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1.
  • Pattaro, Cristian, et al. (författare)
  • Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
  • 2016
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
  • 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.
  • Shrestha, Sarita, 1991-, et al. (författare)
  • The use of ICD codes to identify IBD subtypes and phenotypes of the Montreal classification in the Swedish National Patient Register
  • 2020
  • Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 55:4, s. 430-435
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Whether data on International Classification of Diseases (ICD)-codes from the Swedish National Patient Register (NPR) correctly correspond to subtypes of inflammatory bowel disease (IBD) and phenotypes of the Montreal classification scheme among patients with prevalent disease is unknown. Materials and methods: We obtained information on IBD subtypes and phenotypes from the medical records of 1403 patients with known IBD who underwent biological treatment at ten Swedish hospitals and retrieved information on their IBD-associated diagnostic codes from the NPR. We used previously described algorithms to define IBD subtypes and phenotypes. Finally, we compared these register-generated subtypes and phenotypes with the corresponding information from the medical records and calculated positive predictive values (PPV) with 95% confidence intervals. Results: Among patients with clinically confirmed disease and diagnostic listings of IBD in the NPR (N = 1401), the PPV was 97 (96-99)% for Crohn's disease, 98 (97-100)% for ulcerative colitis, and 8 (4-11)% for IBD-unclassified. The overall accuracy for age at diagnosis was 95% (when defined as A1, A2, or A3). Examining the validity of codes representing disease phenotype, the PPV was 36 (32-40)% for colonic Crohn's disease (L2), 61 (56-65)% for non-stricturing/non-penetrating Crohn's disease behaviour (B1) and 83 (78-87)% for perianal disease. Correspondingly, the PPV was 80 (71-89)% for proctitis (E1)/left-sided colitis (E2) in ulcerative colitis. Conclusions: Among people with known IBD, the NPR is a reliable source of data to classify most subtypes of prevalent IBD, even though misclassification commonly occurred in Crohn's disease location and behaviour and also among IBD-unclassified patients.
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3.
  • Hillert, J., et al. (författare)
  • Expert opinion on the use of contraception in people with multiple sclerosis
  • 2022
  • Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 28:Suppl. 3, s. 187-188
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Introduction: The most appropriate use, type, and timing of contraception in people with multiple sclerosis (PwMS) is poorly understood, and specific guidance is absent.Aims  and  Objectives: To  provide  insight  into  potential  clinical  guidelines for the use of contraception by PwMS through development  of  recommendations  by a  consensus-based  program  led  by international clinical experts.Methods:  A  multidisciplinary  steering  committee  (SC)  of  13  international expert healthcare professionals (HCPs) identified 15 key clinical questions on the use of contraception in PwMS, which addressed issues relating to patient-centred care, selection of contraception for PwMS, and time needed to use contraception since the last dose of disease modifying therapies (DMTs). Twenty-five clinical recommendations  addressing  the  questions  were  drafted  using evidence obtained from a comprehensive systematic literature  review  combined  with expert  opinion  from  the  SC.  An  extended faculty of 32 HCPs from 18 countries including a patient association representative, and the SC members (n=12), voted on the   recommendations.   Consensus   on   recommendations   was   achieved when  ⩾75%  of  respondents  expressed  an  agreement  score of 7–9, on a 9-point scale.Results: Overall, consensus was achieved on 24 out of 25 clinical recommendations. In detail, consensus in the range of 90–100% was  achieved on 11  recommendations,  12  recommendations  achieved  80–89%  consensus,  and 1  recommendation  achieved  75–79%  consensus  (n=44).  The  strength  of recommendations  ranged from 7–9. The one statement failing to achieve consensus scored 74.1%. Clinical recommendations are provided on the process of prescribing contraception for PwMS, including the recommended types of HCPs involved and optimal topics to discuss; the range of contraceptive options and the key considerations involved in selecting an appropriate method of contraception; and the timing of starting and stopping contraception in relation to the use of DMTs.Conclusions: These  expert  recommendations  were  based  on  a  robust consensus approach, providing timely and practical guidance on the use of contraception for HCPs treating PwMS and will form the basis of further publications and clinical tools.
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5.
  • Vattulainen, P., et al. (författare)
  • 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
  • Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 25:Suppl. 2, s. 619-619
  • 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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6.
  • Björk, Tabita, 1966-, et al. (författare)
  • Laterality, hand control and scholastic performance : a British birth cohort study
  • 2012
  • Ingår i: BMJ Open. - London, United Kingdom : BMJ. - 2044-6055. ; 2:2, s. e000314-
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To use simple measures of laterality and hand control that can identify a greater risk of poorer scholastic ability, potentially signalling suboptimal hemispheric lateralisation.Design: Analysis of material from a birth cohort study.Setting: Members of the National Child Development Study, a British birth cohort study following people born in 1958.Participants: 10 612 children who undertook tests at age 11 years.Primary outcome measures: Teacher-administered tests of non-verbal general ability, verbal general ability, reading comprehension and mathematics. Results Linear regression produced associations (and 95% CIs) with tests of verbal general ability, non-verbal general ability, reading comprehension and mathematics scores for the lowest third (compared with highest) of a left-hand control test involving picking up matches of −1.21 (−1.73 to −0.68; p<0.001), −0.72 (−1.14 to −0.29; p=0.001), −0.70 (−1.06 to −0.35; p<0.001) and −1.32 (−1.90 to −0.73; p<0.001). Among those in the lowest third of the right-hand control test score, mixed-handedness compared with right-handedness was associated with poorer scholastic performance, with regression coefficients (and 95% CIs; p values) of 1.90 (−3.01 to −0.80; p=0.001), −1.25 (−2.15 to −0.35; p=0.007), −1.28 (2.04 to −0.53; p=0.001) and −1.33 (−2.53 to −0.13; p=0.030). The estimates are for a point change in the scholastic test scores, after adjustment for sex, left-hand motor function and social class. Statistically significant associations with mixed-handedness were only observed for the lowest third of right-hand motor function.Conclusions Measures involving poorer left-hand motor function may represent useful markers of reduced cognitive function possibly reflecting suboptimal hemispheric lateralisation. Crude measures of laterality such as reported non-right-handedness may be more useful for research when combined with measures of motor function.                        
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7.
  • Burkill, Sarah M., et al. (författare)
  • Pain and Painkiller Use Among Multiple Sclerosis Patients in Sweden
  • 2017
  • Ingår i: Pharmacoepidemiology and Drug Safety. - : John Wiley & Sons. - 1053-8569 .- 1099-1557. ; 26:Suppl. 2, s. 634-634
  • 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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8.
  • Ekbäck, Gunnar, 1954-, et al. (författare)
  • Self-perceived oral health and obesity among 65 years old in two Swedish counties
  • 2010
  • Ingår i: SWEDISH DENTAL JOURNAL. - : Swedish Dental Journal (Sveriges Tandlakarforbund). - 0347-9994. ; 34:4, s. 207-216
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to explore the association between oral health and obesity. The study was conducted in the spring of 2007 as a postal survey of all inhabitants born in 1942 and living in the two Swedish counties of Orebro and Ostergotland. This questionnaire survey has been conducted every five years since 1992 but has been updated continually with additional questions and for the sweep used here, height and weight data were collected. A total of 8,313 individuals received the questionnaire and 6,078 of those responded (73,1%). The outcome variable oral health was measured using one global question and four detailed questions representing different aspects of oral health. The independent variable Body Mass Index (BMI) was calculated using self-reported height and weight. A difference in oral health between various BMI groups was found. The difference was both statistically significant and of clinical importance, particularly among the group with severe obesity who reported poorer self-perceived chewing capacity, lower satisfaction with dental appearance, increased mouth dryness and fewer teeth and lower overall satisfaction with oral health. In view of the increased risk of poor oral health demonstrated in this study for those with severe obesity, it may be of value to increase cooperation between dental care and primary health care for these patients.
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9.
  • Fadl, Helena, 1965-, et al. (författare)
  • Changing diagnostic criteria for gestational diabetes in Sweden-a stepped wedge national cluster randomised controlled trial-the CDC4G study protocol
  • 2019
  • Ingår i: Bmc Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393. ; 19:1
  • 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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10.
  • Fang, X., et al. (författare)
  • 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
  • Ingår i: Nutrients. - Basel, Switzerland : MDPIAG. - 2072-6643. ; 8:11
  • 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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