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Sökning: WFRF:(Wiklund Stefan)

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1.
  • Speliotes, Elizabeth K., et al. (författare)
  • Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
  • 2010
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
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2.
  • CARLSSON, STEFAN, 1987, et al. (författare)
  • Age at surgery, educational level and long-term urinary incontinence after radical prostatectomy
  • 2011
  • Ingår i: BJU International. - 1464-4096 .- 1464-410X. ; 108:10, s. 1572-1577
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE To identify predictors for long-term urinary leakage after radical prostatectomy. PATIENTS AND METHODS A consecutive series of 1411 patients who underwent radical prostatectomy (open surgery or robot-assisted laparoscopic surgery) at Karolinska University Hospital between 2002 and 2006 were invited to complete a study-specific questionnaire. Urinary leakage was defined as use of two or more pads per day. RESULTS Questionnaires were received from 1288 (91%) patients with a median follow-up of 2.2 years. Age at surgery predicts in an exponential manner long-term urinary incontinence at follow-up with an estimated relative increase of 6% per year. Among the oldest patients, 19% had urinary incontinence compared with 6% in the youngest age group, translating to a prevalence ratio of 2.4 (95% confidence interval [CI], 1.5-8.1). Low educational level, as compared with high, yielded an increased age-adjusted prevalence ratio of 2.5 (95% CI, 1.7-3.9). Patients who had undergone salvage radiation therapy had an increased prevalence of urinary incontinence (2.5; 95% CI, 1.6-3.8), as did those with respiratory disease (2.4; 95% CI, 1.3-4.4). Body mass index, prostate weight, presence of diabetes or previous transurethral resection did not appear to influence the prevalence of urinary incontinence. CONCLUSIONS In this series, a patient's age at radical prostatectomy influenced, in an exponential manner, his risk of long-term urinary incontinence. Other predictors are low educational level, salvage radiation therapy and respiratory disease. Intervention studies are needed to understand if these data are relevant to the prevalence of urinary leakage if a radical prostatectomy is postponed in an active monitoring programme.
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3.
  • CARLSSON, STEFAN, 1987, et al. (författare)
  • Orgasm-Associated Urinary Incontinence and Sexual Life after Radical Prostatectomy.
  • 2011
  • Ingår i: The journal of sexual medicine. - : Oxford University Press (OUP). - 1743-6109 .- 1743-6095.
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction. Involuntary release of urine during sexual climax, orgasm-associated urinary incontinence, occurs frequently after radical prostatectomy. We know little about its prevalence and its effect on sexual satisfaction. Aim. To determine the prevalence of orgasm-associated incontinence after radical prostatectomy and its effect on sexual satisfaction. Methods. Consecutive series, follow-up at one point in calendar time of men having undergone radical prostatectomy (open surgery or robot-assisted laparoscopic surgery) at Karolinska University Hospital, Stockholm, Sweden, 2002-2006. Of the 1,411 eligible men, 1,288 (91%) men completed a study-specific questionnaire. Main Outcome Measure. Prevalence rate of orgasm-associated incontinence. Results. Of the 1,288 men providing information, 691 were sexually active. Altogether, 268 men reported orgasm-associated urinary incontinence, of whom 230 (86%) were otherwise continent. When comparing them with the 422 not reporting the symptom but being sexually active, we found a prevalence ratio (with 95% confidence interval) of 1.5 (1.2-1.8) for not being able to satisfy the partner, 2.1 (1.1-3.5) for avoiding sexual activity because of fear of failing, 1.5 (1.1-2.1) for low orgasmic satisfaction, and 1.4 (1.2-1.7) for having sexual intercourse infrequently. Prevalence ratios increase in prostate-cancer survivors with a higher frequency of orgasm-associated urinary incontinence. Conclusion. We found orgasm-associated urinary incontinence to occur among a fifth of prostate cancer survivors having undergone radical prostatectomy, most of whom are continent when not engaged in sexual activity. The symptom was associated with several aspects of sexual life. Nilsson AE, Carlsson S, Johansson E, Jonsson MN, Adding C, Nyberg T, Steineck G, and Wiklund NP. Orgasm-associated urinary incontinence and sexual life after radical prostatectomy. J Sex Med **;**:**-**.
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4.
  • Cortés-González, Jeff R, et al. (författare)
  • Early salvage radiation therapy combined with short-term hormonal therapy in recurrent prostate cancer after radical prostatectomy: Single-institution 4-year data on outcome, toxicity, health-related quality of life and co-morbidities from 184 consecutive patients treated with 70 Gy.
  • 2013
  • Ingår i: International journal of oncology. - : Spandidos Publications. - 1791-2423 .- 1019-6439. ; 42:1, s. 109-17
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to investigate the role of 70Gy salvage radiotherapy (SRT) combined with short-term neoadjuvant hormonal therapy (NHT) in the treatment of recurrent disease after radical prostatectomy (RP), and to consider quality of life (QoL), survival outcomes and impact of co-morbidities on treatment-related rectal-genitourinary toxicity. Electronic records of 184 SRT patients treated consecutively between October 2001 and February 2007 were analyzed. Median age was 64 years (median follow-up 48months). NHT was given to 165 patients (median 3 months). Pre-RP and pre-SRT PSA, PSA doubling time, Gleason score (GS), seminal vesicle invasion (SVI) and detectable post-SRT PSA were recorded. Any detectable PSA or PSA >0.1 ng/ml + nadir was considered biochemical failure (BcF). The Charlson co-morbidity index was used to correlate co-morbidities and rectal-genitourinary toxicity. Scores from the health-related QoL EORTC QLQ-C30 and PR-25 questionnaires were also evaluated. In 116 (63%) patients, a long-lasting curative effect was indicated by undetectable PSA levels. In univariate analysis, using BcF as an outcome variable, p<0.001 was found for GS, pre-SRT PSA, SVI and detectable post-SRT PSA. Multivariate analysis showed p=0.01 for SVI, p=0.09 for GS, and detectable post-SRT PSA (p=0.01); with metastases as an outcome variable, only SVI was significant (p=0.007). Cancer-specific and overall survival were 99 and 95%, respectively. Although microscopy showed SVI or GS 8-10 in the prostatectomy specimens 17/40(43%) and 13/29 (45%), respectively, of patients still showed undetectable PSA at long-term follow-up (median 55 months) after SRT. Likewise, 11/31 (36%) patients with pre-SRT PSA >1.0 ng/ml and 80/134 (60%) patients with PSA doubling time (PSADT) <10 still showed undetectable PSA after 50 months. Slightly elevated acute and late rectal-genitourinary grade 3-4 toxicity was observed. No association with co-morbidity/toxicity was found. EORTC QLQ-C30 scores were similar to or slightly better than reference values. SRT with 70 Gy combined with 3-month NHT results in long-term undetectable PSA in >50% of patients with recurrence after RP with acceptable rectal-genitourinary toxicity and without negatively affecting long-term QoL. Non-metastatic patients should not be disqualified from receiving SRT although presenting with poor prognostic factors at surgery.
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5.
  • Ingelsson, Pernilla, 1968- (författare)
  • How to create a commercial experience : Focus on Leadership, Values and Organizational Culture
  • 2009
  • Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • A new kind of commercial offer is on the rise, that of a commercial experience. It is said to be the next progression of value after a service and that it is distinct from a service in several ways, two important being a) the provider having to create something new or memorable to the customer, i.e. creating attractive quality, and b) the offer being a co-creation between the customer and the provider. Little has been written though about how creating a commercial experience can affect the way organizations should work. One of the areas that ought to be affected is the way organizations work to shape and coordinate co-workers and leaders behaviors by having a common set of values, or in other words a strong organizational culture.  A number of studies show that the leaders in an organization have a strong influence on its culture while others show that working with Total Quality Management (TQM) can enhance the corporate values and lead to profitable organizations. The purpose of this thesis was to explore and contribute knowledge about how to create a commercial experience. The more specific purpose was to explore this area in relation to leadership, values, organizational culture and TQM. To fulfill these purposes two case studies were carried out with the intention of finding ways of working. The first focused on how a renowned organization that offers commercial experiences works and the second on organizations offering commercial experiences in the region of Jämtland. One conclusion drawn from the research is that methodologies and tools that aim directly to enhance the organization´s values and hence its culture might be of even more importance in organizations offering a commercial experience. It seems to be important to be aware that values need to be translated into behaviors to make them understandable in the organization. Storytelling is one tool that can be used as an enhancer of organizational culture, a tool that might be a fairly unrecognized for this purpose. It is also evident that the leadership practiced within the organization is crucial if a strong organizational culture is to be achieved. Further, strategies for selecting the right values appear to be important when trying to create a strong organizational culture - a strategy not so evident within TQM. This could be one area where TQM needs to be developed in order to support the creation of a commercial experience but also to implement TQM more effectively.
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8.
  • Stranne, Johan, 1970, et al. (författare)
  • Inguinal Hernia After Radical Prostatectomy for Prostate Cancer : Results From a Randomized Setting and a Nonrandomized Setting
  • 2010
  • Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 58:5, s. 719-726
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Observational data indicate that retropubic radical prostatectomy (RRP) for prostate cancer (PCa) may induce inguinal hernia (IH) formation. Little is known about the influence of robot-assisted radical prostatectomy (RALP) on IH risk. Objective: To compare the incidence of IH after RRP and RALP to that of nonoperated patients with PCa and to a population control. Design, setting, and participants: We studied two groups. All 376 men included in the Scandinavian Prostate Cancer Group Study Number 4 constitute study group 1. Patients were randomly assigned RRP or watchful waiting (WW). The 1411 consecutive patients who underwent RRP or RALP at Karolinska University Hospital constitute study group 2. Men without PCa, matched for age and residence to each study group, constitute controls. Measurements: Postoperative IH incidence was detected through a validated questionnaire. The participation rates were 82.7% and 88.4% for study groups 1 and 2, respectively. Results and limitations: The Kaplan-Meier cumulative occurrence of IH development after 48 mo in study group 1 was 9.3%, 2.4%, and 0.9% for the RRP, the WW, and the control groups, respectively. There were statistically significant differences between the RRP group and the WW and control groups, but not between the last two. In study group 2 the cumulative risk of IH development at 48 mo was 12.2%, 5.8%, and 2.6% for the RRP, the RALP, and the control group, respectively. There were statistically significant differences between the RRP group and the RALP and control groups, but not between the last two. Conclusions: RRP for PCa leads to an increased risk of IH development. RALP may lower the risk as compared to open surgery.
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9.
  • Wild, Philipp S., et al. (författare)
  • A Genome-Wide Association Study Identifies LIPA as a Susceptibility Gene for Coronary Artery Disease
  • 2011
  • Ingår i: Circulation: Cardiovascular Genetics. - : American Heart Association/Lippincott, Williams & Wilkins. - 1942-325X .- 1942-3268. ; 4:4, s. 203-403
  • Tidskriftsartikel (refereegranskat)abstract
    • Background-eQTL analyses are important to improve the understanding of genetic association results. We performed a genome-wide association and global gene expression study to identify functionally relevant variants affecting the risk of coronary artery disease (CAD). Methods and Results-In a genome-wide association analysis of 2078 CAD cases and 2953 control subjects, we identified 950 single-nucleotide polymorphisms (SNPs) that were associated with CAD at P<10(-3). Subsequent in silico and wet-laboratory replication stages and a final meta-analysis of 21 428 CAD cases and 38 361 control subjects revealed a novel association signal at chromosome 10q23.31 within the LIPA (lysosomal acid lipase A) gene (P=3.7 x 10(-8); odds ratio, 1.1; 95% confidence interval, 1.07 to 1.14). The association of this locus with global gene expression was assessed by genome-wide expression analyses in the monocyte transcriptome of 1494 individuals. The results showed a strong association of this locus with expression of the LIPA transcript (P=1.3 x 10(-96)). An assessment of LIPA SNPs and transcript with cardiovascular phenotypes revealed an association of LIPA transcript levels with impaired endothelial function (P=4.4 x 10(-3)). Conclusions-The use of data on genetic variants and the addition of data on global monocytic gene expression led to the identification of the novel functional CAD susceptibility locus LIPA, located on chromosome 10q23.31. The respective eSNPs associated with CAD strongly affect LIPA gene expression level, which was related to endothelial dysfunction, a precursor of CAD. (Circ Cardiovasc Genet. 2011;4:403-412.)
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10.
  • Adding, Christofer, et al. (författare)
  • Robotkirurgi ger bra resultat vid radikal prostatektomi. Prostatacancer kan behandlas mer effektivt och skonsamt : [Good results in robot-assisted radical prostatectomy. Prostatic cancer can be treated more effectively and carefully].
  • 2011
  • Ingår i: Läkartidningen. - 0023-7205. ; 108:19, s. 1053-1057
  • Tidskriftsartikel (refereegranskat)abstract
    • Operationsresultat redovisas för män opererade med radikal prostatektomi – öppen kirurgi jämfört med robotassisterad laparaskopi – under 2002–2006 vid Karolinska universitetssjukhuset, Solna. Män som följdes under minst 1 år besvarade enkätfrågor; 768 robotkirurgiska och 411 öppenkirurgiska operationer utvärderades. Under perioden minskade andelen män med positiv resektionsrand från 37 procent till 22 procent och med erektil dysfunktion från 66 procent till 60 procent. Andelen optimala operationsresultat (»trifecta«) ökade från 19 procent till 28 procent. Vi har inte hittat några indikationer på att införandet av robotkirurgi har försämrat situationen för män diagnostiserade med prostatacancer. Vi kan inte avgöra om de positiva operationsresultaten skulle ha blivit bättre eller sämre om ett utvecklingsprogram för öppen radikal prostatektomi i stället initierats. En nationell studie, LAPPRO, avseende effekterna av de två operationsformerna pågår.
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