| 1. |
- Pattaro, Cristian, et al.
(författare)
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Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
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| 2. |
- Vattulainen, P., et al.
(författare)
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Prevalence of infant outcomes at birth after exposure to interferon beta prior to or during pregnancy : a register-based cohort study in Finland and Sweden among women with MS
- 2019
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 25:Suppl. 2, s. 619-619
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Women with multiple sclerosis (MS) are often diagnosed and treated at childbearing age. Systematic reviews and registry studies suggest that MS and interferon-beta (IFNβ) expo-sure might affect birth weight and head circumference.Objectives: To determine the prevalence of categorical measures of birth weight for gestational age (small for gestational age (SGA), large for gestational age (LGA)), low birth weight, and low head circumference in IFNβ exposed and unexposed pregnant women with MS from health registers in Finland and Sweden.Methods: In this cohort study, health register data from Finland (1996-2014) and Sweden (2005-2014) were used to study women with MS 1) dispensed only IFNβ within 6 months prior to date of last menstrual period or during pregnancy (IFNβ-exposed) and 2) without any dispensed MS disease modifying drugs (MSDMDs) (unexposed). The prevalence, with 95% confidence interval (CI), of the following birth outcomes was described for the IFNβ-exposed and the unexposed: SGA, LGA, low birth weight for live births, and low head circumference for infants with full term live birth (at least 37 gestational weeks). For SGA, LGA, and head circumference, national gestational age and sex-specific national references were used. No adjustments for potential confounding factors were performed.Results: Among 666 IFNβ-exposed and 1330 unexposed live births, the prevalence of the infant outcomes were similar between the IFNβ-exposed vs the unexposed. Comparing the exposed vs unexposed, SGA was 2.1% (95%CI 1.2-3.5) vs 2.0% (95%CI 1.3-2.9), and LGA 0.8% (95%CI 0.2-1.7) vs 0.8% (95%CI 0.4-1.5).The prevalence of low birth weight was 3.9% (95%CI 2.6-5.7) among IFNβ-exposed and 4.8% (95%CI 3.7-6.1) among the unexposed live births. Among 619 IFNβ-exposed and 1219 unexposed full term live births, the prevalence of low head circumfer-ence was 1.9% (95%CI 1.0-3.4) among the IFNβ-exposed vs 1.1% (95%CI 0.6-1.8) among the unexposed births.Conclusions: The data from Finnish and Swedish health registers showed no evidence that IFNβ exposure before and during pregnancy affected infant birth weight and head circumference.
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| 3. |
- Burkill, Sarah M., et al.
(författare)
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Pain and Painkiller Use Among Multiple Sclerosis Patients in Sweden
- 2017
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Ingår i: Pharmacoepidemiology and Drug Safety. - : John Wiley & Sons. - 1053-8569 .- 1099-1557. ; 26:Suppl. 2, s. 634-634
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Multiple sclerosis is an autoimmune disease which leads to demyelination and subsequent damage of axons and neurons. Pain is known to commonly affect MS patients, however the clinical characteristics of this pain are not fully described. Prescribed pain medication identifies more severe and chronic pain and different drug types can be used to identify other pain characteristics.Objectives: To assess whether MS patients in Sweden are at increased risk of receiving medication for pain relative to non-MS comparators. We aim to study overall pain, neuropathic pain, musculoskeletal pain and migraine.Methods: This cohort study using data on 5,555 MS patients in Sweden individually matched to 5,555 non-MS Swedish residents on sex, year of birth and place of residence at the time of MS diagnosis. We used Cox PH models using date of entry or 1stJuly 2006 as the beginning of follow up, whichever occurred later, and end of study was date of death, date of prescription of a painkiller or December 31st 2014, whichever occurred first. Painkillers were identified through relevant ATC codes. For neuropathic pain, pregabalin, gabapentin, amitriptyline, capsaicin or nortriptyline were used for identification, and for migraine prescriptions of anti-migraine preparations were included in the outcome. Musculoskeletal pain was identified primarily through topical products for joint and muscular pain.Results: Cox PH models showed MS patients to be at a 2.43 (CI 2.31–2.55) times increased risk of being prescribed any painkiller. The risk increased to 5.63 (CI 5.03–6.31) for neuropathic painkillers, however there was no significant difference for musculoskeletal painkillers (RR = 0.92 (CI 0.79–1.07)). MS patients were at a 1.28 (CI 1.10-1.50) times increased risk of being prescribed anti-migraine preparations. Restricting the data to MS patients showed that exposure to neuropathic painkillers was present in 32.8% of MS patients, and is associated with lower educational attainment and female sex. Conclusions: MS patients are at significantly increased risk of pain overall, with a particularly elevated risk for neuropathic pain. It seems that lower educational attainment and female sex are risk factors of neuropathic pain. However, the reason for this is not fully understood.*We would like to acknowledge the funding from the Science for Life - Astra Zeneca collaborative grant that supported this research
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| 4. |
- Fadl, Helena, 1965-, et al.
(författare)
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Changing diagnostic criteria for gestational diabetes in Sweden-a stepped wedge national cluster randomised controlled trial-the CDC4G study protocol
- 2019
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Ingår i: Bmc Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background The optimal criteria to diagnose gestational diabetes mellitus (GDM) remain contested. The Swedish National Board of Health introduced the 2013 WHO criteria in 2015 as a recommendation for initiation of treatment for hyperglycaemia during pregnancy. With variation in GDM screening and diagnostic practice across the country, it was agreed that the shift to new guidelines should be in a scientific and structured way. The aim of the Changing Diagnostic Criteria for Gestational Diabetes (CDC4G) in Sweden () is to evaluate the clinical and health economic impacts of changing diagnostic criteria for GDM in Sweden and to create a prospective cohort to compare the many long-term outcomes in mother and baby under the old and new diagnostic approaches. Methods This is a stepped wedge cluster randomised controlled trial, comparing pregnancy outcomes before and after the switch in GDM criteria across 11 centres in a randomised manner. The trial includes all pregnant women screened for GDM across the participating centres during January-December 2018, approximately two thirds of all pregnancies in Sweden in a year. Women with pre-existing diabetes will be excluded. Data will be collected through the national Swedish Pregnancy register and for follow up studies other health registers will be included. Discussion The stepped wedge RCT was chosen to be the best study design for evaluating the shift from old to new diagnostic criteria of GDM in Sweden. The national quality registers provide data on the whole pregnant population and gives a possibility for follow up studies of both mother and child. The health economic analysis from the study will give a solid evidence base for future changes in order to improve immediate pregnancy, as well as long term, outcomes for mother and child.
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| 5. |
- Fang, X., et al.
(författare)
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Dose-Response Relationship between Dietary Magnesium Intake and Risk of Type 2 Diabetes Mellitus : A Systematic Review and Meta-Regression Analysis of Prospective Cohort Studies
- 2016
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Ingår i: Nutrients. - Basel, Switzerland : MDPIAG. - 2072-6643. ; 8:11
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Forskningsöversikt (refereegranskat)abstract
- The epidemiological evidence for a dose-response relationship between magnesium intake and risk of type 2 diabetes mellitus (T2D) is sparse. The aim of the study was to summarize the evidence for the association of dietary magnesium intake with risk of T2D and evaluate the dose-response relationship. We conducted a systematic review and meta-analysis of prospective cohort studies that reported dietary magnesium intake and risk of incident T2D. We identified relevant studies by searching major scientific literature databases and grey literature resources from their inception to February 2016. We included cohort studies that provided risk ratios, i.e., relative risks (RRs), odds ratios (ORs) or hazard ratios (HRs), for T2D. Linear dose-response relationships were assessed using random-effects meta-regression. Potential nonlinear associations were evaluated using restricted cubic splines. A total of 25 studies met the eligibility criteria. These studies comprised 637,922 individuals including 26,828 with a T2D diagnosis. Compared with the lowest magnesium consumption group in the population, the risk of T2D was reduced by 17% across all the studies; 19% in women and 16% in men. A statistically significant linear dose-response relationship was found between incremental magnesium intake and T2D risk. After adjusting for age and body mass index, the risk of T2D incidence was reduced by 8%-13% for per 100 mg/day increment in dietary magnesium intake. There was no evidence to support a nonlinear dose-response relationship between dietary magnesium intake and T2D risk. The combined data supports a role for magnesium in reducing risk of T2D, with a statistically significant linear dose-response pattern within the reference dose range of dietary intake among Asian and US populations. The evidence from Europe and black people is limited and more prospective studies are needed for the two subgroups.
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| 6. |
- Lindahl Norberg, Annika, et al.
(författare)
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Short-term and long-term effects of childhood cancer on income from employment and employment status : A national cohort study in Sweden
- 2017
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Ingår i: Cancer. - Hoboken, USA : John Wiley & Sons. - 0008-543X .- 1097-0142. ; 123:7, s. 1238-1248
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is insufficient knowledge regarding the economic impact of childhood cancer on parents. The objectives of the current study were to investigate the short-term and long-term effects of childhood cancer on mothers' and fathers' income from employment and employment status.Methods: The study sample consisted of the parents of children diagnosed with cancer from 2004 to 2009 in Sweden (3626 parents of 1899 children). Annual register data concerning income from employment and employment status (employed/not employed) were retrieved from the Longitudinal Integration Database for Health Insurance and Labor Market Studies. Using generalized linear models, the mean income from employment and employment status were compared with a matched control cohort of 34,874 parents sampled from the general population.Results: Parents' income was found to decrease significantly after the child's cancer diagnosis. The effect was most pronounced for mothers, whose income was reduced for 6 years after diagnosis, whereas fathers' income was similar to that of control fathers 3 years after the diagnosis. Mothers were more likely to stop working after a child's cancer diagnosis compared with controls. No association was found for fathers' employment status. Younger age of parents; lower level of education; and, among mothers, being born outside of Sweden were found to be associated with more adverse effects on income.Conclusions: Parents' income from employment and employment status appear to be adversely affected by having a child with cancer. Socioeconomic consequences are not distributed equally: the income of fathers appears to catch up after a few years, whereas mothers tend to be disadvantaged in their professional life for several years after a child's cancer diagnosis.
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| 7. |
- Maghsoudlou, Siavash, et al.
(författare)
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Consanguineous marriage, prepregnancy maternal characteristics and stillbirth risk : a population-based case-control study
- 2015
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley-Blackwell. - 0001-6349 .- 1600-0412. ; 94:10, s. 1095-1101
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Consanguineous marriage is associated with increased risks for congenital anomalies, low birthweight, and other adverse perinatal outcomes. In this population-based, case-control study we investigated the association between consanguineous marriage (first-cousin marriage) and stillbirth risk, using prospectively collected information from prepregnancy visits.Material and methods: From 2007 to 2009, we identified 283 stillbirths (cases) and 2088 randomly selected live control births through prepregnancy visits in rural Golestan, Iran. The associations between consanguinity and prepregnancy maternal characteristics and stillbirth risk were examined using multivariate logistic regression.Results: The rate of consanguineous marriage was 19.4% among cases and 13.6% among controls. Consanguinity was associated with increased stillbirth risk [ odds ratio (OR) 1.53; 95% CI 1.10-2.14]. The association was significantly increased for preterm stillbirth (< 37 gestational weeks) (OR 2.43; 95% CI 1.46-4.04) but not for term stillbirth (>= 37 weeks) (OR 1.14; 95% CI 0.75-1.74). Low and high maternal age, underweight, obesity, nulliparity, a history of infertility or miscarriage, previous obstetric complications (preeclampsia, preterm delivery, and stillbirth in previous pregnancies) were also associated with increased stillbirth risks.Conclusions: Consanguineous marriage is associated with increased risk of stillbirth, particularly preterm stillbirth. Findings for other maternal risk factors for stillbirth in rural Iran are consistent with previously reported findings from high-income countries.
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| 8. |
- Maghsoudlou, Siavash, et al.
(författare)
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Maternal haemoglobin concentrations before and during pregnancy and stillbirth risk : a population-based case-control study
- 2016
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Ingår i: BMC Pregnancy and Childbirth. - London, United Kingdom : BioMed Central. - 1471-2393 .- 1471-2393. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Results of previous studies on the association between maternal haemoglobin concentration during pregnancy and stillbirth risk are inconclusive. It is not clear if haemoglobin concentration before pregnancy has a role. Using prospectively collected information from pre-pregnancy and antenatal visits, we investigated associations of maternal haemoglobin concentrations before and during pregnancy and haemoglobin dilution with stillbirth risk.Methods: In a population-based case-control study from rural Golestan, a province in northern Iran, we identified 495 stillbirths (cases) and randomly selected 2,888 control live births among antenatal health-care visits between 2007 and 2009. Using logistic regression, we estimated associations of maternal haemoglobin concentrations, haemoglobin dilution at different stages of pregnancy, with stillbirth risk.Results: Compared with normal maternal haemoglobin concentration (110-120 g/l) at the end of the second trimester, high maternal haemoglobin concentration (≥140 g/l) was associated with a more than two-fold increased stillbirth risk (OR = 2.31, 95 % CI [1.30-4.10]), while low maternal haemoglobin concentration (<110 g/l) was associated with a 37 % reduction in stillbirth risk. Haemoglobin concentration before pregnancy was not associated with stillbirth risk. Decreased haemoglobin concentration, as measured during pregnancy (OR = 0.61, 95 % CI [0.46, 0.80]), or only during the second trimester (OR = 0.75, 95 % CI [0.62, 0.90]), were associated with reduced stillbirth risk. The associations were essentially similar for preterm and term stillbirths.Conclusions: Haemoglobin concentration before pregnancy is not associated with stillbirth risk. High haemoglobin level and absence of haemoglobin dilution during pregnancy could be considered as indicators of a high-risk pregnancy.
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| 9. |
- Montgomery, Scott, 1961-, et al.
(författare)
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Infections in patients with multiple sclerosis : a nationwide cohort study in Sweden
- 2019
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 25:Suppl. 2, s. 388-388
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Previous studies suggest that susceptibility to infections is not raised among multiple sclerosis (MS) patients in general, but certain specific infections, such as those of the urinary or respiratory tract, are more common in patients with higher disability. However, contemporary MS cohorts to a higher degree are treated with newer disease-modifying treatments (DMTs) that exert stronger effects on the immune defence. Here we investigated the rate of infections in patients before and after MS diagnosis as compared with a matched MS-free population.Methods: Incident MS patients diagnosed in 2008-2016 were identified in the Swedish National Patient Register. MS patients were matched to 10 MS-free individuals by age, sex, and region of residence. Incidence rates per 10,000 person-years and incidence rate ratios (IRRs) of first infection by site and type were calculated after the MS diagnosis date.Results: In total, 6,602 MS patients were identified and compared with 61,828 without MS (female, 69%; median age, 40 years). During the year before MS diagnosis, MS patients showed higher proportions of urinary and kidney infections, meningitis and encephalitis, and bacterial infections compared with the MS-free cohort.After MS diagnosis, an increased risk of non-serious (IRR 1.65; 95% CI 1.56-1.75) and serious (admitted to hospital) infections (IRR 2.59; 95% CI 2.33-2.89) was detected among MS patients relative to the MS-free cohort. The risk of some bacterial (IRR 2.23; 95% CI 1.98-2.52) and some viral infections (IRR 1.70; 95% CI 1.48-1.96) was higher in MS patients of both sexes while only males showed an increased risk of fungal infections (IRR 1.91; 95% CI 1.26-2.89). Relative to the MS-free cohort, MS patients had an increased risk of all infection types, such as meningitis and encephalitis (IRR 6.16; 95% CI 4.47-8.48), other opportunistic infections (IRR 2.72; 95% CI 2.08-3.55), urinary and kidney infections (IRR 2.44; 95% CI 2.24-2.66), herpes virus (IRR 2.32; 95% CI 1.77-3.05), pneumonia and influenza (IRR 1.92; 95% CI 1.66-2.23), and skin infections (IRR 1.89; 95% CI 1.65-2.16).Conclusions: After MS diagnosis, patients had higher incidences of non-serious and serious infections compared with a cohort without MS. MS patients had an increased risk of being diagnosed during follow-up with most infection types compared with controls. This risk was particularly high for meningitis and encephalitis.
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| 10. |
- Montgomery, Scott M., 1961-, et al.
(författare)
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Multiple sclerosis and risk of young-adult-onset Hodgkin lymphoma
- 2016
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Ingår i: Neurology. - Philadelphia, USA : Lippincott Williams & Wilkins. - 2332-7812. ; 3:3
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To determine whether there is an association between multiple sclerosis (MS) and young-adult-onset Hodgkin lymphoma (YAHL) as this will signal etiologic similarities relevant both to inherited characteristics and environmental exposures in childhood.Methods: Swedish general population registers identified a cohort of 29,617 with an MS diagnosis between 1968 and 2012, matched with a cohort of 296,164 without MS. Cox regression was used to assess the association of MS with subsequent YAHL (defined as onset between ages 15 and 39 years; n = 20), with adjustment, for age/period, sex, county of residence, and level of education.Results: The adjusted hazard ratio (and 95% confidence interval) for the association of MS with YAHL is 3.30 (1.01-10.73), resulting from 4 and 16 events in the MS and non-MS cohorts, respectively. All 4 of the YAHL diagnoses in MS occurred in women, and the association of MS with YAHL has a hazard ratio of 4.04 (1.17-13.94) among women. There was no notable association of MS with older-onset Hodgkin lymphoma.Conclusion: There may be common risks for YAHL and MS, consistent with an etiologic role in MS for early-life exposures, such as to infectious agents.
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