| 21. |
- Louka, A S, et al.
(författare)
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HLA in coeliac disease families: a novel test of risk modification by the 'other' haplotype when at least one DQA1*05-DQB1*02 haplotype is carried.
- 2002
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Ingår i: Tissue antigens. - 0001-2815 .- 1399-0039. ; 60:2, s. 147-54
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Tidskriftsartikel (refereegranskat)abstract
- Predisposition to coeliac disease (CD) involves HLA genes. We investigated whether any haplotypes modify risk when carried trans to a known high-risk haplotype, DQA1*05-DQB1*02. Earlier attempts to rank levels of risk contributed by the 'other' haplotype were burdened by use of case-control populations; haplotype frequencies were estimated and homozygosity was only presumed. In contrast, exact haplotypes can be determined and allele transmission can be traced in families. A similar study in narcolepsy reported strata of different degrees of predisposition, attributable to the 'other' haplotype. A gene dosage effect similar to that described for DQB1*02 in CD, has also been reported in narcolepsy. We genotyped 439 simplex/multiplex trios for DQA1 and DQB1. We designed a new statistic to test risk modulation by the trans haplotype, even if the affected offspring was homozygous. We tested for significant deviation in transmission of the 'other' haplotype, i.e., modification of DQA1*05-DQB1*02 risk. We also addressed the proposed difference in risk, between DQA1*05-DQB1*02 homozygotes and DQA1*05-DQB1*02/DQA1*0201-DQB1*02 heterozygotes, reported in Southern Europe. We confirmed a DQB1*02 gene dosage effect. However, no haplotypes were found to modify risk when carried trans to DQA1*05-DQB1*02, except DQA1*05-DQB1*02 and DQA1*0201-DQB1*02 which were already known. We did not find credible evidence for a difference in risk conferred by DQA1*05-DQB1*02 and DQA1*0201-DQB1*02, when carried with DQA1*05-DQB1*02. The new test, which directly inspects haplotype transmissions rather than estimated haplotype frequencies, was used to demonstrate that the 'other' haplotype (except DQA1*05-DQB1*02 and DQA1*0201-DQB1*02) does not modify risk conferred by DQA1*05-DQB1*02. The test is applicable to other diseases.
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| 22. |
- Næss, Sigrid, et al.
(författare)
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Refinement of the MHC risk map in a scandinavian primary sclerosing cholangitis population
- 2014
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:12
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within the major histocompatibility complex (MHC) represent the strongest genetic susceptibility factors for primary sclerosing cholangitis (PSC). Identifying the causal variants within this genetic complex represents a major challenge due to strong linkage disequilibrium and an overall high physical density of candidate variants. We aimed to refine the MHC association in a geographically restricted PSC patient panel.
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| 23. |
- Olaya-Contreras, Patricia, 1964, et al.
(författare)
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THE INFLUENCE OF DISTRESS ON DISABILITY, PHYSICAL ACTIVITY AND PAIN INTENSITY AFTER 7 DAYS OF ACUTE SEVERE LOW BACK PAIN
- 2011
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Ingår i: Journal of Epidemiology and Community Health. - : BMJ. - 0143-005X. ; 65:8, s. A348-A349
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Tidskriftsartikel (refereegranskat)abstract
- Low back pain (LBP) is described as highly recurrent and frequently persistent public health worldwide. The “stay active” concept has been regarded as the most appropriate treatment recommendation for patients with acute LBP. The objective of this study was to evaluate the influence of distress on disability, physical activity and pain intensity in subjects with severe acute LBP. Methods A Randomised Control Trial (RCT) was conducted, 99 employed subjects (mean age 45 years, 20–63), 61% white- and 39% blue-collar workers with acute LBP were examined within 48 h after the onset of pain. All patients were initially assessed using the Depression Anxiety and Positive Outlook Scale (DAPOS) and the Tampa Scale of Kinesiophobia (TSK) questionnaires. Thereafter, the patients documented the following in a diary over a 7-day period: pain intensity, disability rating index (DRI) and step count (pedometer). Linear Mixed Models (LMM) for repeated measures were employed for the statistical analyses. All results were adjusted for age, gender, treatment, number of days and for the interaction term (treatment *DAPOS-D). Results Prospectively, DRI and pain intensity responses were differentially mediated by the treatment, in interaction with the scores of DAPOS (p<0.05). Patients with high scores on DAPOS exhibited higher risk for worse pain-disability after follow-up. Additionally, patients with higher baseline scores on TSK (>38) had a lower step count over time (p<0.05). Conclusion Depressed mood and fear of movement affect the outcomes of disability, the level of physical activity and the pain intensity in patients with acute LBP.
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| 24. |
- Olsson, Marita, 1965, et al.
(författare)
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Contemporary Risk Estimates of Three HbA(1c) Variables for Myocardial Infarction in 101,799 Patients Following Diagnosis of Type 2 Diabetes
- 2015
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 38:8, s. 1481-1486
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE This study evaluated the risk of myocardial infarction (MI) by impaired glycemic control in a contemporary large cohort of patients with type 2 diabetes followed from diagnosis. Patients with type 2 diabetes diagnosed between 1995 and 2011 were retrieved from the Clinical Practice Research Datalink in the U.K., and followed from diagnosis until event of MI or end of study in 2013. Two subcohorts were defined: an early cohort with those diagnosed from 1997 to 2004 and a recent cohort with those diagnosed from 2004 to 2011. Association between each of three HbA(1c) metrics and MI was estimated using adjusted proportional hazards models. In the overall cohort (n = 101,799), the risk increase for MI per 1% (10 mmol/mol) increase in HbA(1c) was higher for updated latest and updated mean HbA(1c) of 1.11 (95% CI 1.09-1.13) and 1.15 (1.13-1.18) than for baseline HbA(1c) of 1.05 (1.03-1.06). In the early subcohort, the corresponding risk estimates were greater than those in the recent subcohort. When categorized, the updated latest variable showed an increased risk for HbA(1c) <6% (42 mmol/mol), relative category 6-7%, in the recent but not in the early subcohort, with hazard ratios of 1.23 (1.08-1.40) and 1.01 (0.84-1.22), respectively. The two time-updated HbA(1c) variables show a stronger relation with MI than baseline HbA(1c). The risk association between HbA(1c) and MI has decreased over time. In recently diagnosed patients with type 2 diabetes, an increased risk of MI exists at a current HbA(1c) of <6.0% (42 mmol/mol).
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| 25. |
- Olsson, Marita, 1965
(författare)
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EM Estimation in Phase Type Models
- 1995
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis consists of four articles whose theme in common is the class of phase type distributions. In the first article an EM algorithm is presented to estimate the parameters of a phase type distribution of fixed order. Also, it is shown that the algorithm can be used to approximate other continuous distributions by phase type distributions. In article number two, the EM algorithm is adjusted to handle fitting of phase type distributions to samples containing right censored and/or interval censored observations. The third article deals with approximations of standard errors of identifiable functions (e.g. the distribution function at a fixed point) of a fitted phase type distribution. Standard error approximations are calculated both by using asymptotic theory and by using the jackknife technique. The two methods are compared and evaluated by simulations in several examples. The last article presents a parametric model for estimation of the relapse time of a disease in certain clinical trials. The model is a special phase type model where the state space of the underlying Markov process is split into two parts; the first set of states represents the patient still being healthy, a transition to a second set of states takes place when the patient get a relapse, and a transition to an absorbing state represents the patient getting symptoms of the disease.
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| 26. |
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| 27. |
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| 28. |
- Sim, S, et al.
(författare)
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Association between CYP2C19 polymorphism and depressive symptoms
- 2010
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Ingår i: American Journal of Medical Genetics, Part B, Neuropsychiatric Genetics. - : Wiley. - 1552-485X .- 1552-4841. ; 153B:6, s. 1160-1166
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Tidskriftsartikel (refereegranskat)abstract
- Cytochrome P450 2C19 (CYP2C19) is a polymorphic enzyme active in the metabolism of for example diazepam and the antidepressants sertraline, citalopram, and escitalopram, whereby allelic variants cause increased (CYP2C19*17) or abolished (mainly CYP2C19*2) enzymatic activity in drug metabolism. In light of the importance of CYP2C19 in the metabolism of psychoactive substances we considered it of interest to investigate the relationship between CYP2C19 polymorphisms and depressive symptoms in 1,472 subjects of European ancestry (45-98 years old) from the Swedish Twin Registry. Depressive symptoms were assessed using the Center of Epidemiologic Studies Depression (CES-D) scale. We found that poor metabolizers lacking CYP2C19 activity (PMs, CYP2C19*2/*2) had significantly lower levels of depressive symptoms than extensive metabolizers (EMs, CYP2C19*1/*1) (P = 0.0018). The size of this difference was in the same range as that between subjects reported taking antidepressants (n = 104) and those without antidepressant treatment (P < 0.0001). Our results suggest for the first time that the CYP2C19 polymorphism might be of importance for depressive symptoms, as here shown for older European adults.
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| 29. |
- Skrtic, Stanko, 1970, et al.
(författare)
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Contemporary risk estimates of three HbA(1c) variables in relation to heart failure following diagnosis of type 2 diabetes
- 2017
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Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 103:5, s. 355-360
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Tidskriftsartikel (refereegranskat)abstract
- Background We evaluated the association between glycaemic control and the risk of heart failure (HF) in a contemporary cohort of persons followed after diagnosis of type 2 diabetes (T2D). Methods and results Persons with T2D diagnosed between 1998 and 2012 were retrieved from the Clinical Practice Research Data Link in the UK and followed from diagnosis until the event of HF, mortality, drop out from the database due to any other reason, or the end of the study on 1 July 2015. The association between each of three different haemoglobin A(1C) (HbA1c) metrics and HF was estimated using adjusted proportional hazard models. In the overall cohort (n= 94 332), the increased risk for HF per 1% (10 mmol/mol) increase in HbA(1c) was 1.15 (95% CI 1.13 to 1.18) for updated mean HbA(1c), and 1.06 (1.04 to 1.07) and 1.06 (1.04 to 1.08) for baseline HbA(1c) and updated latest HbA(1c), respectively. When categorised, the hazard risk (HR) for the updated mean HbA(1c) in relation to HF became higher than for baseline and updated latest HbA(1c) above HbA(1c) levels of 9%, but did not differ at lower HbA(1c) levels. The updated latest variable showed an increased risk for HbA(1c)
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| 30. |
- Skrtic, Stanko, 1970, et al.
(författare)
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Impact of CKD Progression on Cardiovascular Disease Risk in a Contemporary UK Cohort of Individuals With Diabetes
- 2020
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Ingår i: Kidney International Reports. - : Elsevier BV. - 2468-0249. ; 5:10, s. 1651-1660
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: It remains unclear whether an increased progression rate of chronic kidney disease (CKD) adds predictive information regarding cardiovascular disease (CVD) risk. The aim of this study was to evaluate the association between CKD progression, based on estimated glomerular filtration rate (eGFR) slope estimates and the risk for CVD. Methods: We compared the updated eGFR slope calculated over multiple overlapping 2-year periods and the updated mean eGFR. Incident CKD subjects were selected from a prevalent population with diabetes (T2DM). Subjects from the UK Clinical Practice Research Data Link GOLD (CPRD) were followed from CKD diagnosis (n = 30,222) until heart failure (HF), myocardial infarction (MI), ischemic stroke (IS), or a composite end point including all 3 event types (MACE plus), mortality, database dropout, or end of study follow-up. Results: Both the updated eGFR slope and updated mean eGFR were associated with MACE plus and HF. Updated eGFR slope decline of > -3 ml/min/1.73 m(2) increased the risk for MACE plus (adjusted hazard ratio [HR] = 1.45; 95% confidence interval [CI], 1.26-1.67), HF (HR = 1.50; 95% CI, 1.27-1.76), and MI (HR = 1.39; 95% CI, 1.01-1.91). Conclusions: This study strongly supports current evidence that CKD is an independent risk factor for CVD. From a clinical perspective, both rate of progression and cumulative status of CKD describe distinct aspects of the cardiorenal risk among persons with diabetes. This evidence is essential to enable more timely and improved use of treatments in this population.
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