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Sökning: WFRF:(Rylander Lars) > Uppsala universitet

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1.
  • Holmer, Helene, et al. (författare)
  • Fracture incidence in GH-deficient patients on complete hormone replacement including GH
  • 2007
  • Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 22:12, s. 1842-1850
  • Tidskriftsartikel (refereegranskat)abstract
    • Fracture risk in GHD patients is not definitely established. Studying fracture incidence in 832 patients on GH therapy and 2581 matched population controls, we recorded a doubled fracture risk in CO GHD women, but a significantly lower fracture risk in AO GHD men. Introduction: The objective of this study was to evaluate fracture incidence in patients wilh confirmed growth hormone deficiency (GHD) on replacement therapy (including growth hormone [GH]) compared with population controls, while also taking potential confounders and effect modifiers into account. Materials and Methods: Eight hundred thirty-two patients with GHD and 2581 matched population controls answered a questionnaire about fractures and other background information. Incidence rate ratio (IRR) and 95% CI for first fracture were estimated. The median time on GH therapy for childhood onset (CO) GHD men and women was 15 and 12 yr, respectively, and 6 and 5 yr for adult onset (AO) GHD men and women, respectively. Results: A more than doubled risk (IRR, 2.29; 95% CI, 1.23-4.28) for nonosteoporotic fractures was recorded in women with CO GHD, whereas no risk increase was observed among CO GHD men (IRR. 0.61) and AO GHD women (IRR, 1.08). A significantly decreased incidence of fractures (IRR, 0.54; 95% CI 0.34-0.86) was recorded in AO GHD men. Conclusions: Increased fracture risk in CO GHD women can most likely be explained by interaction between oral estrogen and the GH-IGF-I axis. The adequate substitution rate of testosterone (90%) and GH (94%) may have resulted in significantly lower fracture risk in AO GHD men.
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2.
  • Holmer, Helene, et al. (författare)
  • Nonfatal stroke, cardiac disease, and diabetes mellitus in hypopituitary patients on hormone replacement including growth hormone
  • 2007
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 92:9, s. 3560-3567
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: The impact of long-term GH replacement on cerebrovascular and cardiovascular diseases and diabetes mellitus in hypopituitary patients is unknown. Objective: The incidence of nonfatal stroke and cardiac events, and prevalence of type 2 diabetes mellitus ( T2D) and cardioprotective medication were compared between cohorts of GH-deficient (GHD) patients and population controls. Design and Participants: The incidence of nonfatal stroke and cardiac events was estimated retrospectively from questionnaires in 750 GHD patients and 2314 matched population controls. A prevalence of T2D and cardioprotective medication was recorded at the distribution of questionnaires. Time since first pituitary deficiency to start of GH therapy was 4 and 2 yr, and time on GH therapy was 6 yr for GHD women and men, respectively. Results: Lifelong incidence of nonfatal stroke was tripled in GHD women and doubled in GHD men, but a decline was seen in both genders during periods after first pituitary hormone deficiency and GHD, during which most patients had GH therapy. The lifelong incidence of nonfatal cardiac events declined in GHD men during first pituitary hormone deficiency and GHD periods. GHD women had a higher prevalence of T2D and lipid-lowering medication, whereas GHD men had a higher prevalence of antihypertensive medication. Conclusions: The declined risks of nonfatal stroke in both genders and of nonfatal cardiac events in GHD men during periods on GH replacement may be caused by prescription of cardioprotective drugs and 6-yr GH replacement. GHD women had an increased prevalence of T2D, partly attributed to higher body mass index and lower physical activity.
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3.
  • Taylor, Kyla W., et al. (författare)
  • Evaluation of the Association between Persistent Organic Pollutants (POPs) and Diabetes in Epidemiological Studies: A National Toxicology Program Workshop Review
  • 2013
  • Ingår i: Environmental Health Perspectives. - : Environmental Health Perspectives. - 1552-9924 .- 0091-6765. ; 121:7, s. 774-783
  • Forskningsöversikt (refereegranskat)abstract
    • BACKGROUND: Diabetes is a major threat to public health in the United States and worldwide. Understanding the role of environmental chemicals in the development or progression of diabetes is an emerging issue in environmental health. OBJECTIVE: We assessed the epidemiologic literature for evidence of associations between persistent organic pollutants (POPs) and type 2 diabetes. METHODS: Using a PubMed search and reference lists from relevant studies or review articles, we identified 72 epidemiological studies that investigated associations of persistent organic pollutants (POPs) with diabetes. We evaluated these studies for consistency, strengths and weaknesses of study design (including power and statistical methods), clinical diagnosis, exposure assessment, study population characteristics, and identification of data gaps and areas for future research. CONCLUSIONS: Heterogeneity of the studies precluded conducting a meta-analysis, but the overall evidence is sufficient for a positive association of some organochlorine POPs with type 2 diabetes. Collectively, these data are not sufficient to establish causality. Initial data mining revealed that the strongest positive correlation of diabetes with POPs occurred with organochlorine compounds, such as trans-nonachlor, dichlorodiphenyldichloroethylene (DDE), polychlorinated biphenyls (PCBs), and dioxins and dioxin-like chemicals. There is less indication of an association between other nonorganochlorine POPs, such as perfluoroalkyl acids and brominated compounds, and type 2 diabetes. Experimental data are needed to confirm the causality of these POPs, which will shed new light on the pathogenesis of diabetes. This new information should be considered by governmental bodies involved in the regulation of environmental contaminants.
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4.
  • Al-Jebari, Yahia, et al. (författare)
  • Cancer therapy and risk of congenital malformations in children fathered by men treated for testicular germ-cell cancer : A nationwide register study
  • 2019
  • Ingår i: PLoS Medicine. - : PUBLIC LIBRARY SCIENCE. - 1549-1277 .- 1549-1676. ; 16:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Because of the potential mutagenic effects of chemo- and radiotherapy, there is concern regarding increased risk of congenital malformations (CMs) among children of fathers with cancer. Previous register studies indicate increased CM risk among children conceived after paternal cancer but lack data on oncological treatment. Increased CM risk was recently reported in children born before paternal cancer. This study aims to investigate whether anti-neoplastic treatment for testicular germ-cell cancer (TGCC) implies additional CM risk. Methods and findings In this nationwide register study, all singletons born in Sweden 1994-2014 (n = 2,027,997) were included. Paternal TGCC diagnoses (n = 2,380), anti-neoplastic treatment, and offspring CMs were gathered from the Swedish Norwegian Testicular Cancer Group (SWENOTECA) and the Swedish Medical Birth Register. Children were grouped based on +/- paternal TGCC; treatment regimen: surveillance (n = 1,340), chemotherapy (n = 2,533), or radiotherapy (n = 360); and according to time of conception: pre- (n = 2,770) or post-treatment (n = 1,437). Odds ratios (ORs) for CMs were calculated using logistic regression with adjustment for parental ages, maternal body mass index (BMI), and maternal smoking. Children conceived before a specific treatment acted as reference for children conceived after the same treatment. Among children fathered by men with TGCC (n = 4,207), 184 had a CM. The risk of malformations was higher among children of fathers with TGCC compared with children fathered by men without TGCC (OR 1.28, 95% confidence interval [CI] 1.19-1.38, p = 0.001, 4.4% versus 3.5%). However, no additional risk increase was associated with oncological treatment when comparing post-treatment-to pretreatment-conceived children (chemotherapy, OR = 0.82, 95% CI 0.54-1.25, p = 0.37, 4.1% versus 4.6%; radiotherapy, OR = 1.01, 95% CI 0.25-4.12, p = 0.98, 3.2% versus 3.0%). Study limitations include lack of data on use of cryopreserved or donor sperm and on seminoma patients for the period 1995-2000-both tending to decrease the difference between the groups with TGCC and without TGCC. Furthermore, the power of analyses on chemotherapy intensity and radiotherapy was limited. Conclusions No additional increased risk of CMs was observed in children of men with TGCC treated with radio- or chemotherapy. However, paternal TGCC per se was associated with modestly increased risk for offspring malformations. Clinically, this information can reassure concerned patients.
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5.
  • Blennow Nordström, Erik, et al. (författare)
  • Neuropsychological outcome after cardiac arrest : results from a sub-study of the targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest (TTM2) trial
  • 2023
  • Ingår i: Critical Care. - : BioMed Central (BMC). - 1364-8535 .- 1466-609X. ; 27:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Cognitive impairment is common following out-of-hospital cardiac arrest (OHCA), but the nature of the impairment is poorly understood. Our objective was to describe cognitive impairment in OHCA survivors, with the hypothesis that OHCA survivors would perform significantly worse on neuropsychological tests of cognition than controls with acute myocardial infarction (MI). Another aim was to investigate the relationship between cognitive performance and the associated factors of emotional problems, fatigue, insomnia, and cardiovascular risk factors following OHCA.METHODS: This was a prospective case-control sub-study of The Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial. Eight of 61 TTM2-sites in Sweden, Denmark, and the United Kingdom included adults with OHCA of presumed cardiac or unknown cause. A matched non-arrest control group with acute MI was recruited. At approximately 7 months post-event, we administered an extensive neuropsychological test battery and questionnaires on anxiety, depression, fatigue, and insomnia, and collected information on the cardiovascular risk factors hypertension and diabetes.RESULTS: Of 184 eligible OHCA survivors, 108 were included, with 92 MI controls enrolled. Amongst OHCA survivors, 29% performed z-score ≤ - 1 (at least borderline-mild impairment) in ≥ 2 cognitive domains, 14% performed z-score ≤ - 2 (major impairment) in ≥ 1 cognitive domain while 54% performed without impairment in any domain. Impairment was most pronounced in episodic memory, executive functions, and processing speed. OHCA survivors performed significantly worse than MI controls in episodic memory (mean difference, MD = - 0.37, 95% confidence intervals [- 0.61, - 0.12]), verbal (MD = - 0.34 [- 0.62, - 0.07]), and visual/constructive functions (MD = - 0.26 [- 0.47, - 0.04]) on linear regressions adjusted for educational attainment and sex. When additionally adjusting for anxiety, depression, fatigue, insomnia, hypertension, and diabetes, executive functions (MD = - 0.44 [- 0.82, - 0.06]) were also worse following OHCA. Diabetes, symptoms of anxiety, depression, and fatigue were significantly associated with worse cognitive performance.CONCLUSIONS: In our study population, cognitive impairment was generally mild following OHCA. OHCA survivors performed worse than MI controls in 3 of 6 domains. These results support current guidelines that a post-OHCA follow-up service should screen for cognitive impairment, emotional problems, and fatigue.TRIAL REGISTRATION: ClinicalTrials.gov, NCT03543371. Registered 1 June 2018.
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6.
  • Cronberg, Tobias, et al. (författare)
  • Neurological prognostication after cardiac arrest : Recommendations from the Swedish Resuscitation Council
  • 2013
  • Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 84:7, s. 867-872
  • Tidskriftsartikel (refereegranskat)abstract
    • Cardiopulmonary resuscitation is started in 5000 victims of out-of-hospital cardiac arrest in Sweden each year and the survival rate is approximately 10%. The subsequent development of a global ischaemic brain injury is the major determinant of the neurological prognosis for those patients who reach the hospital alive. Induced hypothermia is a recommended treatment after cardiac arrest and has been implemented in most Swedish hospitals.Recent studies indicate that induced hypothermia may affect neurological prognostication and previous international recommendations are therefore no longer valid when hypothermia is applied. An expert group from the Swedish Resuscitation Council has reviewed the literature and made recommendations taking into account the effects of induced hypothermia and concomitant sedation.A delayed neurological evaluation at 72h after rewarming is recommended for hypothermia treated patients. This evaluation should be based on several independent methods and the possibility of lingering pharmacological effects should be considered.
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8.
  • Hagmar, L., et al. (författare)
  • Intra-individual variations and time trends 1991-2001 in human serum levels of PCB, DDE and hexachlorobenzene
  • 2006
  • Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 64:9, s. 1507-1513
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: An important question is whether human serum levels of persistent organic pollutants has continued to decrease during the last decades. The aim of this study was to assess intra-individual variations over time of serum levels of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153), 1,1-dichloro-2,2-bis(4-chlorophenyl)-ethene (p,p'-DDE) and hexachlorobenzene (HCB), considering the impact of a number of possible determinants. Methods: Blood samples were drawn for the same 39 subjects in 1991 and 2001. Interviews were made at both occasions. Lipid adjusted serum concentrations of CB-153, p,p'-DDE and HCB were determined in both sets of blood samples using gas chromatography-mass spectrometry. The fatty acid composition of the serum lipids was analyzed by means of gas-liquid chromatography. Result: The CB-153 concentrations in serum had averagely decreased with 34% in between 1991 and 2001 (p < 0.001). Of individual determinants only increasing BMI was associated with decreasing CB-153 levels (beta = -1.0, 95% CI -1.8, -0.2, p = 0.01), explaining 13% of the variation. The average decrease of p,p'-DDE was 55%, and could only weakly be associated with a relative increase of BMI (beta = - 1.0, 95% CI-2.3, 0.2, p=0.09), explaining only 5% of the variation. The average decrease of HCB was 53%, and was associated only with high fish consumption in 1991, explaining 12% of the variation. Conclusions: The results support a continuing decrease in human body burdens of PCBs, DDE and HCB during the 1990s. The explanatory factors relative change of BMI and fish consumption explained only a minor part of the time-related variations in serum levels.
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9.
  • Holmberg, Sara, et al. (författare)
  • High levels of vitamin D associated with less ischemic heart disease - a nested case-control study among rural men in Sweden
  • 2017
  • Ingår i: AAEM. - : Institute of Rural Health. - 1232-1966 .- 1898-2263. ; 24:2, s. 288-293
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction and objective. Low levels of serum vitamin D have been associated with increased occurrence of ischemic heart disease (IHD), but findings are inconsistent, e.g. seasonal variation is not always considered in the analyses. The aim of this study was to investigate whether vitamin D is associated with IHD among rural middle-aged men in Sweden when seasonal variation is taken into account. Materials and method. A nested case-control study was performed within a population-based cohort of Swedish farmers and rural residents followed for 20 years. Outcomes were from national health registers. For 276 cases (IHD at any time during follow-up), and for 276 aged-matched controls free of cardiovascular diseases or diabetes, serum levels of vitamin D (25-hydroxyvitamin D-3) were analyzed with liquid chromatography/tandem mass spectrometry (LC/MS/MS), in stored blood samples drawn at the baseline survey in 1990-91. The odds ratio (OR) with 95% confidence intervals (CI) of IHD for vitamin D-quartiles (based on measured as well as adjusted for month of sampling) was evaluated in logistic regression models; potential confounders were taken into account. Results. The measured mean vitamin D levels were 27.6 ng/ml(standard deviation (sd) 8.2 ng/ml) and 28.8 ng/ml (sd 9.0) among cases and controls, respectively. Compared to the quartile with the lowest month-adjusted vitamin D levels, the risk of IHD was significantly lower in the highest quartile (OR=0.46, 95% CI 0.25-0.84, p=0.012) in the fully-adjusted model. Conclusion. Rural Swedish men in the highest quartile of serum vitamin D had halved relative risk of IHD, compared to those in the lowest quartile.
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10.
  • Holmer, Helene, et al. (författare)
  • Psychosocial health and levels of employment in 851 hypopituitary Swedish patients on long-term GH therapy
  • 2013
  • Ingår i: Psychoneuroendocrinology. - : Elsevier. - 0306-4530 .- 1873-3360. ; 38:6, s. 842-852
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: The psychosocial health and working capacity in hypopituitary patients receiving long-term growth hormone (GH) therapy are unknown. less thanbrgreater than less thanbrgreater thanObjective: Psychosocial health and levels of employment were compared between GH deficient (GHD) patients on long-term replacement and the general population. less thanbrgreater than less thanbrgreater thanDesign and participants: In a Swedish nationwide study, 851 GHD patients [101 childhood onset (CO) and 750 adult onset (AO)] and 2622 population controls answered a questionnaire regarding current living, employment and educational level, alcohol consumption and smoking habits. The median time on GH therapy for both men and women with CO GHD was 9 years and for AO GHD 6 years, respectively. less thanbrgreater than less thanbrgreater thanResults: As compared to the controls, the GHD patients were less often working full time, more often on sick leave/disability pension, and to a larger extent alcohol abstainers and never smokers (all; P andlt; 0.05). Predominantly CO GHD women and men, but to some extent also AO GHD women and men, lived less frequently with a partner and more often with their parents. Particularly AO GHD craniopharyngioma women used more antidepressants, while AO GHD men with a craniopharyngioma used more analgesics. less thanbrgreater than less thanbrgreater thanConclusions: A working capacity to the level of the general population was not achieved among hypopituitary patients, although receiving long-term GH therapy. Patients were less likely to use alcohol and tobacco. The CO GHD population lived a less independent life.
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