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- Bottai, M, et al.
(författare)
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Nonlinear parametric quantile models
- 2020
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Ingår i: Statistical methods in medical research. - : SAGE Publications. - 1477-0334 .- 0962-2802. ; 29:12, s. 3757-3769
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Tidskriftsartikel (refereegranskat)abstract
- Quantile regression is widely used to estimate conditional quantiles of an outcome variable of interest given covariates. This method can estimate one quantile at a time without imposing any constraints on the quantile process other than the linear combination of covariates and parameters specified by the regression model. While this is a flexible modeling tool, it generally yields erratic estimates of conditional quantiles and regression coefficients. Recently, parametric models for the regression coefficients have been proposed that can help balance bias and sampling variability. So far, however, only models that are linear in the parameters and covariates have been explored. This paper presents the general case of nonlinear parametric quantile models. These can be nonlinear with respect to the parameters, the covariates, or both. Some important features and asymptotic properties of the proposed estimator are described, and its finite-sample behavior is assessed in a simulation study. Nonlinear parametric quantile models are applied to estimate extreme quantiles of longitudinal measures of respiratory mechanics in asthmatic children from an epidemiological study and to evaluate a dose–response relationship in a toxicological laboratory experiment.
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15. |
- Ecke, Frauke
(författare)
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Vattenvegetation som indikator för vattenkvalitet och sjökaraktär : baserad på förändringar i vattenkemi och vegetation i svenska sjöar 1929 - 2005
- 2006
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Water vegetation as indicator of water quality and lake character - Based on changes in water chemistry, and vegetation in Swedish lakes 1929 - 2005In the 1930ies, Gunnar Lohammar analyzed macrophyte vegetation and biogeochemistry in 151 Swedish lakes. These data completed with data from resampling open up a unique opportunity to study the relation among macrophytes, biogeochemistry and land-use. 17 of the Lohammar-lakes were re-sampled in summer 2005 (eight in the county of Uppland and nine in Norrbotten) to understand these relations and their temporal changes. Macrophytes showed clear preferences along the biogeochemical gradients. The response of isoetids and lemnids along the gradients was consistent within respective group. In contrast, within elodeids and nymphaeids, species showed varying responses. The preferences were used to develop preliminary macrophyte-based indicator-values. These deviated from the English indicator-values that are used in Sweden at present. Macrophyte vegetation, biogeochemistry and land-use changed considerably from 1930 - 2005. Analysing the whole material, only the number of nymphaeid-speices changed 1930 - 2005. Differences in macrophyte abundance were most obvious between the two regions. Lakes in Norrbotten had more isoetid-species than Uppland whereas for lemnids the situation was the opposite in the 1930ies. The differences between the regions were more pronounced 2005 than 1930 and could be explained with increased nutrient concentrations in general and increased tot-N concentrations in specific. Nutrient concentrations (mainly tot-N, but also tot-Na and conductivity) increased in Uppland and Norrbotten and were explained by amongst others increased N-deposition and increased use of salt in traffic and households. Tot-P concentrations did not change significantly between 1930 - 2005 but showed a correlation to the land-use in respective drainage area, e.g. distance to nearest village. Macrophyte abundance and lake biogeochemistry were related to land-use within drainage areas and within 1-km buffer zones from the lakes. Remarkable is especially the positive correlation of the length of ditches as well as area of agricultural land and the number of macrophyte species that prefer nutrient rich environments. Macrophyte abundance could be explained by a combination of land-use and lake biogeochemistry. The increased area of clear-cuts during the study period resulted probably in a decreased number of species preferring nutrient poor environments and low TOC-concentrations. Correlations among macro- and trace element fractionation indicate that it might be the bioavailable fraction of the elements that might determine the abundance of lemnids. The results illustrate the effects of land-use and land-use change on macrophytes and biogeochemistry. The results should be regarded as a first step to better understand the link among land-use, macrophytes and biogeochemistry.
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17. |
- Efe, C., et al.
(författare)
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Efficacy and Safety of Mycophenolate Mofetil and Tacrolimus as Second-line Therapy for Patients With Autoimmune Hepatitis
- 2017
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Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565 .- 1542-7714. ; 15:12
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Predniso(lo) ne, alone or in combination with azathioprine, is the standard-of-care (SOC) therapy for autoimmune hepatitis (AIH). However, the SOC therapy is poorly tolerated or does not control disease activity in up to 20% of patients. We assessed the efficacy of mycophenolate mofetil (MMF) and tacrolimus as second-line therapy for patients with AIH. METHODS: We performed a retrospective study of data (from 19 centers in Europe, the United States, Canada, and China) from 201 patients with AIH who received second-line therapy (121 received MMF and 80 received tacrolimus), for a median of 62 months (range, 6-190 mo). Patients were categorized according to their response to SOC. Patients in group 1 (n = 108) had a complete response to the SOC, but were switched to second-line therapy as a result of side effects of predniso(lo) ne or azathioprine, whereas patients in group 2 (n = 93) had not responded to SOC. RESULTS: There was no significant difference in the proportion of patients with a complete response to MMF (69.4%) vs tacrolimus (72.5%) (P = .639). In group 1, MMF and tacrolimus maintained a biochemical remission in 91.9% and 94.1% of patients, respectively (P = .682). Significantly more group 2 patients given tacrolimus compared with MMF had a complete response (56.5% vs 34%, respectively; P = .029) There were similar proportions of liver-related deaths or liver transplantation among patients given MMF (13.2%) vs tacrolimus (10.3%) (log-rank, P = .472). Ten patients receiving MMF (8.3%) and 10 patients receiving tacrolimus (12.5%) developed side effects that required therapy withdrawal. CONCLUSIONS: Long-term therapy with MMF or tacrolimus generally was well tolerated by patients with AIH. The agents were equally effective in previous complete responders who did not tolerate SOC therapy. Tacrolimus led to a complete response in a greater proportion of previous nonresponder patients compared with MMF.
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19. |
- Efe, Cumali, et al.
(författare)
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Tacrolimus and Mycophenolate Mofetil as Second-Line Therapies for Pediatric Patients with Autoimmune Hepatitis
- 2018
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Ingår i: Digestive Diseases and Sciences. - : SPRINGER. - 0163-2116 .- 1573-2568. ; 63:5, s. 1348-1354
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Tidskriftsartikel (refereegranskat)abstract
- We studied the efficacy and safety of mycophenolate mofetil (MMF) and tacrolimus as second-line therapy in pediatric patients with autoimmune hepatitis (AIH) who were intolerant or non-responders to standard therapy (corticosteroid and azathioprine). We performed a retrospective study of data from 13 centers in Europe, USA, and Canada. Thirty-eight patients (< 18 years old) who received second-line therapy (18 MMF and 20 tacrolimus), for a median of 72 months (range 8-182) were evaluated. Patients were categorized into two groups: Group 1 (n = 17) were intolerant to corticosteroid or azathioprine, and group 2 (n = 21) were non-responders to standard therapy. Overall complete response rates were similar in patients treated with MMF and tacrolimus (55.6 vs. 65%, p = 0.552). In group 1, MMF and tacrolimus maintained a biochemical remission in 88.9 and 87.5% of patients, respectively (p = 0.929). More patients in group 2 given tacrolimus compared to MMF had a complete response, but the difference was not statistically significant (50.0 vs. 22.2%, p = 0.195). Biochemical remission was achieved in 71.1% (27/38) of patients by tacrolimus and/or MMF. Decompensated cirrhosis was more commonly seen in MMF and/or tacrolimus non-responders than in responders (45.5 vs. 7.4%, p = 0.006). Five patients who received second-line therapy (2 MMF and 3 tacrolimus) developed side effects that led to therapy withdrawal. Long-term therapy with MMF or tacrolimus was generally well tolerated by pediatric patients with AIH. Both MMF and tacrolimus had excellent efficacy in patients intolerant to corticosteroid or azathioprine. Tacrolimus might be more effective than MMF in patients failing previous therapy.
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20. |
- Ejerblad, Elisabeth
(författare)
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Some lifestyle-related factors and risk of chronic renal failure : a population-based approach
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Some renal diseases, i.e. rapidly progressive glomerulonephritis, are sufficient causes of a rapid, permanent total loss of renal function. However, the majority of renal diseases progress slowly over decades, initially often without symptoms, sometimes making it difficult to define the aetiologies. There is growing evidence that a multitude of lifestyle-related and environmental factors influence the risk and the progression rate of chronic renal failure (CRF), although genetic factors also appear to be of importance. Prevention is important since the prognosis of end-stage renal disease treated with dialysis is poor, but mortality is substantially increased also in patients with mild CRF. To identify risk factors for CRF, we performed a population-based nation-wide case-control study. The study base was the entire Swedish population born in Sweden and aged 1874 years. Eligible as cases were subjects who had a serum creatinine that for the first time and permanently exceeded 300 µmol/l (men) or 250 µmol/l (women) during the two-year study period, 1996-1998. The final study population included 926 cases and 998 randomly selected controls from the study base. A face-to-face interview and a self-administered questionnaire provided information about various exposures. Despite an overall non-significant association, high daily smoking dose, long duration of the smoking habit, and a high cumulative dose were associated with a significant excess risk of CRF. In smokers with a cumulative dose of >30 pack-years, the risk was increased by 52 % compared to non-smokers. A more than two-fold increased risk among heavy smokers was observed for CRF classified as nephrosclerosis, but significant positive associations were also noted with glomerulonephritis, and among women - also with diabetic nephropathy. Other tobacco use than smoking was unrelated to risk of CRF. A high protein intake was strongly and positively related to an increased risk of diabetic nephropathy. We cannot rule out that this association might be the result of reverse causality and recall bias, however, in an analysis confined to diabetic cases and controls, an almost 3fold risk gradient with protein intake remained, albeit imprecise due to small numbers. Protein intake was not associated with other types of renal disease. We could not confirm our hypothesis that a high intake of antioxidants reduces risk of CRF, with the possible exception that a high intake of vitamin E was linked to a low risk in individuals with hypertension. Being overweight in early adulthood and obese at anytime in life was associated with an increased risk of CRF. A body mass index exceeding 30 kg/m2 in men and 35 kg/m2 in women anytime during lifetime was linked to 3-to 4-fold increases in risk. Although much of the excess risk was driven by the higher prevalence of hypertension and diabetes among obese, an additional pathway may exist. Birth weight was unrelated to risk of CRF, while a short stature was associated with CRF, at least in men. Isolated regular use of either paracetamol or aspirin was associated with a 2.5-fold increased risk of CRF overall, with a positive dose-response. The elevations in risk were observed for most types of underlying renal diseases, albeit not always statistically significant. To avoid bias due to analgesic use triggered by CRF symptoms, we disregarded more recent use, but the risks became only slightly attenuated. Our results are consistent with an exacerbating effect of paracetamol and aspirin, but, we cannot exclude that predisposing conditions of CRF may have prompted analgesic use.
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