| 1. |
- Groenen, M. A., et al.
(author)
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Analyses of pig genomes provide insight into porcine demography and evolution
- 2012
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 491:7424, s. 393-398
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Journal article (peer-reviewed)abstract
- For 10,000 years pigs and humans have shared a close and complex relationship. From domestication to modern breeding practices, humans have shaped the genomes of domestic pigs. Here we present the assembly and analysis of the genome sequence of a female domestic Duroc pig (Sus scrofa) and a comparison with the genomes of wild and domestic pigs from Europe and Asia. Wild pigs emerged in South East Asia and subsequently spread across Eurasia. Our results reveal a deep phylogenetic split between European and Asian wild boars approximately 1 million years ago, and a selective sweep analysis indicates selection on genes involved in RNA processing and regulation. Genes associated with immune response and olfaction exhibit fast evolution. Pigs have the largest repertoire of functional olfactory receptor genes, reflecting the importance of smell in this scavenging animal. The pig genome sequence provides an important resource for further improvements of this important livestock species, and our identification of many putative disease-causing variants extends the potential of the pig as a biomedical model.
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| 2. |
- Sumpter, N. A., et al.
(author)
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Association of Gout Polygenic Risk Score With Age at Disease Onset and Tophaceous Disease in European and Polynesian Men With Gout
- 2023
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In: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 75:5, s. 816-825
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Journal article (peer-reviewed)abstract
- Objective. To determine whether a gout polygenic risk score (PRS) is associated with age at gout onset and tophaceous disease in European, East Polynesian, and West Polynesian men and women with gout. Methods. A 19-variant gout PRS was produced in 7 European gout cohorts (N = 4,016), 2 East Polynesian gout cohorts (N = 682), and 1 West Polynesian gout cohort (N = 490). Sex-stratified regression models were used to estimate the relationship between the PRS and age at gout onset and tophaceous disease. Results. The PRS was associated with earlier age at gout onset in men (beta = -3.61 in years per unit PRS [95% confidence interval (95% CI) -4.32, -2.90] in European men; beta = -6.35 [95% CI -8.91, -3.80] in East Polynesian men; beta = -3.51 [95% CI -5.46, -1.57] in West Polynesian men) but not in women (beta = 0.07 [95% CI -2.32, 2.45] in European women; beta = 0.20 [95% CI -7.21, 7.62] in East Polynesian women; beta -3.33 [95% CI -9.28, 2.62] in West Polynesian women). The PRS showed a positive association with tophaceous disease in men (odds ratio [OR] for the association 1.15 [95% CI 1.00, 1.31] in European men; OR 2.60 [95% CI 1.66, 4.06] in East Polynesian men; OR 1.53 [95% CI 1.07, 2.19] in West Polynesian men) but not in women (OR for the association 0.68 [95% CI 0.42, 1.10] in European women; OR 1.45 [95% CI 0.39, 5.36] in East Polynesian women). The PRS association with age at gout onset was robust to the removal of ABCG2 variants from the PRS in European and East Polynesian men (beta = -2.42 [95% CI -3.37, -1.46] and beta = -6.80 [95% CI -10.06, -3.55], respectively) but not in West Polynesian men (beta = -1.79 [95% CI -4.74, 1.16]). Conclusion. Genetic risk variants for gout also harbor risk for earlier age at gout onset and tophaceous disease in European and Polynesian men. Our findings suggest that earlier gout onset involves the accumulation of gout risk alleles in men but perhaps not in women, and that this genetic risk is shared across multiple ancestral groups.
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| 3. |
- Hetland, M. L., et al.
(author)
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Active conventional treatment and three different biological treatments in early rheumatoid arthritis: phase IV investigator initiated, randomised, observer blinded clinical trial
- 2020
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In: Bmj-British Medical Journal. - : BMJ. - 1756-1833. ; 371
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Journal article (peer-reviewed)abstract
- OBJECTIVE To evaluate and compare benefits and harms of three biological treatments with different modes of action versus active conventional treatment in patients with early rheumatoid arthritis. DESIGN Investigator initiated, randomised, open label, blinded assessor, multiarm, phase IV study. SETTING Twenty nine rheumatology departments in Sweden, Denmark, Norway, Finland, the Netherlands, and Iceland between 2012 and 2018. PARTICIPANTS Patients aged 18 years and older with treatment naive rheumatoid arthritis, symptom duration less than 24 months, moderate to severe disease activity, and rheumatoid factor or anti-citrullinated protein antibody positivity, or increased C reactive protein. INTERVENTIONS Randomised 1:1:1:1, stratified by country, sex, and anti-citrullinated protein antibody status. All participants started methotrexate combined with (a) active conventional treatment (either prednisolone tapered to 5 mg/day, or sulfasalazine combined with hydroxychloroquine and intraarticular corticosteroids), (b) certolizumab pegol, (c) abatacept, or (d) tocilizumab. MAIN OUTCOME MEASURES The primary outcome was adjusted clinical disease activity index remission (CDAI <= 2.8) at 24 weeks with active conventional treatment as the reference. Key secondary outcomes and analyses included CDAI remission at 12 weeks and over time, other remission criteria, a non-inferiority analysis, and harms. RESULTS 812 patients underwent randomisation. The mean age was 54.3 years (standard deviation 14.7) and 68.8% were women. Baseline disease activity score of 28 joints was 5.0 (standard deviation 1.1). Adjusted 24 week CDAI remission rates were 42.7% (95% confidence interval 36.1% to 49.3%) for active conventional treatment, 46.5% (39.9% to 53.1%) for certolizumab pegol, 52.0% (45.5% to 58.6%) for abatacept, and 42.1% (35.3% to 48.8%) for tocilizumab. Corresponding absolute differences were 3.9% (95% confidence interval -5.5% to 13.2%) for certolizumab pegol, 9.4% (0.1% to 18.7%) for abatacept, and -0.6% (-10.1% to 8.9%) for tocilizumab. Key secondary outcomes showed no major differences among the four treatments. Differences in CDAI remission rates for active conventional treatment versus certolizumab pegol and tocilizumab, but not abatacept, remained within the prespecified non-inferiority margin of 15% (per protocol population). The total number of serious adverse events was 13 (percentage of patients who experienced at least one event 5.6%) for active conventional treatment, 20 (8.4%) for certolizumab pegol, 10 (4.9%) for abatacept, and 10 (4.9%) for tocilizumab. Eleven patients treated with abatacept stopped treatment early compared with 20-23 patients in the other arms. CONCLUSIONS All four treatments achieved high remission rates. Higher CDAI remission rate was observed for abatacept versus active conventional treatment, but not for certolizumab pegol or tocilizumab versus active conventional treatment. Other remission rates were similar across treatments. Non-inferiority analysis indicated that active conventional treatment was non-inferior to certolizumab pegol and tocilizumab, but not to abatacept. The results highlight the efficacy and safety of active conventional treatment based on methotrexate combined with corticosteroids, with nominally better results for abatacept, in treatment naive early rheumatoid arthritis.
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| 8. |
- Martin, Myriam, et al.
(author)
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Citrullination of C1-inhibitor as a mechanism of impaired complement regulation in rheumatoid arthritis
- 2023
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In: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 14
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Journal article (peer-reviewed)abstract
- BackgroundDysregulated complement activation, increased protein citrullination, and production of autoantibodies against citrullinated proteins are hallmarks of rheumatoid arthritis (RA). Citrullination is induced by immune cell-derived peptidyl-Arg deiminases (PADs), which are overactivated in the inflamed synovium. We characterized the effect of PAD2- and PAD4-induced citrullination on the ability of the plasma-derived serpin C1-inhibitor (C1-INH) to inhibit complement and contact system activation. MethodsCitrullination of the C1-INH was confirmed by ELISA and Western blotting using a biotinylated phenylglyoxal probe. C1-INH-mediated inhibition of complement activation was analyzed by C1-esterase activity assay. Downstream inhibition of complement was studied by C4b deposition on heat-aggregated IgGs by ELISA, using pooled normal human serum as a complement source. Inhibition of the contact system was investigated by chromogenic activity assays for factor XIIa, plasma kallikrein, and factor XIa. In addition, autoantibody reactivity to native and citrullinated C1-INH was measured by ELISA in 101 RA patient samples. ResultsC1-INH was efficiently citrullinated by PAD2 and PAD4. Citrullinated C1-INH was not able to bind the serine protease C1s and inhibit its activity. Citrullination of the C1-INH abrogated its ability to dissociate the C1-complex and thus inhibit complement activation. Consequently, citrullinated C1-INH had a decreased capacity to inhibit C4b deposition via the classical and lectin pathways. The inhibitory effect of C1-INH on the contact system components factor XIIa, plasma kallikrein, and factor XIa was also strongly reduced by citrullination. In RA patient samples, autoantibody binding to PAD2- and PAD4-citrullinated C1-INH was detected. Significantly more binding was observed in anti-citrullinated protein antibody (ACPA)-positive than in ACPA-negative samples. ConclusionCitrullination of the C1-INH by recombinant human PAD2 and PAD4 enzymes impaired its ability to inhibit the complement and contact systems in vitro. Citrullination seems to render C1-INH more immunogenic, and citrullinated C1-INH might thus be an additional target of the autoantibody response observed in RA patients.
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| 9. |
- de Rooy, D. P. C., et al.
(author)
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Smoking as a risk factor for the radiological severity of rheumatoid arthritis: a study on six cohorts
- 2014
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In: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 73:7, s. 1384-1387
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Journal article (peer-reviewed)abstract
- Background Smoking is a risk factor for the development of anti -citrullinated protein antibodies (ACPA) positive rheumatoid arthritis (RA). Whether smoking predisposes to severe joint damage progression is not known, since deleterious, protective and neutral observations have been made. Objective To determine the effect of smoking on joint damage progression. Methods Smoking status was assessed in 3158 RA patients included in six cohorts (Leiden Early Arthritis Clinic (Leiden-EAC), BARFOT, Lund, Iceland, NDB and Wichita). In total 9412 radiographs were assessed. Multivariate normal regression and linear regression analyses were performed. Data were summarised in a random effects inverse variance meta-analysis. Results When comparing radiological progression for RA patients that were never, past and current smokers, smoking was significantly associated with more severe joint damage in Leiden-EAC (p=0.042) and BARFOT (p=0.015) RA patients. No significant associations were found in the other cohorts, though a meta-analysis on the six cohorts showed significantly more severe joint damage progression in smokers (p=0.01). Since smoking predisposes to ACPA, analyses were repeated with ACPA as additional adjustment factor. Then the association was lost (meta-analysis p=0.29). Conclusions This multi-cohort study indicated that the effect of smoking on joint damage is mediated via ACPA and that smoking is not an independent risk factor for radiological progression in RA.
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| 10. |
- Frodlund, M., et al.
(author)
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Predictors Of Antibody Response To Covid-19 Vaccine In Rituximab Treated Patients With Inflammatory Rheumatic Diseases. A Swedish Nationwide Study (Covid19-Reuma)
- 2022
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 368-369
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Journal article (other academic/artistic)abstract
- In line with other reports, our group showed that patients treated with rituximab had significant impaired antibody response compared to patients treated with other biologic and targeted and synthetic disease modifying anti-rheumatic drugs (csDMARD).ObjectivesTo investigate predictors of response to COVID-19 vaccination (2 doses of mRNA vaccines, 2 doses of virus vector vaccines or combinations of these) in patients with inflammatory rheumatic diseases (IRD) treated with rituximab and controls.MethodsAntibody levels to three antigens: Spike protein full length, Spike S1 and Nucleocapsid C-terminal fragment (to confirm previous COVID-19 infection) were measured in sera collected before vaccination and 2-12 weeks after the second vaccine using a multiplex bead-based serology assay. The antigen-specific cut-off was defined as the median fluorescence intensity signal plus 6x standard deviations across 12 pre-pandemic controls. A good vaccine response was defined as having antibodies over the cut-off level for both spike antigens. Proportion (%) responders was compared between patients and controls (Chi2 test).Patients with IRD receiving last rituximab treatment within a mean (range) 193 (23-501) days before first vaccination participated. Individuals without IRD served as a control group. Predictors of a good vaccine response were explored using multivariate logistic regression analysis adjusted for age, sex, disease duration, diagnosis (systemic vasculitis/RA/JIA/other), concomitant csDMARD, rituximab dose and prednisolone dose. Hazard ratio (chanse) of a good antibody response in relation to time between the last rituximab treatment and vaccination was studied by Kaplan-Meier survival analysis.ResultsIn total, 145 patients receiving rituximab and 61 controls were inclyded. Of these, 82 received rituximab as monotherapy (67% women; mean age 66 years, mean disease duration 13 years; 33% had RA/JIA and 60% vasculitis) and 63 received rituximab+csDMARD (62% women; mean age 66 years; mean disease duration 17 years; 76% had RA/JIA and 10 % vasculitis). Controls (n=61) were 74% women and mean age 49 years. Compared to controls, rituximab patients had lower antibody levels for both spike proteins (p<0.001). Proportion (%) responders among patients receiving rituximab as monotherapy (40.2%) and rituximab+DMARDs (25.4%) was significantly lower than in controls (98.4%) (p<0.001, Chi2). Higher age, concomitant csDMARD at vaccination and shorter time from last rituximab treatment predicted impaired antibody response (multivariate logistic regression model) (Table 1). Longer time between the last rituximab course and vaccination was associated with better antibody response (Figure 1).Table 1.Predictors of good antibody response to two doses of COVID-19 vaccine defined as antibodies over the cut-off level for both spike antigensBp-valueOR95% CIAge at vaccination (years)-0.040.0090.960.93-0.99Sex (male/female)-9.550.2090.580.24-1.36csDMARD at vaccination (yes/no)-1.080.0260.340.13-0.88Prednisolone (mg/dag)-0.100.1030.900.80-1.02Rituximab dos (1000 mg vs 500 mg)-0.010.3700.990.99-1.00Time between the last rituximab and vaccination (months)0.200.0011.311.11-1.55Diagnosis at vaccination (systemic vasculitis vs others)-0.510.3150.600.21-1.64Figure 1.The chance of good antibody response following two doses of COVID-19 vaccine in relation to time between the last rituximab course and vaccination.ConclusionPatients with IRD getting vaccinated with two doses of COVID19 vaccine during the treatment with rituximab have the ability to develop antibody response although the response is impaired. For each month passed after the last rituximab course, the chance of good antibody response increases with 30%. Younger patients receiving rituximab as monotherapy and vaccinated preferably several months after the last rituximab treatment have the highest chance of achieving a good antibody response.AcknowledgementsUnrestricted research grants have been received from Roche and starting grants from The Swedish Rheumatism AssociationDisclosure of InterestsMartina Frodlund: None declared, Katerina Chatzidionysiou Consultant of: consultancy fees from Eli Lilly, AbbVie and Pfizer., Anna Södergren: None declared, Eva Klingberg: None declared, Monika Hansson: None declared, Elisa Pin: None declared, Sophie Olsson: None declared, Anders Bengtsson: None declared, Lars Klareskog Grant/research support from: has eceived research grants from Pfizer, BMS, Affibody, Sonoma Biotherapeutics, Meliha C Kapetanovic Consultant of: have received consultancy fees from Abbvie, Pfizer and GSK, Grant/research support from: have received unrestricted research grants from Roche and Pfizer
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| 11. |
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| 12. |
- Frodlund, M., et al.
(author)
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The impact of immunomodulating treatment on the serological immunogenicity following three doses of covid-19 vaccine and persistence of immunogenicity of two vaccine doses in patients with inflammatory rheumatic diseases - a swedish study (covid19-reuma)
- 2023
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 82, s. 533-533
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Journal article (other academic/artistic)abstract
- Background Data on serological immunity after three doses and the long-term immunogenicity (persistence) of COVID-19 vaccine in patients with inflammatory rheumatic diseases (IRD) treated with different immunomodulating drugs are still limited.Objectives To elucidate if 1) a third dose COVID-19 vaccine improves antibody responses, compared to two doses, in patients with IRD treated with biologic or targeted synthetic DMARD (b/tsDMARDs) treatment given as monotherapy or in combination with conventional synthetic DMARDs (csDMARDs) compared to controls, and 2) the persistence of antibody response after two doses of COVID-19 vaccine in IRD patients.Methods Antibody levels to two antigens representing Spike full length protein and Spike S1 and a Nucleocapsid C-terminal fragment (used to confirm previous COVID-19 infection) were measured in serum samples collected 2-12 and 21-40 weeks after the second vaccine dose and 2-12 weeks after the third dose using a multiplex bead-based serology assay. A sufficient antibody response (seropositivity) was defined as having antibodies over the cut-off level for both spike antigens (1). WT (wild type) anti-Spike IgG and omicron BA.1 and BA.2 variants were measured. Patients with IRD receiving immunomodulating treatment, regularly followed at a rheumatology department and a group of controls were recruited from five Swedish region.Results In total, 323 of 414 patients with IRD and 36 controls who received three vaccine doses participated in this part of the study. Following treatment groups were included: rituximab (n=118; 68% female; mean age 67 years), abatacept (n=18; 72% female; mean age 64 years), IL6r inhibitors (n=60; 73% female; mean age 64 years), JAK-inhibitors (n=44; 80% female, mean age 52 years), TNF-inhibitors (n=59; 70% female; mean age 47 years;), IL12/23/17 inhibitors (n=24; 46% female; mean age 54 years) and controls (n=36; 75% female, mean age 51 years). b/ts DMARD treatment was given as monotherapy or in combination with csDMARD, methotrexate (MTX) being the most frequently used csDMARD (32.5%). Compared to results after two vaccine doses, proportion (%) of seropositivity after three vaccine doses increased significantly in groups rituximab +/- DMARD (p=0.003 and p=0.004, respectively), IL6r inhibitors +DMARD (p=0.02), and abatacept+DMARD (p=0.01). However, the proportion of seropositivity after three vaccine doses was still significantly lower in rituximab treated patients (52%) compared to other treatment groups or controls (p<0.001) (Figure 1A/B). Antibody response to WT, omicron sBA.1 and sBA.2 showed similar pattern with the lowest levels among patients treated with rituximab.When antibody response was compared between 2-12 weeks and 21-40 weeks after second dose, the proportion of seropositive rituximab treated patients decreased from 34.9 % to 32.6%. All patients with JAK inhibitors and with JAK-inhibitors and IL6r-inhibitors seropositive 21-40 weeks after the second vaccine dose. Patients treated with other bDMARDs were not included in this analysis due to limited number participants.Conclusion In this Swedish study including IRD patients receiving different b/t DMARDs, a sufficient immunogenicity of the third dose of COVID-19 vaccine was observed in all treatments with exception for rituximab. However, the increased proportion of seropositivity after the third COVID-19 vaccine doses in rituximab and other patients with insufficient response to two doses including response to the omicron variants, supports the current recommendations on additional booster doses. The immunogenicity of two vaccine doses was preserved to 40 weeks in majority of patients treated with different immunomodulating treatment with exception for rituximab.
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| 13. |
- Furer, Victoria, et al.
(author)
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2019 update of EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases
- 2020
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 79:1, s. 39-52
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Journal article (peer-reviewed)abstract
- To update the European League Against Rheumatism (EULAR) recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD) published in 2011. Four systematic literature reviews were performed regarding the incidence/prevalence of vaccine-preventable infections among patients with AIIRD; efficacy, immunogenicity and safety of vaccines; effect of anti-rheumatic drugs on the response to vaccines; effect of vaccination of household of AIIRDs patients. Subsequently, recommendations were formulated based on the evidence and expert opinion. The updated recommendations comprise six overarching principles and nine recommendations. The former address the need for an annual vaccination status assessment, shared decision-making and timing of vaccination, favouring vaccination during quiescent disease, preferably prior to the initiation of immunosuppression. Non-live vaccines can be safely provided to AIIRD patients regardless of underlying therapy, whereas live-attenuated vaccines may be considered with caution. Influenza and pneumococcal vaccination should be strongly considered for the majority of patients with AIIRD. Tetanus toxoid and human papilloma virus vaccination should be provided to AIIRD patients as recommended for the general population. Hepatitis A, hepatitis B and herpes zoster vaccination should be administered to AIIRD patients at risk. Immunocompetent household members of patients with AIIRD should receive vaccines according to national guidelines, except for the oral poliomyelitis vaccine. Live-attenuated vaccines should be avoided during the first 6 months of life in newborns of mothers treated with biologics during the second half of pregnancy. These 2019 EULAR recommendations provide an up-to-date guidance on the management of vaccinations in patients with AIIRD.
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| 14. |
- Butt, M. M., et al.
(author)
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Maximizing Minimum Throughput Guarantees : The Small Violation Probability Region
- 2013
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In: Wireless Communications Letters. - 2162-2337. ; 2:3, s. 271-274
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Journal article (peer-reviewed)abstract
- Providing minimum throughput guarantees is one of the goals for radio resource allocation schemes. It is difficult to provide these guarantees without defining violation probability due to limited power budget and rapidly changing conditions of the wireless channel. For every practical scheduling scheme, there is a feasibility region defined by the minimum guaranteed throughput and the corresponding probability that the users fail to get the guaranteed throughput (violation probability). In this work, we focus on minimizing the violation probability specifically in the small probability region. We compare our results with major schedulers available in literature and show that our scheme outperforms them in the small violation probability region.
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| 15. |
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| 16. |
- Furer, Victoria, et al.
(author)
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Incidence and prevalence of vaccine preventable infections in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD) : A systemic literature review informing the 2019 update of the EULAR recommendations for vaccination in adult patients with AIIRD
- 2019
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In: RMD Open. - : BMJ. - 2056-5933. ; 5:2
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Journal article (peer-reviewed)abstract
- Objectives The aims of this study were to update the evidence on the incidence and prevalence rates of vaccine preventable infections (VPI) in patients with autoimmune inflammatory rheumatic diseases (AIIRD) and compare the data to the general population when available. Methods A literature search was performed using Medline, Embase and Cochrane library (October 2009 to August 2018). The primary outcome was the incidence or prevalence of VPI in the adult AIIRD population. Meta-analysis was performed when appropriate. Results Sixty-three publications out of 3876 identified records met the inclusion criteria: influenza (n=4), pneumococcal disease (n=7), hepatitis B (n=10), herpes zoster (HZ) (n=29), human papillomavirus (HPV) infection (n=13). An increased incidence of influenza and pneumococcal disease was reported in patients with AIIRD. HZ infection-pooled incidence rate ratio (IRR) was 2.9 (95% CI 2.4 to 3.3) in patients with AIIRD versus general population. Among AIIRD, inflammatory myositis conferred the highest incidence rate (IR) of HZ (pooled IRR 5.1, 95% CI 4.3 to 5.9), followed by systemic lupus erythematosus (SLE) (pooled IRR 4.0, 95% CI 2.3 to 5.7) and rheumatoid arthritis (pooled IRR 2.3, 95% CI 2.1 to 2.6). HPV infection-pooled prevalence ratio was 1.6, 95% CI 0.7 to 3.4 versus general population, based on studies mainly conducted in the SLE population in Latin America and Asia. Pooled prevalence of hepatitis B surface antigen and hepatitis B core antibody in patients with AIIRD was similar to the general population, 3%, 95% CI 1% to 5% and 15%, 95% CI 7% to 26%, respectively. Conclusion Current evidence shows an increased risk of VPI in patients with AIIRD, emphasising that prevention of infections is essential in these patients.
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| 17. |
- Kapetanovic, D., et al.
(author)
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Secondary User Scheduling Under Throughput Guarantees for the Primary Network
- 2013
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In: Proceedings of IEEE 78th Vehicular Technology Conference.
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Conference paper (peer-reviewed)abstract
- This work addresses scheduling in a cognitive radio scenario where a minimum throughput for the downlink primary network (PN) is guaranteed to each user with an associated violation probability (probability of not obtaining the guaranteed throughput). The primary network is surrounded by multiple downlink secondary networks, each aiming to maximize its network throughput. Scheduling in PN is performed independent of the secondary networks. Some information about the PN is available at the central scheduler that is responsible for scheduling the secondary networks. The contribution of this work is to apply a novel scheduler to the PN which is more robust to QoS degradations resulting from the secondary networks than other state of the art schedulers. This is validated by numerical simulations of the cognitive radio network.
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| 18. |
- Rondaan, Christien, et al.
(author)
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Efficacy, immunogenicity and safety of vaccination in adult patients with autoimmune inflammatory rheumatic diseases : A systematic literature review for the 2019 update of EULAR recommendations
- 2019
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In: RMD Open. - : BMJ. - 2056-5933. ; 5:2
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Research review (peer-reviewed)abstract
- Aim To present a systematic literature review (SLR) on efficacy, immunogenicity and safety of vaccination in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD), aiming to provide a basis for updating the EULAR evidence-based recommendations. Methods An SLR was performed according to the standard operating procedures for EULAR-endorsed recommendations. Outcome was determined by efficacy, immunogenicity and safety of vaccination in adult patients with AIIRD, including those receiving immunomodulating therapy. Furthermore, a search was performed on the effect of vaccinating household members of patients with AIIRD on the occurrence of vaccine-preventable infections in patients and their household members (including newborns). The literature search was performed using Medline, Embase and the Cochrane Library (October 2009 to August 2018). Results While most investigated vaccines were efficacious and/or immunogenic in patients with AIIRD, some were less efficacious than in healthy control subjects, and/or in patients receiving immunosuppressive agents. Adverse events of vaccination were generally mild and the rates were comparable to those in healthy persons. Vaccination did not seem to lead to an increase in activity of the underlying AIIRD, but insufficient power of most studies precluded arriving at definite conclusions. The number of studies investigating clinical efficacy of vaccination is still limited. No studies on the effect of vaccinating household members of patients with AIIRD were retrieved. Conclusion Evidence on efficacy, immunogenicity and safety of vaccination in patients with AIIRD was systematically reviewed to provide a basis for updated recommendations.
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| 19. |
- Roseman, C., et al.
(author)
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Persistent pain and its predictors after starting anti-tumour necrosis factor therapy in psoriatic arthritis : what is the role of inflammation control?
- 2023
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In: Scandinavian Journal of Rheumatology. - 0300-9742. ; 53:2, s. 94-103
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Journal article (peer-reviewed)abstract
- Objective: While considerable focus has been placed on pain due to inflammation in psoriatic arthritis (PsA), less is reported on pain despite inflammation control. Here, we aimed to investigate the occurrence/predictors of persistent pain, including non-inflammatory components, after starting anti-tumour necrosis factor (anti-TNF) therapy. Method: Bionaïve PsA patients starting a first anti-TNF therapy 2004–2010 were identified (South Swedish Arthritis Treatment Group register; N = 351). Outcomes included unacceptable pain [visual analogue scale (VAS) pain > 40 mm], and unacceptable pain despite inflammation control (refractory pain; VAS pain > 40 mm + C-reactive protein < 10 mg/L + ≤ 1 swollen joint of 28), assessed at 0, 3, 6, and 12 months. Baseline predictors were estimated by logistic regression. Results: Upon starting anti-TNF therapy, 85% of patients reported unacceptable pain, falling to 43% at 3 months and then remaining stable. After 12 months, refractory pain constituted 63% of all unacceptable pain. Higher baseline VAS pain/global, worse physical function and lower health-related quality-of-life were associated with a higher risk of unacceptable/refractory pain at 12 months. More swollen joints and higher evaluator’s global assessment were associated with a lower risk of 12-month refractory pain. Conclusions: A substantial proportion of PsA patients reported unacceptable pain throughout the first anti-TNF treatment year. At 12 months, refractory pain constituted about two-thirds of this remaining pain load. More objective signs of inflammation at anti-TNF initiation were associated with less future refractory pain. This highlights insufficient effect of biologics in patients with inflammation-independent pain, warranting alternative treatments.
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| 20. |
- C Kapetanovic, Meliha, et al.
(author)
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Prevalence and predictive factors of comorbidity in rheumatoid arthritis patients monitored prospectively from disease onset up to 20 years: lack of association between inflammation and cardiovascular disease.
- 2010
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In: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 1502-7732 .- 0300-9742. ; 39, s. 353-359
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Journal article (peer-reviewed)abstract
- Objectives: To study the prevalence of comorbid conditions at diagnosis and during follow-up in a cohort of patients with early rheumatoid arthritis (RA) followed prospectively over 20 years, and to identify possible early predictive factors for future comorbidities. Methods: A community-based cohort of 183 patients (mean age 52 years, 63% female) with early RA was recruited between 1985 and 1989. The presence of comorbidity at RA diagnosis and the occurrence of additional comorbidities were recorded continuously. Possible predictors of future comorbidities were analysed using the Cox proportional hazards model. Results: At RA diagnosis, at least one comorbid condition was present in 43% of the patients. Cardiovascular diseases (CVDs), including hypertension (16% of patients) and malignancy (6% of patients), were most common. In total, 82% of patients developed additional comorbidities during follow-up. CVD and malignancies remained the most frequent comorbidities. Higher age [p < 0.001, odds ratio (OR) 1.03, 95% confidence interval (CI) 1.01-1.15] and the presence of any comorbidity at diagnosis (p = 0.02; OR 1.64, 95% CI 1.08-2.52) predicted future comorbidity. Measures of inflammation at diagnosis or during follow-up were not predictive for development of CVD. Conclusion: Comorbidity was present in a considerable proportion of patients in this cohort. More than 40% of patients had another disease at inclusion and during follow-up and > 80% developed additional conditions. The pattern of comorbidity remained unchanged, with CVD and malignancy being most common. Older age and the presence of comorbidity at RA diagnosis predicted the development of comorbidities. The degree of inflammation at any time point was not predictive of future CVD.
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| 21. |
- Clausén Gull, Ingela, et al.
(author)
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Neighborhood conditions in a Swedish context - Two studies of reliability and validity of virtual systematic social observation using Google Street View
- 2023
-
In: Frontiers in Psychology. - : Frontiers Media SA. - 1664-1078. ; 14
-
Journal article (peer-reviewed)abstract
- Introduction: The goal of these studies was to investigate the reliability and validity of virtual systematic social observation (virtual SSO) using Google Street View in a Swedish neighborhood context.Methods: This was accomplished in two studies. Study 1 focused on interrater reliability and construct validity, comparing ratings conducted in-person to those done using Google Street View, across 24 study sites within four postal code areas. Study 2 focused on criterion validity of virtual SSO in terms of neighborhoods with low versus high income levels, including 133 study sites within 22 postal code areas in a large Swedish city. In both studies, assessment of the neighborhood context was conducted at each study site, using a protocol adapted to a Swedish context.Results: Scales for Physical Decay, Neighborhood Dangerousness, and Physical Disorder were found to be reliable, with adequate interrater reliability, high consistency across methods, and high internal consistency. In Study 2, significantly higher levels of observed Physical Decay, Neighborhood Dangerousness, and signs of garbage or litter were observed in postal codes areas (site data was aggregated to postal code level) with lower as compared to higher income levels.Discussion: We concluded that the scales within the virtual SSO with Google Street View protocol that were developed in this series of studies represents a reliable and valid measure of several key neighborhood contextual features. Implications for understanding the complex person-context interactions central to many theories of positive development among youth were discussed in relation to the study findings.
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| 22. |
- Dehlin, Mats, 1968, et al.
(author)
-
Consequences of Gout and Hyperuricemia : Gikt och hyperurikemi starkt associerade med folksjukdomar
- 2020
-
In: Läkartidningen. - 1652-7518. ; 117
-
Journal article (peer-reviewed)abstract
- Hyperuricemia (HU) and gout are strongly associated with CVD, associations that are most likely due to shared etiologies rather than causality. HU is for example causally related to the metabolic syndrome and in particular to obesity. Gout and HU can both be caused by and lead to decreased kidney function. On the other hand, there are observational data suggesting that HU may protect against neurodegenerative diseases such as Alzheimer and Parkinson's disease. Ongoing RCTs with urate and urate lowering therapy (ULT) will help to resolve some of these controversies. Nevertheless, gout is a "curable disease" by ULT, a treatment which in adequate doses may also have positive effect on several associated co-morbidities.
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| 23. |
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| 24. |
- Elmér, Evelina, et al.
(author)
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Methotrexate Treatment Suppresses Monocytes in Nonresponders to Pneumococcal Conjugate Vaccine in Rheumatoid Arthritis Patients
- 2022
-
In: Journal of Immunology Research. - : Hindawi Limited. - 2314-8861 .- 2314-7156. ; 2022
-
Journal article (peer-reviewed)abstract
- Patients with rheumatoid arthritis (RA) have an increased risk of infections; therefore, immunization against vaccine-preventable diseases is important. Methotrexate (MTX) impairs the antibody response to pneumococcal conjugate vaccine (PCV) in patients with arthritis, and the underlying mechanism is largely unknown. Here, we investigate the potential role of the innate immune system in the faltering antibody response following PCV vaccination in RA patients treated with MTX. Phenotypes of circulating granulocytes and monocytes were analyzed in 11 RA patients treated with MTX, 13 RA patients without disease-modifying antirheumatic drug treatment (0DMARD), and 13 healthy controls (HC). Peripheral blood samples were collected before and 7 days after vaccination. In addition, the MTX group was sampled before initiating treatment. Frequencies of granulocyte and monocyte subsets were determined using flow cytometry. Serotype-specific IgG were quantified using a multiplex bead assay, pre- and 4-6 weeks after vaccination. At baseline, no differences in granulocyte and monocyte frequencies were observed between the groups. Within the MTX group, the frequency of basophils increased during treatment and was higher compared to the HC and 0DMARD groups at the prevaccination time point. MTX patients were categorized into responders and nonresponders according to the antibody response. Before initiation of MTX, there were no differences in granulocyte and monocyte frequencies between the two subgroups. However, following 6-12 weeks of MTX treatment, both the frequency and concentration of monocytes were lower in PCV nonresponders compared to responders, and the difference in monocyte frequency remained after vaccination. In conclusion, the suppressive effect of MTX on monocyte concentration and frequency could act as a biomarker to identify nonresponders to PCV vaccination.
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| 25. |
- Fatima, Tahzeeb, et al.
(author)
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The absolute risk of gout by clusters of gout-associated comorbidities and lifestyle factors-30 years follow-up of the Malmo Preventive Project
- 2020
-
In: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 22:1
-
Journal article (peer-reviewed)abstract
- Background Gout is predicted by a number of comorbidities and lifestyle factors. We aimed to identify discrete phenotype clusters of these factors in a Swedish population-based health survey. In these clusters, we calculated and compared the incidence and relative risk of gout. Methods Cluster analyses were performed to group variables with close proximity and to obtain homogenous clusters of individuals (n = 22,057) in the Malmo Preventive Project (MPP) cohort. Variables clustered included obesity, kidney dysfunction, diabetes mellitus (DM), hypertension, cardiovascular disease (CVD), dyslipidemia, pulmonary dysfunction (PD), smoking, and the use of diuretics. Incidence rates and hazard ratios (HRs) for gout, adjusted for age and sex, were computed for each cluster. Results Five clusters (C1-C5) were identified. Cluster C1 (n = 16,063) was characterized by few comorbidities. All participants in C2 (n = 750) had kidney dysfunction (100%), and none had CVD. In C3 (n = 528), 100% had CVD and most participants were smokers (74%). C4 (n = 3673) had the greatest fractions of obesity (34%) and dyslipidemia (74%). In C5 (n = 1043), proportions with DM (51%), hypertension (54%), and diuretics (52%) were highest. C1 was by far the most common in the population (73%), followed by C4 (17%). These two pathways included 86% of incident gout cases. The four smaller clusters (C2-C5) had higher incidence rates and a 2- to 3-fold increased risk for incident gout. Conclusions Five distinct clusters based on gout-related comorbidities and lifestyle factors were identified. Most incident gout cases occurred in the cluster of few comorbidities, and the four comorbidity pathways had overall a modest influence on the incidence of gout.
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| 26. |
- Fragoulis, George E., et al.
(author)
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2022 EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in adults with autoimmune inflammatory rheumatic diseases
- 2023
-
In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 82:6, s. 742-753
-
Journal article (peer-reviewed)abstract
- Objectives: To develop EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in patients with autoimmune inflammatory rheumatic diseases (AIIRD). Methods: An international Task Force (TF) (22 members/15 countries) formulated recommendations, supported by systematic literature review findings. Level of evidence and grade of recommendation were assigned for each recommendation. Level of agreement was provided anonymously by each TF member. Results: Four overarching principles (OAP) and eight recommendations were developed. The OAPs highlight the need for infections to be discussed with patients and with other medical specialties, in accordance with national regulations. In addition to biologic/targeted synthetic disease-modifying antirheumatic drugs (DMARDs) for which screening for latent tuberculosis (TB) should be performed, screening could be considered also before conventional synthetic DMARDs, glucocorticoids and immunosuppressants. Interferon gamma release assay should be preferred over tuberculin skin test, where available. Hepatitis B (HBV) antiviral treatment should be guided by HBV status defined prior to starting antirheumatic drugs. All patients positive for hepatitis-C-RNA should be referred for antiviral treatment. Also, patients who are non-immune to varicella zoster virus should be informed about the availability of postexposure prophylaxis should they have contact with this pathogen. Prophylaxis against Pneumocystis jirovecii seems to be beneficial in patients treated with daily doses >15-30 mg of prednisolone or equivalent for >2-4 weeks. Conclusions: These recommendations provide guidance on the screening and prevention of chronic and opportunistic infections. Their adoption in clinical practice is recommended to standardise and optimise care to reduce the burden of opportunistic infections in people living with AIIRD.
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| 27. |
- Frodlund, M, et al.
(author)
-
THE IMPACT OF IMMUNOMODULATING TREATMENT ON THE IMMUNOGENICITY OF COVID-19 VACCINES IN PATIENTS WITH IMMUNE-MEDIATED INFLAMMATORY RHEUMATIC DISEASES COMPARED TO HEALTHY CONTROLS. A SWEDISH NATIONWIDE STUDY (COVID19-REUMA)
- 2022
-
In: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 113-114
-
Conference paper (other academic/artistic)abstract
- Initial studies on the immunogenicity of COVID-19 vaccines in patients with immune-mediated inflammatory rheumatic diseases (IRD) reported diminished antibody response in general, and particularly when treated with rituximab or abatacept (1). Additional data are needed, especially for patients with IRD and immunomodulatory treatments.ObjectivesTo elucidate the antibody response after two doses of COVID-19 vaccine in patients with IRD treated with biologic or targeted synthetic disease modifying anti-rheumatic drugs (b/ts DMARDs) as monotherapy or combined with conventional synthetic DMARDS (csDMARDs).MethodsAntibodies against two antigens representing Spike full length protein and Spike S1 and a Nucleocapsid C-terminal fragment (used to confirm previously COVID-19 infection) were measured in serum obtained before and after the second vaccination using a multiplex bead-based serology assay (2). Patients with IRD receiving immunomodulating treatment, followed at a rheumatology department and healthy individuals (controls) were recruited from five Swedish regions. Antibody positivity was classified as the signal passing an antigen specific cutoff based on the mean intensity signal of 12 selected negative pre-pandemic controls plus 6SD for Spike/S1 and 12SD for Nucleocapsid-C. Good vaccine response was defined as having antibodies over cut-off level for both spike antigens. Percentage of responders in each treatment group was compared to controls (Chi2 test). Predictors of antibody response were determined using logistic regression analysis.ResultsIn total, 414 patients (320 RA/JIA/psoriatic arthritis/axial spondylarthritis, 60 systemic vasculitis and 32 other IRD) and 61 controls participated. Patients receiving rituximab (n=145; 65% female; mean age 65years), abatacept (n=21; 77% female; mean age 66 years), IL6 inhibitors (n=77; 74% female; mean age 64years), JAK-inhibitors (n=58; 75% female, mean age 53years), TNF-inhibitors (n=68; 66% female; mean age 44years;), IL17 inhibitors (n=42; 54% female; mean age 44years) and controls (n=61; 74% female, mean age 49years) were studied. Patients receiving IL6 inhibitor (81.0%), abatacept (43.8%) or rituximab (33.8%) had a significantly lower antibody response rate compared to controls (98.4%), further pronounced if combined with csDMARD (p<0.001) (Figure 1). In the adjusted logistic regression analysis, higher age, rituximab, abatacept, concomitant csDMARD but not IL6 inhibitors, concomitant prednisolone, or a vasculitis diagnosis, remained significant predictors of antibody response (Table 1). All vaccines were well tolerated. 14 (3.4%) patients reported an increased activity in their IRD following vaccination.ConclusionIn this nationwide study including IRD patients receiving b/ts DMARDs a decreased immunogenicity of COVID-19 vaccines was observed in patients receiving rituximab, abatacept and to some extent IL-6 inhibitors. Concomitant csDMARD gave further attenuation. Patients on rituximab and abatacept should be prioritized for booster doses of COVID19 vaccine.References[1]Jena, et al. Response to SARS-CoV-2 vaccination in immune mediated inflammatory diseases: Systematic rev./meta-analysis. Autoim. Rev: 2021;102927[2]Hober, et al. Systematic evaluation of SARS-CoV-2 antigens enables a highly specific and sensitive multiplex serol. C-19 assay. Clin Transl Im. 2021;10(7): e1312Table 1.Predictors of antibody response to COVID-19 vaccineRituximab-1.799<0.0010.170.07-0.42Abatacept-1.9710.0010.140.04-0.45IL6 inhibitor0.0230.9651.020.36-2.94Age (years)-0.0810.0000.920.89-0.96csDMARD-1.1270.0020.320.16-0.66Prednisolone (mg/day)-0.0640.2060.940.85-1.04Frequency (%) of individuals with good antibody response to COVID-19 vaccineAcknowledgementsUnrestricted research grants have been received från Roche and starting grants from the Swedish Rheumatism AssociationDisclosure of InterestsMartina Frodlund Consultant of: Consultancy fees from AstraZeneca and GSK, Katerina Chatzidionysiou Consultant of: Consultancy fees from Eli Lilly, AbbVie and Pfizer, Anna Södergren: None declared, Eva Klingberg: None declared, Anders Bengtsson: None declared, Lars Klareskog Grant/research support from: Research grants from Pfizer, BMS, Affibody, Sonoma Biotherapeutics, Meliha C Kapetanovic: None declared
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| 28. |
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| 29. |
- Kapetanovic, Meliha C., et al.
(author)
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Prevalence and incidence of gout in southern Sweden from the socioeconomic perspective
- 2016
-
In: RMD Open. - : BMJ. - 2056-5933. ; 2:2
-
Journal article (peer-reviewed)abstract
- Objectives To estimate the prevalence and cumulative incidence of gout in southern Sweden with respect to socioeconomic status. Methods Among residents of Skåne region in the year 2013 (total population 1.3 million), adult persons (age 18 years +) who between 1998 and 2013 received a diagnosis of gout (International Classification of Disease 10th Edition (ICD-10) code M10) by any physician were identified using the Skåne Healthcare Register. We calculated the point prevalence by end of 2013 and annual cumulative incidence in 2013 standardised to the whole Skåne population according to sex, individual information on occupation (white collar/blue collar), income (low/middle/high) and level of education (primary school/high school/university). Results The crude 2013 point prevalence of gout and 2013 cumulative incidence (95% CI) were 1.69% (1.66% to 1.71%) and 24 cases per 10 000 persons (23-25), respectively. Compared to women, men had higher point prevalence (2.44% (2.40% to 2.49%) vs 0.96% (0.93% to 0.98%)) and higher annual cumulative incidence (33 cases per 10 000 (32-35)) versus 15 (14-16)). These figures increased with higher age but decreased with higher level of education, being the lowest in individuals with a university degree. Persons with middle income had highest point prevalence and cumulative incidence of gout, while those with white collar occupations had the lowest. Conclusions Gout is the most common inflammatory arthritis in southern Sweden with a prevalence of 1/41.7% in the adult population. There is a socioeconomic gradient with more gout present in the lower level of education and with more manual labour. © 2016 Published by the BMJ Publishing Group Limited.
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| 30. |
- Kapetanovic, Sabina, 1980-, et al.
(author)
-
Cross-Cultural Examination of Links between Parent-Adolescent Communication and Adolescent Psychological Problems in 12 Cultural Groups.
- 2020
-
In: Journal of Youth and Adolescence. - : Springer Science and Business Media LLC. - 0047-2891 .- 1573-6601. ; 49:6, s. 1225-1244
-
Journal article (peer-reviewed)abstract
- Internalizing and externalizing problems increase during adolescence. However, these problems may be mitigated by adequate parenting, including effective parent-adolescent communication. The ways in which parent-driven (i.e., parent behavior control and solicitation) and adolescent-driven (i.e., disclosure and secrecy) communication efforts are linked to adolescent psychological problems universally and cross-culturally is a question that needs more empirical investigation. The current study used a sample of 1087 adolescents (M = 13.19 years, SD = 0.90, 50% girls) from 12 cultural groups in nine countries including China, Colombia, Italy, Jordan, Kenya, Philippines, Sweden, Thailand, and the United States to test the cultural moderation of links between parent solicitation, parent behavior control, adolescent disclosure, and adolescent secrecy with adolescent internalizing and externalizing problems. The results indicate that adolescent-driven communication, and secrecy in particular, is intertwined with adolescents' externalizing problems across all cultures, and intertwined with internalizing problems in specific cultural contexts. Moreover, parent-driven communication efforts were predicted by adolescent disclosure in all cultures. Overall, the findings suggest that adolescent-driven communication efforts, and adolescent secrecy in particular, are important predictors of adolescent psychological problems as well as facilitators of parent-adolescent communication.
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| 31. |
- Kapetanovic, Sabina, 1980-, et al.
(author)
-
Does attending preschool in an economically advantaged or disadvantaged neighborhood moderate the effects of the preschool edition of promoting alternative thinking strategies®?
- 2022
-
In: Frontiers in Education. - : Frontiers Media S.A.. - 2504-284X. ; 7
-
Journal article (peer-reviewed)abstract
- Early interventions that foster the participation, engagement, and development of children attending preschools, including those in economically disadvantaged (low-income) neighborhoods, are of high priority. One such intervention is a universal socioemotional learning (SEL) program called Promoting Alternative Thinking Strategies (PATHS®) which aims to promote social emotional competence and positive adjustment in children, in general, and may have unique benefits for children attending preschool in low incomes areas. In the SEL field, areas in need of exploration include the possible role that neighborhood income level (i.e., all residents’ income in a postal code that a preschool is located in) could have for children’s social emotional competence and positive adjustment and how neighborhood income level may relate to benefits of an intervention such as PATHS. The study aims were to investigate 1) the baseline group differences in social emotional competence and adjustment depending on the neighborhood income level and 2) to determine if neighborhood income level moderated the effects of PATHS on children’s social emotional competence and adjustment from pre to posttest. Participants were 275 children aged four to five years old, from the preschools randomized into an immediate intervention (n = 145 children) or a wait-list control group (n = 130 children). Overall, 42.9% (n = 118) of the children attended preschools in economically disadvantaged neighborhoods and 57.1% (n = 157) of the children attended preschools in economically advantaged neighborhoods. Children’s social emotional competence and adjustment were assessed through child tasks, child observations and teacher reports. The moderation of intervention effects by the preschools’ neighborhood income was tested in a series of just-identified structural equation models (SEM) that explored interaction effects (income*PATHS interactions). At baseline, relative to children attending preschool in economically advantaged preschools, children attending preschool in economically disadvantaged neighborhoods showed lower levels of inhibitory control, working memory, task orientation and higher levels of inattention. Children attending preschools in economically disadvantaged neighborhoods participating in PATHS also showed reductions in inattention, social withdrawal and anxiety compared to control group children also attending preschool in disadvantaged neighborhoods. Additionally, PATHS children from advantaged neighborhoods improved their prosocial behavior, but not their social independence, relative to control group children who also attended preschool in advantaged neighborhoods. Offering PATHS as an SEL intervention in early childhood education and care settings could help to reduce disparities among children in a number of key outcomes.
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| 32. |
- Kapetanovic, Sabina, 1980-, et al.
(author)
-
Parenting, Adolescent Sensation Seeking, and Subsequent Substance Use : Moderation by Adolescent Temperament
- 2023
-
In: Journal of Youth and Adolescence. - : Springer Nature. - 0047-2891 .- 1573-6601. ; 52:6, s. 1235-1254
-
Journal article (peer-reviewed)abstract
- Although previous research has identified links between parenting and adolescent substance use, little is known about therole of adolescent individual processes, such as sensation seeking, and temperamental tendencies for such links. To testtenets from biopsychosocial models of adolescent risk behavior and differential susceptibility theory, this study investigatedlongitudinal associations among positive and harsh parenting, adolescent sensation seeking, and substance use and testedwhether the indirect associations were moderated by adolescent temperament, including activation control, frustration,sadness, and positive emotions. Longitudinal data reported by adolescents (n = 892; 49.66% girls) and their mothers fromeight cultural groups when adolescents were ages 12, 13, and 14 were used. A moderated mediation model showed thatparenting was related to adolescent substance use, both directly and indirectly, through sensation seeking. Indirectassociations were moderated by adolescent temperament. This study advances understanding of the developmental pathsbetween the contextual and individual factors critical for adolescent substance use across a wide range of cultural contexts.
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| 33. |
- Kristensen, Lars Erik, et al.
(author)
-
Predictors of response to anti-TNF therapy according to ACR and EULAR criteria in patients with established RA: results from the South Swedish Arthritis Treatment Group Register.
- 2008
-
In: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 47:4, s. 495-499
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: To identify factors predicting response to first TNF blocking treatment course in patients with established RA with a special focus on gender differences. METHODS: Patients with active RA initiating their first treatment course of TNF-blocking therapy were enrolled. The study period was March 1999 through September 2006. The prospective protocol included information on demographics, clinical characteristics of patients and response measures. Fulfilment of ACR 50-70% improvement and European League Against Rheumatism (EULAR) good response or remission [28-joint disease activity score (DAS28) <2.6] at 3 months were chosen as primary outcome measures. Potential predictors of responses were identified using multivariate binary logistic regression models. RESULTS: In total, 1565 patients were included in the study. Gender did not influence treatment response. Consistently, concomitant methotrexate (MTX) was significantly associated with EULAR remission, EULAR good response, ACR50 response and ACR70 response with odds ratios (ORs) 1.97, 2.13, 2.10 and 1.75, respectively. Concurrent treatment with other DMARDs was also significantly associated with EULAR remission, EULAR good response and ACR50 response (OR: 1.96, 2.24 and 1.94, respectively). Likewise, low HAQ at baseline consistently predicted good clinical outcome. Disease activity at baseline was directly associated with favourable response when measured by ACR50 and ACR70 (OR: 1.59 and 1.60, respectively), whereas DAS28 score at baseline was inversely associated with EULAR remission (OR: 0.78). CONCLUSIONS: In this observational study of patients with established RA, gender did not predict response to anti-TNF therapy, whereas treatment with concomitant DMARDs, especially MTX and low disability were associated with good response. Choice of outcome measures may influence the predictive value of baseline features.
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| 34. |
- Källmark, H., et al.
(author)
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Serologic immunogenicity and safety of herpes zoster subunit vaccine in patients with rheumatoid arthritis receiving Janus kinase inhibitors
- 2023
-
In: Rheumatology. - 1462-0324.
-
Journal article (peer-reviewed)abstract
- Objective Patients with RA treated with Janus kinase inhibitors (JAKis) are at increased risk of herpes zoster (HZ). The objective of this study was to investigate the serological immunogenicity and safety of the HZ subunit (HZ/su) vaccine in RA patients treated with JAKi, for which little is known.Methods RA patients treated with JAKi (n = 82) at the Department of Rheumatology, Skane University Hospital, Lund and Malmo, Sweden, and healthy controls (n = 51) received two doses of the HZ/su vaccine (Shingrix). Vaccine-specific antibody responses were analysed using indirect ELISA. Post-vaccination antibody levels were compared between patients and controls using analysis of covariance. Potential predictors for vaccine response were investigated using a multivariable linear regression analysis. Self-reported adverse events (AEs) and changes in RA disease activity were analysed.Results Following vaccination, vaccine-specific antibody levels increased significantly in both patients and controls (P < 0.0001). A total of 80.5% of patients and 98.0% of controls achieved a >= 4-fold increase in antibody levels. Post-vaccination antibody levels were lower in patients than controls [ratio 0.44 (95% CI 0.31, 0.63)] and lower in patients receiving JAKi + methotrexate than JAKi monotherapy [ratio 0.43 (95% CI 0.24, 0.79)]. AEs, mostly mild/moderate, were common. One patient developed HZ and six patients (6.5%) had increased RA disease activity following vaccination.Conclusion The HZ/su vaccine was serologically immunogenic in most RA patients treated with JAKi. Moreover, the vaccine had an acceptable safety profile. These results support recommendations for use of the HZ/su vaccine in this vulnerable population.Trial registration ClinicalTrials.gov (https://clinicaltrials.gov), NCT03886038.
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| 35. |
- Olsson, Tina M., et al.
(author)
-
Advancing Social Intervention Research Through Program Theory Reconstruction
- 2023
-
In: Research on Social Work Practice. - : Sage Publications. - 1049-7315 .- 1552-7581. ; 33:6, s. 642-655
-
Journal article (peer-reviewed)abstract
- Program theory reconstruction is an often-overlooked aspect of social intervention research. In this paper, we argue that intervention research benefits if the research design is informed by the specific intervention's program theory (i.e., the idea of how the intervention is supposed to lead to the intended outcomes). The purpose of this paper is to offer a comprehensive and accessible guide to program theory reconstruction in research on social interventions and to provide arguments as to how program theory reconstruction can be used to benefit intervention studies. First, we summarize what program theory is and its role in intervention research. Second, we provide a direct “how-to” for researchers, practitioners, and students who may be unfamiliar with the methods of program theory reconstruction but are interested in undertaking a program theory reconstruction. Finally, we conclude with how program theory reconstruction can benefit intervention research.
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| 36. |
- Olsson, Tina M., et al.
(author)
-
Study protocol for a non-randomized controlled trial of the effects of internet-based parent training as a booster to the preschool edition of PATHS® : Universal edition of the Parent Web
- 2023
-
In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 18:4, s. e0284926-e0284926
-
Journal article (peer-reviewed)abstract
- Well implemented, universal parental support is often effective in families with younger children, but research on their effects on families with adolescent children is scarce. In this study, a trial of the universal parent training intervention “Parent Web” in early adolescence is added to the social emotional learning intervention Promoting Alternative Thinking Strategies (PATHS®), completed in early childhood. The Parent Web is a universal online parenting intervention based on social learning theory. The intervention aims to promote positive parenting and family interaction through five weekly modules completed over 6–8 weeks.The main hypothesis is that participants in the intervention group will exhibit significant pre to post- intervention-related benefits relative participants in the comparison group.The aims of this study are: 1) provide Parent Web as a booster aimed at improving parenting support and practices at the transition into adolescence to a cohort of parents whose children have previously participated in preschool PATHS, and 2) examine the effects of the universal edition of Parent Web. The study has a quasi-experimental design with pre- and post-testing.The incremental effects of this internet-delivered parent training intervention are tested in parents of early adolescents (11–13 years) who participated in PATHS when 4–5 years old compared to a matched sample of adolescents with no prior experience of PATHS. The primary outcomes are parent reported child behavior and family relationships. Secondary outcomes include self-reported parent health and stress. The proposed study is one of the few trials to test the effects of universal parental support in families of early adolescents and will therefore contribute to the understanding of how mental health in children and young people can be promoted across developmental periods through a continuum of universal measures.Trial registration: Clinical trials.gov (NCT05172297), prospectively registered on December 29, 2021.
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| 37. |
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| 38. |
- Svärd, A., et al.
(author)
-
Large health benefits can be achieved by better treatment of gout : Stora hälsovinster att uppnå med bättre behandling av gikt
- 2020
-
In: Lakartidningen. - 1652-7518. ; 117
-
Journal article (peer-reviewed)abstract
- Urate lowering therapy (ULT) should, according to recent guidelines, be initiated in the majority of cases already after the first attack of gout. Allopurinol is the first line choice of ULT and should be started with low dose, which is increased until the treatment target is reached. The treatment target should be a blood urate of < 360 µmol/l or < 300 µmol/l (in the presence of topfi), which should be maintained until topfi have resolved. NSAID/cox-inhibitors, colchicine and glucocorticoids are all valid short-term treatments of gout attacks. ULT should not be paused/terminated during attacks and can be initiated during an attack that is adequately treated. Recent RCTs of ULT treatment have demonstrated the importance of thorough and adequate information to the patient and regular follow-up until treatment targets are reached. Such a strategy improve both compliance and outcomes of ULT treatment.
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| 39. |
- Tran, Thao Thanh, et al.
(author)
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Inhibition of the master regulator of Listeria monocytogenes virulence enables bacterial clearance from spacious replication vacuoles in infected macrophages
- 2022
-
In: PLoS Pathogens. - : Public Library Science. - 1553-7366 .- 1553-7374. ; 18:1
-
Journal article (peer-reviewed)abstract
- A hallmark of Listeria (L.) monocytogenes pathogenesis is bacterial escape from maturing entry vacuoles, which is required for rapid bacterial replication in the host cell cytoplasm and cell-to-cell spread. The bacterial transcriptional activator PrfA controls expression of key virulence factors that enable exploitation of this intracellular niche. The transcriptional activity of PrfA within infected host cells is controlled by allosteric coactivation. Inhibitory occupation of the coactivator site has been shown to impair PrfA functions, but consequences of PrfA inhibition for L. monocytogenes infection and pathogenesis are unknown. Here we report the crystal structure of PrfA with a small molecule inhibitor occupying the coactivator site at 2.0 Å resolution. Using molecular imaging and infection studies in macrophages, we demonstrate that PrfA inhibition prevents the vacuolar escape of L. monocytogenes and enables extensive bacterial replication inside spacious vacuoles. In contrast to previously described spacious Listeria-containing vacuoles, which have been implicated in supporting chronic infection, PrfA inhibition facilitated progressive clearance of intracellular L. monocytogenes from spacious vacuoles through lysosomal degradation. Thus, inhibitory occupation of the PrfA coactivator site facilitates formation of a transient intravacuolar L. monocytogenes replication niche that licenses macrophages to effectively eliminate intracellular bacteria. Our findings encourage further exploration of PrfA as a potential target for antimicrobials and highlight that intra-vacuolar residence of L. monocytogenes in macrophages is not inevitably tied to bacterial persistence.
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| 40. |
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| 41. |
- Wändell, P., et al.
(author)
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The use of anthropometric measures in the prediction of incident gout : results from a Swedish community-based cohort study
- 2019
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In: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 48:4, s. 294-299
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Journal article (peer-reviewed)abstract
- Objectives: To study associations between different anthropometric measures and incident gout, and to find the best predictive measure. Method: We used the baseline investigation from the Malmö Diet and Cancer study, excluding cases of prevalent gout (n = 28 081). Cox regression for each anthropometric measurement was calculated per standard deviation increment for men and women, with hazard ratios (HRs) and 95% confidence intervals (CIs), using a hospital diagnosis of incident gout (M10) during follow-up as the outcome. Incremental C-statistics for each anthropometric measure were used to determine the measure with the best predictive capacity, in models adjusted for age, socio-economic data, lifestyle factors, comorbidities, and antihypertensive medications. Results: The study population included 11 049 men and 17 032 women, with 633 incident gout cases, 393 in men (3.6%) and 240 in women (1.4%). For both men and women, the five anthropometric measurements with highest C-statistics were weight, body mass index (BMI), waist circumference (WC), hip circumference, and waist-to-height ratio; in men, the measurement with the highest C-statistic was BMI (0.7361; fully adjusted HR 1.52, 95% CI 1.39–1.68), and in women WC (0.8085; fully adjusted HR 1.62, 95% CI 1.46–1.81). The increment in C-statistic with anthropometric measures was good, around 0.035. Waist-to-hip ratio, waist-to-hip-to-height ratio, body fat percentages, and especially A Body Shape Index had lower C-statistics. Conclusions: Both BMI and WC showed good predictive ability for incident gout. The clinically used cut-offs for BMI and WC appeared to be relevant in the assessment of increased risk of gout.
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