| 1. |
- Nilsson, Anna G, 1968, et al.
(författare)
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Type 2 Diabetes Mellitus is Associated with Better Bone Microarchitecture But Lower Bone Material Strength and Poorer Physical Function in Elderly Women - a Population-Based Study.
- 2017
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Ingår i: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - : Wiley. - 1523-4681. ; 32:5
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Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes mellitus (T2DM) is associated with an increased risk of fractures according to several studies. The underlying mechanisms remain unclear, although small case-control studies indicate poor quality of the cortical bone. We have studied a population-based sample of women aged 75-80 in Gothenburg, randomly invited from the population registry. Areal bone mineral density (aBMD) was measured by dual energy x-ray absorptiometry (Hologic Discovery A), bone microarchitecture by high-resolution peripheral quantitative computed tomography (HR-pQCT; ExtremeCT from Scanco Medical AG), and reference point indentation was performed with Osteoprobe (Active Life Scientific). Women with T2DM (n=99) had higher aBMD compared to controls (n=954). Ultradistal tibial and radial trabecular bone volume fraction (+11% and +15%, respectively), distal cortical volumetric BMD (+1.6% and +1.7%), cortical area (+11.5% and +9.3%), and failure load (+7.7% and +12.9%) were higher in diabetics than in controls. Cortical porosity was lower (mean±SD: 1.5±1.1 vs 2.0±1.7%, p=0.001) in T2DM in the distal radius but not in the ultradistal radius or the tibia. Adjustment for covariates (age, body mass index, glucocorticoid treatment, smoking, physical activity, calcium intake, bone-active drugs) eliminated the differences in aBMD but not in HR-pQCT bone variables. However, bone material strength index (BMSi) by reference point indentation was lower in T2DM (74.6±7.6 vs 78.2±7.5, p<0.01), also after adjustment, and women with T2DM performed clearly worse in measures of physical function (one leg standing: -26%, 30s chair-stand test: -7%, timed up and go: +12%, walking speed: +8%; p<0.05-0.001) compared to controls. In conclusion, we observed a more favorable bone microarchitecture but no difference in adjusted aBMD in elderly women with T2DM in the population compared to non-diabetics. Reduced BMSi and impaired physical function may explain the increased fracture risk in T2DM. This article is protected by copyright. All rights reserved.
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| 2. |
- Barbosa, Edna J L, 1961, et al.
(författare)
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Extracellular water and blood pressure in adults with growth hormone (GH) deficiency: a genotype-phenotype association study.
- 2014
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 9:8
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Tidskriftsartikel (refereegranskat)abstract
- Growth hormone deficiency (GHD) in adults is associated with decreased extracellular water volume (ECW). In response to GH replacement therapy (GHRT), ECW increases and blood pressure (BP) reduces or remains unchanged. Our primary aim was to study the association between polymorphisms in genes related to renal tubular function with ECW and BP before and 1 year after GHRT. The ECW measures using bioimpedance analysis (BIA) and bioimpedance spectroscopy (BIS) were validated against a reference method, the sodium bromide dilution method (Br(-)).
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| 3. |
- Barbosa, Edna J L, 1961, et al.
(författare)
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Genotypes associated with lipid metabolism contribute to differences in serum lipid profile of GH-deficient adults before and after GH replacement therapy.
- 2012
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Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - 1479-683X .- 0804-4643. ; 167:3, s. 353-62
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Tidskriftsartikel (refereegranskat)abstract
- bjective: GH deficiency (GHD) in adults is associated with an altered serum lipid profile that responds to GH replacement therapy (GHRT). This study evaluated the influence of polymorphisms in genes related to lipid metabolism on serum lipid profile before and after 1 year of GHRT in adults. Design and methods: In 318 GHD patients, total cholesterol (TC) serum concentrations, LDL-C, HDL-C, and triglycerides (TG) were assessed. Using a candidate gene approach, 20 single nucleotide polymorphisms (SNPs) were genotyped. GH dose was individually titrated to obtain normal serum IGF1 concentrations. Results: At baseline, the minor alleles of cholesteryl ester transfer protein (CETP) gene SNPs rs708272 and rs1800775 were associated with higher serum TC and apolipoprotein E (APOE) gene SNP rs7412 with lower TC concentrations; CETP SNPs rs708272, rs1800775, and rs3764261 and apolipoprotein B (APOB) gene SNP rs693 with higher serum HDL-C; APOE SNP rs7412, peroxisome proliferator-activated receptor gamma (PPARG) gene SNP rs10865710 with lower LDL-C, and CETP SNP rs1800775 with higher LDL-C; and APOE/C1/C4/C2 cluster SNP rs35136575 with lower serum TG. After treatment, APOB SNP rs676210 GG genotype was associated with larger reductions in TC and LDL-C and PPARG SNP rs10865710 CC genotype with greater TC reduction. All associations remained significant when adjusted for age, sex, and BMI. Conclusions: In GHD adults, multiple SNPs in genes related to lipid metabolism contributed to individual differences in baseline serum lipid profile. The GH treatment response in TC and LDL-C was influenced by polymorphisms in the APOB and PPARG genes.
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| 4. |
- Decker, Ralph, 1968, et al.
(författare)
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Long-term Effects of Growth Hormone in Children
- 2014
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Ingår i: Update on GH and IGFs, 22-23 maj 2014, Stockholm, Sverige. Nobelforum Karolinska institutet - Svenska Endokrinolog Föreningen.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 5. |
- Glad, Camilla A M, 1981, et al.
(författare)
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SNPs within the GH-signaling pathway are associated with the early IGF1 response to GH replacement therapy in GHD adults.
- 2014
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Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - 1479-683X .- 0804-4643. ; 170:1, s. 101-7
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Tidskriftsartikel (refereegranskat)abstract
- GH-deficient (GHD) adults have reduced serum concentrations of IGF1. GH replacement therapy increases serum IGF1 concentrations, but the interindividual variation in treatment response is large and likely influenced by genetic factors. This study was designed to test the hypothesis that single-nucleotide polymorphisms (SNPs) in genes within the GH signaling pathway influence the serum IGF1 response to GH replacement.
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| 6. |
- Johansson, Lisa, et al.
(författare)
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The Prevalence of Vertebral Fractures Is Associated With Reduced Hip Bone Density and Inferior Peripheral Appendicular Volumetric Bone Density and Structure in Older Women
- 2018
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Ingår i: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - : Wiley. - 1523-4681. ; 33:2, s. 250-260
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Tidskriftsartikel (refereegranskat)abstract
- Vertebral fractures (VFs) are among the most severe and prevalent osteoporotic fractures. Their association with bone microstructure have been investigated in several retrospective case-control studies with spine radiography for diagnosis of VF. The aim of this population-based cross-sectional study of 1027 women aged 75 to 80 years was to investigate if prevalent VF, identified by vertebral fracture assessment (VFA) by dual-energy X-ray absorptiometry (DXA), was associated with appendicular volumetric bone density, structure, and bone material strength index (BMSi), independently of hip areal bone mineral density (aBMD). aBMD was measured using DXA (Discovery; Hologic); BMSi with microindentation (Osteoprobe); and bone geometry, volumetric BMD, and microstructure with high-resolution peripheral quantitative computed tomography (HRpQCT) (XtremeCT; Scanco Medical AG). aBMD was lower (spine 3.2%, total hip [TH] 3.8%) at all sites in women with VF, but tibia BMSi did not differ significantly compared to women without VF. In multivariable adjusted logistic regression models, radius trabecular bone volume fraction and tibia cortical area (odds ratio [OR] 1.26; 95% confidence interval [CI], [1.06 to 1.49]; and OR 1.27 [95% CI, 1.08 to 1.49], respectively) were associated with VF prevalence, whereas BMSi and cortical porosity were not. The risk of having one, two, or more than two VFs was increased 1.27 (95% CI, 1.04 to 1.54), 1.83 (95% CI, 1.28 to 2.61), and 1.78 (95% CI, 1.03 to 3.09) times, respectively, for each SD decrease in TH aBMD. When including either cortical area, trabecular bone volume fraction or TBS in the model together with TH aBMD and covariates, only TH aBMD remained independently associated with presence of any VF. In conclusion, TH aBMD was consistently associated with prevalent VFA-verified VF, whereas neither trabecular bone volume fraction, cortical area, cortical porosity, nor BMSi were independently associated with VF in older women. © 2017 American Society for Bone and Mineral Research.
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| 7. |
- Sundh, Daniel, 1985, et al.
(författare)
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A High Amount of Local Adipose Tissue Is Associated With High Cortical Porosity and Low Bone Material Strength in Older Women
- 2016
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 31:4, s. 749-757
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is associated with increased risk of fractures, especially at skeletal sites with a large proportion of cortical bone, such as the humerus and ankle. Obesity increases fracture risk independently of BMD, indicating that increased adipose tissue could have negative effects on bone quality. Microindentation assesses bone material strength index (BMSi) in vivo in humans. The aim of this study was to investigate if different depots of adipose tissue were associated with BMSi and cortical bone microstructure in a population based group of 202 women, 78.2 +/- 1.1 (mean +/- SD) years old. Bone parameters and subcutaneous (s.c.) fat were measured at the tibia with an XtremeCT device. BMSi was assessed using the OsteoProbe device, and based on at least 11 valid reference point indentations at the mid-tibia. Body composition was measured with dual X-ray absorptiometry. BMSi was inversely correlated to body mass index (BMI) (r=-0.17, p=0.01), whole body fat mass (r=-0.16,p=0.02), and, in particular, to tibia s.c. fat (r=-0.33, p<0.001). Tibia s.c. fat was also correlated to cortical porosity (Ct.Po; r=0.19, p=0.01) and cortical volumetric BMD (Ct.vBMD; r=-0.23, p=0.001). Using linear regression analyses, tibia s.c. fat was found to be independent of covariates (age, height, log weight, bisphosphonates or glucocorticoid use, smoking, calcium intake, walking speed, and BMSi operator) and associated with BMSi (=-0.34,p<0.001), Ct.Po (=0.18, p=0.01), and Ct.vBMD (=-0.32, p<0.001). BMSi was independent of covariates associated with cortical porosity (=-0.14, p=0.04) and cortical volumetric BMD (=0.21, p=0.02) at the distal tibia, but these bone parameters could only explain 3.3% and 5.1% of the variation in BMSi, respectively. In conclusion, fat mass was independently and inversely associated with BMSi and Ct.vBMD, but positively associated with Ct.Po, indicating a possible adverse effect of adipose tissue on bone quality and bone microstructure. Local s.c. fat in tibia was most strongly associated with these bone traits, suggesting a local or paracrine, rather than systemic, negative effect of fat on bone. (c) 2015 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR).
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| 8. |
- Sundh, Daniel, 1985, et al.
(författare)
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Increased cortical porosity in women with hip fracture
- 2017
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820. ; 281:5, s. 496-506
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Tidskriftsartikel (refereegranskat)abstract
- Background. Hip fractures cause increased mortality and disability and consume enormous healthcare resources. Only 46% of hip fracture patients have osteoporosis at the total hip according to dual-energy X-ray absorptiometry (DXA) measurement. Cortical porosity increases with ageing and is believed to be important for bone strength. Objective. To investigate whether older women with hip fracture have higher cortical porosity than controls, and if so whether this difference is independent of clinical risk factors and areal bone mineral density (aBMD). Methods. From an ongoing population-based study, we identified 46 women with a prevalent X-rayverified hip fracture and 361 control subjects without any fractures. aBMD was measured with DXA. High-resolution peripheral quantitative computed tomography was used to measure bone microstructure at the standard (ultradistal) site and at 14% (distal) of the tibial length. Results. Women with a previous hip fracture had lower aBMD at the femoral neck (-11.8%) and total hip (-14.6%) as well as higher cortical porosity at the ultradistal (32.1%) and distal (29.3%) tibia compared with controls. In multivariable logistic regression analysis, with adjustment for covariates (age, height, weight, smoking, calcium intake, physical activity, walk time, oral glucocorticoids, parental hip fracture, rheumatoid arthritis, previous fall, current bisphosphonate treatment and femoral neck aBMD), cortical porosity at the ultradistal [odds ratio per standard deviation increase (95% confidence interval) 2.61 (1.77-3.85)] and distal [1.57 (1.12-2.20)] sites was associated with prevalent hip fracture. Conclusion. Cortical porosity was associated with prevalent hip fracture in older women independently of femoral neck aBMD and clinical risk factors.
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| 9. |
- Sundh, Daniel, 1985, et al.
(författare)
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Low serum vitamin D is associated with higher cortical porosity in elderly men
- 2016
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 280:5, s. 496-508
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Bone loss at peripheral sites in the elderly is mainly cortical and involves increased cortical porosity. However, an association between bone loss at these sites and 25-hydroxyvitamin D has not been reported. OBJECTIVE: To investigate the association between serum levels of 25-hydroxyvitamin D, bone microstructure and areal bone mineral density (BMD) in elderly men. METHODS: A population-based cohort of 444 elderly men (mean +/- SD age 80.2 +/- 3.5 years) was investigated. Bone microstructure was measured by high-resolution peripheral quantitative computed tomography, areal BMD by dual-energy X-ray absorptiometry and serum 25-hydroxyvitamin D and parathyroid hormone levels by immunoassay. RESULTS: Mean cortical porosity at the distal tibia was 14.7% higher (12.5 +/- 4.3% vs. 10.9 +/- 4.1%, P < 0.05) whilst cortical volumetric BMD, area, trabecular bone volume fraction and femoral neck areal BMD were lower in men in the lowest quartile of vitamin D levels compared to the highest. In men with vitamin D deficiency (<25 nmol L-1 ) or insufficiency [25-49 nmol L-1 , in combination with an elevated serum level of parathyroid hormone (>6.8 pmol L-1 )], cortical porosity was 17.2% higher than in vitamin D-sufficient men (P < 0.01). A linear regression model including age, weight, height, daily calcium intake, physical activity, smoking vitamin D supplementation and parathyroid hormone showed that 25-hydroxyvitamin D independently predicted cortical porosity (standardized beta = -0.110, R2 = 1.1%, P = 0.024), area (beta = 0.123, R2 = 1.4%, P = 0.007) and cortical volumetric BMD (beta = 0.125, R2 = 1.4%, P = 0.007) of the tibia as well as areal BMD of the femoral neck (beta = 0.102, R2 = 0.9%, P = 0.04). CONCLUSION: Serum vitamin D is associated with cortical porosity, area and density, indicating that bone fragility as a result of low vitamin D could be due to changes in cortical bone microstructure and geometry.
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| 10. |
- Axelsson, Kristian F, 1973, et al.
(författare)
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Association Between Alendronate Use and Hip Fracture Risk in Older Patients Using Oral Prednisolone
- 2017
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Ingår i: Jama-Journal of the American Medical Association. - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 318:2, s. 146-155
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Oral glucocorticoid treatment increases fracture risk, and evidence is lacking regarding the efficacy of alendronate to protect against hip fracture in older patients using glucocorticoids. OBJECTIVE To investigate whether alendronate treatment in older patients using oral prednisolone is associated with decreased hip fracture risk and adverse effects. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study using a national database (N = 433 195) of patients aged 65 years or older undergoing a health evaluation (baseline) at Swedish health care facilities; 1802 patients who were prescribed alendronate after at least 3 months of oral prednisolone treatment (>= 5mg/d) were identified. Propensity score matching was used to select 1802 patients without alendronate use from 6076 patients taking prednisolone with the same dose and treatment time criteria. Follow-up occurred between January 2008 and December 2014. EXPOSURES Alendronate vs no alendronate use; no patients had previously taken alendronate at the time of prednisolone initiation. MAIN OUTCOMES AND MEASURES The primary outcome was incident hip fracture. RESULTS Of the 3604 included patients, the mean age was 79.9 (SD, 7.5) years, and 2524 (70%) were women. After a median follow-up of 1.32 years (interquartile range, 0.57-2.34 years), there were 27 hip fractures in the alendronate group and 73 in the no-alendronate group, corresponding to incidence rates of 9.5 (95% CI, 6.5-13.9) and 27.2 (95% CI, 21.6-34.2) fractures per 1000 person-years, with an absolute rate difference of -17.6 (95% CI, -24.8 to -10.4). The use of alendronate was associated with a lower risk of hip fracture in a multivariable-adjusted Cox model (hazard ratio, 0.35; 95% CI, 0.22-0.54). Alendronate treatment was not associated with increased risk of mild upper gastrointestinal tract symptoms (alendronate vs no alendronate, 15.6 [95% CI, 11.6-21.0] vs 12.9 [95% CI, 9.3-18.0] per 1000 person-years; P=.40) or peptic ulcers (10.9 [95% CI, 7.7-15.5] vs 11.4 [95% CI, 8.0-16.2] per 1000 person-years; P=.86). There were no cases of incident drug-induced osteonecrosis and only 1 case of femoral shaft fracture in each group. CONCLUSIONS AND RELEVANCE Among older patients using medium to high doses of prednisolone, alendronate treatment was associated with a significantly lower risk of hip fracture over a median of 1.32 years. Although the findings are limited by the observational study design and the small number of events, these results support the use of alendronate in this patient group.
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| 11. |
- Hammarstrand, Casper, 1990, et al.
(författare)
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Higher glucocorticoid replacement doses are associated with increased mortality in patients with pituitary adenoma
- 2017
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Ingår i: European Journal of Endocrinology. - 1479-683X. ; 177:3, s. 251-256
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Patients with secondary adrenal insufficiency (AI) have an excess mortality. The objective was to investigate the impact of the daily glucocorticoid replacement dose on mortality in patients with hypopituitarism due to non-functioning pituitary adenoma (NFPA). METHODS: Patients with NFPA were followed between years 1997 and 2014 and cross-referenced with the National Swedish Death Register. Standardized mortality ratio (SMR) was calculated with the general population as reference and Cox-regression was used to analyse the mortality. RESULTS: The analysis included 392 patients (140 women) with NFPA. Mean±s.d. age at diagnosis was 58.7±14.6 years and mean follow-up was 12.7±7.2 years. AI was present in 193 patients, receiving a mean daily hydrocortisone equivalent (HCeq) dose of 20±6mg. SMR (95% confidence interval (CI)) for patients with AI was similar to that for patients without, 0.88 (0.68-1.12) and 0.87 (0.63-1.18) respectively. SMR was higher for patients with a daily HCeq dose of >20mg (1.42 (0.88-2.17)) than that in patients with a daily HCeq dose of 20mg (0.71 (0.49-0.99)), P=0.017. In a Cox-regression analysis, a daily HCeq dose of >20mg was independently associated with a higher mortality (HR: 1.88 (1.06-3.33)). Patients with daily HCeq doses of ≤20mg had a mortality risk comparable to patients without glucocorticoid replacement and to the general population. CONCLUSION: Patients with NFPA and AI receiving more than 20mg HCeq per day have an increased mortality. Our data also show that mortality in patients substituted with 20mg HCeq per day or less is not increased. © 2017 European Society of Endocrinology.
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| 12. |
- Hurtsén, Anna Stene, 1992-, et al.
(författare)
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A randomized porcine study of hemorrhagic shock comparing end-tidal carbon dioxide targeted and proximal systolic blood pressure targeted partial resuscitative endovascular balloon occlusion of the aorta in the mitigation of metabolic injury
- 2023
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Ingår i: Intensive Care Medicine Experimental. - : Springer. - 2197-425X. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The definition of partial resuscitative endovascular balloon occlusion of the aorta (pREBOA) is not yet determined and clinical markers of the degree of occlusion, metabolic effects and end-organ injury that are clinically monitored in real time are lacking. The aim of the study was to test the hypothesis that end-tidal carbon dioxide (ETCO2) targeted pREBOA causes less metabolic disturbance compared to proximal systolic blood pressure (SBP) targeted pREBOA in a porcine model of hemorrhagic shock.MATERIALS AND METHODS: Twenty anesthetized pigs (26-35 kg) were randomized to 45 min of either ETCO2 targeted pREBOA (pREBOAETCO2, ETCO2 90-110% of values before start of occlusion, n = 10) or proximal SBP targeted pREBOA (pREBOASBP, SBP 80-100 mmHg, n = 10), during controlled grade IV hemorrhagic shock. Autotransfusion and reperfusion over 3 h followed. Hemodynamic and respiratory parameters, blood samples and jejunal specimens were analyzed.RESULTS: ETCO2 was significantly higher in the pREBOAETCO2 group during the occlusion compared to the pREBOASBP group, whereas SBP, femoral arterial mean pressure and abdominal aortic blood flow were similar. During reperfusion, arterial and mesenteric lactate, plasma creatinine and plasma troponin concentrations were higher in the pREBOASBP group.CONCLUSIONS: In a porcine model of hemorrhagic shock, ETCO2 targeted pREBOA caused less metabolic disturbance and end-organ damage compared to proximal SBP targeted pREBOA, with no disadvantageous hemodynamic impact. End-tidal CO2 should be investigated in clinical studies as a complementary clinical tool for mitigating ischemic-reperfusion injury when using pREBOA.
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| 13. |
- Johannsson, Gudmundur, 1960, et al.
(författare)
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Improved cortisol exposure-time profile and outcome in patients with adrenal insufficiency : a prospective randomised trial of a novel hydrocortisone dual-release formulation
- 2012
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 97:2, s. 473-481
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Tidskriftsartikel (refereegranskat)abstract
- Context: Patients with treated adrenal insufficiency (AI) have increased morbidity and mortality rate. Our goal was to improve outcome by developing a once-daily (OD) oral hydrocortisone dual-release tablet with a more physiological exposure-time cortisol profile.Objective: The aim was to compare pharmacokinetics and metabolic outcome between OD and the same daily dose of thrice-daily (TID) dose of conventional hydrocortisone tablets.Design and Setting: We conducted an open, randomized, two-period, 12-wk crossover multicenter trial with a 24-wk extension at five university hospital centers.Patients: The trial enrolled 64 adults with primary AI; 11 had concomitant diabetes mellitus (DM).Intervention: The same daily dose of hydrocortisone was administered as OD dual-release or TID.Main Outcome Measure: We evaluated cortisol pharmacokinetics.Results: Compared with conventional TID, OD provided a sustained serum cortisol profile 0-4 h after the morning intake and reduced the late afternoon and the 24-h cortisol exposure. The mean weight (difference = -0.7 kg, P = 0.005), systolic blood pressure (difference = -5.5 mm Hg, P = 0.0001) and diastolic blood pressure (difference: -2.3 mm Hg; P = 0.03), and glycated hemoglobin (absolute difference = -0.1%, P = 0.0006) were all reduced after OD compared with TID at 12 wk. Compared with TID, a reduction in glycated hemoglobin by 0.6% was observed in patients with concomitant DM during OD (P = 0.004).Conclusion: The OD dual-release tablet provided a more circadian-based serum cortisol profile. Reduced body weight, reduced blood pressure, and improved glucose metabolism were observed during OD treatment. In particular, glucose metabolism improved in patients with concomitant DM.
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| 14. |
- Johannsson, Gudmundur, 1960, et al.
(författare)
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Improving glucocorticoid replacement therapy using a novel modified-release hydrocortisone tablet: a pharmacokinetic study.
- 2009
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Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - 1479-683X .- 0804-4643. ; 161:1, s. 119-30
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Endogenous plasma cortisol levels have a well-defined circadian rhythm. The aim of this project is to develop a once daily oral dual-release formulation for cortisol replacement therapy that mimics the diurnal variation in the plasma cortisol profile. OBJECTIVE: To determine single-dose plasma pharmacokinetics and dose-proportionality of oral 5 and 20 mg dual-release hydrocortisone tablets in healthy volunteers. In addition, the effect of food intake was investigated for the 20 mg dose. DESIGN: A randomised, controlled, two-way cross-over, double-blind, phase I study of oral hydrocortisone (modified (dual) release; 5 and 20 mg) with an open food-interaction arm. METHODS: The single dose pharmacokinetic studies were performed with betamethasone suppression. The two first study days were blinded and randomised between morning administration of 5 and 20 mg tablet in a fasting state. The third day was open with a 20 mg tablet taken 30 min after a high-calorie, high-fat meal. The plasma samples were assayed using both a validated LC-MS/MS and an immunoassay. The plasma pharmacokinetic variables were calculated using non-compartmental data analysis. RESULTS: The time to reach a clinically significant plasma concentration of cortisol (>200 nmol/l) was within 20 min and a mean peak of 431 (s.d. 126) nmol/l was obtained within 50 min after administration of the 20 mg tablet. Plasma cortisol levels remained above 200 nmol/l for around 6 h thereafter and all plasma concentrations 18-24 h after intake were below 50 nmol/l. In the fed state the time to reach 200 nmol/l was delayed by 28 and 9 min based on LC-MS/MS and immunoassay, respectively. The 5 and 20 mg tablets produced an increase in plasma exposure of cortisol that was not fully dose proportional. CONCLUSION: The dual release hydrocortisone tablet with once-daily administration produced a diurnal plasma cortisol profile mimicking the physiological serum cortisol profile.
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| 15. |
- Johannsson, Gudmundur, 1960, et al.
(författare)
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Low dose dehydroepiandrosterone affects behavior in hypopituitary androgen-deficient women: a placebo-controlled trial.
- 2002
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 87:5, s. 2046-52
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Tidskriftsartikel (refereegranskat)abstract
- Thirty-eight women, aged 25-65 yr, with androgen deficiency due to hypopituitarism were treated with oral dehydroepiandrosterone (DHEA; 30 mg/d if <45 yr of age and 20 mg if > or =45 yr of age) for 6 months in a randomized, placebo-controlled, double blind study, followed by a 6-month open treatment period. The administration of DHEA raised the serum levels of DHEAS to normal age-related reference ranges and increased androstenedione and T to subnormal levels. Androgen effects on skin and/or pubic and/or axillary hair were observed in 84% (32 of 38) of the women after all received 6 months of DHEA treatment. No such effects were observed after the placebo treatment. These effects after 6 months were correlated with the serum levels of DHEAS (r = 0.37; P = 0.03), androstenedione (r = 0.42; P = 0.01), and T (r = 0.37; P = 0.03). The percentages of partners who reported improved alertness, stamina, and initiative by their spouses were 70%, 64%, and 55%, respectively, in the DHEA group and 11%, 6%, and 11%, respectively, in the placebo group (P < 0.05). According to the partners, sexual relations tended to improve compared with placebo (P = 0.06). After 6 months of treatment, increased sexual interest or activity was reported by 50% of the women taking 30 mg DHEA, by none taking 20 mg DHEA, and by two women taking placebo (P = NS). Compared with levels after placebo administration, high density lipoprotein cholesterol and apolipoprotein A-1 levels decreased after DHEA. Serum concentrations of IGF-I, serum markers of bone metabolism, and bone density did not change. In conclusion, oral administration of a low dose of DHEA to adult hypopituitary women induced androgen effects on skin and axillary and pubic hair as well as changes in behavior, with only minor effects on metabolism.
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| 16. |
- Johansson, Lisa, et al.
(författare)
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Grade 1 Vertebral Fractures Identified by Densitometric Lateral Spine Imaging Predict Incident Major Osteoporotic Fracture Independently of Clinical Risk Factors and Bone Mineral Density in Older Women
- 2020
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 35:10, s. 1942-1951
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Tidskriftsartikel (refereegranskat)abstract
- Because prevalent vertebral fracture (VF) is a strong predictor of future fractures, they are important to identify in clinical practice as osteoporosis medications are effective and can be used to reduce fracture risk in postmenopausal women with VF. Lateral spine imaging (LSI) with dual-energy X-ray absorptiometry (DXA) can be used to diagnose VFs accurately but is not widespread in clinical practice. The prognostic value of grade 1 (20% to 25% compression) VFs diagnosed by LSI with DXA has been insufficiently studied. The aim of this study was to determine if grade 1 VF is associated with incident fracture in older women. Sahlgrenska University Hospital Prospective Evaluation of Risk of Bone Fractures (SUPERB) is a population-based study of 3028 older women from Gothenburg, Sweden. Included women were 75 to 80 years of age at baseline, answered questionnaires, and were scanned with DXA (Discovery A, Hologic, Waltham, MA, USA). LSI was used to diagnose VFs, which were classified using the Genant semiquantitative method. Cox regression models were used to estimate the association between VFs at baseline and X-ray-verified incident fractures, with adjustment for confounders. Women with a grade 1 VF (n= 264) or a grade 2-3 VF (n= 349) were compared with women without any fracture (n= 1482). During 3.6 years (median, interquartile range [IQR] 1.5 years) of follow-up, 260 women had any incident fracture and 213 a major osteoporotic fracture (MOF). Women with only grade 1 VF had increased risk of any fracture (hazard ratio [HR] = 1.67; 95% confidence interval [CI] 1.18-2.36) and MOF (HR = 1.86; 95% CI 1.28-2.72). For MOF, this association remained after adjustment for clinical risk factors and femoral neck bone mineral density (BMD). In conclusion, grade 1 VFs were associated with incident MOF, also after adjustment for clinical risk factors and BMD, indicating that all VF identified by DXA should be considered in the evaluation of fracture risk in older women. (c) 2020 The Authors.Journal of Bone and Mineral Researchpublished by American Society for Bone and Mineral Research..
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| 17. |
- Karlsson, Jonas, 1977-, et al.
(författare)
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Performance Evaluation for TCP in Tactical Mobile Ad hoc Networks
- 2012
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Ingår i: Proceedings of International Conference on Wireless Information Networks and Systems. - : SciTePress. - 9789898425737 ; , s. 277-282
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Konferensbidrag (refereegranskat)abstract
- Tactical networks are used in military and rescue operations to provide timely and accurate information to operating teams. Tactical networks have traditionally used long distance narrow band radio links. However, although these links provide robust real-time communication the limited bandwidth makes them less suited for high data-rate applications. To support high-data rate TCP applications such as providing digital images and maps, emerging tactical networks use shorter range but higher data-rate wide band radio links and multi-hop. Due to the requirement of cheap up-front cost, most MANET research has focused on Carrier Sense Multiple Access (CSMA) networks. However, in tactical networks, where bounded delays are important, Time Division Multiple Access (TDMA) can give better possibility to support the Quality of Service needed for real-time communication. The purpose of this paper is to assess and compare the throughput of three state-of-the-art TCP versions and two routing protocols over TDMA based MANETs.
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| 18. |
- Larsson, Berit A M, et al.
(författare)
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Association between cortical bone microstructure and statin use in older women.
- 2019
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 104:2, s. 250-7
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Tidskriftsartikel (refereegranskat)abstract
- Treatment with statins has been associated with increased bone mineral density (BMD), but if this association depends on differences in cortical or trabecular volumetric bone microstructure is unknown.The aim of this study was to investigate if treatment with statins is associated with bone microstructure and geometry in older women.Older women were included in a population-based study of 3,028 women (mean age ± SD: 77.8 ± 1.6 years) from the greater Gothenburg area in Sweden. Information regarding medical history, medication and life-style factors was obtained from validated questionnaires.Bone geometry and microstructure were measured at the ultradistal and distal (14%) site of radius and tibia using high-resolution peripheral quantitative computed tomography (HR-pQCT; XtremeCT).The 803 women in the cohort who used statins had higher body weight, worse physical function and more frequently cardiovascular disease and diabetes than nonusers (p<0.05). Statin users had lower cortical porosity (radius 2.2± 1.9 vs. 2.5± 2.0%; tibia 5.2± 2.4 vs. 5.4± 2.5, p=0.01), higher cortical bone density (radius 1008 ± 39.1 vs. 1001 ± 38.4 mg/cm3; tibia 919 ± 42.6 vs. 914 ± 41.5, p<0.01), and greater cortical area (radius 60.5 ± 9.6 vs. 58.6 ± 9.7 mm2; tibia 150.0 ± 23.6 vs. 146.7 ± 23.8, p<0.01) than non-users, also after adjustment for a large number of confounders, including age, weight, smoking, other medications and prevalent diseases.Use of statins was associated with better cortical bone characteristics in older women.
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| 19. |
- Larsson, Berit A M, et al.
(författare)
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Normal Bone Microstructure and Density But Worse Physical Function in Older Women Treated with Selective Serotonin Reuptake Inhibitors, a Cross-Sectional Population-Based Study.
- 2018
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Ingår i: Calcified tissue international. - : Springer Science and Business Media LLC. - 1432-0827 .- 0171-967X. ; 103:3, s. 278-288
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Tidskriftsartikel (refereegranskat)abstract
- Depression in the elderly is today often treated with selective serotonin reuptake inhibitors (SSRIs) because of their favorable adverse effect profile. However, treatment with SSRIs is associated with increased risk of fractures. Whether this increased risk depends on reduced bone strength or increased fall risk due to reduced physical function is not certain. The aim was therefore to investigate if treatment with SSRIs is associated with impaired bone microstructure, bone density, or physical function in older women. From an ongoing population-based study, 1057 women (77.7±1.5years) were included. Validated questionnaires were used to assess information regarding medical history, medications, smoking, mental and physical health, and physical activity. Physical function was measured using clinically used tests: timed up and go, walking speed, grip strength, chair stand test, and one leg standing. Bone mineral density (BMD) was measured at the hip and spine with dual-energy X-ray absorptiometry (Hologic Discovery A). Bone geometry and microstructure were measured at the ultradistal and distal (14%) site of radius and tibia using high-resolution peripheral quantitative computed tomography (HR-pQCT; XtremeCT). Treatment with SSRIs was associated with higher BMD at the femoral neck, total hip, and lumbar spine, whereas no associations were found for any HR-pQCT-derived measurements. The use of SSRIs was associated with lower grip strength, walking speed, and fewer chair stand rises. These associations were valid also after adjustments for known risk factors for falls. Treatment with SSRIs was, independently of covariates, associated with worse physical function without any signs of inferior bone geometry and microstructure.
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| 20. |
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| 21. |
- Lorentzon, Mattias, 1970, et al.
(författare)
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Extensive undertreatment of osteoporosis in older Swedish women
- 2019
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 30:6, s. 1297-1305
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Tidskriftsartikel (refereegranskat)abstract
- Summary: In a population-based study of older Swedish women, we investigated the proportion of women treated with osteoporosis medication in relation to the proportion of women eligible for treatment according to national guidelines. We found that only a minority (22%) of those eligible for treatment were prescribed osteoporosis medication. Introduction: Fracture rates increase markedly in old age and the incidence of hip fracture in Swedish women is among the highest in the world. Although effective pharmacological treatment is available, treatment rates remain low. Limited data are available regarding treatment rates in relation to fracture risk in a population-based setting in older women. Therefore, we aimed to investigate the proportion of older women eligible for treatment according to Swedish Osteoporosis Society (SvOS) guidelines. Methods: A population-based study was performed in Gothenburg in 3028 older women (77.8 ± 1.6years [mean ± SD]). Bone mineral density of the spine and hip was measured with dual-energy X-ray absorptiometry. Clinical risk factors for fracture and data regarding osteoporosis medication was collected with self-administered questionnaires. Logistic regression was used to evaluate whether the 10-year probability of sustaining a major osteoporotic fracture (FRAX-score) or its components predicted treatment with osteoporosis medication. Results: For the 2983 women with complete data, 1107 (37%) women were eligible for treatment using SvOS criteria. The proportion of these women receiving treatment was 21.8%. For women eligible for treatment according to SvOS guidelines, strong predictors for receiving osteoporosis medication were glucocorticoid treatment (odds ratio (95% CI) 2.88 (1.80–4.59)) and prior fracture (2.58 (1.84–3.61)). Conclusion: This study demonstrates that a substantial proportion of older Swedish women should be considered for osteoporosis medication given their high fracture risk, but that only a minority receives treatment. © 2019, The Author(s).
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| 22. |
- Nilsson, Anna G, 1968
(författare)
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Bone research: An issue of maturity
- 2015
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820. ; 277:6, s. 626-629
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Tidskriftsartikel (refereegranskat)
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| 23. |
- Nilsson, Anna G, 1968, et al.
(författare)
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Lactobacillus reuteri reduces bone loss in older women with low bone mineral density: a randomized, placebo-controlled, double-blind, clinical trial
- 2018
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820. ; 284:3, s. 307-317
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe importance of the gut microbiome for bone metabolism in mice has recently been demonstrated, but no studies are available in humans. Lactobacillus reuteri ATCCPTA 6475 (L. reuteri 6475) has been reported to increase bone mineral density (BMD) in mice but its effect on the human skeleton is unknown. The objective of this trial was to investigate if L. reuteri 6475 affects bone loss in older women with low BMD. MethodsIn this double-blind, placebo-controlled study, women from the population who were 75 to 80 years old and had low BMD were randomized to orally receive 10(10) colony-forming units of L. reuteri 6475 daily or placebo. The predefined primary end-point was relative change after 12 months in tibia total volumetric BMD (vBMD). ResultsNinety women were included and 70 completed the study. L. reuteri 6475 reduced loss of total vBMD compared to placebo both in the intention-to-treat (ITT) analysis [-0.83% (95% confidence interval [CI], -1.47 to -0.19%) vs. -1.85% (95% CI, -2.64 to -1.07%); mean difference 1.02% (95% CI, 0.02-2.03)] and per protocol analysis [-0.93% (95% CI, -1.45 to -0.40) vs. -1.86% (95% CI, -2.35 to -1.36); mean difference 0.93% (95% CI, 0.21-1.65)]. In general, similar but smaller effects were observed in the secondary bone variable outcomes, but these differences did not reach statistical significance in the ITT population. Adverse events did not differ between groups. ConclusionsSupplementation with L. reuteri 6475 should be further explored as a novel approach to prevent age-associated bone loss and osteoporosis.
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| 24. |
- Nilsson, Anna G, 1968, et al.
(författare)
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Long-term safety of once-daily, dual-release hydrocortisone in patients with adrenal insufficiency: a phase 3b, open-label, extension study.
- 2017
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Ingår i: European journal of endocrinology. - : BIOSCIENTIFICA LTD. - 1479-683X .- 0804-4643. ; 176:6, s. 715-725
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the long-term safety and tolerability of a once-daily, dual-release hydrocortisone (DR-HC) tablet as oral glucocorticoid replacement therapy in patients with primary adrenal insufficiency (AI).Prospective, open-label, multicenter, 5-year extension study of DR-HC conducted at five university clinics in Sweden.Seventy-one adult patients diagnosed with primary AI who were receiving stable glucocorticoid replacement therapy were recruited. Safety and tolerability outcomes included adverse events (AEs), intercurrent illness episodes, laboratory parameters and vital signs. Quality of life (QoL) was evaluated using generic questionnaires.Total DR-HC exposure was 328 patient-treatment years. Seventy patients reported 1060 AEs (323 per 100 patient-years); 85% were considered unrelated to DR-HC by the investigator. The most common AEs were nasopharyngitis (70%), fatigue (52%) and gastroenteritis (48%). Of 65 serious AEs reported by 32 patients (20 per 100 patient-years), four were considered to be possibly related to DR-HC: acute AI (n=2), gastritis (n=1) and syncope (n=1). Two deaths were reported (fall from height and subarachnoid hemorrhage), both considered to be unrelated to DR-HC. From baseline to 5 years, intercurrent illness episodes remained relatively stable (mean 2.6-5.4 episodes per patient per year), fasting plasma glucose (0.7mmol/L; P<0.0001) and HDL cholesterol (0.2mmol/L; P<0.0001) increased and patient-/investigator-assessed tolerability improved. QoL total scores were unchanged but worsening physical functioning was recorded (P=0.008).In the first prospective study evaluating the long-term safety of glucocorticoid replacement therapy in patients with primary AI, DR-HC was well tolerated with no safety concerns observed during 5-year treatment.
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| 25. |
- Nilsson, Anna G, 1968, et al.
(författare)
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Management of growth hormone deficiency in adults.
- 2007
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Ingår i: Growth Hormone IGF Res. - : Elsevier BV. - 1096-6374. ; 2007:92 (10), s. 3293-9
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Tidskriftsartikel (refereegranskat)abstract
- Growth hormone (GH) deficiency in adults is a recognised clinical entity. There is still, however, an ongoing debate of the clinical need and the importance of replacing GH in adults with severe GH deficiency. This review will focus on the overall management of adults with GH deficiency and highlight published data on dose management and treatment goals for various age groups. The efficacy data on quality of life and well-being is discussed and available and growing experience on long-term effects of GH replacement in adults and safety in terms of diabetes mellitus, pituitary tumour recurrence/regrowth and malignancy risk will be reviewed.
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| 26. |
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| 27. |
- Nilsson, Anna G, 1968, et al.
(författare)
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Replacement therapy in adult hypopituitarism
- 2014
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Ingår i: Endocrinology in Clinical Practice, 2nd ed. Harris, P.E. & Bouloux, P.G. (red.). - : CRC Press. - 9781841849515 ; , s. 103-124
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 28. |
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| 29. |
- Olsson, Daniel S, 1983, et al.
(författare)
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Comparing progression of non-functioning pituitary adenomas in hypopituitarism patients with and without long-term GH replacement therapy.
- 2009
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Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - 1479-683X. ; 161:5, s. 663-9
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: An important safety issue with GH replacement therapy (GHRT) in hypopituitary patients with a history of a pituitary adenoma is the risk for tumour recurrence or enlargement. Design Case-control study. SUBJECTS AND METHODS: We studied tumour progression rate in 121 patients with hypopituitarism on the basis of non-functioning pituitary adenomas (NFPA) receiving long-term GHRT. A group of 114 NFPA patients not receiving GHRT who were matched in terms of duration of follow-up, gender, age, age at diagnosis and radiotherapy status were used as a control population. The average duration of GHRT was 10+/-4 years (range 2-17). RESULTS: In patients with a known residual adenoma, 63% had no detectable enlargement of tumour during the study. In patients who had no visible residual tumour prior to GHRT, 90% did not suffer from recurrence. In total, the 10-year tumour progression-free survival rate in patients with NFPA receiving GHRT was 74%. In the control population not receiving GHRT, the 10-year progression-free survival rate was 70%. Radiotherapy as part of the initial tumour treatment reduced the rate of tumour progression in both GHRT and non-GHRT patients to a similar extent. CONCLUSIONS: The rate of tumour progression was similar in this large group of GHRT patients and the control population not receiving GHRT. Our results provide further support that long-term use of GH replacement in hypopituitarism may be considered safe in patients with residual pituitary adenomas.
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| 30. |
- Olsson, Daniel S, 1983, et al.
(författare)
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Excess Mortality in Women and Young Adults With Nonfunctioning Pituitary Adenoma: A Swedish Nationwide Study
- 2015
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Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 100:7, s. 2651-2658
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Tidskriftsartikel (refereegranskat)abstract
- Context: Patients with hypopituitarism of various etiologies have excess mortality. The mortality in patients with nonfunctioning pituitary adenoma (NFPA), regardless of pituitary function, is less well studied. Objective: Our aim was to investigate mortality in patients with NFPA and to examine whether age at diagnosis, gender, tumor treatments, or hormonal deficiencies influence the outcome. Design: NFPA patients were identified and followed up in nationwide health registries in Sweden, 1987-2011. The criteria for identification were tested and validated in a subpopulation of the patients. Patients: A total of 2795 unique patients with NFPA (1502 men, 1293 women) were identified and included in the study. Mean age at diagnosis was 58 years (men, 60 y; women, 56 y) and mean follow-up time was 7 years (range 0-25 y). Main Outcome Measures: Standardized mortality ratios (SMRs) and annual incidence rates were calculated using the Swedish population as reference and presented with 95% confidence intervals. Results: Annual incidence of NFPA was 20.3 (18.8-21.9) cases per 1 million inhabitants. During the observation period, 473 patients died against an expected 431, resulting in an SMR of 1.10 (1.00-1.20). Patients diagnosed at younger than 40 years of age had an increased SMR of 2.68 (1.23-5.09). The SMR for patients with hypopituitarism (n = 1500) was 1.06 (0.94-1.19), and for patients with diabetes insipidus (n = 145), it was 1.71 (1.07-2.58). The SMR was increased in women with NFPA (1.29; 1.11-1.48) but not in men (1.00; 0.88-1.12). Women, but not men, with a diagnosis of hypopituitarism and/or diabetes insipidus also had an increased mortality ratio. SMRs due to cerebrovascular (1.73; 1.34-2.19) and infectious diseases (2.08; 1.17-3.44) were increased, whereas the SMR for malignant tumors was decreased (0.76; 0.61-0.94). Conclusions: This nationwide study of patients with NFPA showed an overall excess mortality in women and in patients with a young age at diagnosis. Increased mortality was seen for cerebrovascular and infectious diseases.
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| 31. |
- Olsson, Daniel S, 1983, et al.
(författare)
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Incidence of malignant tumours in patients with a non-functioning pituitary adenoma.
- 2017
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Ingår i: Endocrine-Related Cancer. - : BioScientifica Ltd.. - 1351-0088 .- 1479-6821. ; 24:5, s. 227-235
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Tidskriftsartikel (refereegranskat)abstract
- Whether patients with non-functioning pituitary adenoma (NFPA) are at increased risk of developing malignant tumours has been sparsely studied and is a matter of debate. In this study, we have investigated the incidence of malignant tumours in a large and unselected group of patients with NFPA. The study was nationwide and included all patients diagnosed with NFPA between 1987 and 2011 (n = 2795) in Sweden, identified in the National Patient Register. Malignant tumours, occurring after the NFPA diagnosis, were identified in the Swedish Cancer Register between 1987 and 2014. Standardised incidence ratios (SIRs) for malignant tumours with 95% confidence intervals (CI) were calculated using the Swedish population as reference. In total, 448 malignant tumours were detected in 386 patients with NFPA, as compared to 368 expected malignancies in the general population (SIR 1.22 (95% CI 1.11-1.33)). The incidence of neoplasms of the brain was increased (SIR 5.83 (95% CI 4.03-8.14)). When analysing the total incidence of malignancies excluding neoplasms of the brain, the overall SIR was still increased (SIR 1.14 (95% CI 1.03-1.26)). The incidence of malignant neoplasm of skin other than malignant melanoma (SIR 1.99 (95% CI 1.55-2.52)) and malignant melanoma (SIR 1.62 (95% CI 1.04-2.38)) were increased, whereas the incidence of breast cancer (SIR 0.65 (95% CI 0.42-0.97)) was decreased. The incidence of other types of malignancies did not differ significantly from the expected incidence in the general population. In conclusion, patients with NFPA have an increased overall risk of developing malignancies. To what extent these findings are due to more frequent medical surveillance, genetic predisposition or endocrine changes, remains unknown.
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| 32. |
- Olsson, Daniel S, 1983, et al.
(författare)
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Life expectancy in patients with pituitary adenoma receiving growth hormone replacement.
- 2017
-
Ingår i: European journal of endocrinology. - 1479-683X. ; 176:1, s. 67-75
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Tidskriftsartikel (refereegranskat)abstract
- Hypopituitarism has been associated with increased mortality. The excess mortality may be due to untreated growth hormone (GH) deficiency but also due to various underlying disorders. We therefore analysed mortality in patients with only one underlying disorder, non-functioning pituitary adenoma (NFPA), with and without GH replacement therapy (GHRT).Patients with NFPA in the western region of Sweden, 1997-2011, were identified through the National Patient Registry and cross-referenced with several National Health Registries. All patient records were reviewed. Standardised mortality ratios (SMRs) with 95% confidence intervals (CIs) were calculated using the general population as reference. Cox-regression models were performed to identify predictors of mortality.A total of 426 NFPA patients with 4599 patient-years were included, of whom 207 had used GHRT and 219 had not received GHRT. Median (range) follow-up in patients with and without GHRT was 12.2 (0-25) and 8.2 (0-27) years, respectively. Other pituitary hormone deficiencies were more frequent in the GHRT group than those in the non-GHRT group. SMR was 0.65 (95% CI, 0.44-0.94; P=0.018) for the GHRT group and 1.16 (0.94-1.42; P=0.17) for the non-GHRT group. Direct comparison between the groups showed reduced mortality among those who were GH replaced (P=0.0063). The SMR for malignant tumours was reduced in the GHRT-group (0.29; 0.08-0.73; P=0.004) but not in untreated patients.Selection bias explaining some of the results cannot be excluded. However, NFPA patients with GHRT had reduced overall mortality compared with the general population, and death due to malignancy was not increased. This suggests that long-term GHRT is safe in adult patients selected for treatment.
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| 33. |
- Olsson, Daniel S, 1983, et al.
(författare)
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Tumour recurrence and enlargement in patients with craniopharyngioma with and without GH replacement therapy during more than 10 years of follow-up.
- 2012
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Ingår i: European journal of endocrinology. - 1479-683X. ; 166:6, s. 1061-8
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Tidskriftsartikel (refereegranskat)abstract
- Most patients who have been treated for craniopharyngioma (CP) are GH deficient (GHD). GH replacement therapy (GHRT) may stimulate tumour regrowth; and one of the concerns with long-term GHRT is the risk of tumour progression. Therefore, the objective was to study tumour progression in CP patients on long-term GHRT.Case-control study.The criteria for inclusion of cases were: i) GHD caused by CP; ii) GHRT >3 years; and iii) regular imaging. This resulted in 56 patients (mean age at diagnosis 25±16 years) with a mean duration of GHRT of 13.6±5.0 years. As controls, 70 CP patients who had not received GHRT were sampled with regard to follow-up, gender, age at diagnosis and initial radiation therapy (RT).The 10-year tumour progression-free survival rate (PFSR) for the entire population was 72%. There was an association (hazard ratio, P value) between PFSR and initial RT (0.13, 0.001) and residual tumour (3.2, 0.001). The 10-year PFSR was 88% for the GHRT group and 57% for the control group. Substitution with GHRT resulted in the following associations to PFSR: GHRT (0.57, 0.17), initial RT (0.16, <0.001), residual tumour (2.6, <0.01) and gender (0.57, 0.10). Adjusted for these factors, the 10-year PFSR was 85% for the GHRT group and 65% for the control group.In patients with CP, the most important prognostic factors for the PFSR were initial RT and residual tumour after initial treatment. Long-term GHRT did not affect the PFSR in patients with CP.
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| 34. |
- Ottarsdottir, Kristin, et al.
(författare)
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Longitudinal associations between sex hormone-binding globulin and insulin resistance
- 2020
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Ingår i: Endocrine Connections. - : Bioscientifica. - 2049-3614. ; 9:5, s. 418-425
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: We aimed to investigate the association between SHBG and the homeostatic model assessment of insulin resistance (HOMA-Ir) in men and women in a prospective observational study. Methods: The Vara-Skovde cohort is a random population of 2816 participants living in southwestern Sweden, aged 30-74. It was recruited between 2002 and 2005, and followed up in 2012-2014. After excluding participants on insulin therapy or hormone replacement therapy, 1193 individuals (649 men, 544 women) were included in the present study. Fasting blood samples were collected at both visits and stored in biobank. All participants were physically examined by a trained nurse. SHBG was measured with immunoassay technique. Linear regressions were computed to investigate the association between SHBG and HOMA-Ir both in cross-sectional and longitudinal analyses, adjusting for confounding factors. Results: The mean follow-up time was 9.7 +/- 1.4 years. Concentrations of SHBG were significantly inversely associated with log transformed HOMA-Ir in all groups with estimated standardized slopes (95% CI): men: -0.20 (-0.3;-0.1), premenopausal women: -0.26 (-0.4;-0.2), postmenopausal women: -0.13 (-0.3;-0.0) at visit 1. At visit 2 the results were similar. When comparing the groups, a statistically significant difference was found between men and post-menopausal women (0.12 (0.0;0.2) P value = 0.04). In the fully adjusted model, SHBG at visit 1 was also associated with HOMA-Ir at visit 2, and the estimated slopes were -0.16 (-0.2;-0.1), -0.16 (-0.3;-0.1) and -0.07 (-0.2;0.0) for men, premenopausal and postmenopausal women, respectively. Main conclusion: Levels of SHBG predicted the development of insulin resistance in both men and women, regardless of menopausal state.
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| 35. |
- Ottarsdottir, Kristin, et al.
(författare)
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The association between serum testosterone and insulin resistance: a longitudinal study
- 2018
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Ingår i: Endocrine Connections. - : Bioscientifica. - 2049-3614. ; 7:12, s. 1491-1500
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to investigate whether there is a bidirectional association between testosterone concentrations and insulin resistance, in a prospective population study. A random population sample of 1400 men, aged 30-74, was examined in 2002-2005 in southwestern Sweden and followed up in 2012-2014 (N=657). After excluding subjects without information on sex hormones and insulin resistance, 1282 men were included in the baseline study. Fasting measurements of plasma glucose, insulin and hormones were performed. Insulin resistance was defined using HOMA-Ir. Mean age at baseline was 47.3 +/- 11.4 years. From the follow-up survey 546 men were included, mean age 57.7 +/- 11.6 years. Low concentrations of total testosterone at baseline were significantly associated with high IogHOMA-Ir at follow-up in a multivariable model including age, waist-hip ratio, physical activity, alcohol intake, smoking, LDL, CRP, hypertension, diabetes and logHOMA-Ir at baseline as covariates (beta = -0.096, P = 0.006). Similar results were observed for bioavailable testosterone. Men within the lowest quartile of total testosterone at baseline had significantly higher IogHOMA-Ir at follow-up than other quartiles (Q1 vs Q2 P = 0.008, Q1 vs Q3 P = 0.001, Q1 vs Q4 P = 0.052). Multivariable analysis of the impact of insulin resistance at baseline on testosterone levels at follow-up revealed no significant associations regarding testosterone concentrations (beta = -0.003, P = 0.928) or bioavailable testosterone (beta = -0.006, P = 0.873), when adjusting for baseline concentrations of total testosterone, age, waist-hip-ratio, LDL, CRP, physical activity, alcohol intake, smoking, hypertension and diabetes. Low testosterone concentrations at baseline predicted higher insulin resistance at follow-up, but high insulin resistance at baseline could not predict low testosterone at follow-up.
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| 36. |
- Uhl, Carina, et al.
(författare)
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High Degree of Desensitization After 1 Year of Early-Life Peanut Oral Immunotherapy : Small Children Oral Immunotherapy (SmaChO) Randomized Controlled Trial
- 2024
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Ingår i: Journal of Allergy and Clinical Immunology. - 2213-2198 .- 2213-2201. ; 12:5, s. 1297-1305
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Tidskriftsartikel (refereegranskat)abstract
- Background: The prevalence of peanut allergy is about 2% and mostly lifelong. Studies of oral immunotherapy (OIT) with peanut (the daily oral intake of an initially low and then increasing dose of peanut) often show problematic side effects, but there are indications of better safety and effect in younger children compared with older children and adults.Objective: To determine the safety and effectiveness of peanut OIT with a slow up-dosing strategy and low maintenance dose in children aged 1 to 3 years who were allergic to peanut, through a 1-year interim analysis.Method: In a randomized controlled trial (2:1 ratio), 75 children, median age 31 months (interquartile range [IQR], 23-40 months) were assigned to receive peanut OIT (n = 50) or peanut avoidance (n = 25).Results: In the OIT and avoidance groups, 43 of 50 and 20 of 25 children, respectively, performed the 1-year open oral peanut challenge. A cumulative dose of 750 mg peanut protein after 1 year was tolerated by 72% (36 of 50 children) in the OIT group compared with 4% (1 of 25) in the avoidance group (P < .001). Median tolerated cumulative dose was 2,750 mg (IQR, 275-5,000 mg) peanut protein in the OIT group compared with 2.8 mg (IQR, 0.3-27.8 mg) in the avoidance group (P < .001). Of the doses administered at home during the first year of OIT, 1.4% resulted in adverse events and 79% were mild, and three doses of epinephrine were given at home to two individuals.Conclusion: In children aged 1 to 3 years, peanut OIT with the combination of slow up-dosing and low maintenance dose seems safe and effective after 1 year.
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| 37. |
- Wallander, Marit, et al.
(författare)
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Type 2 Diabetes and Risk of Hip Fractures and Non-Skeletal Fall Injuries in the Elderly : A Study From The Fractures And Fall Injuries In The Elderly Cohort (Frailco)
- 2017
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Ingår i: Journal of Bone and Mineral Research. - : John Wiley & Sons. - 0884-0431 .- 1523-4681. ; 32:3, s. 449-460
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Tidskriftsartikel (refereegranskat)abstract
- Questions remain about whether the increased risk of fractures in patients with type 2 diabetes (T2DM) is related mainly to increased risk of falling or to bone-specific properties. The primary aim of this study was to investigate the risk of hip fractures and non-skeletal fall injuries in older men and women with and without T2DM. We included 429,313 individuals (aged 80.8 +/- 8.2 years [mean +/- SD], 58% women) from the Swedish registry "Senior Alert" and linked the data to several nationwide registers. We identified 79,159 individuals with T2DM (45% with insulin [T2DM-I], 41% with oral antidiabetics [T2DM-O], and 14% with no antidiabetic treatment [T2DM-none]) and 343,603 individuals without diabetes. During a follow-up of approximately 670,000 person-years, we identified in total 36,132 fractures (15,572 hip fractures) and 20,019 non-skeletal fall injuries. In multivariable Cox regression models where the reference group was patients without diabetes and the outcome was hip fracture, T2DM-I was associated with increased risk (adjusted hazard ratio (HR) [95% CI] 1.24 [1.16-1.32]), T2DM-O with unaffected risk (1.03 [0.97-1.11]), and T2DM-none with reduced risk (0.88 [0.79-0.98]). Both the diagnosis of T2DM-I (1.22 [1.16-1.29]) and T2DM-O (1.12 [1.06-1.18]) but not T2DM-none (1.07 [0.98-1.16]) predicted non-skeletal fall injury. The same pattern was found regarding other fractures (any, upper arm, ankle, and major osteoporotic fracture) but not for wrist fracture. Subset analyses revealed that in men, the risk of hip fracture was only increased in those with T2DM-I, but in women, both the diagnosis of T2DM-O and T2DM-I were related to increased hip fracture risk. In conclusion, the risk of fractures differs substantially among patients with T2DM and an increased risk of hip fracture was primarily found in insulin-treated patients, whereas the risk of non-skeletal fall injury was consistently increased in T2DM with any diabetes medication.
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