Publications by authors named "Leif Jorgensen"

32 Publications

Treatment Patterns, Socioeconomic Status and Clinical Burden in Mild COPD: A Swedish Real-World, Retrospective Cohort Study, the ARCTIC Study.

Int J Chron Obstruct Pulmon Dis 2022 21;17:1409-1421. Epub 2022 Jun 21.

Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden.

Background: Patients with mild chronic obstructive pulmonary disease (COPD) account for more than half of the total COPD population but are often undiagnosed and sparsely studied. This real-world, longitudinal study compared the socioeconomic burden, clinical characteristics and treatment patterns in patients with mild COPD and age- and gender-matched controls.

Patients And Methods: Our population included mild COPD patients (forced expiratory volume in one second ≥80% of predicted value) and reference controls from 52 Swedish primary care centres over 15 years (2000-2014). We linked electronic medical record (EMR) data to Sweden's National Health Registries. The outcomes analyzed were socioeconomic status including annual income from work, presence of comorbidities and the use of medications.

Results: 844 patients with mild COPD were included in this study and matched with 844 reference controls. Compared with the reference controls, mild COPD patients had a significantly lower annual income from work (mean difference, men: 12,559€ and women: 7143€) and were significantly less likely to be married or employed. The presence of comorbidities, including cardiovascular disease, anxiety and depression (only women) was significantly higher in mild COPD patients. The use of medications, such as proton pump inhibitors, antidepressants, central painkillers and sleep medications, was significantly higher in the mild COPD group.

Conclusion: Mild COPD presents a considerable socioeconomic and clinical burden compared with reference controls The findings suggest that COPD constitutes a condition that influences health status even in mild disease clearly demanding an increased need for early detection and treatment.
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http://dx.doi.org/10.2147/COPD.S364932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9233559PMC
June 2022

The Impact of Exacerbation Frequency on Clinical and Economic Outcomes in Swedish COPD Patients: The ARCTIC Study.

Int J Chron Obstruct Pulmon Dis 2021;16:701-713. Epub 2021 Mar 18.

IQVIA Solutions, Real World Evidence Solutions, Copenhagen, Denmark.

Purpose: The aim of this study was to assess the association between exacerbation frequency and clinical and economic outcomes in patients with COPD.

Patients And Methods: Electronic medical record data linked to National Health Registries were collected from COPD patients at 52 Swedish primary care centers (2000-2014). The outcomes analyzed were exacerbation rate, mortality, COPD treatments, lung function and healthcare costs during the follow-up period. Based on the exacerbation rate two years before index date, the patients were initially classified into three groups, either 0, 1 or ≥2 exacerbations per year. After the index date, the classification into exacerbation groups was updated each year based on the exacerbation rate during the last year of follow-up. A sensitivity analysis was conducted excluding patients with asthma diagnosis from the analysis.

Results: In total 18,586 COPD patients were analyzed. A majority of the patients (60-70%) who either have had no exacerbation or frequent exacerbations (≥2/year) during the pre-index period remained in their group (ie, with 0 or ≥2 annual exacerbations) during up to 11 years of follow-up. Compared with having no exacerbation, mortality was higher in patients having 1 (HR; 2.06 [1.93-2.20]) and ≥2 (4.58 [4.33-4.84]) exacerbations at any time during the follow-up. Lung function decline was more rapid in patients with frequent exacerbations and there was an almost linear relationship between exacerbations frequency and mortality. Total healthcare costs were higher in the frequent exacerbation group (≥2/year) than in patients with no or one exacerbation annually (p<0.0001 for both). The results did not differ from the main analysis after exclusion of patients with a concurrent asthma diagnosis.

Conclusion: In addition to faster lung function decline and increased mortality, frequent exacerbations in COPD patients imply a significant economic burden.
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http://dx.doi.org/10.2147/COPD.S297943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987259PMC
June 2021

Inhaled corticosteroids and the risk of type 2 diabetes among Swedish COPD patients.

NPJ Prim Care Respir Med 2020 10 20;30(1):47. Epub 2020 Oct 20.

Integrative Toxicology, The National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

This study reports the association of ICS use and the risk of type 2 diabetes mellitus (T2DM) in Swedish patients with COPD using data from real-world, primary care settings. A total of 7078 patients with COPD were included in this analysis and the 5-year cumulative incidence rate per 100,000 person years was 1506.9. The yearly incidence rate per 100,000 person years ranged from 850 to 1919. Use of ICS especially at a high dose in patients with COPD was related to an increased risk of T2DM.
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http://dx.doi.org/10.1038/s41533-020-00207-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576803PMC
October 2020

Osteoporosis and fracture risk associated with inhaled corticosteroid use among Swedish COPD patients: the ARCTIC study.

Eur Respir J 2021 02 17;57(2). Epub 2021 Feb 17.

Intergrative Toxicology, National Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.

The effect of inhaled corticosteroids (ICS) on the risk of osteoporosis and fracture in patients with chronic obstructive pulmonary disease (COPD) remains uncertain. The aim of this study was to assess this risk in patients with COPD.Electronic medical record data linked to National Health Registries were collected from COPD patients and matched reference controls at 52 Swedish primary care centres from 2000 to 2014. The outcomes analysed were the effect of ICS on all fractures, fractures typically related to osteoporosis, recorded osteoporosis diagnosis, prescriptions of drugs for osteoporosis and a combined measure of any osteoporosis-related event. The COPD patients were stratified by the level of ICS exposure.A total of 9651 patients with COPD and 59 454 matched reference controls were analysed. During the follow-up, 19.9% of COPD patients had at least one osteoporosis-related event compared with 12.9% of reference controls (p<0.0001). Multivariate analysis in the COPD population demonstrated a dose-effect relationship, with high-dose ICS being significantly associated with any osteoporosis-related event (risk ratio 1.52 (95% CI 1.24-1.62)), while the corresponding estimate for low-dose ICS was 1.27 (95% CI 1.13-1.56) compared with COPD patients not using ICS. A similar dose-related adverse effect was found for all four of the specific osteoporosis-related events: all fractures, fractures typically related to osteoporosis, prescriptions of drugs for osteoporosis and diagnosis of osteoporosis.We conclude that patients with COPD have a greater risk of bone fractures and osteoporosis, and high-dose ICS use increased this risk further.
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http://dx.doi.org/10.1183/13993003.00515-2020DOI Listing
February 2021

Natural language processing and machine learning to enable automatic extraction and classification of patients' smoking status from electronic medical records.

Ups J Med Sci 2020 Nov 22;125(4):316-324. Epub 2020 Jul 22.

Department of Learning, Informatics, Management and Ethics, Karolinska Institutet, Stockholm, Sweden.

Background: The electronic medical record (EMR) offers unique possibilities for clinical research, but some important patient attributes are not readily available due to its unstructured properties. We applied text mining using machine learning to enable automatic classification of unstructured information on smoking status from Swedish EMR data.

Methods: Data on patients' smoking status from EMRs were used to develop 32 different predictive models that were trained using Weka, changing sentence frequency, classifier type, tokenization, and attribute selection in a database of 85,000 classified sentences. The models were evaluated using F-score and accuracy based on out-of-sample test data including 8500 sentences. The error weight matrix was used to select the best model, assigning a weight to each type of misclassification and applying it to the model confusion matrices. The best performing model was then compared to a rule-based method.

Results: The best performing model was based on the Support Vector Machine (SVM) Sequential Minimal Optimization (SMO) classifier using a combination of unigrams and bigrams as tokens. Sentence frequency and attributes selection did not improve model performance. SMO achieved 98.14% accuracy and 0.981 F-score versus 79.32% and 0.756 for the rule-based model.

Conclusion: A model using machine-learning algorithms to automatically classify patients' smoking status was successfully developed. Such algorithms may enable automatic assessment of smoking status and other unstructured data directly from EMRs without manual classification of complete case notes.
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http://dx.doi.org/10.1080/03009734.2020.1792010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594865PMC
November 2020

Gender differences among Swedish COPD patients: results from the ARCTIC, a real-world retrospective cohort study.

NPJ Prim Care Respir Med 2019 12 10;29(1):45. Epub 2019 Dec 10.

Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden.

The present study aimed to generate real-world evidence regarding gender differences among chronic obstructive pulmonary disease (COPD) patients, especially as regards the diagnosis and outcomes in order to identify areas for improvement and management and optimize the associated healthcare resource allocation. ARCTIC is a large, real-world, retrospective cohort study conducted in Swedish COPD patients and a matched reference population from 52 primary care centers in 2000-2014. The incidence of COPD, prevalence of asthma and other comorbidities, risk of exacerbations, mortality rate, COPD drug prescriptions, and healthcare resource utilization were analyzed. In total, 17,479 patients with COPD were included in the study. During the study period, COPD was more frequent among women (53.8%) and women with COPD experienced more exacerbations vs. men (6.66 vs. 4.66). However, the overall mortality rate was higher in men compared with women (45% vs. 38%), but no difference for mortality due to COPD was seen between genders over the study period. Women seemed to have a greater susceptibility to asthma, fractures, osteoporosis, rheumatoid arthritis, rhinitis, depression, and anxiety, but appeared less likely to have diabetes, kidney diseases, and cardiovascular diseases. Furthermore, women had a greater risk of COPD-related hospitalization and were likely to receive a significantly higher number of COPD drug prescriptions compared with men. These results support the need to reduce disease burden among women with COPD and highlight the role of healthcare professionals in primary care who should consider all these parameters in order to properly diagnose and treat women with COPD.
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http://dx.doi.org/10.1038/s41533-019-0157-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904454PMC
December 2019

A registry-based study evaluating overall survival and treatment duration in Swedish patients with metastatic castration-resistant prostate cancer treated with enzalutamide.

Scand J Urol 2019 Oct 6;53(5):312-318. Epub 2019 Sep 6.

Department of Urology, Skåne University Hospital, Malmö, Sweden.

This retrospective, single-centre, non-interventional, registry-based study evaluated patients with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide in daily clinical practice at Skåne University Hospital, Malmö, Sweden. Registry data were reviewed for patients treated with enzalutamide pre- or post-chemotherapy initiated between December 2013 and June 2017. The primary endpoint was overall survival (OS) in post-chemotherapy patients. Secondary endpoints were enzalutamide treatment duration in the pre- and post-chemotherapy setting. This study was approved by the Lund regional Ethics Review Board (Dnr:2017/716) and is registered with ClinicalTrials.gov (NCT03328364). A total of 102 pre-chemotherapy and 98 post-chemotherapy patients were included. Median age was higher in the pre- than in the post-chemotherapy group (77 vs 72 years, respectively). Median OS in post-chemotherapy patients from initiation of enzalutamide until death from any cause was 14.3 months [95% confidence interval (CI) = 11.00-18.20]. Median treatment duration was 13.8 months (95% CI = 11.4-20.2) and 7.6 months (95% CI = 6.3-10.2) for pre- and post-chemotherapy patients, respectively. Enzalutamide can be used to effectively treat mCRPC patients in daily clinical settings, despite the patients being older and less healthy than those enrolled in the previous randomised, clinical registration studies.
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http://dx.doi.org/10.1080/21681805.2019.1657494DOI Listing
October 2019

Impact of COPD diagnosis timing on clinical and economic outcomes: the ARCTIC observational cohort study.

Int J Chron Obstruct Pulmon Dis 2019 13;14:995-1008. Epub 2019 May 13.

Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden.

Assess the clinical and economic consequences associated with an early versus late diagnosis in patients with COPD. In a retrospective, observational cohort study, electronic medical record data (2000-2014) were collected from Swedish primary care patients with COPD. COPD indicators (pneumonia, other respiratory diseases, oral corticosteroids, antibiotics for respiratory infections, prescribed drugs for respiratory symptoms, lung function measurement) registered prior to diagnosis were applied to categorize patients into those receiving early (2 or less indicators) or late diagnosis (3 or more indicators registered >90 days preceding a COPD diagnosis). Outcome measures included annual rate of and time to first exacerbation, mortality risk, prevalence of comorbidities and health care utilization. More patients with late diagnosis (n=8827) than with early diagnosis (n=3870) had a recent comorbid diagnosis of asthma (22.0% vs 3.9%; <0.0001). Compared with early diagnosis, patients with late diagnosis had a higher exacerbation rate (hazard ratio [HR] 1.89, 95% confidence interval [CI]: 1.83-1.96; <0.0001) and shorter time to first exacerbation (HR 1.61, 95% CI: 1.54-1.69; <0.0001). Mortality was not different between groups overall but higher for late versus early diagnosis, after excluding patients with past asthma diagnosis (HR 1.10, 95% CI: 1.02-1.18; =0.0095). Late diagnosis was also associated with higher direct costs than early diagnosis. Late COPD diagnosis is associated with higher exacerbation rate and increased comorbidities and costs compared with early diagnosis. The study highlights the need for accurate diagnosis of COPD in primary care in order to reduce exacerbations and the economic burden of COPD.
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http://dx.doi.org/10.2147/COPD.S195382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6526023PMC
January 2020

Real-world retrospective cohort study ARCTIC shows burden of comorbidities in Swedish COPD versus non-COPD patients.

NPJ Prim Care Respir Med 2018 09 10;28(1):33. Epub 2018 Sep 10.

Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden.

This study aimed to generate real-world evidence to assess the burden of comorbidities in COPD patients, to effectively manage these patients and optimize the associated healthcare resource allocation. ARCTIC is a large, real-world, retrospective cohort study conducted in Swedish COPD patients using electronic medical record data collected between 2000 and 2014. These patients were studied for prevalence of various comorbidities and for association of these comorbidities with exacerbations, mortality, and healthcare costs compared with an age-, sex-, and comorbidities-matched non-COPD reference population. A total of 17,479 patients with COPD were compared with 84,514 non-COPD reference population. A significantly higher prevalence of various comorbidities was observed in COPD patients 2 years post-diagnosis vs. reference population, with the highest percentage increase observed for cardiovascular diseases (81.8% vs. 30.7%). Among the selected comorbidities, lung cancer was relatively more prevalent in COPD patients vs. reference population (relative risk, RR = 5.97, p < 0.0001). Ischemic heart disease, hypertension, depression, anxiety, sleep disorders, osteoporosis, osteoarthritis, and asthma caused increased mortality rates in COPD patients. Comorbidities that were observed to be significantly associated with increased number of severe exacerbations in COPD patients included heart failure, ischemic heart disease, depression/anxiety, sleep disorders, osteoporosis, lung cancer, and stroke. The cumulative healthcare costs associated with comorbidities over 2 years after the index date were observed to be significantly higher in COPD patients (€27,692) vs. reference population (€5141) (p < 0.0001). The data support the need for patient-centered treatment strategies and targeted healthcare resource allocation to reduce the humanistic and economic burden associated with COPD comorbidities.
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http://dx.doi.org/10.1038/s41533-018-0101-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6131165PMC
September 2018

 Identifying the associated risks of pneumonia in COPD patients: ARCTIC an observational study.

Respir Res 2018 Sep 10;19(1):172. Epub 2018 Sep 10.

Karolinska Institutet, Solna, Sweden.

Background: Inhaled corticosteroids (ICS) are associated with an increased risk of pneumonia in patients with chronic obstructive pulmonary disease (COPD). Other factors such as severity of airflow limitation and concurrent asthma may further raise the possibility of developing pneumonia. This study assessed the risk of pneumonia associated with ICS in patients with COPD.

Methods: Electronic Medical Record data linked to National Health Registries were collected from COPD patients and matched reference controls in 52 Swedish primary care centers (2000-2014). Levels of ICS treatment (high, low, no ICS) and associated comorbidities were assessed. Patients were categorized by airflow limitation severity.

Results: A total of 6623 patients with COPD and 48,566 controls were analyzed. Patients with COPD had a more than 4-fold increase in pneumonia versus reference controls (hazard ratio [HR] 4.76, 95% confidence interval [CI]: 4.48-5.06). ICS use increased the risk of pneumonia by 20-30% in patients with COPD with forced expiratory volume in 1 s ≥ 50% versus patients not using ICS. Asthma was an independent risk factor for pneumonia in the COPD population. Multivariate analysis identified independent predictors of pneumonia in the overall population. The highest risk of pneumonia was associated with high dose ICS (HR 1.41, 95% CI: 1.23-1.62).

Conclusions: Patients with COPD have a greater risk of pneumonia versus reference controls; ICS use and concurrent asthma increased the risk of pneumonia further.
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http://dx.doi.org/10.1186/s12931-018-0868-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6131919PMC
September 2018

Economic burden of COPD in a Swedish cohort: the ARCTIC study.

Int J Chron Obstruct Pulmon Dis 2018 11;13:275-285. Epub 2018 Jan 11.

Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala.

Background: We assessed direct and indirect costs associated with COPD in Sweden and examined how these costs vary across time, age, and disease stage in a cohort of patients with COPD and matched controls in a real-world, primary care (PC) setting.

Patients And Methods: Data from electronic medical records linked to the mandatory national health registers were collected for COPD patients and a matched reference population in 52 PC centers from 2000 to 2014. Direct health care costs (drug, outpatient or inpatient, PC, both COPD related and not COPD related) and indirect health care costs (loss of income, absenteeism, loss of productivity) were assessed.

Results: A total of 17,479 patients with COPD and 84,514 reference controls were analyzed. During 2013, direct costs were considerably higher among the COPD patient population (€13,179) versus the reference population (€2,716), largely due to hospital nights unrelated to COPD. Direct costs increased with increasing disease severity and increasing age and were driven by higher respiratory drug costs and non-COPD-related hospital nights. Indirect costs (~€28,000 per patient) were the largest economic burden in COPD patients of working age during 2013.

Conclusion: As non-COPD-related hospital nights represent the largest direct cost, management of comorbidities in COPD would offer clinical benefits and relieve the financial burden of disease.
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http://dx.doi.org/10.2147/COPD.S149633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5769573PMC
September 2018

Epidemiology of cutaneous melanoma in Sweden-Stage-specific survival and rate of recurrence.

Int J Cancer 2016 Dec 22;139(12):2722-2729. Epub 2016 Sep 22.

Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, Solna, Sweden 171 76.

Cutaneous malignant melanoma (CMM) incidence is increasing globally, making a thorough understanding of the disease and its outcomes essential for optimizing care even more urgent. In this population-based, retrospective study, we investigated stage-specific survival and recurrence/progression rates of CMM among patients diagnosed in Stockholm County Council during 2005-2012, before the wide introduction of targeted therapy. A total of 3,554 CMM patients from the Stockholm Melanoma Register were included. Information on comorbidities, progression, death, and treatments was obtained from nationwide registers and hospital electronic medical records. Unadjusted 5-year survival varied from 91.4% for stage I to 24.6% for stage IV patients. Stage, age and gender were predictors of survival, with gender an independent predictor of survival for stages IA and IIA. 74.6% of patients remained recurrence/progression-free during follow-up, with 5-year recurrence/progression-free survival rates varying from 85.3% to 12.9% among stages I and IV patients, respectively. In addition to stage, male gender, and age, circulatory system comorbidities increased the risk for recurrence/progression. No statistically significant differences in progression rate for operated and non-operated patients could be detected, possibly due to high rate (98.9%) of surgery. Our estimates of survival and recurrence rates are consistent with historical and global expectations and can serve as a baseline to gauge population-level improvements with use of novel melanoma treatments.
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http://dx.doi.org/10.1002/ijc.30407DOI Listing
December 2016

Clinical Effectiveness of Liraglutide vs Sitagliptin on Glycemic Control and Body Weight in Patients with Type 2 Diabetes: A Retrospective Assessment in Sweden.

Diabetes Ther 2016 Jun 23;7(2):321-33. Epub 2016 May 23.

Department of Caring Sciences and Family Medicine, Uppsala University, Uppsala, Sweden.

Introduction: The aim of the present study was to use real-world data from Swedish primary-care and national registries to understand clinical outcomes in patients with Type 2 diabetes (T2D) treated with liraglutide in clinical practice, and to compare with data from those treated with sitagliptin.

Methods: This was a non-interventional, retrospective study conducted between February 2014 and September 2014 using T2D patient data from Swedish primary-care centers and national healthcare registries. The primary objective was to assess the effectiveness of liraglutide in control of glycemia and body weight in clinical practice (stage 1). The secondary objective was to compare the clinical effectiveness of liraglutide with sitagliptin on glycemic control and body weight in clinical practice in a propensity-score-matched population (stage 2).

Results: In stage 1 (n = 402), 39.4% of patients treated with liraglutide achieved ≥1.0% (10.9 mmol/mol) reduction in glycated hemoglobin (HbA1c) after 180 days of treatment and 54.9% achieved the target HbA1c of <7.0% (53.0 mmol/mol). Moreover, compared with baseline, 22.5% of patients treated with liraglutide achieved both ≥1.0% reduction in HbA1c and ≥3.0% reduction in body weight. In stage 2, a significantly greater proportion of patients receiving liraglutide (n = 180) than sitagliptin (n = 208) achieved ≥1.0% reduction in HbA1c [52.9% vs 33.5%, respectively (P = 0.0002)]. Mean body-weight loss was also significantly greater in patients receiving liraglutide vs sitagliptin [-3.5 vs -1.3 kg, respectively (P < 0.0001)].

Conclusion: This study provides real-world evidence from Sweden corroborating previous clinical trials that demonstrate greater efficacy of liraglutide over sitagliptin on glycemic control and body-weight reduction in patients with T2D.

Funding: Novo Nordisk A/S.

Trial Registration: ClinicalTrials.gov identifier NCT02077946.
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http://dx.doi.org/10.1007/s13300-016-0173-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4900983PMC
June 2016

Combination of budesonide/formoterol on demand improves asthma control by reducing exercise-induced bronchoconstriction.

Thorax 2014 Feb 3;69(2):130-6. Epub 2013 Oct 3.

Division of Respiratory Medicine and Allergy, Department of Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, , Stockholm, Sweden.

Background: In mild asthma exercise-induced bronchoconstriction (EIB) is usually treated with inhaled short-acting β2 agonists (SABAs) on demand.

Objective: The hypothesis was that a combination of budesonide and formoterol on demand diminishes EIB equally to regular inhalation of budesonide and is more effective than terbutaline inhaled on demand.

Methods: Sixty-six patients with asthma (>12 years of age) with verified EIB were randomised to terbutaline (0.5 mg) on demand, regular budesonide (400 μg) and terbutaline (0.5 mg) on demand, or a combination of budesonide (200 μg)  + formoterol (6 μg) on demand in a 6-week, double-blind, parallel-group study (ClinicalTrials.gov identifier: NCT00989833). The patients were instructed to perform three to four working sessions per week. The main outcome was EIB 24 h after the last dosing of study medication.

Results: After 6 weeks of treatment with regular budesonide or budesonide+formoterol on demand the maximum post-exercise forced expiratory volume in 1 s fall, 24 h after the last medication, was 6.6% (mean; 95% CI -10.3 to -3.0) and 5.4% (-8.9 to -1.8) smaller, respectively. This effect was superior to inhalation of terbutaline on demand (+1.5%; -2.1 to +5.1). The total budesonide dose was approximately 2.5 times lower in the budesonide+formoterol group than in the regular budesonide group. The need for extra medication was similar in the three groups.

Conclusions: The combination of budesonide and formoterol on demand improves asthma control by reducing EIB in the same order of magnitude as regular budesonide treatment despite a substantially lower total steroid dose. Both these treatments were superior to terbutaline on demand, which did not alter the bronchial response to exercise. The results question the recommendation of prescribing SABAs as the only treatment for EIB in mild asthma.
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http://dx.doi.org/10.1136/thoraxjnl-2013-203557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3913208PMC
February 2014

Use of quetiapine XR and quetiapine IR in clinical practice for hospitalized patients with schizophrenia: a retrospective study.

Ther Adv Psychopharmacol 2012 Dec;2(6):217-26

Sahlgrenska University Hospital, Lillhagsparken 3, Hisings-Backa, SE42250, Gothenburg, Sweden.

Quetiapine fumarate, a first-line treatment for schizophrenia, exists in two formulations: extended release (XR) and immediate release (IR). This naturalistic, noninterventional study evaluated use of quetiapine XR/IR among in-patients with schizophrenia [ClinicalTrials.gov identifier: NCT01214135]. Data were collected from medical records. Categorical and numerical outcomes were compared using χ(2) and t tests. Of 178 enrolled patients, 66% and 34% used quetiapine XR and IR respectively. Based on mean daily dose, XR was used as antipsychotic medication in 64% of patients compared with 40% of patients on IR (dose ≥ 400 mg/day; p = 0.002) and in higher doses than IR (494 versus 345 mg/day; p = 0.001; calculated averages). Schizophrenia was more commonly reported as reason for use of XR than IR (20% versus 0%; p = 0.0003). Patients with comorbid substance abuse or somatic disease were more likely to receive XR (p = 0.003; p = 0.03). Treatment cessation due to nonadherence was less common in patients on XR (3.4% versus 12%; p = 0.03). Polypharmacy was seen in 98% of patients. Quetiapine XR/IR usage varies in hospitalized patients with schizophrenia. XR is more often used in antipsychotic dosage; IR is more commonly used at lower doses as add-on therapy. Both quetiapine XR and IR have their place in clinical practice and provide treatment choice in schizophrenia.
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http://dx.doi.org/10.1177/2045125312453935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3736955PMC
December 2012

Extended-release quetiapine fumarate (quetiapine XR) monotherapy and quetiapine XR or lithium as add-on to antidepressants in patients with treatment-resistant major depressive disorder.

J Affect Disord 2013 Oct 27;151(1):209-19. Epub 2013 Jun 27.

Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, D-01307 Dresden, Germany.

Background: Patients with treatment-resistant major depressive disorder (MDD) remain a common clinical challenge.

Methods: This 6-week, randomised, open-label, rater-blinded trial evaluated once-daily extended-release quetiapine fumarate (quetiapine XR; 300 mg/day) as add-on to ongoing antidepressant and quetiapine XR monotherapy (300 mg/day) compared with add-on lithium (0.6-1.2 mmol/L) in patients with treatment-resistant MDD. Primary efficacy measure: change in Montgomery Åsberg Depression Rating Scale (MADRS) total score from randomisation to week 6 with a pre-specified non-inferiority limit of 3 points on the MADRS.

Results: At week 6, both add-on quetiapine XR (n=231) and quetiapine XR monotherapy (n=228) were non-inferior to add-on lithium (n=229); least squares means (LSM) differences (97.5% CI) in MADRS total score changes were -2.32 (-4.6, -0.05) and -0.97 (-3.24, 1.31), respectively. LSM MADRS total score change was numerically greater at day 4 for both quetiapine XR groups (add-on and monotherapy; p<0.01) compared with add-on lithium. At week 6, the differences between groups for the secondary endpoints of MADRS response (≥ 50% reduction in total score), MADRS remission (total score ≤ 10, add-on quetiapine XR only) and Clinical Global Impressions ('much'/'very much' improved) were numerically similar. Overall tolerability was consistent with the known profiles of both treatments.

Limitations: Limitations included the open-label study design (although MADRS and laboratory measurements were performed by treatment-blinded raters) and relatively short study duration with no assessments in the continuation phase.

Conclusions: Add-on quetiapine XR (300 mg/day) and quetiapine XR monotherapy (300 mg/day) are non-inferior to add-on lithium in the management of patients with treatment-resistant MDD.
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http://dx.doi.org/10.1016/j.jad.2013.05.079DOI Listing
October 2013

Pneumonia and pneumonia related mortality in patients with COPD treated with fixed combinations of inhaled corticosteroid and long acting β2 agonist: observational matched cohort study (PATHOS).

BMJ 2013 May 29;346:f3306. Epub 2013 May 29.

Department of Medical Sciences, Respiratory Medicine, Uppsala University, Uppsala, Sweden.

Objective: To investigate the occurrence of pneumonia and pneumonia related events in patients with chronic obstructive pulmonary disease (COPD) treated with two different fixed combinations of inhaled corticosteroid/long acting β2 agonist.

Design: Observational retrospective pairwise cohort study matched (1:1) for propensity score.

Setting: Primary care medical records data linked to Swedish hospital, drug, and cause of death registry data for years 1999-2009.

Participants: Patients with COPD diagnosed by a physician and prescriptions of either budesonide/formoterol or fluticasone/salmeterol.

Main Outcome Measures: Yearly pneumonia event rates, admission to hospital related to pneumonia, and mortality.

Results: 9893 patients were eligible for matching (2738 in the fluticasone/salmeterol group; 7155 in the budesonide/formoterol group), yielding two matched cohorts of 2734 patients each. In these patients, 2115 (39%) had at least one recorded episode of pneumonia during the study period, with 2746 episodes recorded during 19,170 patient years of follow up. Compared with budesonide/formoterol, rate of pneumonia and admission to hospital were higher in patients treated with fluticasone/salmeterol: rate ratio 1.73 (95% confidence interval 1.57 to 1.90; P<0.001) and 1.74 (1.56 to 1.94; P<0.001), respectively. The pneumonia event rate per 100 patient years for fluticasone/salmeterol versus budesonide/formoterol was 11.0 (10.4 to 11.8) versus 6.4 (6.0 to 6.9) and the rate of admission to hospital was 7.4 (6.9 to 8.0) versus 4.3 (3.9 to 4.6). The mean duration of admissions related to pneumonia was similar for both groups, but mortality related to pneumonia was higher in the fluticasone/salmeterol group (97 deaths) than in the budesonide/formoterol group (52 deaths) (hazard ratio 1.76, 1.22 to 2.53; P=0.003). All cause mortality did not differ between the treatments (1.08, 0.93 to 1.14; P=0.59).

Conclusions: There is an intra-class difference between fixed combinations of inhaled corticosteroid/long acting β2 agonist with regard to the risk of pneumonia and pneumonia related events in the treatment of patients with COPD.

Trial Registration: Clinical Trials.gov NCT01146392.
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http://dx.doi.org/10.1136/bmj.f3306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3666306PMC
May 2013

A retrospective study of clinical usage of quetiapine XR and quetiapine IR in outpatients with schizophrenia in Denmark.

Hum Psychopharmacol 2012 Sep;27(5):492-8

OPUS Klinikken, Risskov, Denmark.

Objectives: The atypical antipsychotic quetiapine is a first-line treatment for schizophrenia. This non-interventional study (NCT01212575) evaluated the clinical use of its two formulations, extended release (XR) and immediate release (IR), in outpatients with schizophrenia spectrum disorder.

Methods: Patients who had received at least one dose of quetiapine XR and/or IR were included. A dosage ≥400 mg/day was defined as antipsychotic. Medical records data were collected retrospectively.

Results: Of 186 enrolled patients, 99 (53%) and 87 (47%) received quetiapine XR and IR, respectively. Use in antipsychotic dosage was seen for 89% XR versus 63% IR patients (mean daily dose ≥400 mg/day; p < 0.0001). 75% XR and 53% IR patients used dosages ≥600 mg/day (p = 0.0019). Quetiapine XR was used at higher mean daily dosages than IR (748 vs 566 mg/day; p = 0.006). Forty-three patients (23%) used both formulations concomitantly; 55 patients (30%) used either XR or IR. Quetiapine IR was used as-needed in 44 patients (23%); one patient used XR as-needed.

Conclusions: Quetiapine XR was used more often in higher (antipsychotic) dosages; quetiapine IR more frequently on an as-needed administration basis. Concomitant use was seen. These findings probably reflect the different profiles of XR/IR and advocate the need for both formulations to offer treatment choice.
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http://dx.doi.org/10.1002/hup.2254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494380PMC
September 2012

A clinical-pathological review of hidradenitis suppurativa: using immunohistochemistry one disease becomes two.

APMIS 2012 Jun 11;120(6):433-40. Epub 2012 Apr 11.

Department of Pathology, University Hospital Northern Norway, Tromsø, Norway.

We report the results of a re-examination of a series of 57 biopsies from 50 patients with the clinical diagnosis of hidradenitis suppurativa, submitted to the Department of Pathology at the University Hospital of Northern Norway, Tromsø, Norway. The biopsy material came from hospitals and physicians all over northern Norway in the years 2000-2007. All tissue material was resectioned and stained with the immunohistochemical reagent, cytokeratin (AE1/AE3/PKC26), and that made it possible to divide the material into two different disease categories: (1) 36 biopsies from 30 cases had tissue inflammation after rupture of keratin-rich epidermal cysts, which we call 'horny cell inflammation', followed by extensive cutaneous thrombi and infarcts, and (2) 21 biopsies from 20 cases had 'apocrinitis' defined here as an inflammatory destruction of apocrine skin glands, and partly of close eccrine glands. The two disease populations differed: the patients with a diagnosis of horny cell inflammation were younger and mainly women; those with a diagnosis of apocrinitis, as defined here, were older, men and women equally represented.
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http://dx.doi.org/10.1111/j.1600-0463.2011.02771.xDOI Listing
June 2012

Improved prediction of COPD in at-risk patients using lung function pre-screening in primary care: a real-life study and cost-effectiveness analysis.

Prim Care Respir J 2012 Jun;21(2):159-66

Sahlgrenska School of Public Health and Community Medicine, Section of Primary Health Care, University of Gothenburg, Sweden.

Background: The importance of identifying chronic obstructive pulmonary disease (COPD) at an early stage is recognised. Improved and easily accessible identification of individuals at risk of COPD in primary care is needed to select patients for spirometry more accurately.

Aims: To explore whether use of a mini-spirometer can predict a diagnosis of COPD in patients at risk of COPD in primary care, and to assess its cost-effectiveness in detecting patients with COPD.

Methods: Primary care patients aged 45-85 years with a smoking history of >15 pack-years were selected. Data were collected on the Clinical COPD Questionnaire (CCQ), Medical Research Council (MRC) dyspnoea scale and smoking habits. Lung function (forced expiratory volume in 1 and 6 s; FEV1 and FEV6, respectively) was measured by mini-spirometer (copd-6), followed by diagnostic standard spirometry (COPD diagnosis post-bronchodilation ratio of FEV1 to forced vital capacity (FVC) <0.7). Time consumed was recorded. Univariate logistic regression and receiver operating characteristic (ROC) curves were used.

Results: A total of 305 patients (57% females) of mean (SD) age 61.2 (8.4) years, mean (SD) total CCQ 1.0 (0.8) and mean (SD) MRC 0.8 (0.8) were recruited from 21 centres. COPD was diagnosed in 77 patients (25.2%) by standard diagnostic spirometry. Using the copd-6 device, mean (SD) FEV1/FEV6 was 68 (8)% in patients with COPD and 78 (10)% in patients without COPD. Sensitivity and specificity at a FEV1/FEV6 cut-off of 73% were 79.2% and 80.3%, respectively. The area under the ROC curve was 0.84. Screening with the copd-6 device significantly predicted COPD. Gender, CCQ, and MRC were not found to predict COPD.

Conclusions: Using the copd-6 as a pre-screening device, the rate of COPD diagnoses by standard diagnostic spirometry increased from 25.2% to 79.2%. Although the sensitivity and specificity of the copd-6 could be improved, it might be an important device for prescreening of COPD in primary care and may reduce the number of unnecessary spirometric tests performed.
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http://dx.doi.org/10.4104/pcrj.2011.00104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6548026PMC
June 2012

Burden of informal care giving to patients with psychoses: a descriptive and methodological study.

Int J Soc Psychiatry 2013 Mar 17;59(2):137-46. Epub 2011 Nov 17.

Department of Clinical Neurosciences, Stockholm Centre of Psychiatric Research, Karolinska Institutet, Stockholm, Sweden.

Background: There is a lack of studies of the size of burden associated with informal care giving in psychosis.

Aims: To evaluate the objective and subjective burden of informal care giving to patients with psychoses, and to compare a diary and recall method for assessments of objective burden.

Method: Patients and their informal caregivers were recruited from nine Swedish psychiatric outpatient centres. Subjective burden was assessed at inclusion using the CarerQoL and COPE index scales. The objective burden (time and money spent) was assessed by the caregivers daily using diaries over four weeks and by recall at the end of weeks 1 and 2.

Results: One-hundred and seven patients (53% females; mean age 43 ± 11) and 118 informal caregivers (67%; 58 ± 15 years) were recruited. Informal caregivers spent 22.5 hours/week and about 14% of their gross income on care-related activities. The time spent was underestimated by two to 20 hours when assessed by recall than by daily diary records. The most prominent aspects of the subjective burden were mental problems.

Conclusion: Despite a substantial amount of time and money spent on care giving, the informal caregivers perceived the mental aspects of burden as the most troublesome. The informal caregiver burden is considerable and should be taken into account when evaluating effects of health care provided to patients with psychoses.
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http://dx.doi.org/10.1177/0020764011427239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3652598PMC
March 2013

Effect of adding gefitinib to neoadjuvant chemotherapy in estrogen receptor negative early breast cancer in a randomized phase II trial.

Breast Cancer Res Treat 2011 Apr 15;126(2):463-70. Epub 2011 Jan 15.

Department of Oncology, Copenhagen University Hospital, Blegdamsvej 9, 2100, Copenhagen O, Denmark.

Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, has shown both anti-proliferative and anti-tumoral activity in breast cancer. This study was designed to determine the effect of adding gefitinib to neoadjuvant epirubicin and cyclophosphamide (EC) on tumor response rates. Women with unilateral, primary operable, estrogen receptor negative invasive breast cancer ≥ 2 cm were eligible for inclusion. Randomized patients were to receive four cycles of neoadjuvant EC plus 12 weeks of either gefitinib (250 mg daily) or placebo. Primary endpoint was pathologic complete response (pCR), and secondary endpoints were complete response (CR) and overall objective response (OR). 181 patients were randomized. A pCR was observed in 17% (12/71) of patients treated with gefitinib and in 12% (9/73) of patients treated with placebo (4.57% difference, 95% CI -7.19 to 6.33; P = 0.44). CR was observed in 10% of patients in both the gefitinib (7/71) and the placebo group (7/73) (0.27% difference, 95% CI -9.6 to 10.2; P = 0.96). There was no significant difference in OR (5.96%; 95% CI -9.9 to 21.9; P = 0.45) between the two groups. Post hoc subgroup analysis showed a significant difference in pCR between triple negative breast cancer (TNBC) and non-TNBC tumors (P = 0.03). More patients in the gefitinib arm had hematological toxicity (P = 0.15) and discontinued treatment (9/94 vs. 2/86) because of adverse events (AE). Tumor response rates were similar in the two groups. A significantly higher pCR rate was observed post hoc in TNBC versus non-TNBC independent of treatment. More patients in the gefitinib group discontinued treatment because of AE.
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http://dx.doi.org/10.1007/s10549-011-1352-2DOI Listing
April 2011

Obstruction of the lung capillaries by blood platelet aggregates and leucocytes in sudden infant death syndrome.

APMIS 2010 Dec 11;118(12):958-67. Epub 2010 Oct 11.

Department of Clinical Pathology, University Hospital Northern Norway, Tromsø, Norway.

Altogether 34 cases of sudden infant death were studied postmortem with particular emphasis on the pathological changes in the lungs. Light microscopy, including application of immunohistochemical methods, and transmission electron microscopy were used for the identification of blood platelets and white blood cell types in alveolar capillaries. The main findings were platelet aggregates and a varying number of neutrophil polymorphonuclear granulocytes in the lung capillaries, mixed with a smaller number of lymphocytes. The findings may be interpreted as an early sign of inflammation with capillary thrombosis, resulting in ischaemia, i.e. arrest of flow. In 21% of the cases, inflammatory cells had also expanded focally into alveolar spaces, creating the picture of localized areas of bronchopneumonia. An infant dying suddenly of a traumatic head injury served as a control. Neither platelets nor leucocytes were observed in the alveolar capillaries of this infant. In conclusion, in lungs from cases of sudden infant death syndrome, the alveolar capillaries are obstructed by platelet aggregates and leucocytes, interpreted as signs of an initial stage of lung inflammation with ischaemia.
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http://dx.doi.org/10.1111/j.1600-0463.2010.02651.xDOI Listing
December 2010

COPD health care in Sweden - A study in primary and secondary care.

Respir Med 2010 Mar 5;104(3):404-11. Epub 2009 Dec 5.

Department of Respiratory Medicine and Allergology, Lund University Hospital, SE-222 41 Lund, Sweden.

Objectives: To map out-patients with Chronic Obstructive Pulmonary Disease (COPD) with special reference to patients suffering from acute exacerbations, and to describe COPD health care structure and process in Swedish clinical practice in a real life setting.

Design: Retrospective, non-interventional, epidemiological survey.

Setting: 141 hospital based out patient clinics (OPC, n=30) and primary health care clinics (PC, n=111) were included in the structure evaluation.

Subjects: 1004 COPD diagnosed patients from 100 of the centres (OPC, n=26) participated in the process evaluation.

Methods: All Swedish OPC (n=40) and a random sample of 180 PC were asked to answer a questionnaire regarding COPD care. In addition, data from 10 randomly selected patients with a documented COPD disease were analysed from the centres.

Results: Spirometers were available at all OPCs and at 99% of the PCs. Spirometry had been performed in 52% of PC-patients and in 89% of OPC-patients during the last 2 years prior to the study. More severe patients, as judged by investigator and lung function data, were treated at OPCs than at PCs. Physiotherapists, occupational therapists and dieticians were available at >80% of centres. Exacerbation rate was higher at PCs without a specialized nurse, 2.2/year versus 0.9/year at centres with a specialized nurse.

Conclusions: Special attention to COPD, marked by a specialised nurse in primary care improves the quality, as assessed by a lower number of exacerbations. The structure of COPD care in Sweden for diagnosed individuals seems satisfactory, but could be improved mainly through higher availability and educational activities.
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http://dx.doi.org/10.1016/j.rmed.2009.10.007DOI Listing
March 2010

Platelet deposition in rabbit common carotid arteries promoted by arterial stenosisand spasm. A quantitative and morphological study.

APMIS 2008 Sep;116(9):801-10

Department of Pathology, McMaster University, Hamilton, Ontario, Canada.

Coronary arteriograhy in patients with ischemic heart disease often shows spasm of the coronary arteries. The question is whether spasm is a triggering factor for thrombosis in a stenotic artery. If so, what are the mechanisms for this? A stenosing teflon ring was applied to the right common carotid artery of anesthetized rabbits and 1-nor-epinephrine was dripped over the outer surface of both carotid arteries, causing spasm. In control animals an indifferent solution did not cause spasm. Nineteen rabbits were killed 30 min or 24 h after treatment. Microscopically, arteries with stenosis and spasm contained thrombi nearby the stenosis significantly more often than arteries in control animals. In another 14 rabbits, killed at 30 min, the number of platelets on the intimal surface away from the stenosis was quantified. In arteries with both stenosis and spasm the counts were significantly greater than in arteries with no treatment. The intimal surface in stenotic and spastic arteries showed assumed imprints of eddying flow and endothelial injury downstream and upstream of the stenosis. Spastic arteries showed increased folding of the internal elastic membrane, altered endothelial cells, and adhering platelets. Spasm in a rabbit artery with a preformed stenosis facilitates thrombosis probably by creating increased flow disturbances. Spasm may induce endothelial injury, causing adherence of platelets.
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http://dx.doi.org/10.1111/j.1600-0463.2008.01022.xDOI Listing
September 2008

Evidence at autopsy of spasm in the distal right coronary artery in persons with coronary heart disease dying suddenly.

Cardiovasc Pathol 2007 Nov-Dec;16(6):336-43. Epub 2007 Jul 25.

Department of Pathology, Institute of Medical Biology, University of Tromsø, Tromsø, Norway.

The aim of this study was to examine whether there are morphological signs in spasm in the coronary arteries at autopsy in persons with coronary artery disease dying suddenly. From a forensic autopsy service, 48 cases of sudden and unexpected deaths were selected: 24 cases with a preliminary diagnosis of coronary heart disease and 24 cases involving persons dying of noncoronary causes. A complete autopsy according to a preset protocol was followed with particular emphasis on the heart examination. The myocardium and the coronary arteries were sampled and examined without knowledge to which group the case belonged. The degree of folding of the internal elastic lamina of the proximal and distal parts of the coronary arteries was measured by picture analysis of elastin-stained cross sections of the arteries. The degree of folding was significantly greater in the distal section of the right coronary artery in cases of the coronary group compared to the folding in the same section in cases of the noncoronary group. In the proximal part of the right coronary artery and in the left coronary artery with its two branches, there were no differences in the folding of the internal elastic membrane between the groups. Our findings indicate that a spasmic contracture of an artery may be diagnosed postmortem. The spasm of the distal part of the right coronary artery may have caused focal ischemia in the central parts of the cardiac conducting system, precipitating a lethal arrhythmia.
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http://dx.doi.org/10.1016/j.carpath.2007.05.006DOI Listing
January 2008

Glomerular expression of large polyomavirus T antigen in binary tet-off regulated transgenic mice induces apoptosis, release of chromatin and initiates a lupus-like nephritis.

Mol Immunol 2008 Feb 24;45(3):728-39. Epub 2007 Aug 24.

Department of Medical Biochemistry, University Hospital of Northern Norway, N-9038 Tromsø, Norway.

Binary tetracycline-regulated polyomavirus large T antigen transgenic mice were generated to study immunological tolerance for nucleosomes. Expression of T antigen resulted in binding of the protein to chromatin, and released T antigen-nucleosome complexes from dying cells maintained anti-dsDNA and anti-nucleosome antibody-production by activating autoimmune nucleosome-specific B cells and CD4+ and CD8+ T antigen specific T cells. Glomerular T antigen expression was observed in these mice. Here, we demonstrate that this expression was linked to glomerular cell apoptosis, release of nucleosomes and association of nucleosomes with glomerulus basement membranes, detected as electron dense structures. Immune electron microscopy (IEM) revealed that these structures were glomerular targets for induced anti-dsDNA and anti-T antigen antibodies. Co-localization IEM demonstrated that in vivo-bound auto-antibodies co-localized with experimental monoclonal antibodies to dsDNA and to T antigen. A comparative analysis of glomeruli from nephritic (NZWxNZB)F1 and T antigen expressing transgenic mice revealed deposition of nucleosomes in glomerular capillary and mesangial matrix membranes and binding of anti-nucleosome antibodies in both mice strains. A controlled experimental model that may elucidate the initial events accounting for nucleosome-mediated nephritis has not been available. The transgenic mouse may be important to describe early immunological and cellular events accounting for the enigmatic lupus nephritis.
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http://dx.doi.org/10.1016/j.molimm.2007.07.010DOI Listing
February 2008

Histopathology of material captured by embolic protection device after percutaneous coronary interventions in atherosclerotic saphenous vein grafts.

EuroIntervention 2006 Aug;2(2):244-9

Department of Pathology, University Hospital of Northern Norway, Tromsø, Norway.

Aims: Different distal protections devices have been developed to prevent embolisation during percutaneous coronary intervention (PCI) in atherosclerotic saphenous vein grafts (SVG). The purpose of this descriptive study was to characterise the composition of material captured by embolic protection device from saphenous vein graft interventions by light and electron microscopy, to determine the age of the thrombotic component and to relate the pathological findings to the clinical condition, lesion characteristics and to the use of conventional or membrane covered self-expanding stents during the intervention.

Methods And Results: Forty consecutive patients treated with the FilterWire EX (Boston Scientific) during 42 SVG interventions were included. Plaque was found in 4.8%, thrombus in 16.7%, both plaque and thrombus in 69.0% of the filter bags, and 9.5% were empty. In 93% of the thrombus containing samples we found platelet aggregates that were formed within the last 10-15 minutes before fixation. This indicated platelet stimulation and aggregation during the PCI procedures. No relation was found between the composition of filter wire material and clinical condition, coronary lesion characteristics or the use of membrane covered self-expanding stents (Symbiot(R)).

Conclusion: The present study on material captured by embolic protein device after SVG interventions generated the hypothesis that these interventions were associated with acute platelet activation. In consequence, the use of glycoprotein IIb/IIIa inhibitors might be reconsidered in distal protected SVG interventions.
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August 2006

Nephritogenic lupus antibodies recognize glomerular basement membrane-associated chromatin fragments released from apoptotic intraglomerular cells.

Am J Pathol 2006 Jun;168(6):1779-92

Department of Biochemistry, Institute of Medical Biology, University of Tromsø, N-9037 Tromsø, Norway.

Antibodies to dsDNA represent a classification criterion for systemic lupus erythematosus. Subpopulations of these antibodies are involved in lupus nephritis. No known marker separates nephritogenic from non-nephritogenic anti-dsDNA antibodies. It is not clear whether specificity for glomerular target antigens or intrinsic antibody-affinity for dsDNA or nucleosomes is a critical parameter. Furthermore, it is still controversial whether glomerular target antigen(s) is constituted by nucleosomes or by non-nucleosomal glomerular structures. Previously, we have demonstrated that antibodies eluted from murine nephritic kidneys recognize nucleosomes, but not other glomerular antigens. In this study, we determined the structures that bind nephritogenic autoantibodies in vivo by transmission electron microscopy, immune electron microscopy, and colocalization immune electron microscopy using experimental antibodies to dsDNA, to histones and transcription factors, or to laminin. The data obtained are consistent and point at glomerular basement membrane-associated nucleosomes as target structures for the nephritogenic autoantibodies. Terminal deoxynucleotidyl-transferase-mediated dUTP nick end-labeling or caspase-3 assays demonstrate that lupus nephritis is linked to intraglomerular cell apoptosis. The data suggest that nucleosomes are released by apoptosis and associate with glomerulus basement membranes, which may then be targeted by pathogenic anti-nucleosome antibodies. Thus, apoptotic nucleosomes may represent both inducer and target structures for nephritogenic autoantibodies in systemic lupus erythematosus.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1606630PMC
http://dx.doi.org/10.2353/ajpath.2006.051329DOI Listing
June 2006
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