1. |
- Alping, Peter, et al.
(author)
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Cancer Risk for Fingolimod, Natalizumab, and Rituximab in Multiple Sclerosis Patients
- 2020
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In: Annals of Neurology. - : John Wiley & Sons. - 0364-5134 .- 1531-8249. ; 87:5, s. 688-699
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Novel, highly effective disease-modifying therapies have revolutionized multiple sclerosis (MS) care. However, evidence from large comparative studies on important safety outcomes, such as cancer, is still lacking.METHODS: In this nationwide register-based cohort study, we linked data from the Swedish MS register to the Swedish Cancer Register and other national health care and census registers. We included 4,187 first-ever initiations of rituximab, 1,620 of fingolimod, and 1,670 of natalizumab in 6,136 MS patients matched for age, sex, and location to 37,801 non-MS general population subjects. Primary outcome was time to first invasive cancer.RESULTS: We identified 78 invasive cancers among treated patients: rituximab 33 (incidence rate [IR] per 10,000 person-years = 34.4, 95% confidence interval [CI] = 23.7-48.3), fingolimod 28 (IR = 44.0, 95% CI = 29.2-63.5), and natalizumab 17 (IR = 26.0, 95% CI = 15.1-41.6). The general population IR was 31.0 (95% CI = 27.8-34.4). Adjusting for baseline characteristics, we found no difference in risk of invasive cancer between rituximab, natalizumab, and the general population but a possibly higher risk with fingolimod compared to the general population (hazard ratio [HR] = 1.53, 95% CI = 0.98-2.38) and rituximab (HR = 1.68, 95% CI = 1.00-2.84).INTERPRETATION: In this first large comparative study of 3 highly effective MS disease-modifying therapies, no increased risk of invasive cancer was seen with rituximab and natalizumab, compared to the general population. However, there was a borderline-significant increased risk with fingolimod, compared to both the general population and rituximab. It was not possible to attribute this increased risk to any specific type of cancer, and further studies are warranted to validate these findings.
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2. |
- Alping, Peter, et al.
(author)
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Safety of Alemtuzumab and Autologous Hematopoietic Stem Cell Transplantation Compared to Noninduction Therapies for Multiple Sclerosis
- 2021
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In: Neurology. - : Wolters Kluwer. - 0028-3878 .- 1526-632X. ; 96:11, s. E1574-E1584
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Journal article (peer-reviewed)abstract
- Objective To assess safety outcomes for the induction therapies alemtuzumab and autologous hematopoietic stem cell transplantation (AHSCT) compared to noninduction disease-modifying therapies.Methods We performed a population-based cohort study linking the Swedish Multiple Sclerosis Register to national health care registers. Alemtuzumab, AHSCT, and a matched reference group of noninduction therapies (natalizumab, dimethyl fumarate, rituximab, fingolimod) were included if started between 2008 and 2017. Main outcomes were death, thyroid disease, nonthyroid autoimmune disease, and infection.Results We identified 132 alemtuzumab-treated and 139 AHSCT-treated (68% high-dose cyclo-phosphamide and anti-thymocyte globulin [ATG], 32% BCNU, etoposide, cytosine-arabinoside, and melphalan/ATG) patients, together with 2,486 matched patients treated with noninduction therapies. Four patients in the alemtuzumab group died (incidence rate [IR] per 1,000 person-years 8.6, 95% confidence interval [CI] 2.3-22.0) compared to 1 patient in the AHSCT group (IR 1.7, 95% CI 0.0-9.6), and the mortality rate in the reference group was 0.7 (95% CI 0.3-1.3). Thyroid disease was most frequent in the alemtuzumab group (IR 109, 95% CI 75-154) but also occurred more often for AHSCT (IR 34, 95% CI 18-56) compared to the reference (IR 5.3 95% CI 3.9-7.1). The incidence of nonthyroid autoimmune disease was similar in all groups. IR for infection diagnosed >= 6 months from therapy initiation was 53 (95% CI 30-87) for alemtuzumab, 108 (95% CI 75-150) for AHSCT, and 51 (95% CI 46-57) for the reference.Conclusion We confirmed a high incidence of thyroid disease in alemtuzumab- and, to a smaller extent, AHSCT-treated patients and found a higher incidence of infection for AHSCT compared to both alemtuzumab and noninduction therapies. The incidence of nonthyroid autoimmune disease was low for both therapies.Classification of evidence This study provides Class III evidence of an increased risk of thyroid disease with alemtuzumab and an increased risk of infection with AHSCT treatment.
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3. |
- Alping, Peter, et al.
(author)
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Safety of Alemtuzumab and Autologous Hematopoietic Stem Cell Transplantation Compared to Noninduction Therapies for Multiple Sclerosis
- 2021
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In: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 96:11
-
Journal article (peer-reviewed)abstract
- Objective To assess safety outcomes for the induction therapies alemtuzumab and autologous hematopoietic stem cell transplantation (AHSCT) compared to noninduction disease-modifying therapies. Methods We performed a population-based cohort study linking the Swedish Multiple Sclerosis Register to national health care registers. Alemtuzumab, AHSCT, and a matched reference group of noninduction therapies (natalizumab, dimethyl fumarate, rituximab, fingolimod) were included if started between 2008 and 2017. Main outcomes were death, thyroid disease, nonthyroid autoimmune disease, and infection. Results We identified 132 alemtuzumab-treated and 139 AHSCT-treated (68% high-dose cyclo-phosphamide and anti-thymocyte globulin [ATG], 32% BCNU, etoposide, cytosine-arabinoside, and melphalan/ATG) patients, together with 2,486 matched patients treated with noninduction therapies. Four patients in the alemtuzumab group died (incidence rate [IR] per 1,000 person-years 8.6, 95% confidence interval [CI] 2.3-22.0) compared to 1 patient in the AHSCT group (IR 1.7, 95% CI 0.0-9.6), and the mortality rate in the reference group was 0.7 (95% CI 0.3-1.3). Thyroid disease was most frequent in the alemtuzumab group (IR 109, 95% CI 75-154) but also occurred more often for AHSCT (IR 34, 95% CI 18-56) compared to the reference (IR 5.3 95% CI 3.9-7.1). The incidence of nonthyroid autoimmune disease was similar in all groups. IR for infection diagnosed >= 6 months from therapy initiation was 53 (95% CI 30-87) for alemtuzumab, 108 (95% CI 75-150) for AHSCT, and 51 (95% CI 46-57) for the reference. Conclusion We confirmed a high incidence of thyroid disease in alemtuzumab- and, to a smaller extent, AHSCT-treated patients and found a higher incidence of infection for AHSCT compared to both alemtuzumab and noninduction therapies. The incidence of nonthyroid autoimmune disease was low for both therapies. Classification of evidence This study provides Class III evidence of an increased risk of thyroid disease with alemtuzumab and an increased risk of infection with AHSCT treatment.
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4. |
- Alping, Peter, et al.
(author)
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Validation of the Swedish Multiple Sclerosis Register Further Improving a Resource for Pharmacoepidemiologic Evaluations
- 2019
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In: Epidemiology. - : Lippincott Williams & Wilkins. - 1044-3983 .- 1531-5487. ; 30:2, s. 230-233
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Journal article (peer-reviewed)abstract
- The Swedish Multiple Sclerosis Register is a national register monitoring treatment and clinical course for all Swedish multiple sclerosis (MS) patients, with high coverage and close integration with the clinic. Despite its great value for epidemiologic research, it has not previously been validated. In this brief report, we summarize a large validation of >3,000 patients in the register using clinical chart review in the context of the COMBAT-MS study. While further improving the data quality for a central cohort of patients available for future epidemiologic research, this study also allowed us to estimate the accuracy and completeness of the register data.
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5. |
- Altman, Maria, et al.
(author)
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Prolonged second stage of labor is associated with low Apgar score
- 2015
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In: European Journal of Epidemiology. - Stockholm : Karolinska Institutet, Dept of Medicine, Solna. - 0393-2990 .- 1573-7284.
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Journal article (peer-reviewed)abstract
- There is no consensus on the effects of a prolonged second stage of labor on neonatal outcomes. In this large Swedish population-based cohort study, our objective was to investigate prolonged second stage and risk of low Apgar score at 5 minutes. All nulliparous women (n= 32 796) delivering a live born singleton infant in cephalic presentation at ≥37 completed weeks after spontaneous onset of labor between 2008 and 2012 in the counties of Stockholm and Gotland were included. Data were obtained from computerized records. Exposure was time from fully retracted cervix until delivery. Logistic regression analyses were used to estimate crude and adjusted odds ratios (OR) with 95% confidence intervals (CI). Adjustments were made for maternal age, height, BMI, smoking, sex, gestational age, sex-specific birth weight for gestational age and head circumference. Epidural analgesia was included in a second model. The primary outcome measure was Apgar score at 5 minutes <7 and <4. We found that the overall rates of 5 minute Apgar score <7 and <4 were 7.0 and 1.3 per 1000 births, respectively. Compared to women with <1 hour from retracted cervix to birth, adjusted ORs of Apgar score <7 at 5 minutes generally increased with length of second stage of labor: 1-<2 hours: OR 1.78 (95% CI 1.19-2.66); 2- <3 hours: OR 1.66 (1.05-2.62); 3-<4 hours: OR 2.08 (1.29-3.35); and ≥4 hours: OR 2.71 (1.67-4.40). We conclude that prolonged second stage of labor is associated with an increased risk of low 5 minute Apgar score.
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6. |
- Beckley, Amber L., et al.
(author)
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Association of height and violent criminality : results from a Swedish total population study
- 2014
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In: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 43:3, s. 835-842
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Journal article (peer-reviewed)abstract
- Background: Violent criminality is at least moderately heritable, but the mechanisms behind this remain largely unexplained. Height, a highly heritable trait, may be involved but no study has estimated the effect of height on crime while simultaneously accounting for important demographic, biological and other heritable confounders. Methods: We linked nationwide, longitudinal registers for 760 000 men who underwent mandatory military conscription from 1980 through 1992 in Sweden, to assess the association between height and being convicted of a violent crime. We used Cox proportional hazard modelling and controlled for three types of potential confounders: physical characteristics, childhood demographics and general cognitive ability (intelligence). Results: In unadjusted analyses, height had a moderate negative relationship to violent crime; the shortest of men were twice as likely to be convicted of a violent crime as the tallest. However, when simultaneously controlling for all measured confounders, height was weakly and positively related to violent crime. Intelligence had the individually strongest mitigating effect on the height-crime relationship. Conclusions: Although shorter stature was associated with increased risk of violent offending, our analyses strongly suggested that this relationship was explained by intelligence and other confounding factors. Hence, it is unlikely that height, a highly heritable physical characteristic, accounts for much of the unexplained heritability of violent criminality.
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7. |
- Bergqvist, D, et al.
(author)
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Low molecular weight heparin given the evening before surgery compared with conventional low-dose heparin in prevention of thrombosis
- 1988
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In: British Journal of Surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 75:9, s. 888-891
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Journal article (peer-reviewed)abstract
- A prospective randomized double-blind trial was performed comparing conventional low-dose heparin with a low molecular weight heparin fragment for thromboprophylaxis in elective general abdominal surgical patients. The first dose of the heparin fragment was given the evening before surgery, and further doses were given thereafter every evening. There were 1002 analysable patients, 826 having received correct prophylaxis. Of these 1002 patients, 64 per cent were operated on for malignant disease. A total of 20 patients died, 10 in each group. The frequency of deep vein thrombosis was significantly reduced among patients with correct prophylaxis with the heparin fragment (9.2-5.0 per cent, P = 0.02) [corrected]. The frequency of bleeding was 6.7 per cent among the heparin fragment patients and 2.7 per cent among the patients given conventional heparin (P = 0.01), but all bleeds were of minor degree and there was no difference in the reoperation rate for bleeding, or in the transfusion requirements. Local pain at the injection site was reported significantly less often among patients given the heparin fragment.
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8. |
- Bergqvist, D, et al.
(author)
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Thromboprophylactic effect of low molecular weight heparin started in the evening before elective general abdominal surgery: a comparison with low-dose heparin
- 1990
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In: Seminars in Thrombosis and Hemostasis. - 1098-9064. ; 16:Suppl., s. 19-24
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Journal article (peer-reviewed)abstract
- A prospective randomized double-blind trial was performed comparing conventional low-dose heparin with a LMWH fragment (Kabi 2165, Fragmin) for thromboprophylaxis in elective general abdominal surgical patients. The first dose of the fragment was given in the evening before surgery, and thereafter every evening. There were 1002 analyzable patients, 826 having received correct prophylaxis. Sixty three percent of the patients were operated on for malignant diseases. The frequency of DVT was significantly reduced among patients with correct prophylaxis with the heparin fragment (9.2 to 5.0%, p = 0.02). In patients with malignancies the reduction was from 11.2 to 6.4% (p = 0.06). The frequency of bleeding was 6.7% among the heparin fragment patients and 2.7% among the patients given conventional heparin (p = 0.01). The corresponding frequencies for patients with malignancies were 3.2 and 2.8%, respectively (p = 0.28). All bleedings were minor and of no clinical significance. Local pain at the injection site was reported significantly less often among patients with the fragment. Twenty patients died, 13 with malignant disease, mortality being the same in the two groups. It is concluded that heparin fragment administered in the evening before surgery and then every evening is a practically acceptable alternative to prevent postoperative DVT in patients undergoing elective abdominal surgery, also when the histology shows malignancy. Thus, the advantages of using LMWH compared with conventional low-dose heparin are simplified administration routines, better thromboprophylactic effect, and less local pain at injection sites. A disadvantage is the slight increase in hemorrhagic side effects, all of minor clinical importance and not seen in patients undergoing surgery for malignancy.
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9. |
- Bergqvist, D, et al.
(author)
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Thromboprophylaxis in emergency surgery
- 1993
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In: Haemostasis. - 0301-0147. ; 23:Suppl. 1, s. 51-56
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Journal article (peer-reviewed)abstract
- Except for hip fracture surgery, emergency surgery has been only exceptionally studied concerning thromboprophylaxis. There are, however, several reasons to believe the frequency to be fairly high and that the patient group would be in need of prophylaxis. This paper discusses various emergency situations and also gives the design for an ongoing controlled study on the effect of postoperative start of thromboprophylaxis with low molecular weight heparin in emergency abdominal surgery.
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10. |
- Bergqvist, D, et al.
(author)
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Thromboprophylaxis with a low molecular weight heparin (tinzaparin) in emergency abdominal surgery. A double-blind multicenter trial
- 1996
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In: Vasa: European Journal of Vascular Medicine. - 0301-1526. ; 25:2, s. 156-160
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Journal article (peer-reviewed)abstract
- In this prospective randomized double-blind study the thromboprophylactic effect of postoperative low molecular weight heparin (tinzaparin) was compared with placebo in 80 patients undergoing emergency abdominal surgery. The fibrinogen uptake test was used but because of withdrawal of the labelled fibrinogen from the market the calculated number of patients was not reached. However, this is one of the few studies in emergency abdominal surgery we thought it important to report. The frequency of deep vein thrombosis was reduced with prophylaxis from 22% (95% conf. intervall 11-38%) to 8% (2-21%), a risk reduction of 65%, which is however not significant. Together with data from the few previously published studies it can be concluded that patients undergoing emergency abdominal surgery seem to benefit from prophylaxis, which should be instituted either before operation or at latest 24 hours after. The exact prophylactic relation between pre- and post-operative start would, however, require a separate, randomized study.
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11. |
- Bower, Hannah, et al.
(author)
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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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In: RMD open. - : BMJ Publishing Group Ltd. - 2056-5933. ; 9:4
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Journal article (peer-reviewed)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.
(author)
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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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In: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 80:8, s. 1086-1093
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Journal article (peer-reviewed)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.
(author)
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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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In: European Journal of Epidemiology. - : Springer. - 0393-2990 .- 1573-7284. ; 38:1, s. 109-120
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Journal article (peer-reviewed)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.
(author)
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Predictors of patient-reported fatigue symptom severity in a nationwide multiple sclerosis cohort
- 2023
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In: Multiple Sclerosis and Related Disorders. - : Elsevier. - 2211-0348 .- 2211-0356. ; 70
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Journal article (peer-reviewed)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.
(author)
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The 1 % of the population accountable for 63 % of all violent crime convictions
- 2014
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In: Social Psychiatry and Psychiatric Epidemiology. - : Springer Science and Business Media LLC. - 0933-7954 .- 1433-9285. ; 49:4, s. 559-571
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Journal article (peer-reviewed)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.
(author)
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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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In: Rheumatology (United Kingdom). - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 58:8, s. 1367-1377
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Journal article (peer-reviewed)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
(author)
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Violent crime : addressing causation with family-based methods
- 2012
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Doctoral thesis (other academic/artistic)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.
(author)
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Comparative effectiveness of dimethyl fumarate as the initial and secondary treatment for MS
- 2020
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In: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 26:12, s. 1532-1539
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Journal article (peer-reviewed)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.
(author)
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Comparative Effectiveness of Rituximab and Other Initial Treatment Choices for Multiple Sclerosis
- 2018
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In: JAMA Neurology. - : American Medical Association. - 2168-6149 .- 2168-6157. ; 75:3, s. 320-327
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Journal article (peer-reviewed)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.
(author)
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Hypogammaglobulinaemia during rituximab treatment in multiple sclerosis : a Swedish cohort study
- 2024
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In: European Journal of Neurology. - : John Wiley & Sons. - 1351-5101 .- 1468-1331. ; 31:8
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Journal article (peer-reviewed)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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22. |
- Indremo, Malin, et al.
(author)
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Validity of the Gender Dysphoria diagnosis and incidence trends in Sweden : a nationwide register study
- 2021
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In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11:1
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Journal article (peer-reviewed)abstract
- The aim of this study was to examine the validity of the Gender Dysphoria (GD) diagnoses in the Swedish National Patient Register (NPR), to discuss different register-based definitions of GD and to investigate incidence trends. We collected data on all individuals with registered GD diagnoses between 2001 and 2016 as well as data on the coverage in the NPR. We regarded gender confirming medical intervention (GCMI) as one proxy for a clinically valid diagnosis and calculated the positive predictive value (PPV) for receiving GCMI for increasing number of registered GD diagnoses. We assessed crude and coverage-adjusted time trends of GD during 2004-2015 with a Poisson regression, using assigned sex and age as interaction terms. The PPV for receiving GCMI was 68% for >= 1 and 79% for >= 4 GD-diagnoses. The incidence of GD was on average 35% higher with the definition of >= 1 compared to the definition of >= 4 diagnoses. The incidence of GD, defined as >= 4 diagnoses increased significantly during the study period and mostly in the age categories 10-17 and 18-30 years, even after adjusting for register coverage. We concluded that the validity of a single ICD code denoting clinical GD in the Swedish NPR can be questioned. For future research, we propose to carefully weight the advantages and disadvantages of different register-based definitions according to the individual study's needs, the time periods involved and the age-groups under study.
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23. |
- Jansson, Fredrik, et al.
(author)
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Concordance of Non-Low-Risk Disease Among Pairs of Brothers With Prostate Cancer
- 2018
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In: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 36:18, s. 1847-1852
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Journal article (peer-reviewed)abstract
- Purpose: Prostate cancer among first-degree relatives is a strong risk factor for diagnosis of prostate cancer, and the contribution of heritable factors in prostate cancer etiology is high. We investigated how the concordance of non-low-risk prostate cancer among brothers is affected by their genetic relation.Methods:We identified 4,262 pairs of brothers with prostate cancer in the Prostate Cancer Database Sweden. Their cancers were categorized as low risk (Gleason score 6; clinical stage T1-2, Nx/N0, Mx/M0; and prostate-specific antigen 10 ng/mL) or non-low risk. The odds ratio (OR) for concordance of non-low-risk cancer was calculated with logistic regression for the different types of fraternity (monozygotic twins, dizygotic twins, full brothers, and half-brothers)Results: Among monozygotic twins who both were diagnosed with prostate cancer, the OR for both brothers being in the non-low-risk category was 3.82 (95% CI, 0.99 to 16.72) after adjusting for age and year of diagnosis. Among full brothers, the corresponding adjusted OR was 1.21 (95% CI, 1.04 to 1.39). When the analysis was restricted to brothers who both were diagnosed within 4 years, the results were similar.Conclusion: Non-low-risk prostate cancer has a heritable pattern suggesting shared genetic factors, with the highest concordance among monozygotic twins. Our results suggest that a man whose brother has been diagnosed with a non-low-risk prostate cancer is at a clinically relevant increased risk of developing an aggressive prostate cancer himself.
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25. |
- Karalexi, Maria, et al.
(author)
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Cardiovascular outcomes in transgender individuals in Sweden after initiation of gender-affirming hormone therapy
- 2022
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In: European Journal of Preventive Cardiology. - : Oxford University Press. - 2047-4873 .- 2047-4881. ; 29:15, s. 2017-2026
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Journal article (peer-reviewed)abstract
- Aims We compared the incidence of cardiovascular disease (CVD) in transgender participants with a diagnosis of gender dysphoria (GD) with and without gender-affirming hormone therapy (GAHT) to the incidence observed in the general population. Methods and results The population-based cohort included all individuals >10 years in Sweden linked to Swedish nationwide healthcare Registers (2006-16). Two comparator groups without GD/GAHT were matched (1:10) on age, county of residence, and on male and female birth-assigned sex, respectively. Cox proportional models provided hazard ratios (HRs) and 95% confidence intervals (CI) for CVD outcomes. Among 1779 transgender individuals [48% birth-assigned males (AMAB), 52% birth-assigned females (AFAB)], 18 developed CVD, most of which were conduction disorders. The incidence of CVD for AFAB individuals with GD was 3.7 per 1000 person-years (95% CI: 1.4-10.0). Assigned male at birth individuals with GD had an incidence of CVD event of 7.1 per 1000 person-years (95% CI: 4.2-12.0). The risk of CVD event was 2.4 times higher in AMAB individuals (HR: 2.4, 95% CI: 1.3-4.2) compared with cisgender women, and 1.7 higher compared with cisgender men (HR: 1.7, 95% CI: 1.0-2.9). Analysis limited to transgender individuals without GAHT yielded similar results to those with GAHT treatment. Conclusion The incidence of CVD among GD/GAHT individuals was low, although increased compared with matched individuals without GD and similar to the incidence among GD/no GAHT individuals, thus not lending support for a causal relationship between treatment and CVD outcomes. Larger studies with longer follow-up are needed to verify these findings, as well as possible effect modification by comorbidity.
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