| 1. |
- Aidas, Kestutis, et al.
(författare)
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The Dalton quantum chemistry program system
- 2014
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Ingår i: WIREs Computational Molecular Science. - : Wiley. - 1759-0876 .- 1759-0884. ; 4:3, s. 269-284
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Tidskriftsartikel (refereegranskat)abstract
- Dalton is a powerful general-purpose program system for the study of molecular electronic structure at the Hartree-Fock, Kohn-Sham, multiconfigurational self-consistent-field, MOller-Plesset, configuration-interaction, and coupled-cluster levels of theory. Apart from the total energy, a wide variety of molecular properties may be calculated using these electronic-structure models. Molecular gradients and Hessians are available for geometry optimizations, molecular dynamics, and vibrational studies, whereas magnetic resonance and optical activity can be studied in a gauge-origin-invariant manner. Frequency-dependent molecular properties can be calculated using linear, quadratic, and cubic response theory. A large number of singlet and triplet perturbation operators are available for the study of one-, two-, and three-photon processes. Environmental effects may be included using various dielectric-medium and quantum-mechanics/molecular-mechanics models. Large molecules may be studied using linear-scaling and massively parallel algorithms. Dalton is distributed at no cost from for a number of UNIX platforms.
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| 2. |
- Bartels, Stefan, et al.
(författare)
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Total Hip Arthroplasty Leads to Better Results After Low-Energy Displaced Femoral Neck Fracture in Patients Aged 55 to 70 Years : A Randomized Controlled Multicenter Trial Comparing Internal Fixation and Total Hip Arthroplasty
- 2022
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Ingår i: Journal of Bone and Joint Surgery. - 0021-9355. ; 104:15, s. 1341-1351
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Tidskriftsartikel (refereegranskat)abstract
- Background:The optimal treatment of displaced femoral neck fractures in patients 55 to 70 years old remains controversial. The aim of the present study was to assess the effect of closed reduction and internal fixation with cannulated screws (IF) compared with total hip arthroplasty (THA) on hip pain and function, with use of data for outcome measures, complications, and reoperations.Methods:This multicenter randomized controlled trial included all patients 55 to 70 years old who presented with a low-energy displaced femoral neck fracture between December 2013 and December 2018. Patients were randomly allocated to undergo either IF or THA. The primary outcome was the Harris Hip Score (HHS) at 12 months postoperatively. Secondary outcomes were the HHS at 4 and 24 months postoperatively, Oxford Hip Score (OHS), Hip Disability and Osteoarthritis Outcome Score (HOOS), health-related quality of life (EQ-5D-3L [EuroQol 5 Dimensions 3 Levels] index score and EQ-VAS [visual analogue scale]), VAS for pain, and VAS for patient satisfaction at 4, 12, and 24 months postoperatively. Complications and reoperations were continuously monitored. The primary analyses were performed according to the intention-to-treat principle.Results:A total of 102 patients with a mean (± standard deviation) age of 63.7 ± 4.2 years were allocated to IF (n = 51) or THA (n = 51). The mean difference in the primary outcome, the HHS at 12 months postoperatively (5.3; 95% confidence interval, 0.9 to 9.7; p = 0.017), was below the predefined minimal clinically important difference of 10 points. However, patients who underwent THA had a significantly higher HHS at 4 and 12 months, better OHS at 4 and 12 months, and better HOOS at 4, 12, and 24 months postoperatively. Patients who underwent THA also reported better health-related quality of life at 4 months postoperatively and reported greater satisfaction and less pain at 4 and 12 months postoperatively. A total of 26 patients in the IF group (51%; 95% confidence interval, 37% to 65%) and 2 patients in the THA group (4%; 95% confidence interval, 0.5% to 13%) underwent a major reoperation.Conclusions:In this randomized controlled trial, we showed that patients between 55 and 70 years old who underwent THA for a low-energy displaced femoral neck fracture experienced better outcomes than those who underwent closed reduction and internal fixation.Level of Evidence:Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
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| 3. |
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| 4. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 5. |
- Ahadi, Aylin, et al.
(författare)
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Simulation of Nanoindentation Response of Empty and Filled Viral Capsids
- 2009
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Ingår i: DCE Technical Memorandum. - 1901-7278. ; 11
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Konferensbidrag (refereegranskat)abstract
- The nanoindentation response of empty and filled viral capsids is modelled using three dimensional finite element analysis. Simulation with two different geometries, spherical and icosahedral, are performed using the finite element code Abaqus. The capsids are modeled as non-linear Hookean elastic and both small and large deformation analysis is performed. Force-indentation curves for three different viral capsids are directly compared to experimental data and the Young’s modulus is determined by calibrating the force-indentation curve to data from atomic force microscopy (AFM) experiments. Predictions are made for two additional viral capsids. The results from the simulation showed a good agreement with AFM data, see [1].
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| 6. |
- Berthelsen, Ragna, et al.
(författare)
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Combining in vitro and in silico methods for better prediction of surfactant effects on the absorption of poorly water soluble drugs-a fenofibrate case example
- 2014
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 473:1-2, s. 356-365
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to develop a sensitive and discriminative in vitro-in silico model able to simulate the in vivo performance of three fenofibrate immediate release formulations containing different surfactants. In addition, the study was designed to investigate the effect of dissolution volume when predicting the oral bioavailability of the formulations. In vitro dissolution studies were carried out using the USP apparatus 2 or a mini paddle assembly, containing 1000 mL or 100 mL fasted state biorelevant medium, respectively. In silico simulations of small intestinal absorption were performed using the GI-Sim absorption model. All simulation runs were performed twice adopting either a total small intestinal volume of 533 mL or 105 mL, in order to examine the implication of free luminal water volumes for the in silico predictions. For the tested formulations, the use of a small biorelevant dissolution volume was critical for in vitro-in silico prediction of drug absorption. Good predictions, demonstrating rank order in vivo-in vitro-in silico correlations for C-max, were obtained with in silico predictions utilizing a 105 mL estimate for the human intestinal water content combined with solubility and dissolution data performed in a mini paddle apparatus with 100 mL fasted state simulated media.
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| 7. |
- Björck, Inger, et al.
(författare)
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Cereal grains for nutrition and health benefits: Overview of results from in vitro, animal and human studies in the HEALTHGRAIN project
- 2012
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Ingår i: Trends in Food Science & Technology. - : Elsevier BV. - 1879-3053 .- 0924-2244. ; 25:2, s. 87-100
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Tidskriftsartikel (refereegranskat)abstract
- Epidemiological studies have linked whole grain intake to the prevention of the metabolic syndrome, obesity and associated chronic diseases such as CVD and T2D. The Nutrition module within the HEALTHGRAIN project, included 10 partners and undertook in vitro, animal and humanin vivo studies with the overall aims of elucidating the components and mechanisms underlying the health benefits of cereal grains. This review summarises the major outcomes of these studies, including yet unpublished findings.
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| 8. |
- Bovinder Ylitalo, Erik, 1985-
(författare)
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Molecular heterogeneity of prostate cancer bone metastasis
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Castration-resistant prostate cancer (CRPC) develops after androgen deprivation therapy of advanced PC, often with metastatic growth in bone. Patients with metastatic CRPC have very poor prognosis. Growth of CRPC, in most but not all patients, seems to involve androgen receptor (AR) activity, despite castrate levels of serum testosterone. Multiple mechanisms behind AR activation in castrated patients have been described, such as AR amplification, AR mutations, expression of constitutively active AR variants, and intra-tumoral steroid synthesis. However, other mechanisms beside AR activation are also involved and CRPC patients with tumors circumventing the need for AR stimulation will probably not benefit from AR targeting therapies but will need alternative treatments.Available treatments for CRPC are chemotherapy, AR antagonists or inhibition of androgen-synthesis. Novel drugs are constantly under development and several new therapies has recently been approved for clinical use. These include, in addition to new AR targeting therapies also immunotherapy, osteoclast inhibitors and bone-targeting radiopharmaceuticals. Due to heterogeneous mechanisms behind CRPC and that newly developed therapies are based on different mechanisms of action, there are reasons to believe that CRPC patients show different therapy responses due to diverse molecular properties of individual tumors. Although there are promising prospects, no biomarkers are used today for patient stratification into different treatments. Another important aspect is that, when effective, any therapy will probably induce tumor responses that subsequently cause further molecular diversities and alternative paths for development of tumor relapse and castration-resistance. Such mechanisms are important to understand in order to develop new treatment strategies.In this thesis, global gene expression and methylation patterns were studied in bone metastases obtained from PC patients going through metastasis surgery for spinal cord compression. Gene expression patterns were analyzed by multivariate statistics and ontology analysis with the aim to identify subgroups of biological/pathological relevance. Interesting findings from array analysis were verified using qRT-PCR and immunohistochemical analysis. In addition, a xenograft mouse model was used to study the effects of abiraterone (steroidogenesis inhibitor) and cabazitaxel (taxane), and subsequently developed resistance mechanisms in the 22Rv1 PC cell line expressing high levels of AR-V7; a constitutively active AR splice variant associated with a poor prognosis and resistance to AR targeting therapies.In summary, results showed that the majority of CRPC bone metastases were AR-driven, defined from high levels of AR-regulated gene transcripts, while a smaller sub-group was non-AR-driven (paper I). AR-driven bone metastases had high metabolic activity in combination with downregulated immune responses while non-AR-driven cases had a more pronounced immune response (paper I) and higher bone cell activity (paper II). Paper III identified pronounced hypermethylation in primary prostate tumors probably causing a suppressed anti-tumor immune-response whereas metastases showed a different methylation pattern related to increased AR activity and patient outcome. In paper IV, 22Rv1 xenografts showed poor response to abiraterone and initially excellent response to cabazitaxel, but eventually resistance occurred probably due to an upregulation of the ABCB1 transporter protein. Anti-androgens partly reversed the resistance.In conclusion, we have identified molecular heterogeneities in clinical bone metastases associated with biological characteristics, which could perhaps be used both for stratifying patients into treatment modalities, and to aid in further development of effective therapies for CRPC.
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| 9. |
- C Kapetanovic, Meliha, et al.
(författare)
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Impact of anti-rheumatic treatment on immunogenicity of pandemic H1N1 influenza vaccine in patients with arthritis.
- 2014
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Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- An adjuvanted pandemic H1N1 influenza (pH1N1) vaccine (Pandemrix®) was reported as highly immunogenic resulting in seroconversion in 77 to 94% of adults after administration of a single dose. The aim of the study was to investigate the impact of different anti-rheumatic treatments on antibody response to pH1N1 vaccination in patients with rheumatoid arthritis (RA) and spondylarthropathy (SpA).
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| 10. |
- Chatzidionysiou, K, et al.
(författare)
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Effectiveness and survival-on-drug of certolizumab pegol in rheumatoid arthritis in clinical practice : results from the national Swedish register
- 2015
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Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 44:6, s. 431-437
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Evidence regarding the efficacy and effectiveness of certolizumab pegol (CZP) in rheumatoid arthritis (RA) patients who have failed to respond to treatment with a tumour necrosis factor inhibitor (TNFi) is limited. The aim of this study was to describe the effectiveness and survival-on-drug of CZP in a real-life setting, both in TNFi-naïve patients and in patients who had previously failed TNFis, and in relation to disease activity at baseline.METHOD: The national Swedish Rheumatology Quality Register (SRQ) was used to identify patients with RA starting treatment with CZP between 2009 and 2013. The effectiveness of treatment was assessed using the 28-joint Disease Activity Score (DAS28), the Health Assessment Questionnaire (HAQ), measures of remission, the European League Against Rheumatism (EULAR) response during 0-6 months from start of treatment, and survival-on-drug during the first 30 months.RESULTS: A total of 945 RA patients started treatment with CZP. Of these, 540 (57.1%) received CZP as the first biological treatment, 215 (23%) had failed one previous TNFi, and 190 (20%) had failed at least two TNFis. Overall, 71% achieved at least a EULAR moderate response and 38% had a EULAR good response at 6 months from baseline. TNFi-naïve patients achieved significantly better results and had better survival-on-drug compared to patients who had failed previous TNFis. Around 20% of patients who had not responded to two or more prior TNFis achieved EULAR good response to therapy and a similar percentage achieved remission. Patients who had high baseline disease activity had a higher risk of discontinuing treatment compared to those without high disease activity.CONCLUSIONS: In this real-life RA cohort, CZP was associated with significant clinical improvement. The effectiveness and survival-on-drug vary markedly depending on the line of treatment.
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| 11. |
- Chatzidionysiou, Katerina, et al.
(författare)
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Effectiveness of TNF inhibitor switch in RA: results from the national Swedish register
- 2014
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 74:5, s. 890-896
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Tidskriftsartikel (refereegranskat)abstract
- Background Switching to a second tumour necrosis factor inhibitor (TNFi) after discontinuation of a first in rheumatoid arthritis (RA) is a common strategy. The reason for the switch from the first TNFi could potentially influence the response to therapy. Data on direct comparisons between TNFi after switching are limited. Methods The national Swedish register was used. RA patients who switched to a second TNFi (infliximab, etanercept or adalimumab) after failure of a TNFi as first-ever biologic were identified. Effectiveness of treatment was compared across the three drugs according to the first TNFi used, the reason for discontinuing and the drug survival. Drug survival across TNFi used as second biologic was compared. Results Half of all patients starting infliximab, adalimumab or etanercept during the period 2005-2012 discontinued treatment for various reasons. Of these patients, a third switched within 2 months to a second TNFi (infliximab, etanercept or adalimumab). Around 35% of all patients achieved low disease activity or remission at 6 months. Regarding the switching strategy, best results were observed among patients who switched from infliximab to etanercept because of (secondary) inefficacy. Etanercept as second TNFi was associated with longer drug survival compared with infliximab. Conclusions Switching to a second TNFi after the failure of the first may lead to good clinical results. The inter-drug differences in drug survival on the second TNFi mirror those reported previously for the first TNFi, suggesting that these differences are not solely due to channelling bias.
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| 12. |
- Dolberg Anderson, Ulrik, et al.
(författare)
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Fetal hemoglobin and alpha(1)-microglobulin as first- and early second-trimester predictive biomarkers for preeclampsia
- 2011
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Ingår i: American Journal of Obstetrics and Gynecology. - : Elsevier BV. - 1097-6868 .- 0002-9378. ; 204:6
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this study was to evaluate fetal hemoglobin (HbF) and alpha(1)-microglobulin (A1M) in maternal serum as first-trimester biomarkers for preeclampsia (PE). STUDY DESIGN: The design was a case-control study. We included 96 patients in the first trimester of pregnancy (60 with PE and 36 controls). Venous serum samples were analyzed for HbF and total hemoglobin (Hb) by enzyme-linked immunosorbent assay and for A1M by radioimmunoassay. Sensitivity and specificity was calculated by logistic regression and receiver operating characteristic curve analysis. RESULTS: The HbF/Hb ratio and A1M concentration were significantly elevated in serum from women with subsequent development of PE (P < .0001). The optimal sensitivity and specificity was obtained using the biomarkers in combination; 69% sensitivity for a 5% screen positive rate and 90% sensitivity for a 23% screen positive rate. CONCLUSION: The study suggests that HbF/Hb ratio in combination with A1M is predictive biomarkers for PE.
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| 13. |
- Eckerberg, Katarina, 1953-, et al.
(författare)
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Miljøinstituttene i Norge : Hovedrapport
- 2015
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Norges forskningsråd har startet en omfattende evaluering av alle forskningsinstitutter som er underlagt Retningslinjer for statlig basisfinansiering. Denne evalueringen er den første i denne runden, og omfatter de åtte instituttene som utgjør miljøarenaen i basisfinansieringssystemet.Utvalget har både vurdert instituttene enkeltvis og sett på det samlede systemet som instituttene inngår i. Hensikten med evalueringen har både vært å gi råd for utforming av nasjonal instituttpolitikk, gi grunnlag for videre utvikling av Forskningsrådets virkemidler og å være til nytte for instituttene selv i deres eget utviklings- og strategiarbeid.Arbeidet med evalueringen har pågått fra mai 2014 til april 2015. I løpet av denne tiden har utvalget hatt fem møter, hvorav én samling hvor utvalget møtte alle instituttene. Som bakgrunn for evalueringen har utvalget hatt instituttenes egenevalueringer, en egen brukerundersøkelse, en faktarapport samt en rekke opplysninger som er skaffet til veie underveis ved hjelp av Forskningsrådet og Nordisk institutt for studier av innovasjon, forskning og utdanning (NIFU). NIFU har også vært sekretær for arbeidet ved forskningsleder Espen Solberg.Evalueringen har bygget på et bredt mandat, som har omfattet en gjennomgang av instituttenes roller, formål og oppgaver, deres rammevilkår, instituttenes samspill og samarbeid, relevans for brukerne samt fremtidige utfordringer og muligheter. Det har vært en meget interessant men også krevende oppgave å dekke disse dimensjonene for en så heterogen gruppe av institutter. Arbeidet har også vist at instituttene har et sterkt fokus på strategisk utvikling og tilpasning til nye utfordringer og muligheter. Utvalget håper at evalueringen vil bidra med verdifulle perspektiver til disse prosessene, og at den vil utgjøre et nyttig kunnskapsgrunnlag for både instituttene, Forskningsrådet, departementer og øvrige myndigheter på feltet.Evalueringsutvalget vil rette en spesiell takk til de åtte miljøinstituttene for den innsatsen da har lagt ned i egenevalueringene og for svært interessante og nyttige samtaler under utvalgets møter med instituttene. Utvalget vil også takke Forskningsrådet for utmerket tilrettelegging gjennom hele prosessen samt til NIFU for et godt samarbeid om utformingen av rapporten og sammenfatningen av materialet fra evalueringen.Evalueringen er utarbeidet i fellesskap og er enstemmig.
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| 14. |
- Einarsson, Jon Thorkell, et al.
(författare)
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Sustained Remission Improves Physical Function in Patients with Established Rheumatoid Arthritis, and Should Be a Treatment Goal : A Prospective Observational Cohort Study from Southern Sweden
- 2016
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Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 43:6, s. 1017-1023
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: It has been proposed that remission should be maintained throughout the course of rheumatoid arthritis (RA); however, the evidence supporting this is limited. Physical function measured by the Health Assessment Questionnaire (HAQ) is a major outcome in RA, and HAQ is shown to be one of the strongest predictors of longterm outcomes. The purpose of this study was to investigate the physical function over a long time in patients with RA who achieved sustained remission (SR) compared with that of patients occasionally achieving remission [non-sustained remission (NSR)].METHODS: Patients with RA treated with antitumor necrosis factor and included in the South Swedish Arthritis Treatment Group register were eligible for this study. We identified patients with a Disease Activity Score at 28 joints (DAS28) < 2.6 or Simplified Disease Activity Index (SDAI) ≤ 3.3 at some point and those who achieved SR, i.e., remission during consecutive visits for at least 6 months. The course of functional status was assessed using the HAQ at each visit.RESULTS: Of the 2416 patients, 1177 (48.7%) reached DAS28 remission at some point. SR was achieved by 382 (15.8%) for the DAS28 and 186 (7.7%) for the SDAI criteria. Comparing the SR and NSR groups, HAQ improved during the first 12 months in the DAS28 remission. HAQ continued to improve relatively as long as SR was maintained. A higher proportion of patients in SR reached full physical function.CONCLUSION: In patients with established RA, physical function measured by the HAQ improves in patients reaching SR compared with patients who only occasionally reach remission. The improvement continues while in remission, which supports that maintaining remission should be a treatment goal.
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| 15. |
- Exarchou, Sofia, et al.
(författare)
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Mortality in ankylosing spondylitis: results from a nationwide population-based study
- 2016
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 75:8, s. 1466-1472
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Information on mortality in ankylosing spondylitis (AS) is scarce. Our study therefore aimed to assess: (1) mortality in AS versus the general population, and (2) predictors of death in the AS population. Methods Nationwide cohorts of patients with AS diagnosed at rheumatology or internal medicine outpatient clinics (n=8600) and age-matched, sex-matched and county-matched general population comparators (n=40 460) were identified from the National Patient Register and the census register, respectively. The follow-up period began on 1 January 2006 or at the first date of registered diagnosis thereafter and extended until death, emigration or 31 December 2012, whichever occurred first. Socioeconomic variables, AS-related clinical manifestations, joint surgery, comorbidities and medication were identified from other national registers. Cox regression models were used to determine mortality and predictors for death in the AS cohort. Results There were 496 deaths in the AS cohort and 1533 deaths in the control cohort resulting in an age-adjusted and sex-adjusted HR of 1.60 (95% CI 1.44 to 1.77), with increased mortality for men (age-adjusted HR=1.53, 95% CI 1.36 to 1.72) and women (ageadjusted HR=1.83, 95% CI 1.50 to 2.22). Within the AS cohort, statistically significant predictors for death were a lower level of education, general comorbidities (diabetes, infections, cardiovascular, pulmonary and malignant diseases) and previous hip replacement surgery. Conclusions Mortality was increased for male and female patients with AS. Predictors of death within the AS cohort included socioeconomic status, general comorbidities and hip replacement surgery.
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| 16. |
- Exarchou, Sofia, et al.
(författare)
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The prevalence of clinically diagnosed ankylosing spondylitis and its clinical manifestations: a nationwide register study
- 2015
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Prevalence estimates of ankylosing spondylitis vary considerably, and there are few nationwide estimates. The present study aimed to describe the national prevalence of clinically diagnosed ankylosing spondylitis in Sweden, stratified according to age, sex, geographical, and socio-economic factors, and according to subgroups with ankylosing spondylitis-related clinical manifestations and pharmacological treatment. Methods: All individuals diagnosed with ankylosing spondylitis according to the World Health Organization International Classification of Disease codes, between 1967 and 2009, were identified from the National Patient Register. Data regarding disease manifestations, patient demographics, level of education, pharmacological treatment, and geographical region were retrieved from the National Patient Register and other national registers. Results: A total of 11,030 cases with an ankylosing spondylitis diagnosis (alive, living in Sweden, and 16 to 64 years old in December 2009) were identified in the National Patient Register, giving a point prevalence of 0.18% in 2009. The prevalence was higher in northern Sweden, and lower in those with a higher level of education. Men had a higher prevalence of ankylosing spondylitis (0.23% versus 0.14%, P < 0.001), a higher frequency of anterior uveitis (25.5% versus 20.0%, P < 0.001) and were more likely to receive tumor necrosis factor inhibitors than women (15.6% versus 11.8% in 2009, P < 0.001). Women were more likely than men to have peripheral arthritis (21.7% versus 15.3%, P < 0.001), psoriasis (8.0% versus 6.9%, P = 0.03), and treatment with oral corticosteroids (14.0% versus 10.4% in 2009, P < 0.001). Conclusion: This nationwide, register-based study demonstrated a prevalence of clinically diagnosed ankylosing spondylitis of 0.18%. It revealed phenotypical and treatment differences between the sexes, as well as geographical and socio-economic differences in disease prevalence.
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| 17. |
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| 18. |
- Fahlström, Karl
(författare)
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Laser welding of boron steels for light-weight vehicle applications
- 2015
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Laser beam welding has gained a significant interest during the last two decades. The suitability of the process for high volume production has the possibility to give a strong advantage compared to several other welding methods. However, it is important to have the process in full control since various quality issues may otherwise occur. During laser welding of boron steels quality issues such as imperfections, changes in local and global geometry as well as strength reduction can occur. The aspects that need to be considered are strongly depending on alloy content, process parameters etc. These problems that can occur could be fatal for the construction and the lowest level of occurrence is wanted, independent of industry.The focus of this study has been to investigate the properties of laser welded boron steel. The study includes laser welding of boron alloyed steels with strengths of 1500 MPa and a recently introduced 1900 MPa grade. Focus has been to investigate weldability and the occurrence of cracks, porosity and strength reducing microstructure that can occur during laser welding, as well as distortion studies for tolerances in geometry. The results show that both conventional and 1900 MPa boron alloyed steel are suitable for laser welding.Due to the martensitic structure of welds the material tends to behave brittle. Cracking and porosity do not seem to be an issue limiting the use of these steels. For tolerances in geometry for larger structures tests has been done simulating laser welding of A-pillars and B-pillars. Measurements have been done with Vernier caliper as well as a more advanced optical method capturing the movements during the welding sequence. Results from the tests done on Ushaped beams indicates that depending on the geometry of the structure and heat input distortions can be controlled to give distortions from 1 to 8 mm, at a welding length of 700 mm. This means that important geometry points can be distorted several millimeters if the laser welding process not is controlled.
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| 19. |
- Falk, John, et al.
(författare)
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Immersion freezing ability of freshly emitted soot with various physico-chemical characteristics
- 2021
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Ingår i: Atmosphere. - : MDPI AG. - 2073-4433. ; 12:9
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Tidskriftsartikel (refereegranskat)abstract
- The immersion freezing ability of soot particles has in previous studies been reported in the range of low/insignificant to very high. The aims of this study were to: (i) perform detailed physico-chemical characterisation of freshly produced soot particles with very different properties, (ii) investigate the immersion freezing ability of the same particles, and (iii) investigate the potential links between physico-chemical particle properties and ice-activity. A miniCAST soot generator was used to produce eight different soot samples representing a wide range of physico-chemical properties. A continuous flow diffusion chamber was used to study each sample online in immersion mode over the temperature (T) range from −41 to −32◦C, at a supersaturation of about 10% with respect to liquid water. All samples exhibited low to no heterogeneous immersion freezing. The most active sample reached ice-activated fractions (AF) of 10−3 and 10−4 at temperatures of 1.7 and 1.9 K, respectively, above the homogeneous freezing temperature. The samples were characterized online with respect to a wide range of physico-chemical properties including effective particle density, optical properties, particle surface oxidation and soot maturity. We did observe indications of increasing immersion freezing ice-activity with increasing effective particle density and increasing particulate PAH fraction . Hence, those properties, or other properties co-varying with those, could potentially enhance the immersion freezing ice-activity of the studied soot particle types. However, we found no significant correlation between the physico-chemical properties and the observed ice-nucleating ability when the particle ensemble was extended to include previously published results including more ice-active biomass combustion soot particles. We conclude that it does not appear possible in general and in any straightforward way to link observed soot particle physico-chemical properties to the ice-nucleating ability using the online instrumentation included in this study. Furthermore, our observations support that freshly produced soot particles with a wide range of physico-chemical properties have low to insignificant immersion freezing ice-nucleating ability.
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| 20. |
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| 21. |
- Forsblad d'Elia, Helena, 1961, et al.
(författare)
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Drug adherence, response and predictors thereof for tocilizumab in patients with rheumatoid arthritis: results from the Swedish biologics register
- 2015
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Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 54:7, s. 1186-1193
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To evaluate drug adherence, clinical response and predictors thereof for tocilizumab in patients with RA in routine care based on prospectively collected data from the Swedish biologics register, Anti-Rheumatic Therapies in Sweden. Methods. RA patients who had started with tocilizumab from September 2008 until March 2012 were identified. Cox regression and logistic regression models were used. Results. A total of 530 RA patients were included, of whom 80.6% were female, 64.7% were on concomitant DMARDs, of which 300 were on MTX and 12% were biologic naive. The overall 6 month, 1 and 2 year estimated drug continuations were 79%, 64% and 50%, respectively. In the multivariate analyses, a low initial level of CRP [hazard ratio (HR) 0.76/1S. D. (95% CI 0.63, 0.91)], high HAQ score [HR 1.23/1S.D. (95% CI 1.06, 1.44)] and prior exposure to different biologics [HR 1.43 (95% CI 1.12, 1.83)] were predictors for drug termination, whereas concomitant DMARD therapy was not. European League Against Rheumatism (EULAR) good, moderate, and no response were achieved by 184 (46.7%), 133 (33.8%) and 77 (19.5%) patients, respectively. Predictors for EULAR good response vs no response (at 2.5-8 months) were low HAQ [odds ratio (OR) 0.56/1S. D. (95% CI 0.40, 0.78)], high 28-joint DAS [OR 2.0/1S. D. (95% CI 1.44, 2.78)] and not being on prednisolone [OR 0.47 (95% CI 0.25, 0.88)] at baseline. Conclusion. In this RA cohort treated with tocilizumab, the estimated 1 year drug continuation was 64% and 80% of the patients achieved a EULAR response. Drug discontinuation was not predicted by no concomitant DMARD, but by low CRP, high HAQ and prior exposure to biologics.
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| 22. |
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| 23. |
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| 24. |
- Graham, Ian, et al.
(författare)
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European guidelines on cardiovascular disease prevention in clinical practice: full text. Fourth Joint Task Force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts).
- 2007
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Ingår i: European journal of cardiovascular prevention and rehabilitation : official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology. - : Oxford University Press (OUP). - 1741-8267. ; 14 Suppl 2
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Tidskriftsartikel (refereegranskat)abstract
- Other experts who contributed to parts of the guidelines: Edmond Walma, Tony Fitzgerald, Marie Therese Cooney, Alexandra Dudina European Society of Cardiology (ESC) Committee for Practice Guidelines (CPG): Alec Vahanian (Chairperson), John Camm, Raffaele De Caterina, Veronica Dean, Kenneth Dickstein, Christian Funck-Brentano, Gerasimos Filippatos, Irene Hellemans, Steen Dalby Kristensen, Keith McGregor, Udo Sechtem, Sigmund Silber, Michal Tendera, Petr Widimsky, Jose Luis Zamorano Document reviewers: Irene Hellemans (CPG Review Co-ordinator), Attila Altiner, Enzo Bonora, Paul N. Durrington, Robert Fagard, Simona Giampaoli, Harry Hemingway, Jan Hakansson, Sverre Erik Kjeldsen, Mogens Lytken Larsen, Giuseppe Mancia, Athanasios J. Manolis, Kristina Orth-Gomer, Terje Pedersen, Mike Rayner, Lars Ryden, Mario Sammut, Neil Schneiderman, Anton F. Stalenhoef, Lale Tokgözoglu, Olov Wiklund, Antonis Zampelas
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| 25. |
- Gülfe, Anders, et al.
(författare)
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Efficacy and drug survival of anti-tumour necrosis factor-alpha therapies in patients with non-radiographic axial spondyloarthritis: an observational cohort study from Southern Sweden.
- 2014
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Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 1502-7732 .- 0300-9742. ; 43:6, s. 493-497
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To evaluate the efficacy and drug survival of anti-tumour necrosis factor (anti-TNF) therapy in non-radiographic axial spondyloarthritis (nr-axSpA) patients treated in clinical practice in Southern Sweden. Method: In this cohort study we prospectively included 112 patients with nr-axSpA and high disease activity as well as inadequate response or intolerance to non-steroidal anti-inflammatory drugs (NSAIDs) receiving their first course of anti-TNF therapy. Patients fulfilling modified New York criteria for ankylosing spondylitis (AS) were excluded. The Assessment of SpondyloArthritis International Society (ASAS) criteria for axial SpA were fulfilled by 77% (n = 86) of the included patients. Results: At baseline, the median age of the cohort was 38 years, 59% were males, 79% of the patients had imaging suggestive of sacroiliitis (primarily inflammation on magnetic resonance imaging, MRI), 71% were HLA-B27 positive, and the median disease duration was 6 years and 10 months. At 6 months of follow-up, the median Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) decreased from 5.6 to 3.2 (p = 0.002), the Bath Ankylosing Spondylitis Functional Index (BASFI) decreased from 3.9 to 1.8 (p = 0.005), and C-reactive protein (CRP) level decreased from 4.4 to 1.7 mg/L (p = 0.001). After 1 year of treatment the Kaplan-Meier estimated drug survival was 76%, and at 2 years of follow-up this value decreased to 65%. Patients with inflammatory MRI findings at baseline had significantly better drug survival [hazard ratio (HR) 0.24, 95% confidence interval (CI) 0.10-0.55, p = 0.001]. Male sex was also associated with higher drug survival (HR 0.45, 95% CI 0.24-0.85, p = 0.011). CRP level at baseline was not associated with drug survival. Conclusions: Anti-TNF treatment of patients with nr-axSpA in clinical practice resulted in reduced BASDAI and BASFI scores and good drug survival. The results from this study suggest that male gender and positive imaging at baseline are associated with a favourable treatment course.
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| 26. |
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| 27. |
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| 28. |
- Gülfe, Anders, et al.
(författare)
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Rapid and sustained health utility gain in anti-TNF treated inflammatory arthritis. Observational data during seven years in southern Sweden.
- 2010
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 69:2, s. 352-357
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Rheumatoid arthritis (RA), psoriatic arthritis (PsA), and other spondylarthritides (SpA) impose great impact on the individual in addition to the costs on society, which may be reduced by effective pharmacological treatment. Industry independent health economic studies should complement studies sponsored by industry. OBJECTIVE: To study secular trends in baseline health utilities in patients commencing TNF blockade for arthritis in clinical practice over 7 years; to address utility changes during treatment; to investigate the influence of previous treatment courses; to study the feasibility of health utility measures, and to compare them across diagnostic entities. METHODS: /B> EuroQoL 5 Dimensions (EQ-5D) utility data were collected from a structured clinical follow-up program of anti-TNF treated patients with RA (N=2554), PsA (N=574) or SpA (N=586). Time trends were calculated. Completer analysis was used. RESULTS: /B> There were weak or non-significant secular trends for increasing baseline utilities over time for RA, PsA and SpA. Maximum gain in utilities occurred already after 2 weeks for all diagnoses and remained stable for patients remaining on therapy. First and second anti-TNF courses performed similarly. CONCLUSIONS: Utilities at inclusion remained largely unchanged for RA, PsA and SpA over 7 years. Improvement occurred early during treatment and not beyond 6 weeks at the group level. Improvement during the first course was not consistently greater than the second. There were no major differences between RA, PsA and SpA. EQ-5D proved feasible and applicable across these diagnoses. These "real world" data may be useful for health economic modelling.
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| 29. |
- Gülfe, Anders, et al.
(författare)
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Six and 12 Weeks Treatment Response Predicts Continuation of Tumor Necrosis Factor Blockade in Rheumatoid Arthritis: An Observational Cohort Study from Southern Sweden.
- 2009
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Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 36, s. 517-521
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate if treatment response predicts continuation of anti-tumor necrosis factor (TNF) treatment in patients with rheumatoid arthritis (RA). METHODS: We investigated if treatment response and/or achieving a certain activity state at 6 weeks or 3 months predicts continuation of treatment in an observational cohort of 1789 anti-TNF-naive patients with established RA disease from southern Sweden. RESULTS: Response to treatment at 6 weeks at overall/American College of Rheumatology (ACR20) or good/major level (except ACR70) significantly predicted drug continuation. Response according to all criteria sets at overall/ACR20 and at good/major/ACR70 level predicted drug continuation at 3 months, as did achieving low disease activity at 3 months irrespective of activity index applied. Remaining in a high disease activity state predicted drug discontinuation at both timepoints and according to all criteria sets. CONCLUSION: Response criteria may be useful aids in deciding on continuation of TNF blockade in RA as early as after 6 weeks of treatment. The various criteria sets perform similarly.
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| 30. |
- Gülfe, Anders, et al.
(författare)
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Utility-based outcomes made easy: The number needed per QALY gained (NNQ). Observational cohort study from Southern Sweden of TNF blockade in inflammatory arthritis.
- 2010
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Ingår i: Arthritis Care and Research. - : Wiley. - 2151-4658 .- 2151-464X. ; 62:10, s. 1399-1406
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE.: To introduce a novel, simple, utility based outcome measure, the Number Needed per Quality adjusted life year (QALY) gained (NNQ), and to apply it in clinical practice in anti-TNF treated patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and spondylarthritis (SpA). METHODS.: The NNQ is the number of patients one has to treat in order to gain 1 QALY. It is calculated as the inverted value of the utility gain (area under curve) over 1 year in a cohort subjected to an intervention. EuroQoL-5-dimensions (EQ-5D) utility data from the South Swedish Arthritis Treatment Register was used. RESULTS.: 1001 RA, 241 PsA, and 255 SpA patients were eligible for the study. First, 2(nd) and 3(rd) treatment courses were studied. For RA, NNQ was 4.5, 6.4 and 5.2 for 1(st), 2(nd) and 3(rd) courses, respectively. For PsA and SpA, NNQ was 4.2-4.5 irrespective of treatment order. Treatment groups with N<50 were not analysed. During the study period 2002-2007, there were no secular trends of utility gains. CONCLUSION.: The NNQ is an easily derived and understandable, utility based outcome measure that may be useful for stakeholders, decision makers as well as for clinicians. It was readily applied in this study of TNF blockade across 3 arthritis diagnoses. NNQ varied little over diagnoses and treatment course order, with a possible exception in 2(nd) treatment course in RA.
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| 31. |
- Hallberg, Håkan, et al.
(författare)
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Modeling of Continuous Dynamic Recrystallization in Aluminum
- 2009
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Ingår i: DCE Technical Memorandum No. 11. - 1901-7278. ; 11, s. 59-62
-
Konferensbidrag (refereegranskat)abstract
- A constitutive model is presented, considering grain size refinement through continuous dynamic recrystallization together with an evolving dislocation density. The grain refinement is allowed to influence both the evolution of the dislocation density and the rate dependence of the material. The model is calibrated against experimental data on aluminum and numerical simulations of equal channel angular pressing (ECAP) material processing illustrates the capabilities of the model.
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| 32. |
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| 33. |
- Hellgren, K., et al.
(författare)
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Cancer risk in patients with spondyloarthritis treated with TNF inhibitors: a collaborative study from the ARTIS and DANBIO registers
- 2017
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 76:1, s. 105-111
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Tidskriftsartikel (refereegranskat)abstract
- Background Safety data on cancer risks following tumour necrosis factor alpha inhibitors (TNFi) in patients with spondyloarthritis (SpA) (here defined as ankylosing spondylitis (AS), undifferentiated spondarthropaties (SpA UNS), psoriatic arthritis (PsA)) are scarce. Our objective was to assess risks for cancer overall and for common subtypes in patients with SpA treated with TNFi compared with TNFi-naive patients with SpA and to the general population. Methods From the Swedish (Anti-Rheumatic Therapy in Sweden (ARTIS)) and Danish (DANBIO) biologics registers, we assembled 8703 (ARTIS=5448, DANBIO=3255) patients with SpA initiating a first TNFi 2001-2011. From the Swedish National Patient and Population Registers we assembled a TNFi-naive SpA cohort (n=28,164) and a Swedish age-matched and sex-matched general population comparator cohort (n=131 687). We identified incident cancers by linkage with the nationwide Swedish and Danish Cancer Registers 2001-2011, and calculated age-standardised and sex-standardised incidence ratios as measures of relative risk (RR). Results Based on 1188 cancers among the TNFi-naive patients with SpA, RR of cancer overall was 1.1 (95% Cl 1.0 to 1.2). Based on 147 cancers among TNFi initiators with SpA, RR versus TNFi-naive was 0.8 (95% CI 0.7 to 1.0) and results were similar for AS and PsA when analysed separately. Site-specific cancer RRs: prostate 0.5 (95% CI 0.3 to 0.8), lung 0.6 (95% CI 0.3 to 1.3), colorectal 1.0 (95% CI 0.5 to 2.0), breast 1.3 (95% Cl 0.9 to 2.0), lymphoma 0.8 (95% CI 0.4 to 1.8) and melanoma 1.4 (95% CI 0.7 to 2.6). Conclusions In patients with SpA, treatment with TNFi was not associated with increased risks of cancer, neither overall nor for the six most common cancer types.
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| 34. |
- Huber, Kurt, et al.
(författare)
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Antiplatelet and anticoagulation agents in acute coronary syndromes : What is the current status and what does the future hold?
- 2014
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 168:5, s. 611-621
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Tidskriftsartikel (refereegranskat)abstract
- Mortality and morbidity in acute coronary syndromes (ACSs), caused principally by plaque erosion or rupture leading to thrombus formation and myocardial ischemia, have been reduced by a combination of antithrombotic agents (antiplatelet drugs and anticoagulants) and early revascularization. Aspirin is the foundation antiplatelet agent. New P2Y(12) receptor inhibitors (prasugrel and ticagrelor) have clear benefits compared with clopidogrel for dual antiplatelet therapy, and cangrelor or vorapaxar, a thrombin receptor inhibitor, may be of value in specific settings. Anticoagulation uses 1 of 4 choices: bivalirudin, unfractionated heparin, enoxaparin, and fondaparinux. Moreover, some patients (such as those who have chronic atrial fibrillation) require triple therapy with aspirin, clopidogrel, plus an anticoagulant, frequently a vitamin K antagonist. New oral anticoagulants have been shown to be at least as effective as vitamin K antagonists in atrial fibrillation and led to fewer bleeding complications. Finally, the combination of aspirin, clopidogrel, and low-dose rivaroxaban has recently been approved by the European Medicines Agency (but not the Food and Drug Administration) for secondary prevention after ACS. Several strategies have been developed to balance the potential benefit of antithrombotic therapy against the risk of bleeding complications, for example, radial access in coronary angiography or restricted use of combination therapy, and others are under investigation, such as discontinuation of aspirin. This overview summarizes the current status of antithrombotic therapy in ACS and describes strategies currently explored to optimize its benefit/risk ratio.
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| 35. |
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| 36. |
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| 37. |
- Johansson, Henrik J., et al.
(författare)
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Breast cancer quantitative proteome and proteogenomic landscape
- 2019
-
Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- In the preceding decades, molecular characterization has revolutionized breast cancer (BC) research and therapeutic approaches. Presented herein, an unbiased analysis of breast tumor proteomes, inclusive of 9995 proteins quantified across all tumors, for the first time recapitulates BC subtypes. Additionally, poor-prognosis basal-like and luminal B tumors are further subdivided by immune component infiltration, suggesting the current classification is incomplete. Proteome-based networks distinguish functional protein modules for breast tumor groups, with co-expression of EGFR and MET marking ductal carcinoma in situ regions of normal-like tumors and lending to a more accurate classification of this poorly defined subtype. Genes included within prognostic mRNA panels have significantly higher than average mRNA-protein correlations, and gene copy number alterations are dampened at the protein-level; underscoring the value of proteome quantification for prognostication and phenotypic classification. Furthermore, protein products mapping to non-coding genomic regions are identified; highlighting a potential new class of tumor-specific immunotherapeutic targets.
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| 38. |
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| 39. |
- Jørgensen, Tanja Schjødt, et al.
(författare)
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EQ-5D utility, response and drug survival in rheumatoid arthritis patients on biologic monotherapy : A prospective observational study of patients registered in the south Swedish SSATG registry
- 2017
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Biologic agents have dramatically changed treatment of rheumatoid arthritis (RA). To date only scarce head-To-head data exist especially when the biological therapies are given as monotherapy without concomitant disease modifying drugs (DMARDs). Thus the objective of the current study is to evaluate treatment response of all available biological therapies with special focus on utility (EQ-5D-3L) and drug survival of biologic DMARDs (bDMARDs) prescribed as monotherapy in RA patients in southern Sweden. Materials and methods All RA patients registered in a regional database as initiating bDMARD as monotherapy, i.e. without concomitant conventional synthetic DMARDs (csDMARDs), from 1st of January 2006 through 31st of December 2012, were included. Patients were followed from initiation of the first dose of bDMARD monotherapy treatment until withdrawal from treatment, loss of follow-up or 31st of December 2012. Descriptive statistics for utility (EQ-5D-3L), effectiveness, and drug survival of bDMARD monotherapy were calculated. Results During the study period, a total of 554 patients were registered in SSATG as initiating bDMARD monotherapy. Most of the patients were women (81%), with a mean age of 57 years. The average disease duration was more than 12 years, and on average the patients had previously been treated with approximately four different csDMARDs. Fifty-five percent of the patients were initiating their first bDMARD, 26% their second, and 19% their third or more. At baseline the average EQ-5D-3L was 0.34. Most patients had moderate to high disease activity, with a mean DAS28 of 5.0, and were substantially disabled, with an average HAQ score of 1.4. At 6 months follow-up, the EQ-5D-3L in patients still on the biologic drug had increased by mean 0.23 (SD 0.4) with no differences between type of bDMARD (p = 0.49). The mean change in EQ-5D-3L ranged from 0.11 (rituximab and infliximab) to 0.42 (tocilizumab). Although the changes were numerically different, no distinct pattern favored any particular bDMARD for EQ-5D-3L (p = 0.49) or other clinical outcomes. Overall, DAS28 defined remission and low disease activity were achieved in 20% and 43% of patients, respectively. Drug survival rates were statistically significantly different between bDMARDs (p = 0.01), with the highest rates observed for rituximab, followed by etanercept. After failing first course of anti-TNF, patients switching to another mode of action had significantly higher drug survival than those switching to a second course of anti-TNF therapy (p = 0.02). Conclusions Utility (EQ-5D-3L) increased after 6 months of all bDMARD treatments in monotherapy, indicating improvement of patients' quality of life. After failure of anti-TNF treatment in monotherapy, switching to another mode of action may be associated with better drug survival than starting a second TNF-inhibitor.
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| 40. |
- Jørgensen, Tanja Schjødt, et al.
(författare)
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Protocol for evaluating and implementing a pragmatic value-based healthcare management model for patients with inflammatory arthritis : A Danish population-based regional cohort and qualitative implementation study
- 2018
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 8:10
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Tidskriftsartikel (refereegranskat)abstract
- Introduction The provision of healthcare for patients with inflammatory arthritis occurs in the context of somewhat conflicting targets, values and drivers. Therefore, there is a need for introducing 'value-based healthcare' defined as the value of patient relevant health outcomes in relation to costs. This term is a central part of tomorrow's healthcare sector, especially for rheumatic diseases, yet the transition is a huge challenge, as it will impact the development, delivery and assessment of healthcare. Aims The aim of this study is to compare medical and patient evaluated impact of the traditional settlement and financing production (DAGS) controlled healthcare setting with a value-based and patient-centred adjunctive to standard care. Methods and analysis Patients with inflammatory arthritis receiving treatment in routine care at the outpatient clinics in the Capital Region of Denmark will prospectively and consecutively be enrolled in a Non-Intervention-Study framework providing a pragmatic value-based management model. A Danish reference cohort, used for comparison will be collected as part of routine clinical care. The enrolment period will be from 1 June 2018 until 31December 2023. Baseline and follow-up visits will be according to routine clinical care. Registry data will be obtained directly from patients and include personal, clinical and outcomes information. The study results will be reported in accordance with the STROBE statement. Ethics and dissemination The study has been notified to the Danish Data Protection Agency and granted authorisation for the period June 2018 to January 2025 (pending). Informed consent will be obtained from all patients before enrolment in the study. The study is approved by the ethics committee, Capital Region of Denmark (H-18013158). Results of the study will be disseminated through publication in international peer-reviewed journals.
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| 41. |
- Karlsson, Johan, et al.
(författare)
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National EQ-5D tariffs and quality-adjusted life-year estimation: comparison of UK, US and Danish utilities in south Swedish rheumatoid arthritis patients.
- 2011
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 70, s. 2163-2166
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To study how the choice of national EQ-5D tariff may affect utility and incremental quality-adjusted life-year (QALY) estimates. METHODS: South Swedish rheumatoid arthritis patients in an observational study, starting and continuing anti-tumour necrosis factor (TNF) monotherapy (n=54) or anti-TNF plus methotrexate (n=215) for 1 year during May 2002 to April 2009, were included. EQ-5D questionnaires were completed at baseline, 3, 6 and 12 months. Utilities and accumulated QALY were compared using the UK, US and Danish EQ-5D tariffs. Utilities for all 243 possible EQ-5D health states were also compared. RESULTS: US utilities were generally higher than UK, with Danish falling in between. A substantial 1-year mean utility improvement was seen in both study groups using all tariffs (UK 0.28 vs 0.29; US 0.18 vs 0.19; Danish 0.20 vs 0.22). Adjusting for baseline differences between groups, the incremental QALY gain of combined treatment was 0.09 using the UK tariff, while 0.06 according to both US and Danish tariffs. Inter-tariff disagreement in utility and accumulated QALY varied irregularly across the range of utilities. CONCLUSIONS: Applying different national EQ-5D tariffs to the same data may result in substantially different incremental QALY estimates, crucial knowledge when interpreting cost-utility analyses. Studies using different tariffs cannot be directly compared.
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| 42. |
- Karlsson, JA, et al.
(författare)
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Treatment response to a second or third TNF-inhibitor in RA: results from the South Swedish Arthritis Treatment Group Register.
- 2008
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Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 47:4, s. 507-513
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. To study treatment response rates of RA patients undergoing second- and third-line anti-TNF therapy and to identify baseline predictors of response to second-line treatment. Methods. RA patients monitored in a prospective, observational study, having switched anti-TNF therapy once (first-time switchers, n = 337) or twice (second-time switchers, n = 36)-i.e. following failures with one antibody- and one receptor-type agent-between March 1999 and December 2006, were studied. Treatment responses at 3 months were assessed by the ACR and European League Against Rheumatism (EULAR) response criteria. Predictive potentials for response to second-line treatment of demographics, baseline disease activity measures, disease and treatment characteristics were analysed using logistic regression. Results. ACR20 response was met by 51% of first-time and 35% of second-time switchers. Corresponding ACR50 rates were 27 and 18%; EULAR overall rates (EULAR good or moderate response) 71 and 58%; EULAR good rates 25 and 9% and 28-joint disease activity score (DAS28) remission rates 16 and 6%. Identified baseline predictors of response to second-line treatment were lower age and HAQ scores, elevated DAS28 values and having ceased the former anti-TNF treatment due to adverse events rather than inefficacy. No variable was predictive for all examined response criteria. Conclusions. Response rates of first-time anti-TNF switchers are somewhat below those of anti-TNF naïve RA patients, while the markedly inferior response rates of second-time switchers suggest other therapeutic options to be considered in this situation. Identified baseline predictors of response may be useful indicators to second-line anti-TNF therapy, but vary depending on the response criteria set studied.
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| 43. |
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| 44. |
- KARLSSON WALLMAN, JOHAN, et al.
(författare)
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Costs in Relation to Disability, Disease Activity, and Health-related Quality of Life in Rheumatoid Arthritis : Observational Data from Southern Sweden
- 2016
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Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 43:7, s. 1292-1299
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To compare how costs relate to disability, disease activity, and health-related quality of life (HRQOL) in rheumatoid arthritis (RA). Methods. Antitumor necrosis factor (anti-TNF)-treated patients with RA in southern Sweden (n = 2341) were monitored 2005-2010. Health Assessment Questionnaire (HAQ), 28-joint Disease Activity Score (DAS28), and EQ-5D scores were linked to register-derived costs of antirheumatic drugs (excluding anti-TNF agents), patient care, and work loss from 30 days before to 30 days after each visit (n = 13,289). Associations of HAQ/DAS28/EQ-5D to healthcare (patient care and drugs) and work loss costs (patients <65 yrs) were studied in separate regression models, comparing standardized â coefficients by nonparametric bootstrapping to assess which measure best reflects costs. Analyses were conducted based on both individual means (linear regression, comparing between-patient associations) and by generalized estimating equations (GEE), using all observations to also account for within-patient associations of HAQ/DAS28/EQ-5D to costs. Results. Regardless of the methodology (linear or GEE regression), HAQ was most closely related to both cost types, while work loss costs were also more closely associated with EQ-5D than DAS28. The results of the linear models for healthcare costs were standardized β = 0.21 (95% CI 0.15-0.27), 0.16 (0.11-0.21), and -0.15 (-0.21 to -0.10) for HAQ/DAS28/EQ-5D, respectively (p <0.05 for HAQ vs DAS28/EQ-5D). For work loss costs, the results were standardized β = 0.43 (95% CI 0.39-0.48), 0.27 (0.23-0.32), and -0.34 (-0.38 to 0.29) for HAQ/DAS28/EQ-5D, respectively (p <0.05 for HAQ vs DAS28/EQ-5D and for EQ-5D vs DAS28). Conclusion. Overall, HAQ disability is a better marker of RA costs than DAS28 or EQ-5D HRQOL.
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| 45. |
- Krag Jakobsen, Ane, et al.
(författare)
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Is Nephrolithiasis an Unrecognized Extra-Articular Manifestation in Ankylosing Spondylitis? A Prospective Population-Based Swedish National Cohort Study with Matched General Population Comparator Subjects
- 2014
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 9:11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Ankylosing spondylitis (AS) is associated with several extra-articular manifestations. Nephrolithiasis (NL) has not been recognized as one of those, however, several factors known to increase the risk of NL are at play in AS patients. The objective was to estimate rates and predictors of NL in Swedish patients with AS compared to the general population. Methods and Findings: We performed a prospective population-based nationwide cohort study based on linkage of data from Swedish registries. 8,572 AS patients were followed for 49,258 person-years (py) and 39,639 matched general population comparators were followed for 223,985 py. Patients were followed prospectively together with comparator subjects from January 2001 through December 2009. The first occurrence of NL during follow-up was the primary outcome. Hazard Ratios (HR) were used to compare these rates adjusting for comorbidities and treatment, and to assess predictors for NL. Mean age at study entry was 46 years (inter quartile range 36-56 years), 65% were males. Based on 250 vs. 466 NL events, the adjusted HR of NL in AS patients was 2.1 (95% CI 1.8 to 2.4). Predictors of NL within the AS group included prior diagnosis of inflammatory bowel disease (IBD) (HR 2.3; 95% CI 1.7 to 3.3), prior diagnosis of NL (HR 16.4; 95% CI 11.5 to 23.4), and patients receiving anti-TNF treatment (HR 1.6; 95% CI 1.2 to 2.1). Male sex was a risk factor for NL both in AS patients and in the general population. Limitations: The risk for residual confounding and inability to study the chemical nature of NL were considered the main limitations of the study. Conclusions: Patients with AS are at increased risk of NL, which may be considered a novel extra-articular manifestation. Previous history of NL, IBD, AS disease severity and male sex were identified as predictors of NL in AS.
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| 46. |
- Krag Jakobsen, Ane, et al.
(författare)
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Surgical interventions for nephrolithiasis in ankylosing spondylitis and the general population
- 2015
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 49:6, s. 486-491
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The aim of this study was to estimate rates and type of definitive surgical interventions for nephrolithiasis in Swedish patients with ankylosing spondylitis (AS) compared to the general population. Materials and methods. This national prospective cohort study linked data from Swedish population and healthcare registries. Incidence rates and interventions for nephrolithiasis during follow-up in patients with AS were compared to general population comparator (GPC) subjects. Results. In total, 8572 AS patients were followed for 49,959 person-years and 39,639 matched GPCs were followed for 225,221 person-years. Mean age at study entry was 46 years [interquartile range (IQR) 36-56 years] and 65% were male. In AS patients with a diagnosis of nephrolithiasis during the study period, 29% (72/250) underwent similar intervention for nephrolithiasis compared to 24% (114/466) GPCs (p = 0.21). The incidence rate ratio (RR) in overall AS patients was 2.9 [95% confidence interval (CI) 2.1-3.8] during a median follow-up of 6.2 years (IQR 3.2-8.6 years). With prior diagnosis of nephrolithiasis, the RR for AS patients compared to GPCs was 3.7 (95% CI 1.8-7.7); without prior nephrolithiasis the RR was 2.1 (95% CI 1.5-3.0). Increasing age [odds ratio (OR) 1.02, 95% CI 1.01-1.03], prior nephrolithiasis diagnosis (OR 3.3, 95% CI 1.97-5.62) and atherosclerotic cardiac disease (OR 2.0, 95% CI 1.03-3.91) were identified as predictors of intervention for nephrolithiasis. Conclusions. Patients with AS have an almost three-fold increased risk of surgical intervention for kidney stones, with similar management, compared to the general population.
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| 47. |
- Kristensen, Lars Erik
(författare)
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Anti-TNF treatment of chronic arthritis in clinical practice. New assessment method and predictors of efficacy and tolerability.
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Abstract Treatment of chronic inflammatory arthritis has undergone major changes over the past years following introduction of targeted biological therapies. Tumour necrosis factor (TNF) blocking therapy has been the most important biological treatment of chronic arthritis to date. The overall objective of this thesis was to develop a new assessment method of efficacy of biological therapy in clinical practice. Further objectives were to study efficacy and tolerability and predictors thereof in anti-TNF treated patients with chronic arthritis in an open study setting. The thesis is based on four studies of patients with established rheumatoid arthritis (RA) and one study of patients with psoriatic arthritis (PsA). Patients included in the five studies were monitored according to a standardized clinical protocol of the South Swedish Arthritis Treatment Group (SSATG) developed at the Department of Rheumatology in Lund. The protocol included baseline characteristics such as diagnosis, disease duration, previous and ongoing disease modifying antirheumatic drugs (DMARDs), treatment start and termination. In addition efficacy measures used for calculating treatment response, i.e. EULAR and ACR response criteria, were collected at fixed time-points. Data were prospectively registered from March 1999. To overcome shortcomings of previous methods for reporting response data from long term observational cohorts, LUNDEX (LUND Efficacy indeX) was designed. LUNDEX adjusted response data combines the proportion of patients fulfilling a selected response criterion with the proportion of patients adhering to a particular therapy. LUNDEX applied on RA and PsA patients proved to be a valuable tool for evaluating drug efficacy in observational studies. It has the advantage of integrating both clinical response as well as adherence to therapy in a composite score. Predictors of drug survival in RA and PsA were studied using Cox regression models. The models showed that the risk for premature treatment termination was higher in infliximab compared to etanercept treated patients. Also, regression analysis showed that patients with higher baseline CRP-levels and concomitant MTX treatment had better overall treatment continuation. Good response to anti-TNF therapy in RA was associated with concomitant MTX or other DMARD treatment as well as low disability. Moreover, RA patients who failed their first course of anti-TNF treatment, showed response rates during second anti-TNF treatment course in the range of the initial treatment. In contrast, response to a third anti-TNF treatment was markedly reduced, suggesting that other treatment options should be tried. In conclusion, LUNDEX proved to be a practical and a potentially universal tool, valuable for assessing drug response in an open study setting. Important predictors of efficacy and tolerability of anti-TNF treatment were identified.
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| 48. |
- Kristensen, Lars Erik, et al.
(författare)
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Dose escalation of infliximab therapy in arthritis patients is related to diagnosis and concomitant methotrexate treatment: observational results from the South Swedish Arthritis Treatment Group register.
- 2009
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Ingår i: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 48, s. 243-245
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To study frequency of dose escalation in infliximab-treated patients and to identify possible predictors thereof. Methods. Patients with chronic arthritis initiating their first course of anti-TNF treatment with infliximab at Lund University Hospital were included in a structured clinical follow-up protocol. Information on diagnosis, drug dosage, disease duration, previous and ongoing DMARDs, treatment start and cessation were prospectively collected during the period March 1999 through February 2007. All patients were started on a dose of 3 mg/kg at time 0, week 2, week 6 and then every eighth week independent of diagnosis and were followed for a period of 2 yrs. Results. A total of 206 patients were included in the study. Thirty-two of the patients had PsA, 25 had AS and 149 patients had RA. A minor dose escalation, defined as less than doubling of the dosage, was observed for 53, 48 and 42% of the patients with PsA, AS and RA, respectively. The corresponding values for major dose escalation was observed for 19, 8 and 15% of the patients, respectively. Regression analysis showed that patients with a diagnosis of PsA (P = 0.03), longer follow-up period (P < 0.01), and lack of concomitant MTX treatment (P = 0.03) were significantly associated with risk of dose escalation. Conclusion. Dose escalations were performed in 59% of all infliximab-treated patients during the first 2 yrs of treatment. Our data suggest that PsA patients might require higher dosages than RA and AS patients.
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| 49. |
- Kristensen, Lars Erik, et al.
(författare)
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Efficacy and tolerability of anti-TNF therapy in psoriatic arthritis patients: Results from the South Swedish Arthritis Treatment Group Register.
- 2008
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 67, s. 364-369
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Tidskriftsartikel (refereegranskat)abstract
- Background: The use of tumour necrosis factor (TNF) blocking agents in psoriatic arthritis (PsA) is increasing, and the SSATG register has followed patients with PsA for more than 5 years. The aim of the present work therefore was to present efficacy and tolerability data of TNF-blocking agents on PsA in clinical practice, and to study potential predictors for drug survival (the length of time a patient continues to take a particular drug). Materials and methods: Patients (n = 261) with active PsA, starting anti-TNF therapy for the first time in southern Sweden, were included. Basal characteristics, disease activity measures, and termination reason for blockers were prospectively collected during the period April 1999 to September 2006. Cox proportional hazard models were used to investigate predictors for treatment termination. Results: Overall, response rates at 3–12 months for global visual analogue scale (VASglobal50) and pain VAS (VASpain50) were about 50%, whereas response rates for European League Against Rheumatism (EULAR) scoring "overall" and EULAR "good" were around 75% and 55%, respectively. Concomitant methotrexate (MTX) (hazard ratio (HR) 0.64, 95% CI 0.39–0.95, p = 0.03), etanercept (HR 0.49, 95% CI 0.28–0.86, p = 0.01), and high C-reactive protein (CRP) levels (HR 0.77, 95% CI 0.61–0.97, p = 0.03) at treatment initiation were associated with better overall drug survival. The improved drug survival of concomitant MTX appeared to be related to significantly fewer dropouts because of adverse events (HR = 0.24 (0.11–0.52), p<0.01). The blockers were well tolerated with a rate of serious adverse events of 5–6% per year. No unexpected serious adverse events were observed. Conclusion: Concomitant MTX and high CRP levels are associated with treatment continuation of anti-TNF therapy in patients with PsA regardless of joint distribution. The positive effect of MTX was primarily linked to fewer dropouts because of adverse events.
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| 50. |
- Kristensen, Lars Erik, et al.
(författare)
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Impact of concomitant DMARD therapy on adherence to treatment with etanercept and infliximab in rheumatoid arthritis. Results from a six-year observational study in southern Sweden
- 2006
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Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 8:6
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this work is to compare the adherence to therapy of patients receiving etanercept and infliximab during first tumour necrosis factor (TNF)-blocking treatment course in rheumatoid arthritis. Special emphasis is placed on potential predictors for treatment termination and the impact of concomitant methotrexate (MTX) or other disease-modifying antirheumatic drugs (DMARDs). Patients (n = 1,161) with active rheumatoid arthritis, not responding to at least two DMARDs including MTX starting etanercept or infliximab therapy for the first time, were included in a structured clinical follow-up protocol. Information on diagnosis, disease duration, previous and ongoing DMARDs, treatment start and termination, as well as cause of withdrawal was prospectively collected during the period of March 1999 through December 2004. Patients were divided into six groups according to TNF-blocking drugs and concomitant DMARDs. Five-year level (one-year) of adherence to therapy was 36% (69%) for patients receiving infliximab in combination with MTX compared with 65% (89%) for patients treated with etanercept and MTX (p < 0.001). Cox regression models showed that the risk for premature treatment termination of patients treated with infliximab was threefold higher than for etanercept (p < 0.001). Also, the regression analysis showed that patients receiving concomitant MTX had better treatment continuation than patients treated solely with TNF blockers (p < 0.001). Moreover, patients receiving concomitant MTX had superior drug survival than patients receiving other concomitant DMARDs (p < 0.010). The superior effect of MTX was associated primarily with fewer treatment terminations because of adverse events. In addition, the study identifies low C-reactive protein level, high age, elevated health assessment questionnaire score, and higher previous number of DMARDs as predictors of premature treatment termination. In summary, treatment with etanercept has higher adherence to therapy than treatment with infliximab. Concomitant MTX is associated with improved treatment continuation of biologics when compared with both TNF blockers as monotherapy and TNF blockers combined with other DMARDs.
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