| 11. |
- Bower, Hannah, et al.
(författare)
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Are JAKis more effective among elderly patients with RA, smokers and those with higher cardiovascular risk? A comparative effectiveness study of b/tsDMARDs in Sweden.
- 2023
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Ingår i: RMD open. - : BMJ Publishing Group Ltd. - 2056-5933. ; 9:4
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Tidskriftsartikel (refereegranskat)abstract
- To investigate whether the relative effectiveness of janus kinase inhibitors (JAKis) versus tumour necrosis factor inhibitors (TNFi) or other biological disease-modifying antirheumatic drugs in rheumatoid arthritis differ by the presence or absence of risk factors for cardiovascular (CV) disease, age, sex and smoking.Through Swedish registers, we identified 13493 individuals with 3166 JAKi, 5575 non-TNFi and 11 286 TNFi treatment initiations 2016-2022. All lines of therapy were included, with the majority in second line or higher. Treatment response was defined as the proportion reaching European Alliance of Associations for Rheumatology (EULAR) good response and Clinical Disease Activity Index (CDAI) remission, respectively, within 6 months. Crude percentage point differences in these proportions (JAKis, and non-TNFis, vs TNFis) overall and by risk factors were observed, and adjusted for confounders using linear regression models. Predicted probabilities of response and remission were estimated from adjusted Poisson models, and presented across CV risk and age.Overall, adjusted percentage point differences indicated higher response (+5.0%, 95% CI 2.2% to 7.9%) and remission (+5.8%, 95% CI 3.2% to 8.5%) with JAKis versus TNFis. The adjusted percentage point differences for response in those above 65, at elevated CV risk, and smokers were +5.9% (95% CI 2.7% to 9.0%), +8.3% (95% CI 5.3% to 11.4%) and +6.0% (95% CI 3.3% to 8.7%), respectively. The corresponding estimates for remission were +8.0% (95% CI 5.3% to 10.8%), +5.6% (95% CI 3.0% to 8.2%) and +7.6% (95% CI 5.5% to 9.7%).As used in clinical practice, response and remission at 6 months with JAKis are higher than with TNFi. Among patients with risk factors of concern, effectiveness is similar or numerically further increased. For individualised benefit-to-risk ratios to guide treatment choice, safety and effectiveness in specific patient segments should be considered.
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| 12. |
- Bower, Hannah, et al.
(författare)
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Impact of the COVID-19 pandemic on morbidity and mortality in patients with inflammatory joint diseases and in the general population : a nationwide Swedish cohort study
- 2021
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 80:8, s. 1086-1093
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To estimate absolute and relative risks for all-cause mortality and for severe COVID-19 in inflammatory joint diseases (IJDs) and with antirheumatic therapies.Methods: Through Swedish nationwide multiregister linkages, we selected all adult patients with rheumatoid arthritis (RA, n=53 455 in March 2020), other IJDs (here: spondyloarthropathies, psoriatic arthritis and juvenile idiopathic arthritis, n=57 112), their antirheumatic drug use, and individually matched population referents. We compared annual all-cause mortality March-September 2015 through 2020 within and across cohorts, and assessed absolute and relative risks for hospitalisation, admission to intensive care and death due to COVID-19 March-September 2020, using Cox regression.Results: During March-September 2020, the absolute all-cause mortality in RA and in other IJDs was higher than 2015-2019, but relative risks versus the general population (around 2 and 1.5) remained similar during 2020 compared with 2015-2019. Among patients with IJD, the risks of hospitalisation (0.5% vs 0.3% in their population referents), admission to intensive care (0.04% vs 0.03%) and death (0.10% vs 0.07%) due to COVID-19 were low. Antirheumatic drugs were not associated with increased risk of serious COVID-19 outcomes, although for certain drugs, precision was limited.Conclusions: Risks of severe COVID-19-related outcomes were increased among patients with IJDs, but risk increases were also seen for non-COVID-19 morbidity. Overall absolute and excess risks are low and the level of risk increases are largely proportionate to those in the general population, and explained by comorbidities. With possible exceptions, antirheumatic drugs do not have a major impact on these risks.
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| 13. |
- Cnattingius, Sven, et al.
(författare)
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The Swedish medical birth register during five decades : documentation of the content and quality of the register
- 2023
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Ingår i: European Journal of Epidemiology. - : Springer. - 0393-2990 .- 1573-7284. ; 38:1, s. 109-120
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Tidskriftsartikel (refereegranskat)abstract
- Pregnancy-related factors are important for short- and long-term health in mothers and offspring. The nationwide population-based Swedish Medical Birth Register (MBR) was established in 1973. The present study describes the content and quality of the MBR, using original MBR data, Swedish-language and international publications based on the MBR. The MBR includes around 98% of all births in Sweden. From 1982 onwards, the MBR is based on prospectively recorded information in standardized antenatal, obstetric, and neonatal records. When the mother and infant are discharged from hospital, this information is forwarded to the MBR, which is updated annually. Maternal data include information from first antenatal visit on self-reported obstetric history, infertility, diseases, medication use, cohabitation status, smoking and snuff use, self-reported height and measured weight, allowing calculation of body mass index. Birth and neonatal data include date and time of birth, mode of delivery, singleton or multiple birth, gestational age, stillbirth, birth weight, birth length, head circumference, infant sex, Apgar scores, and maternal and infant diagnoses/procedures, including neonatal care. The overall quality of the MBR is very high, owing to the semi-automated data extraction from the standardized regional electronic health records, Sweden's universal access to antenatal care, and the possibility to compare mothers and offspring to the Total Population Register in order to identify missing records. Through the unique personal identity numbers of mothers and live-born offspring, the MBR can be linked to other health registers. The Swedish MBR contains high-quality pregnancy-related information on more than 5 million births during five decades.
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| 14. |
- Englund, Simon, et al.
(författare)
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Predictors of patient-reported fatigue symptom severity in a nationwide multiple sclerosis cohort
- 2023
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Ingår i: Multiple Sclerosis and Related Disorders. - : Elsevier. - 2211-0348 .- 2211-0356. ; 70
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Fatigue is a debilitating symptom of multiple sclerosis (MS), but its relation to sociodemographic and disease-related characteristics has not been investigated in larger studies. The objectives of this study were to evaluate predictors of self-reported fatigue in a Swedish nationwide register-based MS cohort.METHODS: Using a repeated cross-sectional design, we included 2,165 persons with relapsing- remitting and secondary progressive MS with one or multiple Fatigue Scale for Motor and Cognitive Functions (FSMC) scores, which was modelled using multivariable linear regressions for multiple predictors.RESULTS: Only associations to expanded disability status scale (EDSS) and Symbol Digit Modalities Test (SDMT) were considered clinically meaningful among MS-associated characteristics in our main model; compared to mild disability (EDSS 0-2.5), those with severe disability (EDSS ≥6) scored 17.6 (95% CI 13.1-22.2) FSMC points higher, while the difference was 10.7 (95% CI 8.0-13.4) points for the highest and lowest quartiles of SDMT. Differences between highest and lowest quartiles of health-related quality of life (HRQoL) instruments were even greater and considered clinically meaningful; EuroQoL Visual Analogue Scale (EQ-VAS) 31.9 (95% CI 29.9-33.8), Multiple Sclerosis Impact Scale (MSIS-29) psychological component 35.6 (95% CI 33.8-37.4) and MSIS-29 physical component 45.5 (95% CI 43.7-47.4).CONCLUSION: Higher self-reported fatigue is associated with higher disability level and worse cognitive processing speed, while associations to other MS-associated characteristics including MS type, line of disease modifying therapy (DMT), MS duration, relapse and new cerebral lesions are weak. Furthermore, we found a strong correlation between high fatigue rating and lower ratings on health-related quality of life instruments.
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| 15. |
- Falk, Örjan, et al.
(författare)
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The 1 % of the population accountable for 63 % of all violent crime convictions
- 2014
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Ingår i: Social Psychiatry and Psychiatric Epidemiology. - : Springer Science and Business Media LLC. - 0933-7954 .- 1433-9285. ; 49:4, s. 559-571
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Population-based studies on violent crime and background factors may provide an understanding of the relationships between susceptibility factors and crime. We aimed to determine the distribution of violent crime convictions in the Swedish population 1973-2004 and to identify criminal, academic, parental, and psychiatric risk factors for persistence in violent crime. Method The nationwide multi-generation register was used with many other linked nationwide registers to select participants. All individuals born in 1958-1980 (2,393,765 individuals) were included. Persistent violent offenders (those with a lifetime history of three or more violent crime convictions) were compared with individuals having one or two such convictions, and to matched non-offenders. Independent variables were gender, age of first conviction for a violent crime, nonviolent crime convictions, and diagnoses for major mental disorders, personality disorders, and substance use disorders. Results A total of 93,642 individuals (3.9 %) had at least one violent conviction. The distribution of convictions was highly skewed; 24,342 persistent violent offenders (1.0 % of the total population) accounted for 63.2 % of all convictions. Persistence in violence was associated with male sex (OR 2.5), personality disorder (OR 2.3), violent crime conviction before age 19 (OR 2.0), drug-related offenses (OR 1.9), nonviolent criminality (OR 1.9), substance use disorder (OR 1.9), and major mental disorder (OR 1.3). Conclusions The majority of violent crimes are perpetrated by a small number of persistent violent offenders, typically males, characterized by early onset of violent criminality, substance abuse, personality disorders, and nonviolent criminality.
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| 16. |
- Frisell, Thomas, et al.
(författare)
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Comparative effectiveness of abatacept, rituximab, tocilizumab and TNFi biologics in RA : Results from the nationwide Swedish register
- 2019
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Ingår i: Rheumatology (United Kingdom). - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 58:8, s. 1367-1377
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Current guidelines rank abatacept, rituximab, tocilizumab and TNF-inhibitors (TNFi) as having equal effectiveness for the treatment of RA, at least as second line therapies. These recommendations are mainly based on meta-analysis of randomized controlled trials, with few direct drug-drug comparisons. Our objective was to compare the real-world absolute and relative effectiveness among RA patients starting any of the available biologic DMARDs (bDMARDs). Methods: We used the Swedish Rheumatology Register to identify patients with RA initiating TNFi, rituximab, abatacept or tocilizumab in 2010-2016 as first bDMARD (n = 9333), or after switch from TNFi as first bDMARD (n = 3941). National Swedish registers provided additional covariates and censoring events. Effectiveness was assessed 3 and 12 months after treatment start, as the proportion remaining on therapy and with EULAR Good Response, HAQ improvement >0.2, zero swollen/tender joints and CDAI remission. Adjusted differences were estimated with multivariable linear regression. Results: Patients starting non-TNFi (vs TNFi) as first bDMARD had a higher proportion remaining on drug and reaching most response outcomes as first bDMARD (1-year EULAR Good Response/HAQ improvement: TNFi 24.9/25.4%, rituximab 28.6/37.2%, abatacept 31.9/33.7%, tocilizumab 50.9/43.1%). After switch from a first TNFi, rituximab and tocilizumab, but not abatacept, were associated with significantly better response measures than TNFi (1-year EULAR Good Response/HAQ improvement: TNFi 11.6/16.1%, rituximab 24.8/33.2%, abatacept 13.1/17.5%, tocilizumab 34.1/29.4%). Differences remained significant after adjusting for potential confounders. Conclusion: Treatment outcomes among RA patients treated in Swedish clinical practice are in line with a superior effectiveness of non-TNFi bDMARDs, in particular tocilizumab and rituximab, compared with TNFi.
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| 17. |
- Frisell, Thomas
(författare)
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Violent crime : addressing causation with family-based methods
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Violent crime is an important public health problem, and incurs major costs for society. The effect of interventions has so far been modest, often attributed to a research focus on risk factors for crime, but a relative lack of understanding of the causal mechanisms behind these factors. The four studies in this thesis attempt to address different aspects of the etiology of violent crime by using family-based epidemiologic methods. It has long been known that antisocial behavior runs in families. In Paper I, a nested case-control was used to quantify the familial clustering of violent crime using a linkage of several Swedish total population registers. We were able to provide precise estimates of the familial aggregation among 1st, 2nd, and 3rd degree relatives, and also adoptive relations and spouses. Familial risks were moderate to strong, and were modified by gender, socioeconomic status, type of violent crime, and age at first conviction. Familial clustering suggests that genes and/or family environment influence the propensity for violent offending. In Paper II we attempted to estimate the relative importance of these factors by calculating the heritability in mixed probit regression. Comparing results from twin, adoptee-parent, adoptee-sibling, and sibling designs, and attempting to adjust for non-random mating, we found that about half the variation in violent offending could be attributed to genetic factors. We also found significant gender differences in the etiology of violent crime. In Paper III, we discussed the interpretation of sibling comparison designs. Sibling comparisons have been hailed for their ability to adjust for family-shared confounders, but have received little attention from a methodological standpoint. In line with previous research in economy, we showed that these models are subject to several caveats, and that they may in some situations increase rather than decrease bias. The implications of this were acknowledged in Paper IV, where we analysed the association of general cognitive ability and violent crime, and adjusted for shared family characteristics through sibling comparison analysis. Taking measurement error and non-shared confounding into account, the results indicated that the association was partly confounded by factors shared by siblings, but that most of the association could not be explained by such factors. Together, Papers I and II suggested that violent crime runs in families due to both genetic and environmental factors, and Paper IV offered some support for the hypothesis that intelligence may be one of the factors explaining this familial aggregation. The caveats of sibling comparisons pointed out in Paper III should be taken into account when using co-twin control and other sibling designs to address issues of causality.
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| 18. |
- Granqvist, Mathias, et al.
(författare)
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Comparative effectiveness of dimethyl fumarate as the initial and secondary treatment for MS
- 2020
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 26:12, s. 1532-1539
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Population-based real-world evidence studies of the effectiveness and tolerability of dimethyl fumarate in relation to common treatment alternatives are still limited.OBJECTIVE: To evaluate the clinical effectiveness and tolerability of dimethyl fumarate (DMF) as the initial and secondary treatment for relapsing-remitting multiple sclerosis (RRMS) patients compared with common treatment alternatives in Sweden.METHODS: We conducted a nationwide retrospective observational cohort study of all RRMS patients identified through the Swedish MS registry initiating DMF (n = 641) or interferons/glatiramer acetate (IFN/GA; n = 555) as the initial therapy, or DMF (n = 703) or fingolimod (FGL; n = 194) after switch from IFN/GA between 1 January 2014 and 31 December 2016.RESULTS: The discontinuation rate was lower with DMF as the initial treatment than IFN/GA (adjusted hazard rate (HR): 0.46, 95% confidence interval (CI): 0.37-0.58, p < 0.001), but higher than FGL as the secondary treatment (HR: 1.51, CI: 1.08-2.09, p < 0.05). Annualized relapse rate (ARR) was lower with DMF compared to IFN/GA (0.04, CI: 0.03-0.06 vs 0.10, CI: 0.07-0.13; p < 0.05), but not FGL (0.03, CI: 0.02-0.05 vs 0.02, CI: 0.01-0.04; p = 0.41). Finally, time to first relapse (TTFR) was longer with DMF as the initial, but not secondary, therapy (p < 0.05 and p = 0.20, respectively).CONCLUSION: Our findings indicate that DMF performs better than IFN/GA as the initial treatment for RRMS. Compared to FGL, DMF displayed a lower tolerability, but largely similar effectiveness outcomes.
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| 19. |
- Granqvist, Mathias, et al.
(författare)
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Comparative Effectiveness of Rituximab and Other Initial Treatment Choices for Multiple Sclerosis
- 2018
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Ingår i: JAMA Neurology. - : American Medical Association. - 2168-6149 .- 2168-6157. ; 75:3, s. 320-327
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Comparative real-world effectiveness studies of initial disease-modifying treatment (DMT) choices for relapsing-remitting multiple sclerosis (RRMS) that include rituximab are lacking.OBJECTIVE To assess the effectiveness and drug discontinuation rates of rituximab among patients with newly diagnosed RRMS compared with injectable DMTs, dimethyl fumarate, fingolimod, or natalizumab.DESIGN, SETTING, AND PATIENTS This retrospective cohort study used prospectively collected data to examine specialized care of 2 Swedish county-based community samples of patients with RRMS. Patients with RRMS who received diagnoses from January 1, 2012, to October 31, 2015, who resided in Stockholm or Vasterbotten Counties were identified from a Swedish multiple sclerosis registry.MAIN OUTCOMES AND MEASURES All reasons for drug discontinuation of initial treatment choice (main outcome) and specific reasons for switching (secondary outcomes) were analyzed with multivariable Cox regression, including propensity scores.RESULTS Among 494 patients (median [interquartile range] age, 34.4 [27.4-43.4] years; 158 men [32.0%]), 215 received an injectable DMT (43.5%); 86 (17.4%), dimethyl fumarate; 17 (3.4%), fingolimod; 50 (10.1%), natalizumab; 120 (24.3%), rituximab; and 6 (1.2%), other DMT. Regional preferences were pronounced, with 42 of 52 (81%) and 78 of 442 (18%) receiving rituximab in Vasterbotten and Stockholm, respectively. The annual discontinuation rate for rituximab, injectable DMTs, dimethyl fumarate, fingolimod, and natalizumab were 0.03, 0.53, 0.32, 0.38, and 0.29, respectively. Continued disease activity was the main reason for discontinuation of injectable DMTs, dimethyl fumarate, and fingolimod; positive John Cunningham virus serology results were the main reason for discontinuation of natalizumab. Rate of clinical relapses and/or neuroradiologic disease activity were significantly lower for rituximab compared with injectable DMTs and dimethyl fumarate, with a tendency for lower relapse rates also compared with natalizumab and fingolimod. The annual discontinuation rate of initial treatment choice was significantly lower in Vasterbotten compared with Stockholm (0.09 and 0.37, respectively).CONCLUSIONS AND RELEVANCE Rituximab was superior to all other DMT in terms of drug discontinuation and displayed better clinical efficacy compared with injectable DMTs and dimethyl fumarate with borderline significance compared with natalizumab and fingolimod. The county where rituximab constituted the main initial treatment choice displayed better outcomes in most measured variables. Collectively, our findings suggest that rituximab performs better than other commonly used DMTs in patients with newly diagnosed RRMS.
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| 20. |
- Hallberg, Susanna, et al.
(författare)
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Hypogammaglobulinaemia during rituximab treatment in multiple sclerosis : a Swedish cohort study
- 2024
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Ingår i: European Journal of Neurology. - : John Wiley & Sons. - 1351-5101 .- 1468-1331. ; 31:8
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Mechanisms behind hypogammaglobulinaemia during rituximab treatment are poorly understood.Methods: In this register-based multi-centre retrospective cohort study of multiple sclerosis (MS) patients in Sweden, 2745 patients from six participating Swedish MS centres were identified via the Swedish MS registry and included between 14 March 2008 and 25 January 2021. The exposure was treatment with at least one dose of rituximab for MS or clinically isolated syndrome, including data on treatment duration and doses. The degree of yearly decrease in immunoglobulin G (IgG) and immunoglobulin M (IgM) levels was evaluated.Results: The mean decrease in IgG was 0.27 (95% confidence interval 0.17–0.36) g/L per year on rituximab treatment, slightly less in older patients, and without significant difference between sexes. IgG or IgM below the lower limit of normal (<6.7 or <0.27 g/L) was observed in 8.8% and 8.3% of patients, respectively, as nadir measurements. Six out of 2745 patients (0.2%) developed severe hypogammaglobulinaemia (IgG below 4.0 g/L) during the study period. Time on rituximab and accumulated dose were the main predictors for IgG decrease. Previous treatment with fingolimod and natalizumab, but not teriflunomide, dimethyl fumarate, interferons or glatiramer acetate, were significantly associated with lower baseline IgG levels by 0.80–1.03 g/L, compared with treatment-naïve patients. Switching from dimethyl fumarate or interferons was associated with an additional IgG decline of 0.14–0.19 g/L per year, compared to untreated.Conclusions: Accumulated dose and time on rituximab treatment are associated with a modest but significant decline in immunoglobulin levels. Previous MS therapies may influence additional IgG decline.
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