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  • Franzén, Karin, 1958-, et al. (författare)
  • Validation of the Swedish version of the Incontinence Impact Questionnaire, IIQ-7 and the Urogenital Distress Inventory, UDI-6.
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Introduction and hypothesis:The purpose was to validate the Swedish versions of the Incontinence Impact Questionnaire (IIQ-7) and Urogenital Distress Inventory (UDI-6). Methods: We analyzed reliability, validity, and responsiveness in a clinical sample of 96 women with UI. Result:Test-retest reliability ranged from moderate to almost perfect. Cronbach’s alpha was 0.39 (UDI-6) and 0.83 (IIQ-7). Effect size calculation of change after treatment demonstrated good responsiveness. The effect size at 6 months was moderate in the SUI group and small in the UUI+MUI group. There was a moderate to strong correlation between UDI-6 and IIQ-7 and treatment satisfaction at 6, 12, and 24 months for both groups. ConclusionThe Swedish UDI-6 and IIQ-7 show good responsiveness and are easy to administer and fill out. UDI-6 did not produce the same solid psychometrical results as IIQ-7, but both scales can be of clinical importance and are recommended for clinical use.
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  • Fridén, Michael, et al. (författare)
  • Effects of a low-carbohydrate high polyunsaturated fat diet or a healthy Nordic diet versus usual care on liver fat content and cardiometabolic risk factors in people with type 2 diabetes and prediabetes: a randomized controlled trial (NAFLDiet)
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Previous trials have shown that plant-derived polyunsaturated fatty acids (PUFA) in place of saturated fat reduces liver fat, a prerequisite for non-alcoholic fatty liver disease (NAFLD). The effect on liver fat from a novel “anti-lipogenic diet” replacing carbohydrates with PUFA or a healthy Nordic diet (HND) higher in whole-grains but lower in saturated fat has not yet been examined. Objectives: To investigate the effects on changes in liver fat (primary outcome) and other cardiometabolic risk factors after 12 months of follow-up in individuals with prediabetes or T2D from three different diet comparisons: a low carbohydrate high PUFA (LCPUFA) diet versus a HND, a LCPUFA diet versus usual care (UC) and a HND versus UC. Methods: A three-arm parallel ad libitum randomized trial was conducted. Adult men and women (n=148) were randomized to one of the three diet groups. Participants in all groups received key food items on a monthly/bimonthly basis. Liver fat and cardiometabolic risk factors were assessed at baseline and after 12 months. Dietary adherence was assessed using weighed food diaries and objective biomarkers. General linear models were employed to estimate the intention-to-treat (ITT) effect. Results: Dietary adherence was high for all diet groups. Liver fat was reduced to a similar extent in the LCPUFA and the HND group compared to UC (-1.46% (95% CI: -2.42, -0.51)) and -1.76 % (95% CI: -2.96, -0.57), respectively. No difference in liver fat between LCPUFA and HND was observed. Body weight and HbA1c decreased more in the HND compared to the other diet groups whereas no differences were observed between LCPUFA and UC. Similar reductions in LDL-cholesterol were observed for the HND and the LCPUFA group compared to UC, but only the HND reduced triglycerides and C-reactive protein (CRP) compared with UC. No differences were observed for any other secondary outcomes.Conclusions: A LCPUFA diet and a HND both reduced liver fat as compared with UC. Given the sustained weight loss after the HND compared to the other groups, together with improvements in other cardiometabolic markers, the HND in particular seems to be useful for the treatment of T2D and NAFLD.
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  • Hälleberg-Nyman, Maria, 1968-, et al. (författare)
  • Intermittent versus indwelling urinary catheterisation in hip surgery patients : a randomised controlled trial with cost-effectiveness analysis
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Background:  Hip surgery is associated with a risk for postoperative urinary retention. To avoid urinary retention hip surgery patients undergo urinary catheterisation. Urinary catheterisation, however, is associated with increased risk for urinary tract infection (UTI). Presently, there is limited knowledge whether intermittent or indwelling urinary catheterisation is the preferred choice for short-term bladder drainage in patients undergoing hip surgery.Objectives: The aim of the study was to investigate differences between intermittent and indwelling urinary catheterisation in hip surgery patients in relation to nosocomial UTI and cost-effectiveness.Design: Randomised controlled trial with cost-effectiveness analysis. Setting: The study was carried out at an orthopaedic department at a Swedish university hospital.Method: One hundred seventy hip surgery patients (patients with fractures or with osteoarthritis) were randomly allocated to either intermittent or indwelling urinary catheterisation. Data collection took place at four time points: during stay in hospital, at discharge and at 4 weeks and 4 months after discharge. Results: Eighteen patients contracted nosocomial UTIs, 8 in the intermittent catheterisation group and 10 in the indwelling catheterisation group (p = 0.618).  The patients in the intermittent catheterisation group were more often catheterised (p <0.001) and required more bladder scans (p <0.001) but regained normal bladder function sooner than the patients in the indwelling catheterisation group (p <0.001). Fourteen percent of the patients in the intermittent group did not need any catheterisation. Cost-effectiveness was similar between the indwelling and intermittent urinary catheterisation methods.Conclusions: In the perspective of cost-effectiveness both indwelling and intermittent methods could be appropriate in clinical praxis. Both methods have advantages and disadvantages but by not using indwelling catheterisation routinely in this patient group unnecessary catheterisations might be avoided.
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  • Johansson, Camilla, et al. (författare)
  • Identification of Gene-Therapy Responsive Blood Biomarkers for Duchenne Muscular Dystrophy
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • IntroductionAssessing muscle dystrophin expression systemically is important for understanding the effect of dystrophin-restoring therapies in Duchenne muscular dystrophy (DMD). Many potential blood biomarkers have been identified in DMD patients which are either more or less abundant in blood samples compared to healthy individuals and that have been shown to change with disease progression or respond to pharmacological treatment. In this study, it was suggested that a panel of such blood biomarker candidates could be used to monitor dystrophin rescue in microdystrophin therapies.  MethodsPlasma samples from mdx mice treated with the microdystrophin therapy SGT-001 were analysed with an antibody suspension bead array consisting of 87 antibodies targeting 83 proteins previously identified as biomarker candidates for DMD. Each sample was assayed at two different plasma dilutions to cover a broader concentration range. Median fluorescent intensities (MFI) for each antibody were correlated to dystrophin expression in muscle tissue, as measured by immunohistochemistry and Western blot. 13 targets were selected and validated in a DMD and Becker muscular dystrophy (BMD) longitudinal natural history cohort using a suspension bead array.  Results10 proteins were found significantly elevated in untreated mdx mice compared to C57 wild-type mice and 10 were found to correlate with dystrophin expression (Spearman’s correlation, FDR < 0.05) upon gene transfer. Abundance of TTN, ADSSL1, LONP1, OTUD5, MYL3 as well as DMD protein were associated with dystrophin expression in BMD patients. Of these, MYL3 and ADSSL1 had different abundance in DMD compared to healthy individuals, and MYL3 also displayed different age trajectories between DMD and BMD patients.  DiscussionThe ten proteins identified in mouse plasma are related to muscle contraction (ADSSL1, ASAH1, CA3, MYL3, TTN), microtubule formation (TPI1), and protein degradation (PSMA2, OTUD4, LONP1). Of these, MYL3 and ADSSL1 showed the most promise as a dystrophin monitoring biomarker in patient samples.
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  • Johansson, Camilla, et al. (författare)
  • Monitoring Biomarker Study in Becker Muscular Dystrophy using Data Independent Acquisition LC-MS/MS
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Becker muscular dystrophy (BMD) is a rare and heterogenous form of dystrophinopathy caused by reduced expression of altered dystrophin protein. Gene therapies and exon-skipping therapies for the more severe form of dystrophinopathy, Duchenne muscular dystrophy (DMD), assumes that by promoting partial dystrophin expression in DMD patients, their disease progression could be reduced. Several studies have identified potential progression biomarkers for DMD and hypothesised in their usefulness in monitoring pharmacodynamic response in gene-therapy clinical trials. However, knowledge of progression changes of blood proteome in BMD is lacking. In this study, we aimed at exploring differences in proteomic changes between DMD and BMD in a prospective longitudinal 4-year study as well as explore what proteins relate to functional performance in BMD patients. Serum from 48 BMD patients and 19 DMD patients were analysed using Data Independent Acquisition Tandem Mass Spectrometry (DIA-MS). Linear mixed effects models identified 17 proteins with altered longitudinal signatures between DMD and BMD, among these CKM, PKM and ALDOA. Furthermore, bikunin (product of AMBP gene), C3 and IGHG2 were found related to functional performance in BMD patients. 
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  • Wållberg, Helena, et al. (författare)
  • Specific in vivo imaging of HER2-positive tumors within one hour using a site-specifically 11C-labeled Sel-tagged Affibody molecule
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • A rapid, reliable method for distinguishing tumors or metastases that overexpress human epidermal growth factor receptor 2 (HER2) from those that do not is highly desired for improvement of cancer care. In v ivo imaging methods are available, but are not yet in clinical practice; new methodologies improving speed, sensitivity and specificity are required. Here we describe promising results with a HER2‐binding Affibody molecule, ZHER2:342, recombinantly fused with a C‐terminal selenocysteine‐containing tetrapeptide Sel‐tag and site‐specifically labeled with either 11C or 68Ga for molecular imaging applications with positron emissiontomography (PET). In mice, both the 11C‐ and 68Ga‐labeled tracers initially cleared rapidly from the blood, followed by a slower decrease to 4‐5 %ID/g at 1 h. Final uptake in kidneys was much lower (> 5‐fold) for the 11C‐labeled protein, leading to markedly reduced background radioactivity in the abdomen. Furthermore, 11C‐labeled Sel‐tagged ZHER2:342 showed excellent tumor targeting capability, with almost 10 %ID/g in HER2 expressing tumors within the first hour. High specificity was demonstrated by preblocking the binding sites with excess ligand, which yielded low radiotracer uptakes, comparable to those in tumors with low endogenous HER2 expression. To our knowledge the Sel‐tagging technique is the first that enables site‐specific 11C radiolabelingof proteins. Here we present that, in a favorable combination between radionuclide half‐life and in vivo pharmacokinetics of the Affibody molecules, 11C‐labeled Sel taggedZHER2:342 can successfully be used for rapid and repeated PET studies of HER2 expression in tumors.
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