraging response rates. Although randomized phase III clinical trials with anti-angiogenic molecules are not yet available for GBM patients, this treatment regimen is already applied off protocol in several clinical centers. It should be kept in mind though that tumours can develop escape mechanisms. In particular invasive cells, which migrate away from the highly vascularized tumour core, are not targeted by anti-angiogenic therapies. In our opinion, the future of anti-angiogenic therapy will rely on a combination strategy including chemotherapy and drugs that target invasive glioma cells.

  • 16.
    Peterson, Cecilia
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Gustafsson, Maria
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Characterization of drug-related problems and associated factors at a clinical pharmacist service-naïve hospital in northern Sweden2017In: Drugs - real world outcomes, ISSN 2199-1154, E-ISSN 2198-9788, Vol. 2, no 4, p. 97-107Article in journal (Refereed)
    Abstract [en]

    Background Polypharmacy and increased sensitivity to side effects cause adverse drug events, drug–drug interactions and medication errors in the elderly.

    Objective The objective of this study was to investigate the prevalence and type of drug-related problems and associated factors among patients admitted to a clinical pharmacist service-naïve medical ward in an inland hospital in northern Sweden.

    Methods During September–November 2015 and February–April 2016, clinical pharmacists working as part of a ward team on the medical ward conducted 103 medication reviews. Drug-related problems were identified and classified. Associated factors, drug classes and specific drugs involved were also investigated.

    Results The clinical pharmacists identified 133 drug-related problems in 66% [68/103] of the study population. The most common drug-related problems in this study were inappropriate drug use and interactions. Cardiovascular drugs and psychotropic drugs were most commonly involved. Drug-related problems were more frequently observed at higher age, increasing number of drugs prescribed and in patients with reduced renal function. In the multivariate analysis, only the number of prescribed drugs was still significant.

    Conclusion Drug-related problems were commonly observed among patients admitted to the medical ward. Medication reviews conducted by clinical pharmacists as part of a ward team resulted in several interventions to improve the patients’ drug treatment.

  • 17. Ringbäck Weitoft, G
    et al.
    Ericsson, Ö
    Löfroth, Emil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Centre for Epidemiology, Swedish National Board of Health and Welfare, 106 30, Stockholm, Sweden .
    Rosén, Måns
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. The Swedish Council on Technology Assessment in Health Care, Stockholm, Sweden .
    Equal access to treatment? Population-based follow-up of drugs dispensed to patients after acute myocardial infarction in Sweden.2008In: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 64, no 4, p. 417-424Article in journal (Refereed)
    Abstract [en]

    Background and Objective The establishment of national guidelines is one approach to creating equity in terms of access to care, and both internationally and in Sweden, guidelines have been developed for coronary heart disease. We have analysed drug treatment in Sweden according to national guidelines after acute myocardial infarction (AMI). The aim was to investigate whether there are differences between population groups according to sex, education, country of birth and diabetes.

    Methods Information was obtained from the Swedish Prescribed Drug Register on drugs dispensed between July and October 2005 for incident cases of AMI during the period 2003-2004 (n=28,168). Data on socio-economic and demographic conditions were included. Dispensed drugs after AMI were compared to the recommended drug treatment according to Swedish and European guidelines - acetylsalicylic acid (ASA), beta-blockers, lipid-lowering drugs and angiotensin-converting enzyme inhibitors (ACE inhibitors).

    Results We found that, in general, there were only small differences between the sexes and between educational groups. The greatest differences were found in comparisons between regions of birth. In particular, foreign-born patients resident in Sweden but originally from outside the EU25 countries used fewer drugs than Swedish-born patients. The OR (odds ratio) for ASA was 0.73 [95% confidence interval (CI) 0.63-0.85], for beta-blockers, 0.72 (0.63-0.83), for lipid-lowering drugs, 0.75 (0.65-0.86) and for ACE inhibitors, 0.76 (0.67-0.86).

    Conclusions In general, we found only slight differences - or none at all - between population groups in terms of drug treatment after AMI. Only among immigrants from outside the EU25 countries was there a tendency towards a lesser use of the recommended drugs according to the national guidelines.

  • 18. Salome, Nicolas
    et al.
    Haage, David
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Perrissoud, Daniel
    Moulin, Aline
    Demange, Luc
    Egecioglu, Emil
    Fehrentz, Jean-Alain
    Martinez, Jean
    Dickson, Suzanne L
    Anorexigenic and electrophysiological actions of novel ghrelin receptor (GHS-R1A) antagonists in rats2009In: European Journal of Pharmacology, ISSN 0014-2999, E-ISSN 1879-0712, Vol. 612, no 1-3, p. 167-173Article in journal (Refereed)
    Abstract [en]

    Here we provide the first pharmacological exploration of the impact of acute central nervous system exposure to three recently developed ghrelin receptor (GHS-R1A) ligands on food intake and on the electrical activity of the target cells for ghrelin in the hypothalamus. Central (i.c.v) injection of GHS-R1A antagonists to rats suppressed food intake induced by i.c.v ghrelin injection (1 mu g) in a dose-dependent manner with a total blockade at concentraions of 0.4 mu g and 8 mu g for JMV 3002 and JMV 2959 respectively. JMV 2810, a partial agonist, also suppressed ghrelin-induced food intake (range: 0.02-2 mu g). Moreover all three compounds reduced fasting-induced food intake in rats (i.e. the amount of food eaten during the first hour of food exposure after a 16 h fast). At the single cell level we also explored the effects of the compounds to suppress ghrelin (0.5 mu M)-induced changes in electrical activity of arcuate nucleus cells recorded extracellularly in a slice preparation. Preincubation followed by perfusion with the GHS-R1A ligands suppressed the responsiveness of arcuate cells to ghrelin. Thus, the recently developed GHS-R1A ligands (JMV 3002, 2959 and 2810) suppress ghrelin-induced and fasting-induced food intake at the level of the central nervous system. This appears to be mediated, at least in part, by a modulation of the activity of ghrelin-responsive arcuate nucleus cells. As the central ghrelin signalling system has emerged as an important pro-obesity target, it will be important to establish the efficacy of these GHS-R1A ligands to reduce fast mass in clincal studies.

  • 19. Singer, Andrew C.
    et al.
    Järhult, Josef D.
    Grabic, Roman
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Khan, Ghazanfar A.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Fedorova, Ganna
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Fick, Jerker
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Lindberg, Richard H.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Bowes, Michael J.
    Olsen, Björn
    Söderström, Hanna
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Compliance to Oseltamivir among two populations in Oxfordshire, United Kingdom affected by influenza A(H1N1)pdm09, November 2009: a waste water epidemiology study2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 4, article id e60221Article in journal (Refereed)
    Abstract [en]

    Antiviral provision remains the focus of many pandemic preparedness plans, however, there is considerable uncertainty regarding antiviral compliance rates. Here we employ a waste water epidemiology approach to estimate oseltamivir (Tamiflu®) compliance. Oseltamivir carboxylate (oseltamivir's active metabolite) was recovered from two waste water treatment plant (WWTP) catchments within the United Kingdom at the peak of the autumnal wave of the 2009 Influenza A (H1N1)pdm09 pandemic. Predictions of oseltamivir consumption from detected levels were compared with two sources of national government statistics to derive compliance rates. Scenario and sensitivity analysis indicated between 3-4 and 120-154 people were using oseltamivir during the study period in the two WWTP catchments and a compliance rate between 45-60%. With approximately half the collected antivirals going unused, there is a clear need to alter public health messages to improve compliance. We argue that a near real-time understanding of drug compliance at the scale of the waste water treatment plant (hundreds to millions of people) can potentially help public health messages become more timely, targeted, and demographically sensitive, while potentially leading to less mis- and un-used antiviral, less wastage and ultimately a more robust and efficacious pandemic preparedness plan.

  • 20.
    Sjölander, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Pharmacology.
    Use of secondary preventive drugs after stroke2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background Stroke is a serious condition that can have significant impact on an individual’s health and is a significant burden on public health and public finances. Secondary preventive drug treatment after stroke is important for decreasing the risk of recurrent strokes. Non-adherence to drug treatment hampers the treatment effect, especially in long-term preventive treatments. The aim of this thesis was to study the use of secondary preventive drugs after stroke among Swedish stroke patients in terms of inequalities in implementation in clinical practice and patient adherence to treatment over time.

    Methods Riks-Stroke, the Swedish stroke register, was used to sample stroke patients and as a source of information on background characteristics and medical and health care-related information including information on prescribed preventive drugs. The patients that were included had a stroke between 2004 and 2012. Individual patient data on prescriptions filled in Swedish pharmacies were retrieved from the Swedish Prescribed Drug Register and used to estimate patient adherence to drug treatment. Data on education, income, and country of birth were included from the LISA database at Statistics Sweden. A questionnaire survey was used to collect information about patients’ perceptions about stroke, beliefs about medicines, and self-reported adherence.

    Results Results showed that a larger proportion of men than women were prescribed statins and warfarin after stroke. There was also a social stratification in the prescribing of statins. Patients with higher income and a higher level of education were more likely to be prescribed a statin compared to patients with low income and low level of education. Statins were also more often prescribed to patients born in Nordic countries, Europe, or outside of Europe compared to patients born in Sweden. Primary non-adherence (not continuing treatment at all within 4 months of discharge from hospital) was low for preventive drug treatment after stroke. Data on filled prescriptions, however, indicated that the proportion of patients who continued to use the drugs declined during the first 2 years after stroke. For most drugs, refill adherence in drug treatment was associated with female sex, good self-rated health, and living in institutions and (for antihypertensive drugs and statins) having used the drug before the stroke. For statins and warfarin, a first-ever stroke was also associated with continuous drug use. Self-reported adherence 3 months after stroke also showed associations with patients’ personal beliefs about medicines; non-adherent patients scored higher on negative beliefs and lower on positive beliefs about medicines.

    Conclusion Inequalities between men and women and between different socioeconomic groups were found in the prescribing of secondary preventive drugs after stroke. Only a small proportion of Swedish stroke patients did not continue treatment after discharge from hospital, but the proportion of non-adherent patients increased over time. Poor adherence to preventive drug treatment after stroke is a public health problem, and improving adherence to drug treatment requires consideration of patients’ personal beliefs and perceptions about drugs.

  • 21.
    Sjölander, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Pharmacology.
    Eriksson, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Glader, Eva-Lotta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    The association between patients' beliefs about medicines and adherence to drug treatment after stroke: a cross-sectional questionnaire survey2013In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 3, no 9, article id e003551Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Adherence to preventive drug treatment is a clinical problem and we hypothesised that patients' beliefs about medicines and stroke are associated with adherence. The objective was to examine associations between beliefs of patients with stroke about stroke and drug treatment and their adherence to drug treatment.

    DESIGN: Cross-sectional questionnaire survey.

    SETTING: Patients with stroke from 25 Swedish hospitals were included.

    MEASUREMENTS: Questionnaires were sent to 989 patients to assess their perceptions about stroke (Brief Illness Perception Questionnaire, Brief IPQ), beliefs about medicines (Beliefs about Medicines Questionnaires, BMQ) and adherence to treatment (Medication Adherence Report Scale, MARS) 3 months after stroke onset. Only patients living at home were included in the analysis. The primary outcome was self-reported adherence as measured on MARS. MARS scores were dichotomised into adherent/non-adherent. Background and clinical data from the Swedish Stroke register were included.

    RESULTS: 811 patients were still living at home and 595 answered the questionnaire. Complete MARS data were available for 578 patients and 72 (12.5%) of these were classified as non-adherent. Non-adherent patients scored lower on positive beliefs as measured on BMQ-necessity (OR = 0.90, 95% CI 0.83 to 0.98) and BMQ-benefit (OR=0.77, 95% CI 0.68 to 0.87), and higher on negative beliefs as measured on BMQ-concern (OR=1.12, 95% CI 1.05 to 1.21), BMQ-overuse (OR=1.29, 95% CI 1.14 to 1.45), and BMQ-harm (OR=1.12, 95% CI 1.01 to 1.24). The Brief IPQ showed that non-adherent patients believed their current treatment to be less useful (p=0.001).

    CONCLUSIONS: This study showed associations between beliefs of Swedish patients with stroke about medicines and adherence. Positive beliefs were less common and negative more common among non-adherent. To improve adherence, patients' beliefs about medicines should be considered.

  • 22.
    Sjölander, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Gustafsson, Maria
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Gallego, Gisselle
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology. Univ Notre Dame Australia, Sch Med, 160 Oxford St, Darlinghurst, NSW 2010, Australia.
    Doctors' and nurses' perceptions of a ward-based pharmacist in rural northern Sweden2017In: International Journal of Clinical Pharmacy, ISSN 2210-7703, E-ISSN 2210-7711, Vol. 39, no 4, p. 953-959Article in journal (Refereed)
    Abstract [en]

    Background This project is part of the prospective quasi experimental proof-of-concept investigation of clinical pharmacist intervention study to reduce drug-related problems among people admitted to a ward in a rural hospital in northern Sweden. Objective To explore doctors' and nurses' perceptions and expectations of having a ward-based pharmacist providing clinical pharmacy services. Setting Medical ward in a rural hospital in northern Sweden. Method Eighteen face-to-face semi-structured interviews were conducted with a purposive sample of doctors and nurses working on the ward where the clinical pharmacy service was due to be implemented. Semi-structured interviews were digitally recorded, transcribed and analysed using thematic analysis. Main outcome measure Perceptions and expectations of nurses and doctors. Results Doctors and nurses had limited experience of working with pharmacists. Most had a vague idea of what pharmacists can contribute within a ward setting. Participants, mainly nurses, suggested inventory and drug distribution roles, but few were aware of the pharmacists' skills and clinical competence. Different views were expressed on whether the new clinical pharmacy service would have an impact on workload. However, most participants took a positive view of having a ward-based pharmacist. Conclusion This study provided an opportunity to explore doctors' and nurses' expectations of the role of clinical pharmacists before a clinical pharmacy service was implemented. To successfully implement a clinical pharmacy service, roles, clinical competence and responsibilities should be clearly described. Furthermore, it is important to focus on collaborative working relationships between doctors, nurses and pharmacists.

  • 23.
    Vinterflod, Charlotta
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Gustafsson, Maria
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Mattsson, Sofia
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Gallego, Gisselle
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience. School of Medicine, The University of Notre Dame Australia, Darlinghurst, Australia.
    Physicians' perspectives on clinical pharmacy services in Northern Sweden: a qualitative study2018In: BMC Health Services Research, ISSN 1472-6963, E-ISSN 1472-6963, Vol. 18, article id 35Article in journal (Refereed)
    Abstract [en]

    Background: In many countries, clinical pharmacists are part of health care teams that work to optimize drug therapy and ensure patient safety. However, in Sweden, clinical pharmacy services (CPSs) in hospital settings have not been widely implemented and regional differences exist in the uptake of these services. Physicians' attitudes toward CPSs and collaborating with clinical pharmacists may facilitate or hinder the implementation and expansion of the CPSs and the role of the clinical pharmacist in hospital wards. The aim of this study was to explore physicians' perceptions regarding CPSs performed at hospital wards in Northern Sweden.

    Methods: Face-to-face semi-structured interviews were conducted with a purposive sample of nine physicians who had previously worked with clinical pharmacists between November 2014 and January 2015. Interviews were digitally recorded, transcribed and analysed using a constant comparison method.

    Results: Different themes emerged regarding physicians' views of clinical pharmacy; two main interlinked themes were service factors and pharmacist factors. The service was valued and described in a positive way by all physicians. It was seen as an opportunity for them to learn more about pharmacological treatment and also an opportunity to discuss patient medication treatment in detail. Physicians considered that CPSs could improve patient outcomes and they valued continuity and the ability to build a trusting relationship with the pharmacists over time. However, there was a lack of awareness of the CPSs. All physicians knew that one of the pharmacist's roles is to conduct medication reviews, but most of them were only able to describe a few elements of what this service encompasses. Pharmacists were described as "drug experts" and their recommendations were perceived as clinically relevant. Physicians wanted CPSs to continue and to be implemented in other wards.

    Conclusions: All physicians were positive regarding CPSs and were satisfied with the collaboration with the clinical pharmacists. These findings are important for further implementation and expansion of CPSs, particularly in Northern Sweden.

  • 24.
    Wang, Ming-De
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Rahman, Mozibur
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Zhu, Di
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Protons inhibit Cl- conductance by direct or allosteric interaction with the GABA-binding site in the rat recombinant alpha(1)beta(2)gamma(2L) and alpha(1)beta(2) GABA(A) receptor2005In: European Journal of Pharmacology, ISSN 0014-2999, E-ISSN 1879-0712, Vol. 528, no 1-3, p. 1-6Article in journal (Refereed)
    Abstract [en]

    Functional roles of external pH on the Cl- conductance were examined on Xenopus oocytes expressing rat recombinant alpha(1)beta(2)gamma(2L) and alpha(1)beta(2) GABA(A) receptors. Acidic pH inhibited GABA-response in a reversible and concentration-dependent manner, significantly increasing the EC50 without appreciably changing the slope or maximal currents induced by GABA in the alpha(1)beta(2)gamma(2L) and alpha(1)beta(2) receptors. In contrast, protonation did not influence the pentobarbital-gated Currents in the alpha(1)beta(2)gamma(2L) receptors, suggesting that protons do not modulate channel activity by directly affecting the channel gating process. Protons competitively inhibited the bicuculline-induced antagonism on GABA in the alpha(1)beta(2)gamma(2L) receptors. The data support the hypothesis that protons inhibit GABA(A) receptor function by direct or allosteric interaction with the GABA-binding site.

  • 25.
    Xin, D. L.
    et al.
    Department of Surgery, University of Pennsylvania, USA.
    Hadrevi, Jenny
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Elliott, M. E.
    Department of Neurosurgery, Thomas Jefferson University, USA.
    Amin, M
    Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadephia, USA.
    Harris, M. Y.
    Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, USA.
    Barr-Gillespie, A
    College of Health Professions, Pacific University, USA.
    Barbe, M. F.
    Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, USA.
    Effectiveness of conservative interventions for sickness and pain behaviors induced by a high repetition high force upper extremity task2017In: BMC neuroscience (Online), ISSN 1471-2202, E-ISSN 1471-2202, Vol. 18, article id 36Article in journal (Refereed)
    Abstract [en]

    Background: Systemic inflammation is known to induce sickness behaviors, including decreased social interaction and pain. We have reported increased serum inflammatory cytokines in a rat model of repetitive strain injury (rats perform an upper extremity reaching task for prolonged periods). Here, we sought to determine if sickness behaviors are induced in this model and the effectiveness of conservative treatments.

    Methods: Experimental rats underwent initial training to learn a high force reaching task (10 min/day, 5 days/week for 6 weeks), with or without ibuprofen treatment (TRHF vs. TRHF + IBU rats). Subsets of trained animals went on to perform a high repetition high force (HRHF) task for 6 or 12 weeks (2 h/day, 3 days/week) without treatment, or received two secondary interventions: ibuprofen (HRHF + IBU) or a move to a lower demand low repetition low force task (HRHF-to-LRLF), beginning in task week 5. Mixed-effects models with repeated measures assays were used to assay duration of social interaction, aggression, forepaw withdrawal thresholds and reach performance abilities. One-way and two-way ANOVAs were used to assay tissue responses. Corrections for multiple comparisons were made.

    Results: TRHF + IBU rats did not develop behavioral declines or systemic increases in IL-1beta and IL-6, observed in untreated TRHF rats. Untreated HRHF rats showed social interaction declines, difficulties performing the operant task and forepaw mechanical allodynia. Untreated HRHF rats also had increased serum levels of several inflammatory cytokines and chemokines, neuroinflammatory responses (e.g., increased TNFalpha) in the brain, median nerve and spinal cord, and Substance P and neurokinin 1 immunoexpression in the spinal cord. HRHF + IBU and HRHF-to-LRLF rats showed improved social interaction and reduced inflammatory serum, nerve and brain changes. However, neither secondary treatment rescued HRHF-task induced forepaw allodynia, or completely attenuated task performance declines or spinal cord responses.

    Conclusions: These results suggest that inflammatory mechanisms induced by prolonged performance of high physical demand tasks mediate the development of social interaction declines and aggression. However, persistent spinal cord sensitization was associated with persistent behavioral indices of discomfort, despite use of conservative secondary interventions indicating the need for prevention or more effective interventions.

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