| 1. |
- Bereczky-Veress, Biborka, et al.
(författare)
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Host strain-dependent difference in susceptibility in a rat model of herpes simplex type 1 encephalitis.
- 2008
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Ingår i: Journal of neurovirology. - : Springer Science and Business Media LLC. - 1538-2443 .- 1355-0284. ; 14:2, s. 102-18
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Tidskriftsartikel (refereegranskat)abstract
- Herpes simplex encephalitis (HSE) is characterized by severe focal brain inflammation leading to substantial loss of nervous tissue. The authors established a model of Herpes simplex virus type 1 (HSV)-1-induced acute encephalitis in the rat by injecting into the whiskers' area a virus strain isolated from a fatal human HSE case. The model might resemble natural propagation of HSV-1 in humans; spreading from the mouth and lips via the trigeminal nerve to trigeminal ganglia and subsequently entering the central nervous system (CNS). HSV-1 infected Dark Agouti (DA) rats developed a well-synchronized disease and died 5 days after inoculation. HSV-1 detection by quantitative polymerase chain reaction (qPCR), virus isolation and immunohistochemistry, magnetic resonance imaging, and histopathological examination verified dramatic encephalitis mainly in the brainstem, but also in the olfactory bulb and other segments of the brain of diseased rats. In contrast, Piebald Virol Glaxo (PVG) rats were completely resistant to disease, displaying a more rapid clearance of peripheral infection and no evidence of virus entering into neither the trigeminal ganglia nor the CNS. These results suggest a regulation of susceptibility to HSV-1-induced encephalitis at the level of peripheral infection and subsequent neuronal uptake/transport of the virus. This provides a basis for future positioning of genetic polymorphisms regulating HSE and for dissection of important pathogenetic mechanisms of this severe human disease.
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| 2. |
- Bergdahl, Johan, et al.
(författare)
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Evaluation of an algorithm ascertaining cases of osteonecrosis of the jaw in the Swedish National Patient Register
- 2013
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Ingår i: Clinical Epidemiology. - Macclesfield : Dove Medical Press Ltd.. - 1179-1349. ; 5:1, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- Background: Osteonecrosis of the jaw (ONJ) is a medical condition associated with antiresorptive drugs, among others, used to treat osteoporosis and bone metastasis. Currently, there is no consensus regarding the definition of ONJ, and no ONJ-specific International Classification of Diseases-10 code exists. Therefore, register-based studies of this condition may be troublesome.Purpose: To evaluate an algorithm ascertaining ONJ cases in an attempt to facilitate future assessments of ONJ in clinical and epidemiological studies.Methods: By means of the Patient Register and the Prescribed Drug Register, we identified all postmenopausal female residents in Sweden from 2005 through 2009. To identify potential cases of ONJ, we employed an algorithm including the following conditions: periapical abscess with sinus, inflammatory conditions of jaws, alveolitis of jaws, idiopathic aseptic necrosis of bone, osteonecrosis due to drugs, osteonecrosis due to previous trauma, other secondary osteonecrosis, other osteonecrosis, and unspecified osteonecrosis. Women seen at departments of oral and maxillofacial surgery, with at least one of the conditions, were classified as potential cases of ONJ. Conditions in anatomic sites other than the jaw were excluded. Validation was performed through medical record review. Case confirmation was based on the ONJ definition by the American Association of Oral and Maxillofacial Surgeons. The algorithm was evaluated by positive predictive values (PPVs) stratified by diagnosis.Results: For the 87 potential cases identified through our algorithm, the medical records were obtained for 83. The overall PPV was 18% (95% confidence interval (CI) 10%–28%). The highest PPV was observed in osteonecrosis due to drugs (83%, 95% CI 36%–100%). Several diagnoses had a PPV of 0 or were not used at all (periapical abscess with sinus, alveolitis of jaws, idiopathic aseptic necrosis of bone, osteonecrosis due to previous trauma, other secondary osteonecrosis, other osteonecrosis, and unspecified osteonecrosis).Conclusion: It was possible to ascertain cases of ONJ from the Swedish registers using this algorithm; however, the PPV was low. Thus, further refinements of the algorithm are necessary. © 2013 Bergdahl et al, publisher and licensee Dove Medical Press Ltd.
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| 3. |
- Norenstedt, Sophie, et al.
(författare)
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Breast cancer associated with primary hyperparathyroidism : a nested case control study
- 2011
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Ingår i: Clinical Epidemiology. - 1179-1349. ; 3, s. 103-106
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Primary hyperparathyroidism (pHPT) is associated with an increased risk of developing breast cancer, but little is known about the underlying factors. The aim of this study was to compare women with a history of pHPT and a reference population in terms of standard factors predictive of prognosis and response to therapy for breast cancer. METHODS: We analyzed data collected from the National Swedish Cancer Register and from two regional oncologic center registries. Seventy-one women with breast cancer and a history of parathyroid adenomectomy were compared with 338 matched controls with breast cancer only. Tumor size, stage, hormone receptor status, lymph node status, cause of death, and cumulative survival were analyzed. RESULTS: The mean age was 69 ± 11 years (95% confidence interval [CI]: 68-70) in both groups and the mean time interval between the parathyroid surgery and breast cancer diagnosis was 91 ± 68 months (95% CI: 72-111). There were no differences between the two groups regarding size, stage, lymph node metastases, or survival, but none of the cases with a history of pHPT were found in Stage III or IV. CONCLUSION: In conclusion, factors predictive of prognosis and response to therapy in women with a history of pHPT and breast cancer are similar to those in breast cancer patients without pHPT.
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| 4. |
- Aasa, Jenny, et al.
(författare)
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Cancer risk estimation of glycidol based on rodent carcinogenicity studies, a multiplicative risk model and in vivo dosimetry
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Here we evaluate a multiplicative (relative) risk model for more reliable cancer risk estimations of genotoxic compounds. According to this model, cancer risk is proportional to background tumor incidence and to internal dose of the genotoxic compound. A relative risk coefficient is considered to be common across species, sex, and tumor sites. The model has previously been shown to be successfully applied to rodent carcinogenicity data for a few genotoxic compounds. The aim of the present study was to evaluate this risk model for glycidol, a common food contaminant. Tumor data from published glycidol carcinogenicity studies in mice and rats were evaluated with the model, using internal doses estimated from hemoglobin adduct measurements in blood of B6C3F1 mice and Sprague Dawley rats treated with glycidol in short-term exposure studies.The evaluation demonstrated that the relative risk model is valid for glycidol. A good agreement between predicted and observed tumor incidence was demonstrated in the animals, supporting a relative risk coefficient that is independent of species, sex, and tumor site. There was no significant difference of the risk coefficients between mice (5.1 % per mMh) and rats (7.1 % per mMh) when the internal doses of glycidol were considered. Altogether, this mechanism-based risk model gives a common and more reliable risk coefficient which could be extrapolated to humans via internal dose measurements, and by considering the background cancer incidence.
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| 5. |
- Aasa, Jenny, et al.
(författare)
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Cancer risk estimation of glycidol based on rodent carcinogenicity studies, a multiplicative risk model and in vivo dosimetry
- 2019
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Ingår i: Food and Chemical Toxicology. - : Elsevier BV. - 0278-6915 .- 1873-6351. ; 128, s. 54-60
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Tidskriftsartikel (refereegranskat)abstract
- Here we evaluate a multiplicative (relative) risk model for improved cancer risk estimation of genotoxic compounds. According to this model, cancer risk is proportional to the background tumor incidence and to the internal dose of the genotoxic compound. Furthermore, the relative risk coefficient per internal dose is considered to be approximately the same across tumor sites, sex, and species. In the present study, we demonstrate that the relative risk model is valid for cancer risk estimation of glycidol, a common food contaminant. Published tumor data from glycidol carcinogenicity studies in mice and rats were evaluated in combination with internal dose estimates from hemoglobin adduct measurements in blood from mice and rats treated with glycidol in short-term studies. A good agreement between predicted and observed tumor incidence in responding sites was demonstrated in the animals, supporting a relative risk coefficient that is independent of tumor site, sex, and species. There was no significant difference between the risk coefficients for mice (5.1% per mMh) and rats (5.4% per mMh) when considering internal doses of glycidol. Altogether, this mechanism-based risk model gives a reliable risk coefficient, which then was extrapolated to humans considering internal dose, and background cancer incidence.
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| 6. |
- Aleman, Soo, et al.
(författare)
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A Risk for Hepatocellular Carcinoma Persists Long-term After Sustained Virologic Response in Patients With Hepatitis C-Associated Liver Cirrhosis
- 2013
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1537-6591 .- 1058-4838. ; 57:2, s. 230-236
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Tidskriftsartikel (refereegranskat)abstract
- Background. The long-term effect of sustained virologic response (SVR) to antiviral therapy on the risk of developing hepatocellular carcinoma (HCC), liver complications, liver-related death, and overall death in hepatitis C virus (HCV)-infected patients with liver cirrhosis is not fully known. Methods. These risks were evaluated during long-term follow-up in 351 patients with HCV-related cirrhosis. One hundred ten patients with SVR, 193 with non-SVR, and 48 who were untreated were included in a multicenter cohort that was initiated in 2001 and prospectively followed up for a mean of 5.3 (SD, 2.8) years. Complementary follow-up data from national registries were used to minimize the loss of patients during follow-up. Results. Six patients with SVR developed HCC at 0.04, 0.64, 2.4, 7.4, 7.4, and 7.6 years, respectively, after achieving SVR. The incidences of HCC, any liver complication, liver-related death, and overall death per 100 person-years were significantly lower in SVR time with 1.0, 0.9, 0.7, and 1.9, compared to 2.3, 3.2, 3.0, and 4.1 in non-SVR and 4.0, 4.9, 4.5, and 5.1 in untreated time. The long-term consequences did not decline significantly after >3 years versus during the first 3 years of follow-up. Conclusions. The risk for HCC, liver decompensation, and death in patients with liver cirrhosis related to HCV was markedly reduced after SVR, but a long-term risk of developing HCC remains for up to 8 years. Cirrhotic patients with HCV who achieve SVR should therefore maintain long-term surveillance for HCC. Future studies aimed to better identify those with remaining long-term risk for HCC are needed.
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| 7. |
- Alström, Ulrica, et al.
(författare)
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Platelet inhibition assessed with VerifyNow, flow cytometry and PlateletMapping in patients undergoing heart surgery
- 2009
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Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 124:5, s. 572-577
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: A substantial number of patients with coronary artery disease undergo cardiac surgery within five days of discontinuing anti-platelet treatment with aspirin and clopidogrel. The aims of this study were to describe the degree of platelet inhibition in patients with dual anti-platelet treatment scheduled for coronary artery bypass graft (CABG) surgery and to investigate whether the measured platelet inhibition correlated to intra- and postoperative risk for bleeding and transfusion requirements. MATERIAL AND METHODS: Sixty patients were included. Platelet inhibition was analysed with flow cytometry including phosphorylation status of the vasodilator-stimulated phosphoprotein (VASP-assay) and two bed-side analyzers, VerifyNow-System and PlateletMapping, a modified thrombelastograph. All 60 patients were analysed with VerifyNow and PlateletMapping, and 48 were analysed with flow cytometry and VASP-assay. RESULTS: There was a correlation between the ADP-receptor inhibition as measured by VASP-assay and VerifyNowP2Y(12) (r = -0.29, p<0.05), and between VASP-assay and the expression of P-selectin (r = 0.29, p<0.05) as measured by flow cytometry when platelets were stimulated with 5 microM ADP. VerifyNowP2Y(12) was the only measurement of platelet inhibition correlated to total blood loss (Spearman r = 0.29, p=0.03) and red blood cell transfusion (Spearman r = 0.43, p<0.01) requirements, although this might be confounded by aprotinin treatment. CONCLUSION: We found a modest agreement between the methods for preoperative platelet inhibition, though not for PlateletMapping-MA(ADP). There was a correlation between preoperative platelet inhibition measured by VerifyNowP2Y(12) and surgical blood loss or transfusion requirements. However, for the individual patient, preoperative use of VerifyNowP2Y(12) as an instrument to decide bleeding and transfusion risk does not seem helpful.
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| 8. |
- Alström, Ulrica, et al.
(författare)
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Risk factors for re-exploration due to bleeding after coronary artery bypass grafting
- 2012
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Ingår i: Scandinavian Cardiovascular Journal. - : Informa Healthcare. - 1401-7431 .- 1651-2006. ; 46:1, s. 39-44
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The study aimed to investigate relevant clinical risk factors for re-exploration due to bleeding after primary coronary artery bypass graft (CABG) surgery, and to evaluate the influence of antiplatelet and antifibrinolytic drugs.Design: Three retrospective analyses were performed on patients who underwent CABG: (1) Logistic regression was used to identify clinical risk factors for re-exploration (n = 3000). (2) A case-control study (n = 228) was used to obtain information on exposure of antithrombotic and hemostatic therapy. (3) Based on exposure to antiplatelet and antifibrinolytic therapy, and odds ratios (ORs) in multivariate logistic models, the proportion of re-explorations attributed to these drugs was calculated.Results: A receiver operating characteristic curve was created for clinical risk factors. The C-index was 0.64, indicating limited ability to predict re-exploration for bleeding. Clopidogrel was the only drug influencing the risk of re-exploration (OR 3.2, 95% CI 1.7-5.9). The harmful effect of clopidogrel was confirmed in multivariate model (OR 4.7, 95% CI 2.2-9.9), and aprotinin had a protective effect of the same magnitude (OR 0.2, 95% CI 0.1-0.6).Conclusions: Clopidogrel is an essential risk factor for re-exploration due to bleeding, and attributable to at least one-quarter of surveyed cases. Aside from pharmaceuticals, there are no strong clinical risk factors.
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| 9. |
- Altman, Daniel, et al.
(författare)
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Anticholinergic drug use for overactive bladder in Sweden: a nationwide pharmacoepidemiological study
- 2009
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Ingår i: International Urogynecology Journal. - : Springer Science and Business Media LLC. - 1433-3023 .- 0937-3462. ; 20:11, s. 1285-1291
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Tidskriftsartikel (refereegranskat)abstract
- Nationwide use and costs of anticholinergic drug for overactive bladder are unknown. We performed a nationwide study based on the Swedish Register on Prescribed Pharmaceuticals. From 2000 to 2007, there was a 68.8% increase in dispensed anticholinergic drugs in a population of 9 million. More than 93 million DDDs (calculated average maintenance dose per day) of anticholinergic drugs were dispensed corresponding to an overall DDD/TID (DDD per 1,000 inhabitants per day) of 3.5 per 1,000 persons per year. Approximately two thirds of anticholinergic drugs were prescribed to women, regardless of drug type. In 2007, the cost for anticholinergic drugs was 22 million a,not sign of which tolterodine comprised 70.8%. Solifenacin and darifenacin steadily increased their DDD/TIDs after market introduction. In this nationwide study, there was a 70% increased rate of expedited prescriptions of anticholinergic drugs for the treatment of overactive bladder in a relatively stable population.
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| 10. |
- Askling, Johan, et al.
(författare)
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Anti-TNF therapy in RA and risk of malignant lymphomas Relative risks and time-trends in the Swedish Biologics Register
- 2008
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 68:5, s. 648-653
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Tidskriftsartikel (refereegranskat)abstract
- Background: Tumour necrosis factor (TNF) antagonists have proved effective as treatment against rheumatoid arthritis (RA), but the unresolved issue of whether the use of anti-TNF therapy increases the already elevated risk of lymphoma in RA remains a concern.Methods: Using the Swedish Biologics Register (ARTIS), the Swedish Cancer Register, pre-existing RA cohorts and cross-linkage with other national health and census registers, a national RA cohort (n = 67 743) was assembled and patients who started anti-TNF therapy between 1998 and July 2006 (n = 6604) were identified. A general population comparator (n = 471 024) was also assembled and the incidence of lymphomas from 1999 to 31 December 2006 was assessed and compared in these individuals.Results: Among the 6604 anti-TNF-treated RA patients, 26 malignant lymphomas were observed during 26 981 person-years of follow-up, which corresponded to a relative risk (RR) of 1.35 (95% CI 0.82 to 2.11) versus anti-TNF-naive RA patients (336 lymphomas during 365 026 person-years) and 2.72 (95% CI 1.82 to 4.08) versus the general population comparator (1568 lymphomas during 3 355 849 person-years). RA patients starting anti-TNF therapy in 1998–2001 accounted for the entire increase in lymphoma risk versus the two comparators. By contrast, RR did not vary significantly by time since start of first treatment or with the accumulated duration of treatment, nor with the type of anti-TNF agent.Conclusion: Overall and as used in routine care against RA, TNF antagonists are not associated with any major further increase in the already elevated lymphoma occurrence in RA. Changes in the selection of patients for treatment may influence the observed risk.
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| 11. |
- Askling, Johan, et al.
(författare)
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Cancer risk in patients with rheumatoid arthritis treated with anti-tumor necrosis factor alpha therapies : does the risk change with the time since start of treatment?
- 2009
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 60:11, s. 3180-3189
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:To determine the short-term and medium-term risks of cancer in patients receiving anti-tumor necrosis factor alpha (anti-TNFalpha) therapies that have proven effective in the treatment of chronic inflammatory conditions.METHODS:By linking together data from the Swedish Biologics Register, Swedish registers of RA, and the Swedish Cancer Register, we identified and analyzed for cancer occurrence a national cohort of 6,366 patients with RA who first started anti-TNF therapy between January 1999 and July 2006. As comparators, we used a national biologics-naive RA cohort (n = 61,160), a cohort of RA patients newly starting methotrexate (n = 5,989), a cohort of RA patients newly starting disease-modifying antirheumatic drug combination therapy (n = 1,838), and the general population of Sweden. Relative risks (RRs) were estimated using Cox regression analyses, examining overall RR as well as RR by time since the first start of anti-TNF therapy, by the duration of active anti-TNF therapy, and by the anti-TNF agent received.RESULTS:During 25,693 person-years of followup in 6,366 patients newly starting anti-TNF, 240 first cancers occurred, yielding an RR of 1.00 (95% confidence interval 0.86-1.15) versus the biologics-naive RA cohort, and similar RRs versus the other 2 RA comparators. RRs did not increase with increasing time since the start of anti-TNF therapy, nor with the cumulative duration of active anti-TNF therapy. During the first year following the first treatment start, but not thereafter, dissimilar cancer risks for adalimumab, etanercept, and infliximab were observed.CONCLUSION:During the first 6 years after the start of anti-TNF therapy in routine care, no overall elevation of cancer risk and no increase with followup time were observed.
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| 12. |
- Baecklund, Eva, et al.
(författare)
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Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis
- 2006
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 54:3, s. 692-701
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:Chronic inflammatory conditions such as rheumatoid arthritis (RA) have been associated with malignant lymphomas. This study was undertaken to investigate which patients are at highest risk, and whether antirheumatic treatment is hazardous or protective.METHODS:We performed a matched case-control study of 378 consecutive Swedish RA patients in whom malignant lymphoma occurred between 1964 and 1995 (from a population-based RA cohort of 74,651 RA patients), and 378 controls. Information on disease characteristics and treatment from onset of RA until lymphoma diagnosis was abstracted from medical records. Lymphoma specimens were reclassified and tested for Epstein-Barr virus (EBV). Relative risks (odds ratios [ORs]) for lymphomas (by subtype) associated with deciles of cumulative disease activity were assessed, as were ORs associated with drug treatments.RESULTS:The relative risks of lymphoma were only modestly elevated up to the seventh decile of cumulative disease activity. Thereafter, the relative risk increased dramatically (OR ninth decile 9.4 [95% confidence interval 3.1-28.0], OR tenth decile 61.6 [95% confidence interval 21.0-181.0]). Most lymphomas (48%) were of the diffuse large B cell type, but other lymphoma subtypes also displayed an association with cumulative disease activity. Standard nonbiologic treatments did not increase lymphoma risk. EBV was present in 12% of lymphomas.CONCLUSION:Risk of lymphoma is substantially increased in a subset of patients with RA, those with very severe disease. High inflammatory activity, rather than its treatment, is a major risk determinant.
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| 13. |
- Baecklund, Eva, et al.
(författare)
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Characteristics of diffuse large B cell lymphomas in rheumatoid arthritis
- 2006
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 54:12, s. 3774-3781
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:Patients with rheumatoid arthritis (RA) are at increased risk of malignant lymphomas, with a correlation between RA disease severity and lymphoma risk, most pronounced for diffuse large B cell lymphomas (DLBCLs), which also constitute the majority of RA-associated lymphomas. DLBCLs can be further subdivided into germinal center (GC)-like and non-GC-like subtypes, with different cellular origins and prognoses. This study was undertaken to investigate whether RA displays a specific association with any of the DLBCL subtypes.METHODS:We identified 139 patients with DLBCLs within a population-based case-control study of 378 RA patients with lymphoma. The DLBCLs were examined for CD10, Bcl-6, and interferon regulatory factor 4 expression patterns, subclassified into GC and non-GC subtypes, and then correlated with clinical parameters.RESULTS:We found a statistically significant predominance of the non-GC subtype (97 patients; 70% of all DLBCLs). These patients more often had an advanced stage of lymphoma at diagnosis and had a worse 5-year overall survival rate (16% versus 33%) compared with patients with the GC subtype. There was a strong association with RA disease activity in both subtypes, with >70% of the GC and non-GC cases occurring in RA patients with the highest overall disease activity scores.CONCLUSION: These findings suggest that severe RA is particularly associated with the non-GC subtype of DLBCL, and indicate a critical role of activated peripheral B cells as the cells of origin in these lymphomas.
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| 14. |
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| 15. |
- Bereczky, Sándor, et al.
(författare)
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Multiclonal asymptomatic Plasmodium falciparum infections predict a reduced risk of malaria disease in a Tanzanian population
- 2007
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Ingår i: Microbes and infection. - : Elsevier BV. - 1286-4579 .- 1769-714X. ; 9:1, s. 103-110
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Tidskriftsartikel (refereegranskat)abstract
- Protective immunity to malaria is acquired after repeated exposure to the polymorphic Plasmodium falciparum parasite. Whether the number of concurrent antigenically diverse clones in asymptomatic infections predicts the risk of subsequent clinical malaria needs further understanding. We assessed the diversity of P. falciparum infections by merozoite surface protein 2 genotyping in a longitudinal population based study in Tanzania. The number of clones was highest in children 6–10 years and in individuals with long time to previous anti-malarial treatment. Individual exposure, analysed by circumsporozoite protein antibody levels, was associated with parasite prevalence but not with the number of clones. The risk of subsequent clinical malaria in children free of acute disease or recent treatment was, compared to one clone, reduced in individuals with multiclonal infections or without detectable parasites, with the lowest hazard ratio 0.28 (95% confidence interval 0.10–0.78 Cox regression) for 2–3 clones. The number of clones was not associated with haemoglobin levels. A reduced risk of malaria in asymptomatic individuals with multiclonal persistent P. falciparum infections suggests that controlled maintenance of diverse infections is important for clinical protection in continuously exposed individuals, and needs to be considered in the design and evaluation of new malaria control strategies.
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| 16. |
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| 17. |
- Björnådal, Lena, et al.
(författare)
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Decreasing mortality in patients with rheumatoid arthrithis: results from large population based cohort in Sweden 1964-95
- 2002
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Ingår i: Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 29:5, s. 906-912
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:To assess changes in mortality in patients with rheumatoid arthritis (RA) from 1964 to 1995.METHODS:A population based cohort of 46,917 patients with RA was identified from 1964 to 1994, using the Swedish Hospital Discharge Register, and followed until 1995 through linkage to the Cause of Death Register. Mortality was separately analyzed in each inclusion period (1964-75, 1975-84, 1985-94). The relative risk of death was estimated as standardized mortality ratio (SMR) using the Swedish population as a referenceRESULTS:All-cause mortality was increased twice the expected (SMR = 2.03, 95% CI 2.00, 2.05). Coronary artery disease was the major cause of death and mortality was increased by 80% (SMR = 1.79, 95% CI 1.75, 1.83). Females with RA aged 20-39 at first discharge had a more than 5-fold increased risk of coronary death (SMR = 5.48, 95% CI 3.45-5.71). From 1975 patients with RA had decreasing all-cause mortality. This decline was most pronounced in patients aged 40-59 at first discharge, where SMR was 2.68 (95% CI 2.45, 2.92) from 1964 to 1974 compared to SMR 1.63 (95% CI 1.37, 1.92) from 1985 to 1994.CONCLUSION:The elevated mortality rates in RA patients compared to the general population have decreased during the last 20 years, possibly due to an increased access to specialized rheumatology care. An excess risk for death in coronary artery disease was, however, present in RA patients, especially patients with early onset of disease.
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| 18. |
- Broms, Gabriella, et al.
(författare)
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Anti-TNF treatment during pregnancy and birth outcomes : Apopulation-based study from Denmark, Finland, and Sweden
- 2020
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Ingår i: Pharmacoepidemiology and Drug Safety. - : Wiley. - 1053-8569 .- 1099-1557. ; 29:3, s. 316-327
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To study the risk of preterm birth, caesarean section, and small for gestational age after anti-tumor necrosis factor agent treatment (anti-TNF) in pregnancy.Methods: Population-based study including women with inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and psoriasis, and their infants born 2006 to 2013 from the national health registers in Denmark, Finland, and Sweden. Women treated with anti-TNF were compared with women with nonbiologic systemic treatment. Adalimumab, etanercept, and infliximab were compared pairwise. Continuation of treatment in early pregnancy was compared with discontinuation. Odds ratios with 95% confidence intervals were calculated in logistic regression models adjusted for country and maternal characteristics.Results: Among 1 633 909 births, 1027 infants were to women treated with anti-TNF and 9399 to women with nonbiologic systemic treatment. Compared with non-biologic systemic treatment, women with anti-TNF treatment had a higher risk of preterm birth, odds ratio 1.61 (1.29-2.02) and caesarean section, 1.57 (1.35-1.82). The odds ratio for small for gestational age was 1.36 (0.96-1.92). In pairwise comparisons, infliximab was associated with a higher risk of severely small for gestational age for inflammatory joint and skin diseases but not for inflammatory bowel disease. Discontinuation of anti-TNF had opposite effects on preterm birth for inflammatory bowel disease and inflammatory joint and skin diseases.Conclusions: Anti-TNF agents were associated with increased risks of preterm birth, caesarean section, and small for gestational age. However, the diverse findings across disease groups may indicate an association related to the underlying disease activity, rather than to agent-specific effects.
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| 19. |
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| 20. |
- Bröms, Gabriella, et al.
(författare)
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Paediatric infections in the first 3 years of life after maternal anti-TNF treatment during pregnancy
- 2020
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Ingår i: Alimentary Pharmacology and Therapeutics. - : John Wiley & Sons. - 0269-2813 .- 1365-2036. ; 52:5, s. 843-854
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Tidskriftsartikel (refereegranskat)abstract
- Background: Most anti‐tumour necrosis factor (anti‐TNF) agents are transferred across the placenta and may increase paediatric susceptibility to infections.Aims: To assess the risk of paediatric infections after maternal anti‐TNF treatment.Methods: Population‐based cohort study in Denmark, Finland and Sweden 2006‐2013 in which 1027 children born to women with rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis or inflammatory bowel disease, treated with anti‐TNF, and 9346 children to women with nonbiologic systemic treatment, were compared to 1 617 886 children of the general population. Children were followed for 3 years.Results: Adjusted by maternal age, parity, smoking, body mass index, country and calendar year, the incidence rate ratios with 95% confidence interval (CI) for hospital admissions for infection in the first year were 1.43 (1.23‐1.67) for anti‐TNF and 1.14 (1.07‐1.21) for non‐biologic systemic treatment, and 1.29 (1.11‐1.50) and 1.09 (1.02‐1.15), respectively, when additionally adjusting for adverse birth outcomes. There was a slight increase in antibiotic prescriptions in the second year for anti‐TNF, 1.19 (1.11‐1.29), and for non‐biologic systemic treatment, 1.10 (1.07‐1.13). There was no difference among anti‐TNF agents, treatment in the third trimester, or between mono/combination therapy with non‐biologic systemic treatment.Conclusions: Both anti‐TNF and non‐biologic systemic treatment were associated with an increased risk of paediatric infections. However, reassuringly, the increased risks were present regardless of treatment in the third trimester, with combination of treatments, and were not persistent across the first 3 years of life. Our findings may indicate a true risk, but could also be due to unadjusted confounding by disease severity and healthcare‐seeking behaviour. This may in turn shift the risk‐benefit equation towards continuation of treatment even in the third trimester.
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| 21. |
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| 22. |
- Carr, Hanna, et al.
(författare)
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Preterm Birth and Risk of Heart Failure Up to Early Adulthood
- 2017
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Ingår i: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 69:21, s. 2634-2642
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In small clinical studies, preterm birth was associated with altered cardiac structure and increased cardiovascular mortality in the young.OBJECTIVES: The goal of this study was to determine the association between preterm birth and risk of incident heart failure (HF) in children and young adults.METHODS: This register-based cohort study included 2,665,542 individuals born in Sweden from 1987 to 2012 who were followed up from 1 year of age to December 31, 2013. The main study outcome was diagnosis of HF in the National Patient Register or the Cause of Death Register. The association between preterm birth and risk of incident HF was analyzed by using a Poisson regression model. Estimates were adjusted for maternal and pregnancy characteristics, socioeconomic status, and maternal and paternal cardiovascular disease.RESULTS: During 34.8 million person-years of follow-up (median 13.1 years), there were 501 cases of HF. After exclusion of 52,512 individuals with malformations (n = 196 cases), 305 cases of HF remained (0.88 per 100,000 person-years). Gestational age was inversely associated with the risk of HF. Compared with individuals born at term (>= 37 weeks' gestation), adjusted incidence relative risks for HF were 17.0 (95% confidence interval [CI]: 7.96 to 36.3) after extremely preterm birth (<28 weeks) and 3.58 (95% CI: 1.57 to 8.14) after very preterm birth (28 to 31 weeks). There was no risk increase after moderately preterm birth (32 to 36 weeks) (relative risk: 1.36; 95% CI: 0.87 to 2.13).CONCLUSIONS: There was a strong association between preterm birth before 32 weeks of gestation and HF in childhood and young adulthood. Although the absolute risk of HF is low in young age, our findings indicate that preterm birth may be a previously unknown risk factor for HF. (J Am Coll Cardiol 2017;69:2634-42) (C) 2017 by the American College of Cardiology Foundation.
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| 23. |
- Cnattingius, Sven, et al.
(författare)
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Maternal Obesity and Risk of Preterm Delivery
- 2013
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 309:22, s. 2362-2370
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Tidskriftsartikel (refereegranskat)abstract
- Importance Preterm birth is a leading cause of infant mortality, morbidity, and long-term disability, and these risks increase with decreasing gestational age. Obesity increases the risk of preterm delivery, but the associations between overweight and obesity and subtypes of preterm delivery are not clear. Objective To study the associations between early pregnancy body mass index (BMI) and risk of preterm delivery by gestational age and by precursors of preterm delivery. Design, Setting, and Participants Population-based cohort study of women with live singleton births in Sweden from 1992 through 2010. Maternal and pregnancy characteristics were obtained from the nationwide Swedish Medical Birth Register. Main Outcomes and Measures Risks of preterm deliveries (extremely, 22-27 weeks; very, 28-31 weeks; and moderately, 32-36 weeks). These outcomes were further characterized as spontaneous (related to preterm contractions or preterm premature rupture of membranes) and medically indicated preterm delivery (cesarean delivery before onset of labor or induced onset of labor). Risk estimates were adjusted for maternal age, parity, smoking, education, height, mother's country of birth, and year of delivery. Results Among 1 599 551 deliveries with information on early pregnancy BMI, 3082 were extremely preterm, 6893 were very preterm, and 67 059 were moderately preterm. Risks of extremely, very, and moderately preterm deliveries increased with BMI and the overweight and obesity-related risks were highest for extremely preterm delivery. Among normal-weight women (BMI 18.5-<25), the rate of extremely preterm delivery was 0.17%. As compared with normal-weight women, rates (%) and adjusted odds ratios (ORs [95% CIs]) of extremely preterm delivery were as follows: BMI 25 to less than 30 (0.21%; OR, 1.26; 95% CI, 1.15-1.37), BMI 30 to less than 35 (0.27%; OR, 1.58; 95% CI, 1.39-1.79), BMI 35 to less than 40 (0.35%; OR, 2.01; 95% CI, 1.66-2.45), and BMI of 40 or greater (0.52%; OR, 2.99; 95% CI, 2.28-3.92). Risk of spontaneous extremely preterm delivery increased with BMI among obese women (BMI >= 30). Risks of medically indicated preterm deliveries increased with BMI among overweight and obese women. Conclusions and Relevance In Sweden, maternal overweight and obesity during pregnancy were associated with increased risks of preterm delivery, especially extremely preterm delivery. These associations should be assessed in other populations.
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| 24. |
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| 25. |
- Danielsson, Mattias, et al.
(författare)
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Association between cerebrospinal fluid biomarkers of neuronal injury or amyloidosis and cognitive decline after major surgery.
- 2021
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Ingår i: British journal of anaesthesia. - : Elsevier BV. - 1471-6771 .- 0007-0912. ; 126:2, s. 467-76
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Tidskriftsartikel (refereegranskat)abstract
- Postoperative neurocognitive decline is a frequent complication in adult patients undergoing major surgery with increased risk for morbidity and mortality. The mechanisms behind cognitive decline after anaesthesia and surgery are not known. We studied the association between CSF and blood biomarkers of neuronal injury or brain amyloidosis and long-term changes in neurocognitive function.In patients undergoing major orthopaedic surgery (knee or hip replacement), blood and CSF samples were obtained before surgery and then at 4, 8, 24, 32, and 48 h after skin incision through an indwelling spinal catheter. CSF and blood concentrations of total tau (T-tau), neurofilament light, neurone-specific enolase and amyloid β (Aβ1-42) were measured. Neurocognitive function was assessed using the International Study of Postoperative Cognitive Dysfunction (ISPOCD) test battery 1-2 weeks before surgery, at discharge from the hospital (2-5 days after surgery), and at 3 months after surgery.CSF and blood concentrations of T-tau, neurone-specific enolase, and Aβ1-42 increased after surgery. A similar increase in serum neurofilament light was seen with no overall changes in CSF concentrations. There were no differences between patients having a poor or good late postoperative neurocognitive outcome with respect to these biomarkers of neuronal injury and Aβ1-42.The findings of the present explorative study showed that major orthopaedic surgery causes a release of CSF markers of neural injury and brain amyloidosis, suggesting neuronal damage or stress. We were unable to detect an association between the magnitude of biomarker changes and long-term postoperative neurocognitive dysfunction.
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