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1.
  • Vickers, AJ, et al. (författare)
  • A panel of kallikrein markers can reduce unnecessary biopsy for prostate cancer: data from the European Randomized Study of Prostate Cancer Screening in Göteborg, Sweden.
  • 2008
  • Ingår i: BMC Medicine. - : BioMed Central (BMC). ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Prostate-specific antigen (PSA) is widely used to detect prostate cancer. The low positive predictive value of elevated PSA results in large numbers of unnecessary prostate biopsies. We set out to determine whether a multivariable model including four kallikrein forms (total, free, and intact PSA, and human kallikrein 2 (hK2)) could predict prostate biopsy outcome in previously unscreened men with elevated total PSA. Methods The study cohort comprised 740 men in Göteborg, Sweden, undergoing biopsy during the first round of the European Randomized study of Screening for Prostate Cancer. We calculated the area-under-the-curve (AUC) for predicting prostate cancer at biopsy. AUCs for a model including age and PSA (the 'laboratory' model) and age, PSA and digital rectal exam (the 'clinical' model) were compared with those for models that also included additional kallikreins. Results Addition of free and intact PSA and hK2 improved AUC from 0.68 to 0.83 and from 0.72 to 0.84, for the laboratory and clinical models respectively. Using a 20% risk of prostate cancer as the threshold for biopsy would have reduced the number of biopsies by 424 (57%) and missed only 31 out of 152 low-grade and 3 out of 40 high-grade cancers. Conclusion Multiple kallikrein forms measured in blood can predict the result of biopsy in previously unscreened men with elevated PSA. A multivariable model can determine which men should be advised to undergo biopsy and which might be advised to continue screening, but defer biopsy until there was stronger evidence of malignancy.
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2.
  • Franks, Paul, et al. (författare)
  • Epigenetics and obesity: the devil is in the details
  • 2010
  • Ingår i: BMC Medicine. - : BioMed Central (BMC). - 1741-7015. ; 8
  • Tidskriftsartikel (övrigt vetenskapligt)abstract
    • Obesity is a complex disease with multiple well-defined risk factors. Nevertheless, susceptibility to obesity and its sequelae within obesogenic environments varies greatly from one person to the next, suggesting a role for gene x environment interactions in the etiology of the disorder. Epigenetic regulation of the human genome provides a putative mechanism by which specific environmental exposures convey risk for obesity and other human diseases and is one possible mechanism that underlies the gene x environment/treatment interactions observed in epidemiological studies and clinical trials. A study published in BMC Medicine this month by Wang et al. reports on an examination of DNA methylation in peripheral blood leukocytes of lean and obese adolescents, comparing methylation patterns between the two groups. The authors identified two genes that were differentially methylated, both of which have roles in immune function. Here we overview the findings from this study in the context of those emerging from other recent genetic and epigenetic studies, discuss the strengths and weaknesses of the study and speculate on the future of epigenetics in chronic disease research. See research article: http://www.biomedcentral.com/1741-7015/8/87/abstract
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3.
  • Cotoi, Ovidiu, et al. (författare)
  • Plasma procalcitonin is associated with all-cause and cancer mortality in apparently healthy men: a prospective population-based study.
  • 2013
  • Ingår i: BMC Medicine. - : BioMed Central (BMC). - 1741-7015. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The inflammatory mediator procalcitonin (PCT) has previously been associated with prognosis in myocardial infarction, cancer and sepsis patients. The importance of PCT in the general population is currently unknown. Our aim was to assess the relationship between plasma PCT and the risk of all-cause and cause-specific mortality in apparently healthy individuals with no previous history of cardiovascular disease or cancer.
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5.
  • Hall, Elin, et al. (författare)
  • Effects of palmitate on genome-wide mRNA expression and DNA methylation patterns in human pancreatic islets.
  • 2014
  • Ingår i: BMC Medicine. - : BioMed Central (BMC). - 1741-7015. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Circulating free fatty acids are often elevated in patients with type 2 diabetes (T2D) and obese individuals. Chronic exposure to high levels of saturated fatty acids has detrimental effects on islet function and insulin secretion. Altered gene expression and epigenetics may contribute to T2D and obesity. However, there is limited information on whether fatty acids alter the genome-wide transcriptome profile in conjunction with DNA methylation patterns in human pancreatic islets. To dissect the molecular mechanisms linking lipotoxicity to impaired insulin secretion, we investigated the effects of a 48 h palmitate treatment in vitro on genome-wide mRNA expression and DNA methylation patterns in human pancreatic islets.
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6.
  • Loefmark, Rurik, et al. (författare)
  • Physicians' experiences with end-of-life decision-making: Survey in 6 European countries and Australia
  • 2008
  • Ingår i: BMC Medicine. - : BioMed Central (BMC). - 1741-7015. ; 6:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: In this study we investigated (a) to what extent physicians have experience with performing a range of end-of-life decisions (ELDs), (b) if they have no experience with performing an ELD, would they be willing to do so under certain conditions and (c) which background characteristics are associated with having experience with/or being willing to make such ELDs. Methods: An anonymous questionnaire was sent to 16,486 physicians from specialities in which death is common: Australia, Belgium, Denmark, Italy, the Netherlands, Sweden and Switzerland. Results: The response rate differed between countries (39-68%). The experience of foregoing life-sustaining treatment ranged between 37% and 86%: intensifying the alleviation of pain or other symptoms while taking into account possible hastening of death between 57% and 95%, and experience with deep sedation until death between 12% and 46%. Receiving a request for hastening death differed between 34% and 71%, and intentionally hastening death on the explicit request of a patient between 1% and 56%. Conclusion: There are differences between countries in experiences with ELDs, in willingness to perform ELDs and in receiving requests for euthanasia or physician-assisted suicide. Foregoing treatment and intensifying alleviation of pain and symptoms are practiced and accepted by most physicians in all countries. Physicians with training in palliative care are more inclined to perform ELDs, as are those who attend to higher numbers of terminal patients. Thus, this seems not to be only a matter of opportunity, but also a matter of attitude.
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7.
  • Nordmark, Eva, et al. (författare)
  • Development of lower limb range of motion from early childhood to adolescence in cerebral palsy: a population-based study
  • 2009
  • Ingår i: BMC Medicine. - : BioMed Central (BMC). - 1741-7015. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The decreasing range of joint motion caused by insufficient muscle length is a common problem in children with cerebral palsy (CP), often worsening with age. In 1994 a CP register and health care programme for children with CP was initiated in southern Sweden. The aim of this study was to analyse the development of the passive range of motion (ROM) in the lower limbs during all the growth periods in relation to gross motor function and CP subtype in the total population of children with CP. Methods: In total, 359 children with CP born during 1990-1999, living in the southernmost part of Sweden in the year during which they reached their third birthday and still living in the area in the year of their seventh birthday were analysed. The programme includes a continuous standardized follow-up with goniometric measurements of ROM in the lower limbs. The assessments are made by each child's local physiotherapist twice a year until 6 years of age, then once a year. In total, 5075 assessments from the CPUP database from 1994 to 1 January 2007 were analysed. Results: The study showed a decreasing mean range of motion over the period 2-14 years of age in all joints or muscles measured. The development of ROM varied according to GMFCS level and CP subtype. Conclusion: We found a decreasing ROM in children with CP from 2-14 years of age. This information is important for both the treatment and follow-up planning of the individual child as well as for the planning of health care programmes for all children with CP.
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8.
  • O'Neil, Adrienne, et al. (författare)
  • The impact of statins on psychological wellbeing: a systematic review and meta-analysis
  • 2012
  • Ingår i: BMC Medicine. - : BioMed Central (BMC). - 1741-7015. ; 10
  • Forskningsöversikt (refereegranskat)abstract
    • Background: Cholesterol-lowering medications such as statins have anti-inflammatory and antioxidant properties, which may be beneficial for treating depression and improving mood. However, evidence regarding their effects remains inconsistent, with some studies reporting links to mood disturbances. We aimed to conduct a meta-analysis to determine the impact of statins on psychological wellbeing of individuals with or without hypercholesterolemia. Methods: Articles were identified using medical, health, psychiatric and social science databases, evaluated for quality, and data were synthesized and analyzed in RevMan-5 software using a random effects model. Results: The 7 randomized controlled trials included in the analysis represented 2,105 participants. A test for overall effect demonstrated no statistically significant differences in psychological wellbeing between participants receiving statins or a placebo (standardized mean difference (SMD) = -0.08, 95% CI -0.29 to 0.12; P = 0.42). Sensitivity analyses were conducted to separately analyze depression (n = 5) and mood (n = 2) outcomes; statins were associated with statistically significant improvements in mood scores (SMD = -0.43, 95% CI -0.61 to -0.24). Conclusions: Our findings refute evidence of negative effects of statins on psychological outcomes, providing some support for mood-related benefits. Future studies could examine the effects of statins in depressed populations.
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9.
  • Politis, Marios, et al. (författare)
  • Clinical application of stem cell therapy in Parkinson's disease
  • 2012
  • Ingår i: BMC Medicine. - : BioMed Central (BMC). - 1741-7015. ; 10
  • Forskningsöversikt (refereegranskat)abstract
    • Cell replacement therapies in Parkinson's disease (PD) aim to provide long-lasting relief of patients' symptoms. Previous clinical trials using transplantation of human fetal ventral mesencephalic (hfVM) tissue in the striata of PD patients have provided proof-of-principle that such grafts can restore striatal dopaminergic (DA-ergic) function. The transplants survive, reinnervate the striatum, and generate adequate symptomatic relief in some patients for more than a decade following operation. However, the initial clinical trials lacked homogeneity of outcomes and were hindered by the development of troublesome graft-induced dyskinesias in a subgroup of patients. Although recent knowledge has provided insights for overcoming these obstacles, it is unlikely that transplantation of hfVM tissue will become routine treatment for PD owing to problems with tissue availability and standardization of the grafts. The main focus now is on producing DA-ergic neuroblasts for transplantation from stem cells (SCs). There is a range of emerging sources of SCs for generating a DA-ergic fate in vitro. However, the translation of these efforts in vivo currently lacks efficacy and sustainability. A successful, clinically competitive SC therapy in PD needs to produce longlasting symptomatic relief without side effects while counteracting PD progression.
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10.
  • Rohrmann, Sabine, et al. (författare)
  • Meat consumption and mortality - results from the European Prospective Investigation into Cancer and Nutrition
  • 2013
  • Ingår i: BMC Medicine. - : BioMed Central (BMC). - 1741-7015. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Recently, some US cohorts have shown a moderate association between red and processed meat consumption and mortality supporting the results of previous studies among vegetarians. The aim of this study was to examine the association of red meat, processed meat, and poultry consumption with the risk of early death in the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods: Included in the analysis were 448,568 men and women without prevalent cancer, stroke, or myocardial infarction, and with complete information on diet, smoking, physical activity and body mass index, who were between 35 and 69 years old at baseline. Cox proportional hazards regression was used to examine the association of meat consumption with all-cause and cause-specific mortality. Results: As of June 2009, 26,344 deaths were observed. After multivariate adjustment, a high consumption of red meat was related to higher all-cause mortality (hazard ratio (HR) = 1.14, 95% confidence interval (CI) 1.01 to 1.28, 160+ versus 10 to 19.9 g/day), and the association was stronger for processed meat (HR = 1.44, 95% CI 1.24 to 1.66, 160+ versus 10 to 19.9 g/day). After correction for measurement error, higher all-cause mortality remained significant only for processed meat (HR = 1.18, 95% CI 1.11 to 1.25, per 50 g/d). We estimated that 3.3% (95% CI 1.5% to 5.0%) of deaths could be prevented if all participants had a processed meat consumption of less than 20 g/day. Significant associations with processed meat intake were observed for cardiovascular diseases, cancer, and 'other causes of death'. The consumption of poultry was not related to all-cause mortality. Conclusions: The results of our analysis support a moderate positive association between processed meat consumption and mortality, in particular due to cardiovascular diseases, but also to cancer.
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