| 1. |
- Ahlberg, Mats Steinholtz, et al.
(författare)
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PCASTt/SPCG-17-A randomised trial of active surveillance in prostate cancer: Rationale and design
- 2019
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Overtreatment of localised prostate cancer is substantial despite increased use of active surveillance. No randomised trials help define how to monitor patients or when to initiate treatment with curative intent. Methods and analysis A randomised, multicentre, intervention trial designed to evaluate the safety of an MRI-based active surveillance protocol, with standardised triggers for repeated biopsies and radical treatment. The aim is to reduce overtreatment of prostate cancer. 2000 men will be randomly allocated to either surveillance according to current practice or to standardised triggers at centres in Sweden, Norway, Finland and the UK. Men diagnosed in the past 12 months with prostate cancer, ≤T2a, prostate-specific antigen (PSA) <15 ng/mL, PSA density ≤0.2 ng/mL/cc, any International Society of Urological Pathology (ISUP) grade 1 are eligible. Men with ISUP grade 2 in <30% of cores on systematic biopsy and <10 mm cancer in one core on systematic or targeted biopsy are also eligible. Men diagnosed on systematic biopsy should have an MRI and targeted biopsies against Prostate Imaging and Reporting Data System V.2 3-5 lesions before inclusion. Identical follow-up in the two study arms: biannual PSA testing, yearly clinical examination and MRI every second year. In the experimental arm, standardised triggers based on MRI and PSA density elicit repeated biopsies. MRI and histopathological progression trigger radical treatment. Primary outcome measure is progression-free survival. Secondary outcome measures are cumulative incidence of metastatic disease, treatments with curative intent, pT3-4 at radical prostatectomy, switch to watchful waiting, prostate cancer mortality and quality of life. Inclusion started in October 2016 and in October 2018; 275 patients have been enrolled. Ethics and dissemination Ethical approval was obtained in each participating country. Results for the primary and secondary outcome measures will be submitted for publication in peer-reviewed journals. Trial registration number NCT02914873.
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| 2. |
- Alvinius, Aida, Docent, 1979-, et al.
(författare)
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Do military leaders resist organizational challenges?
- 2019
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Ingår i: Journal of Resistance Studies. - Ed : Irene Publishing. - 2001-9947. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- Armed forces in many Western countries have been facing societal change processes for more than twenty years; including value changes, government savings and, more recently, by the unstable security environment. The starting point here is that there is a relationship between processes of societal change and organizational challenges. The purpose of this study is to examine how military leaders manage and respond to different kinds of organizational challenges, focusing on resistance. The empirical material was collected using a grounded theory approach. Informants possessing wide experience of leadership participated in this study. The qualitative analysis describes the coping strategies, acceptance and resistance found among military leaders when dealing with organizational demands. Challenges caused by societal changes are experienced as negative aspects of organizational structure. This may be an explanation for why military leaders cope with them applying both resistance and acceptance. However, our main conclusion is that resistance to change stays within a culture of obedience.
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| 3. |
- Apró, William, et al.
(författare)
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Amino Acid-induced S6K1 Activity In Human Skeletal Muscle Is Mediated By Increased mTor/Rheb Interaction : 128 June 1, 11: 15 AM - 11: 30 AM.
- 2016
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Ingår i: Medicine And Science In Sports And Exercise 2016 May; Vol. 48 (5S Suppl 1), pp. 17.. - : Ovid Technologies (Wolters Kluwer Health). ; 48:5 Suppl 1, s. 17-
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Konferensbidrag (refereegranskat)abstract
- Cell culture studies have shown that amino acids activate mTORC1 signaling by increasing the interaction between mTOR and its essential activator Rheb. However, the existence of this mechanism in human skeletal muscle remains to be determined.PURPOSE: To determine if increased mTORC1 signaling in response to amino acids in human skeletal muscle is due to an increased interaction between mTOR and Rheb.METHODS: Eight well trained men performed resistance exercise on two separate occasions. In connection with the exercise, subjects were supplemented with flavored water (Pla) and essential amino acids (EAA) in a double-blind, randomized cross-over design. Muscle biopsies were taken in the vastus lateralis muscle before, immediately after and 90 and 180 min post exercise. Activity of the mTORC1 pathway was assessed by a radiolabeled in-vitro kinase assay for its immediate downstream target S6K1. Protein-protein interactions were determined by western blot following co-immunoprecipitation of mTOR with Rheb. Co-immunoprecipitation was performed on pooled muscle samples from three of the eight subjects.RESULTS: Activity of S6K1 remained unchanged immediately after exercise in both trials. However, at 90 min post exercise, S6K1 activity increased by approximately 2- and 8-fold (p<0.05) from baseline the Pla and EAA trials, respectively. At the 180 min time point, S6K1 activity remained elevated in both trials being approx. 3-fold higher in the Pla trial and 5-fold higher (p<0.05) in the EAA trial. The fold-change in mTOR and Rheb interaction largely resembled the activity pattern of S6K1 in both trials; in the Pla trial the fold-change was 0.9, 1.3 and 1.4 while in the EAA trial the fold-change was 1.6, 2.9 and 1.9 immediately after, 90 min after and 180 min after exercise, respectively.CONCLUSIONS: The large increase in S6K1 activity following EAA intake appears to be mediated by an increased interaction between mTOR and its proximal activator Rheb. This is the first time this mechanism has been demonstrated in human skeletal muscle.
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| 4. |
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| 5. |
- Apró, William, et al.
(författare)
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Leucine does not affect mechanistic target of rapamycin complex 1 assembly but is required for maximal ribosomal protein s6 kinase 1 activity in human skeletal muscle following resistance exercise
- 2015
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Ingår i: The FASEB Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 29:10, s. 4358-4373
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Tidskriftsartikel (refereegranskat)abstract
- We examined how the stimulatory effect of leucine on the mechanistic target of rapamycin complex 1 (mTORC1) pathway is affected by the presence of the remaining essential amino acids (EAAs). Nine male subjects performed resistance exercise on 4 occasions and were randomly supplied EAAs with leucine, EAAs without leucine (EAA-Leu), leucine alone, or flavored water (placebo; control). Muscle biopsies were taken from the vastus lateralis before and 60 and 90 min after exercise. Biopsies were analyzed for protein phosphorylation, kinase activity, protein-protein interactions, amino acid concentrations, and tracer incorporation. Leucine alone stimulated ribosomal protein s6 kinase 1 (S6K1) phosphorylation similar to 280% more than placebo and EAA-Leu after exercise. Moreover, this response was enhanced by 60-75% after intake of EAAs compared with that of leucine alone (P < 0.05). Kinase activity of S6K1 reflected that of S6K1 phosphorylation; 60 min after exercise, the activity was elevated 3.3- and 4.2-fold with intake of leucine alone and with EAAs, respectively (P < 0.05). The interaction between mammalian target of rapamycin and regulatory-associated protein of mammalian target of rapamycin was unaltered in response to both resistance exercise and amino acid provision. Leucine alone stimulates mTORC1 signaling, although this response is enhanced by other EAAs and does not appear to be caused by alterations inmTORC1 assembly.
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| 6. |
- Apró, William, et al.
(författare)
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Resistance exercise induced S6K1 kinase activity is not inhibited in human skeletal muscle despite prior activation of AMPK by high intensity interval cycling.
- 2015
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Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 308:6, s. E470-E481
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Tidskriftsartikel (refereegranskat)abstract
- Combining endurance and strength training in the same session has been reported to reduce the anabolic response to the latter form of exercise. The underlying mechanism, based primarily on results from rodent muscle, is proposed to involve AMPK-dependent inhibition of mTORC1 signaling. This hypothesis was tested in eight trained male subjects who in a randomized order performed either resistance exercise only (R) or interval cycling followed by resistance exercise (ER). Biopsies taken from the vastus lateralis before and after endurance exercise and repeatedly after resistance exercise were assessed for glycogen content, kinase activity, protein phosphorylation and gene expression. Mixed muscle fractional synthetic rate was measured at rest and during 3h of recovery using the stable isotope technique. In ER, AMPK activity was elevated immediately after both endurance and resistance exercise (~90%, P<0.05) but was unchanged in R. Thr389 phosphorylation of S6K1 was increased several-fold immediately after exercise (P<0.05) in both trials and increased further throughout recovery. After 90 and 180 min recovery, S6K1 activity was elevated (~55% and ~110%, respectively, P<0.05) and eEF2 phosphorylation was reduced (~55%, P<0.05) with no difference between trials. In contrast, markers for protein catabolism were differently influenced by the two modes of exercise; ER induced a significant increase in gene and protein expression of MuRF1 (P<0.05), which was not observed following R exercise only. In conclusion, cycling-induced elevation in AMPK activity does not inhibit mTORC1 signaling after subsequent resistance exercise, but may instead interfere with the hypertrophic response by influencing key components in protein breakdown.
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| 7. |
- Beckmann, Kerri, et al.
(författare)
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Androgen Deprivation Therapies and Changes in Comorbidity : A Comparison of Gonadotropin-releasing Hormone Agonists and Antiandrogen Monotherapy as Primary Therapy in Men with High-risk Prostate Cancer
- 2019
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Ingår i: European Urology. - : ELSEVIER SCIENCE BV. - 0302-2838 .- 1873-7560. ; 75:4, s. 676-683
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Tidskriftsartikel (refereegranskat)abstract
- Background: Some studies suggest that gonadotropin-releasing hormone (GnRH) agonists are associated with higher risk of adverse events than antiandrogens (AAs) monotherapy. However, it has been unclear whether this is due to indication bias.Objective: To investigate rates of change in comorbidity for men on GnRH agonists versus AA monotherapy in a population-based register study.Design, setting, and participants: Men with advanced nonmetastatic prostate cancer (PCa) who received primary AA (n = 2078) or GnRH agonists (n = 4878) and age- and area-matched PCa-free men were selected from Prostate Cancer Database Sweden 3.0. Increases in comorbidity were measured using the Charlson Comorbidity Index (CCI), from 5 yr before through to 5 yr after starting androgen deprivation therapy (ADT).Outcome measures and statistical methods: Multivariable linear regression was used to determine differences in excess rate of CCI change before and after ADT initiation. Risk of any incremental change in CCI following ADT was assessed using multivariable Cox regression analyses.Results and limitations: Men on GnRH agonists experienced a greater difference in excess rate of CCI change after starting ADT than men on AA monotherapy (5.6% per yr, p < 0.001). Risk of any new CCI change after ADT was greater for GnRH agonists than for AA (hazard ratio, 1.32; 95% confidence interval, 1.20-144).Conclusions: Impact on comorbidity was lower for men on AA monotherapy than for men on GnRH agonists. Our results should be confirmed through randomised trials of effectiveness and adverse effects, comparing AA monotherapy and GnRH agonists in men with advanced nonmetastatic PCa who are unsuitable for curative treatment.Patient summary: Hormone therapies for advanced prostate cancer can increase the risk of other diseases (eg, heart disease, diabetes). This study compared two common forms of hormone therapy and found that the risk of another serious disease was higher for those on gonadotropin-releasing hormone agonists than for those on antiandrogen monotherapy.
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| 8. |
- Bergengren, Oskar, et al.
(författare)
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Determinants for choosing and adhering to active surveillance for localised prostate cancer: A nationwide population-based study
- 2019
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 9:12
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Tidskriftsartikel (refereegranskat)abstract
- Objective Knowledge about factors influencing choice of and adherence to active surveillance (AS) for prostate cancer (PC) is scarce. We aim to identify which factors most affected choosing and adhering to AS and to quantify their relative importance. Design, setting and participants In 2015, we sent a questionnaire to all Swedish men aged ≤70 years registered in the National Prostate Cancer Register of Sweden who were diagnosed in 2008 with low-risk PC and had undergone prostatectomy, radiotherapy or started on AS. Outcome measurements and statistical analysis Logistic regression was used to calculate ORs with 95% CIs for factors potentially affecting choice and adherence to AS. Results 1288 out of 1720 men (75%) responded, 451 (35%) chose AS and 837 (65%) underwent curative treatment. Of those starting on AS, 238 (53%) diverted to treatment within 7years. Most men (83%) choose AS because ‘My doctor recommended AS’. Factors associated with choosing AS over treatment were older age (OR 1.81, 95%CI 1.29 to 2.54), a Charlson Comorbidity Index >2 (OR 1.50, 95%CI 1.06 to 2.13), being unaccompanied when notified of the cancer diagnosis (OR 1.45, 95%CI 1.11 to 1.89). Men with a higher prostate-specific antigen (PSA) at the time of diagnosis were less likely to adhere to AS (OR 0.26, 95%CI 0.10 to 0.63). The reason for having treatment after initial AS was ‘the PSA level was rising’ in 55% and biopsy findings in 36%. Conclusions A doctor’s recommendation strongly affects which treatment is chosen for men with low-risk PC. Rising PSA values were the main factor for initiating treatment for men on AS. These findings need be considered by healthcare providers who wish to increase the uptake of and adherence to AS.
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| 9. |
- Bergengren, Oskar, et al.
(författare)
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Satisfaction with Care Among Men with Localised Prostate Cancer: A Nationwide Population-based Study
- 2018
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Ingår i: European Urology Oncology. - : Elsevier BV. - 2588-9311. ; 1:1, s. 37-45
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Tidskriftsartikel (refereegranskat)abstract
- Background: Information about how men with prostate cancer (PC) experience their medical care and factors associated with their overall satisfaction with care (OSC) is limited. Objective: To investigate OSC and factors associated with OSC among men with low-risk PC. Design, setting, and participants: Men registered in the National Prostate Cancer Register of Sweden as diagnosed in 2008 with low-risk PC at the age of ≤70 yr who had undergone radical prostatectomy (RP), radiotherapy (RT), or started on active surveillance (AS) were invited in 2015 to participate in this nationwide population-based survey (n = 1720). Outcome measurements and statistical analysis: OSC data were analysed using ordinal logistic regression. Odds ratios (ORs) were calculated for comparisons between the highest and lowest possible response categories. Results and limitations: A total of 1288 men (74.9%) responded. High OSC was reported by 958 (74.4%). Factors associated with high OSC were high participation in decision-making (OR 4.18, 95% confidence interval [CI] 2.61–6.69), receiving more information (OR 11.1, 95% CI 7.97–15.6), high-quality information (OR 7.85, 95% CI 5.46–11.3), access to a nurse navigator (OR 1.80, 95% CI 1.44–2.26), and better functional outcomes (defined as 25 points higher on the EPIC-26 questionnaire; OR 1.34, 95% CI 1.21–1.48). OSC was not affected by whether a doctor or specialist nurse conducted follow-up (OR 0.84, 95% CI 0.66–1.07). These findings were similar across treatment groups. Men who had undergone RP or RT reported high OSC more often than men on AS (78.2% vs 84.0% vs 72.6%), high participation in decision-making (70.5% vs 64.5% vs 49.2%), and having received more information (40.5% vs 45.8% vs 28.6%), and were less likely to believe they would die from PC (3.8% vs 3.9% vs 8.0%). Limitations include the nonrandomised retrospective design and potential recall bias. Conclusions: Information and participation in decision-making, as well as access to a nurse navigator, are key factors for OSC, regardless of treatment. Men on AS need more information about their treatment and need to participate more in decision-making. OSC was as high among men who had nurse-led follow-up as among men who had doctor-led follow-up. Patient summary: Information about how men with low-risk prostate cancer experience their medical care is limited. In this nationwide population-based study we found that information and participation in decision-making as well as access to a nurse navigator are key factors for satisfaction regardless of treatment. Men who are being closely watched for prostate cancer without immediate curative treatment need more information than they now receive and need to participate more in decision-making than they currently do. Information and participation in decision-making are key factors for satisfaction with care among men with localised prostate cancer. Men under active surveillance need more information about their treatment and need to participate more in decision-making. © 2018 European Association of Urology
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| 10. |
- Bjerg, Anders, 1982, et al.
(författare)
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Increase in pollen sensitization in Swedish adults and protective effect of keeping animals in childhood
- 2016
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 46:10, s. 1328-1336
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To date, most studies of the "allergy epidemic" have been based on self-reported data. There is still limited knowledge on time trends in allergic sensitization, especially among adults.OBJECTIVE: To study allergic sensitization, its risk factors, and time trends in prevalence.METHODS: Within West Sweden Asthma Study (WSAS) a population-based sample of 788 adults (17-60y) underwent skin prick tests (SPT) for 11 aeroallergens 2009-2012. Specific IgE was analyzed in 750 of the participants. Those aged 20-46y (n=379) were compared with the European Community Respiratory Health Survey sample aged 20-46y from the same area (n=591) in 1991-1992.RESULTS: Among those aged 20-46y the prevalence of positive SPT to pollen increased; timothy from 17.1% to 29.0% (p<0.001) and birch from 15.6% to 23.7% (p=0.002) between 1991-1992 and 2009-2012. Measurements of specific IgE confirmed these increases. Prevalence of sensitization to all other tested allergens was unchanged. In the full WSAS sample aged 17-60y any positive SPT was seen in 41.9%, and the dominating sensitizers were pollen (34.3%), animals (22.8%) and mites (12.6%). Pollen sensitization was strongly associated with rhinitis, whereas indoor allergens were more associated with asthma. Growing up with livestock or furred pets decreased the risk of sensitization, adjusted odds ratio 0.53 (0.28-0.995) and 0.68 (0.47-0.98) respectively.CONCLUSION: Pollen sensitization has increased in Swedish adults since the early 1990's, while the prevalence of sensitization to other allergens has remained unchanged. This is one plausible explanation for the increase in rhinitis 1990-2008 in Swedish adults, during which time the prevalence of asthma, which is more associated with perennial allergens, was stable. Contact with animals in childhood seems to reduce the risk of sensitization well into adulthood. One major factor contributing to the rise in pollen allergy is a significant increase in levels of birch and grass pollen over the past three decades.
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