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1.
  • Adolfsson, Jan, et al. (författare)
  • Clinical characteristics and primary treatment of prostate cancer in Sweden between 1996 and 2005 : Data from the national prostate cancer register in Sweden
  • 2007
  • Ingår i: Scandinavian Journal of Urology and Nephrology. - Stockholm : Taylor & Francis. - 0036-5599 .- 1651-2065. ; 41:6, s. 456-477
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. The incidence of prostate cancer is rising rapidly in Sweden and there is a need to better understand the pattern of diagnosis, tumor characteristics and treatment. Material and methods. Between 1996 and 2005, all new cases of adenocarcinoma of the prostate gland were intended to be registered in the National Prostate Cancer Register (NPCR). This register contains information on diagnosing unit, date of diagnosis, cause of diagnosis, tumor grade, tumor stage according to the TNM classification in force, serum prostate-specific antigen (PSA) levels at diagnosis and primary treatment given within the first 6 months after diagnosis. Results. In total, 72 028 patients were registered, comprising >97% of all pertinent incident cases of prostate cancer in the Swedish Cancer Register (SCR). During the study period there was a considerable decrease in median age at the time of diagnosis, a stage migration towards smaller tumors, a decrease in median serum PSA values at diagnosis, a decrease in the age-standardized incidence rate of men diagnosed with distant metastases or with a PSA level of >100 ng/ml at diagnosis and an increase in the proportion of tumors with Gleason score ≤6. Relatively large geographical differences in the median age at diagnosis and the age-standardized incidence of cases with category T1c tumors were observed. Treatment with curative intent increased dramatically and treatment patterns varied according to geographical region. In men with localized tumors and a PSA level of <20 ng/ml at diagnosis, expectant treatment was more commonly used in those aged ≥75 years than in those aged <75 years. Also, the pattern of endocrine treatment varied in different parts of Sweden. Conclusions. All changes in the register seen over time are consistent with increased diagnostic activity, especially PSA testing, resulting in an increased number of cases with early disease, predominantly tumors in category T1c. The patterns of diagnosis and treatment of prostate cancer vary considerably in different parts of Sweden. The NPCR continues to be an important source for research, epidemiological surveillance of the incidence, diagnosis and treatment of prostate cancer
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2.
  • Adolfsson, Jan, et al. (författare)
  • Clinical characteristics and primary treatment of prostate cancer in Sweden between 1996 and 2005
  • 2007
  • Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 41:6, s. 456-477
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: The incidence of prostate cancer is rising rapidly in Sweden and there is a need to better understand the pattern of diagnosis, tumor characteristics and treatment. MATERIAL AND METHODS: Between 1996 and 2005, all new cases of adenocarcinoma of the prostate gland were intended to be registered in the National Prostate Cancer Register (NPCR). This register contains information on diagnosing unit, date of diagnosis, cause of diagnosis, tumor grade, tumor stage according to the TNM classification in force, serum prostate-specific antigen (PSA) levels at diagnosis and primary treatment given within the first 6 months after diagnosis. RESULTS: In total, 72,028 patients were registered, comprising >97% of all pertinent incident cases of prostate cancer in the Swedish Cancer Register (SCR). During the study period there was a considerable decrease in median age at the time of diagnosis, a stage migration towards smaller tumors, a decrease in median serum PSA values at diagnosis, a decrease in the age-standardized incidence rate of men diagnosed with distant metastases or with a PSA level of > 100 ng/ml at diagnosis and an increase in the proportion of tumors with Gleason score <6. Relatively large geographical differences in the median age at diagnosis and the age-standardized incidence of cases with category T1c tumors were observed. Treatment with curative intent increased dramatically and treatment patterns varied according to geographical region. In men with localized tumors and a PSA level of <20 ng/ml at diagnosis, expectant treatment was more commonly used in those aged > or =75 years than in those aged <75 years. Also, the pattern of endocrine treatment varied in different parts of Sweden. CONCLUSIONS: All changes in the register seen over time are consistent with increased diagnostic activity, especially PSA testing, resulting in an increased number of cases with early disease, predominantly tumors in category T1c. The patterns of diagnosis and treatment of prostate cancer vary considerably in different parts of Sweden. The NPCR continues to be an important source for research, epidemiological surveillance of the incidence, diagnosis and treatment of prostate cancer.
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3.
  • Bratt, Ola, et al. (författare)
  • The Study of Active Monitoring in Sweden (SAMS) : A randomized study comparing two different follow-up schedules for active surveillance of low-risk prostate cancer
  • 2013
  • Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 47:5, s. 347-355
  • Forskningsöversikt (refereegranskat)abstract
    • Objective. Only a minority of patients with low-risk prostate cancer needs treatment, but the methods for optimal selection of patients for treatment are not established. This article describes the Study of Active Monitoring in Sweden (SAMS), which aims to improve those methods. Material and methods. SAMS is a prospective, multicentre study of active surveillance for low-risk prostate cancer. It consists of a randomized part comparing standard rebiopsy and follow-up with an extensive initial rebiopsy coupled with less intensive follow-up and no further scheduled biopsies (SAMS-FU), as well as an observational part (SAMS-ObsQoL). Quality of life is assessed with questionnaires and compared with patients receiving primary curative treatment. SAMS-FU is planned to randomize 500 patients and SAMS-ObsQoL to include at least 500 patients during 5 years. The primary endpoint is conversion to active treatment. The secondary endpoints include symptoms, distant metastases and mortality. All patients will be followed for 10-15 years. Results. Inclusion started in October 2011. In March 2013, 148 patients were included at 13 Swedish urological centres. Conclusions. It is hoped that the results of SAMS will contribute to fewer patients with indolent, low-risk prostate cancer receiving unnecessary treatment and more patients on active surveillance who need treatment receiving it when the disease is still curable. The less intensive investigational follow-up in the SAMS-FU trial would reduce the healthcare resources allocated to this large group of patients if it replaced the present standard schedule.
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4.
  • Kolsrud, Oscar, et al. (författare)
  • Measured and not estimated glomerular filtration rate should be used to assess renal function in heart transplant recipients.
  • 2016
  • Ingår i: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - : Oxford University Press (OUP). - 1460-2385. ; 31:7, s. 1182-9
  • Tidskriftsartikel (refereegranskat)abstract
    • In organ transplanted patients, impaired renal function is of major prognostic importance and influences therapeutic decisions. Therefore, monitoring of renal function with glomerular filtration rate (GFR) is of importance, both before and after heart transplantation (HTx). The GFR can be measured directly (mGFR) or estimated (eGFR) with equations based on circulating creatinine or cystatin C levels. However, these equations have not been thoroughly validated in the HTx population.
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5.
  • Ström, Kristoffer, et al. (författare)
  • Genetic variation at RAB3GAP2 and its role in exercise-related adaptation and recovery
  • 2021
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Skeletal muscle fiber composition and capillary density influence physical performance and whole-body metabolic properties. ~45% of the variance in fiber type is heritable, which motivated us to perform a genome-wide association study of skeletal muscle histology from 656 Swedish men. Four independent variants were associated (p
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6.
  • Ström, Kristoffer, et al. (författare)
  • N1-methylnicotinamide is a signalling molecule produced in skeletal muscle coordinating energy metabolism
  • 2018
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity is a major health problem, and although caloric restriction and exercise are successful strategies to lose adipose tissue in obese individuals, a simultaneous decrease in skeletal muscle mass, negatively effects metabolism and muscle function. To deeper understand molecular events occurring in muscle during weight-loss, we measured the expressional change in human skeletal muscle following a combination of severe caloric restriction and exercise over 4 days in 15 Swedish men. Key metabolic genes were regulated after the intervention, indicating a shift from carbohydrate to fat metabolism. Nicotinamide N-methyltransferase (NNMT) was the most consistently upregulated gene following the energy-deficit exercise. Circulating levels of N1-methylnicotinamide (MNA), the product of NNMT activity, were doubled after the intervention. The fasting-fed state was an important determinant of plasma MNA levels, peaking at ~18 h of fasting and being lowest ~3 h after a meal. In culture, MNA was secreted by isolated human myotubes and stimulated lipolysis directly, with no effect on glucagon or insulin secretion. We propose that MNA is a novel myokine that enhances the utilization of energy stores in response to low muscle energy availability. Future research should focus on applying MNA as a biomarker to identify individuals with metabolic disturbances at an early stage. 
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7.
  • Ahlberg, Mats Steinholtz, et al. (författare)
  • PCASTt/SPCG-17-A randomised trial of active surveillance in prostate cancer: Rationale and design
  • 2019
  • Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 9
  • 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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8.
  • Alkner, Sara, et al. (författare)
  • Protocol for the T-REX-trial: tailored regional external beam radiotherapy in clinically node-negative breast cancer patients with 1-2 sentinel node macrometastases - an open, multicentre, randomised non-inferiority phase 3 trial.
  • 2023
  • Ingår i: BMJ open. - 2044-6055. ; 13:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Modern systemic treatment has reduced incidence of regional recurrences and improved survival in breast cancer (BC). It is thus questionable whether regional radiotherapy (RT) is still beneficial in patients with sentinel lymph node (SLN) macrometastasis. Postoperative regional RT is associated with an increased risk of arm morbidity, pneumonitis, cardiac disease and secondary cancer. Therefore, there is a need to individualise regional RT in relation to the risk of recurrence.In this multicentre, prospective randomised trial, clinically node-negative patients with oestrogen receptor-positive, HER2-negative BC and 1-2 SLN macrometastases are eligible. Participants are randomly assigned to receive regional RT (standard arm) or not (intervention arm). Regional RT includes the axilla level I-III, the supraclavicular fossa and in selected patients the internal mammary nodes. Both groups receive RT to the remaining breast. Chest-wall RT after mastectomy is given in the standard arm, but in the intervention arm only in cases of widespread multifocality according to national guidelines. RT quality assurance is an integral part of the trial.The trial aims to include 1350 patients between March 2023 and December 2028 in Sweden and Norway. Primary outcome is recurrence-free survival (RFS) at 5years. Non-inferiority will be declared if outcome in the de-escalation arm is not >4.5percentage units below that with regional RT, corresponding to an HR of 1.41 assuming 88% 5-year RFS with standard treatment. Secondary outcomes include locoregional recurrence, overall survival, patient-reported arm morbidity and health-related quality of life. Gene expression analysis and tumour tissue-based studies to identify prognostic and predictive markers for benefit of regional RT are included.The trial protocol is approved by the Swedish Ethics Authority (Dnr-2022-02178-01, 2022-05093-02, 2023-00826-02, 2023-03035-02). Results will be presented at scientific conferences and in peer-reviewed journals.NCT05634889.
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9.
  • Bergengren, Oskar, et al. (författare)
  • Changes in lifestyle among prostate cancer survivors: A nationwide population-based study
  • 2020
  • Ingår i: Psycho-Oncology. - : Wiley. - 1057-9249 .- 1099-1611. ; 29:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective Long-term information on lifestyle changes among prostate survivors is lacking. In this nationwide, population-based study we investigated the prevalence of lifestyle changes, factors associated with lifestyle changes and associations between lifestyle changes and general quality of life. Methods All men registered in the National Prostate Cancer Register of Sweden diagnosed in 2008 with low-risk prostate cancer at age 70 years or younger were sent a questionnaire. Logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals for factors potentially associated with lifestyle change. Results Out of 1288, 1720 men (75%) were responded. A total of 279 (22%) reported a positive lifestyle change regarding diet or exercise. Poor functional outcomes after treatment was associated with exercising less (OR 1.6, 95% CI 1.2-2.1) and less interest in social activities and relationships (OR 1.8, 95% CI 1.5-2.1). Men who exercised more (OR 7.9, 95% CI 4.4-14) and men who had an increased interest in relationships and social activities (OR 5.2, 95% CI 2.1-13) reported higher general quality of life. Conclusions A considerable proportion of men reported making positive lifestyle changes after the prostate cancer diagnosis. The time after diagnosis may be a teachable moment that facilitates lifestyle interventions. Poor functional outcomes after treatment may reduce the willingness to engage in positive lifestyle change, which need be considered when supporting men after treatment. Men who made a positive lifestyle change, regardless of whether it was exercise or regarding relationships and social activities more often reported a high level of general quality of life.
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10.
  • Bergengren, Oskar, et al. (författare)
  • Determinants for choosing and adhering to active surveillance for localised prostate cancer: A nationwide population-based study
  • 2019
  • Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 9:12
  • 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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11.
  • Bergengren, Oskar, et al. (författare)
  • Satisfaction with Care Among Men with Localised Prostate Cancer: A Nationwide Population-based Study
  • 2018
  • Ingår i: European Urology Oncology. - : Elsevier BV. - 2588-9311. ; 1:1, s. 37-45
  • 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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12.
  • Berglund, Anders, et al. (författare)
  • Differences according to socioeconomic status in the management and mortality in men with high risk prostate cancer
  • 2012
  • Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 48:1, s. 75-84
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Outcomes for many cancer forms are associated with socioeconomic status (SES).We investigated if SES was associated with management and mortality in men with high risk prostate cancer.Material and methods: A nation-wide population-based cohort in Prostate Cancer Data Base Sweden (PCBaSe), a merged database including data on incident prostate cancer identified in the National Prostate Cancer Register (NPCR) between 1997 and 2006. High risk PCa was defined as T3 tumour, and/or Gleason score 8–10 and/or PSA 20–50 ng/mL. Use of bone scan, curative treatment, and mortality in relation to SES was assessed by logistic, Cox, and competing risk regression with hazard ratios (HR), sub-distributed HR and 95% confidence intervals (CI) adjusted for co-morbidity, age, calendar period and clinical subgroups.Results: Amongst 17,522 high risk prostate cancer patients, a bone scan was more often performed in higher white-collar than in blue-collar workers (OR 1.30; 95% CI 1.21–1.40). Amongst men without metastases, the likelihood of intention to treat was higher in higher white-collar workers (OR 1.43; 95% CI 1.28–1.57). In men who received curative treatment, the likelihood was higher to undergo radical prostatectomy for higher white-collar patients (OR 1.29; 95% CI 1.10–1.47). In men without metastases, not only overall mortality was lower amongst higher white-collar workers (HR, 0.76; 95% CI 0.60–0.97), but also prostate cancer-specific mortality (sHR 0.70; 95% CI, 0.49–0.99).Conclusions: We conclude that socioeconomic disparities in the management and mortality in men with high risk prostate cancer exist also within the setting of a National Health Care System aiming to provide care on equal terms to all residents.
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13.
  • Blimark, Cecilie, et al. (författare)
  • Melphalan 100mg/m(2) with stem cell support as first relapse treatment is safe and effective for myeloma patients with long remission after autologous stem cell transplantation.
  • 2011
  • Ingår i: European journal of haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 87:2, s. 117-22
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Today, a number of therapeutic options are available as the patient with myeloma relapses from initial treatment with high-dose melphalan and autologous stem cell transplantation (ASCT). For patients who experience a durable response to primary ASCT, retreatment with high-dose melphalan is recommended by many current guidelines. Yet, toxicity is an important aspect in the choice of relapse treatment, and a second ASCT in this setting could be associated with enhanced toxicity. As the goal for the treatment for relapsed myeloma should be disease control while maintaining quality of life, lower doses of melphalan might be preferable. Methods and Objectives: In this retrospective study, we account for the outcome of 66 patients with myeloma in first systemic relapse after ASCT, who were treated with intermediate-dose melphalan, 100mg/m(2) , and stem cell support (MEL 100). The aim was to evaluate this treatment in relation to prior response duration after initial ASCT and with respect to response rate, toxicity and survival. Results: The overall response rate was 62%. There was limited, mostly haematological, toxicity, and no treatment-related mortality was observed. The median progression-free survival (PFS) was 8.5months, and the median overall survival was 24months. Patients with time to progression of 34months or more (n=17; ≥75th percentile) after initial ASCT had a median PFS of 12.5months after MEL 100. Conclusion: For patients with a long-lasting response after ASCT, MEL 100 could be a therapeutic option with low toxicity and with efficacy comparable to newer immunomodulatory drugs.
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14.
  • Blimark, Cecilie, et al. (författare)
  • Multiple myeloma and infections: a population-based study on 9253 multiple myeloma patients.
  • 2015
  • Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 100:1, s. 107-13
  • Tidskriftsartikel (refereegranskat)abstract
    • Infections are a major cause of morbidity and mortality in patients with multiple myeloma. To estimate the risk of bacterial and viral infections in multiple myeloma patients, we used population-based data from Sweden to identify all multiple myeloma patients (n=9253) diagnosed from 1988 to 2004 with follow up to 2007 and 34,931 matched controls. Cox proportional hazard models were used to estimate the risk of infections. Overall, multiple myeloma patients had a 7-fold (hazard ratio =7.1; 95% confidence interval = 6.8-7.4) risk of developing any infection compared to matched controls. The increased risk of developing a bacterial infection was 7-fold (7.1; 6.8-7.4), and for viral infections 10-fold (10.0; 8.9-11.4). Multiple myeloma patients diagnosed in the more recent calendar periods had significantly higher risk of infections compared to controls (P<0.001). At one year of follow up, infection was the underlying cause in 22% of deaths in multiple myeloma patients. Mortality due to infections remained constant during the study period. Our findings confirm that infections represent a major threat to multiple myeloma patients. The effect on infectious complications due to novel drugs introduced in the treatment of multiple myeloma needs to be established and trials on prophylactic measures are needed.
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15.
  • Bratt, Ola, et al. (författare)
  • Effects of prostate-specific antigen testing on familial prostate cancer risk estimates
  • 2010
  • Ingår i: Journal of the National Cancer Institute. - : Oxford Journals. - 0027-8874 .- 1460-2105. ; 102:17, s. 1336-1343
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Family history is a strong risk factor for prostate cancer. The aim of this study was to investigate whether increased diagnostic activity is related to the incidence of prostate cancer among brothers of men with prostate cancer. Methods Data were from the nationwide population-based Prostate Cancer Database Sweden (PCBaSe Sweden), which includes data from the National Prostate Cancer Register, the Swedish Cancer Register, the Register of the Total Population, the Multi-Generation Register, and the Census database. We investigated the relationship of tumor characteristics, time from diagnosis of the index patient (ie, prostate cancer patients in the National Prostate Cancer Register for whom at least one brother and their father could be identified), calendar period, geographic factors, and socioeconomic status to standardized incidence ratios (SIRs) for prostate cancer among 22 511 brothers of 13 975 index patients in PCBaSe Sweden. Results Brothers of index patients with prostate cancer were at increased risk for a diagnosis of prostate cancer (SIR = 3.1, 95% confidence interval [CI] = 2.9 to 3.3). Risk was higher for T1c tumors (SIR = 3.4, 95% CI = 3.2 to 3.8) than for metastatic tumors (SIR = 2.0, 95% CI = 1.5 to 2.6), and risk of T1c tumors was especially high during the first year after the diagnosis of the index patient (SIR = 4.3, 95% CI = 3.8 to 4.9), compared with the following years (SIR range = 2.8–3.3), and for brothers of index patients who had a higher socioeconomic status (SIR = 4.2, 95% CI = 3.7 to 4.7), compared with brothers of index patients with lower socioeconomic status (SIR = 2.8, 95% CI = 2.4 to 3.2). Conclusions Increased diagnostic activity among men with a family history of prostate cancer appears to contribute to their increased risk of prostate cancer and to lead to detection bias in epidemiological and genetic studies of familial prostate cancer.
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16.
  • Bratt, Ola, 1963, et al. (författare)
  • The Value of an Extensive Transrectal Repeat Biopsy with Anterior Sampling in Men on Active Surveillance for Low-risk Prostate Cancer: A Comparison from the Randomised Study of Active Monitoring in Sweden (SAMS)
  • 2019
  • Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 76:4, s. 461-466
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: A systematic repeat biopsy is recommended for men starting on active surveillance for prostate cancer, but the optimal number and distribution of cores are unknown. Objective: To evaluate an extensive repeat transrectal biopsy with anterior sampling in men starting on active surveillance. Design, setting, and participants: Randomised multicentre trial. From 2012 to 2016, 340 Swedish men, aged 40-75 yr, with recently diagnosed low-volume Gleason grade group 1 prostate cancer were included. Intervention: Either an extensive transrectal biopsy with anterior sampling (median 19 cores) or a standard transrectal biopsy (median 12 cores). Outcome measurements and statistical analysis: Primary outcome measure: Gleason grade group >= 2 cancer. Secondary outcomes: Cancer in anteriorly directed biopsy cores and postbiopsy infection. Nonparametric statistical tests were applied. Results and limitations: Gleason grade group >= 2 cancer was detected in 16% of 156 men who had an extensive biopsy and in 10% of 164 men who had a standard biopsy, a 5.7% difference (95% confidence interval [CI]-0.2% to 13%, p = 0.09). There was a strong linear association between prostate-specific antigen (PSA) density and cancer in the anteriorly directed biopsy cores. The odds ratios for cancer in the anteriorly directed cores were for any cancer 2.2 (95% CI 1.3-3.9, p = 0.004) and for Gleason grade group >= 2 cancer 2.3 (95% CI 1.2-4.4, p = 0.015) per 0.1-ng/ml/cm(3) increments. Postbiopsy infections were equally common in the two groups. A limitation is that magnetic resonance imaging was not used. Conclusions: The trial did not support general use of the extensive transrectal repeat biopsy template, but cancer in the anteriorly directed cores was common, particularly in men with high PSA density. The higher the PSA density, the stronger the reason to include anterior sampling at a systematic repeat biopsy. Patient summary: This trial compared two different templates for transrectal prostate biopsy in men starting on active surveillance for low-risk prostate cancer. Cancer was often found in the front part of the prostate, which is not sampled on a standard prostate biopsy. (C) 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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17.
  • Carlsson, Sigrid, et al. (författare)
  • Nationwide population-based study on 30-day mortality after radical prostatectomy in Sweden
  • 2009
  • Ingår i: Scandinavian Journal of Urology and Nephrology. - London : Taylor & Francis. - 0036-5599 .- 1651-2065. ; 43:5, s. 350-356
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: The incidence of prostate cancer in Sweden is increasing rapidly, as is treatment with curative intent. Radical prostatectomy (RP) is currently commonly performed, either within or outside large high-volume centres. The aim of this study was to assess the 30-day mortality rate after RP in Sweden. MATERIAL AND METHODS: In this nationwide population-based study, all men diagnosed with localized prostate cancer (< or =70 years, clinical stadium T1-2, prostate-specific antigen < 20 ng/ml) who underwent RP in Sweden between 1997 and 2002 were identified through the National Prostate Cancer Register (NPCR). Mortality within 30 days of RP was analysed through linkage between the follow-up study of the NPCR and the Regional Population Registers. The cause of death in the death certificates were compared with data from the hospitals concerned. To validate the results, a record linkage between the Inpatient Register and the National Population Register was also performed. RESULTS: The number of RPs performed increased over time. Among 3700 RPs performed, four deaths occurred during the first 30 days, yielding a 0.11% 30-day mortality rate. These deaths occurred at three different types of hospital and were all probably related to the RP. CONCLUSION: This study provides further evidence that RP is a procedure with very low perioperative mortality even when performed outside high-volume centres.
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18.
  • Cunningham, Joanne, et al. (författare)
  • Radiation Oncology Safety Information System (ROSIS) - Profiles of participants and the first 1074 incident reports
  • 2010
  • Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 1879-0887 .- 0167-8140. ; 97:3, s. 601-607
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and purpose: The Radiation Oncology Safety Information System (ROSIS) was established in 2001. The aim of ROSIS is to collate and share information on incidents and near-incidents in radiotherapy, and to learn from these incidents in the context of departmental infrastructure and procedures. Materials and methods: A voluntary web-based cross-organisational and international reporting and learning system was developed (cf. the www.rosis.info website). Data is collected via online Department Description and Incident Report Forms. A total of 101 departments, and 1074 incident reports are reviewed. Results: The ROSIS departments represent about 150,000 patients, 343 megavoltage (MV) units, and 114 brachytherapy units. On average, there are 437 patients per MV unit, 281 per radiation oncologist, 387 per physicist and 353 per radiation therapy technologist (RT/RTT). Only 14 departments have a completely networked system of electronic data transfer, while 10 departments have no electronic data transfer. On average seven quality assurance (QA) or quality control (QC) methods are used at each department. A total of 1074 ROSIS reports are analysed; 97.7% relate to external beam radiation treatment and 50% resulted in incorrect irradiation. Many incidents arise during pre-treatment but are not detected until later in the treatment process. Where an incident is not detected prior to treatment, an average of 22% of the prescribed treatment fractions were delivered incorrectly. The most commonly reported detection methods were "found at time of patient treatment" and during "chart-check". Conclusion: While the majority of the incidents that reported to this international cross-organisational reporting system are of minor dosimetric consequence, they affect on average more than 20% of the patient's treatment fractions. Nonetheless, defence-in-depth is apparent in departments registered with ROSIS. This indicates a need for further evaluation of the effectiveness of quality controls. (C) 2010 Published by Elsevier Ireland Ltd. Radiotherapy and Oncology 97 (2010) 601-607
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19.
  • Egelberg, Moa, et al. (författare)
  • Low levels of WRAP53 predict decreased efficacy of radiotherapy and are prognostic for local recurrence and death from breast cancer : a long-term follow-up of the SweBCG91RT randomized trial
  • 2023
  • Ingår i: Molecular Oncology. - : Wiley. - 1574-7891 .- 1878-0261. ; 17:10, s. 2029-2040
  • Tidskriftsartikel (refereegranskat)abstract
    • Downregulation of the DNA repair protein WD40-encoding RNA antisense to p53 (WRAP53) has been associated with radiotherapy resistance and reduced cancer survival. The aim of this study was to evaluate WRAP53 protein and RNA levels as prognostic and predictive markers in the SweBCG91RT trial, in which breast cancer patients were randomized for postoperative radiotherapy. Using tissue microarray and microarray-based gene expression, 965 and 759 tumors were assessed for WRAP53 protein and RNA levels, respectively. Correlation with local recurrence and breast cancer-related death was assessed for prognosis, and the interaction between WRAP53 and radiotherapy in relation to local recurrence was assessed for radioresistance prediction. Tumors with low WRAP53 protein levels had a higher subhazard ratio (SHR) for local recurrence [1.76 (95% CI 1.10–2.79)] and breast cancer-related death [1.55 (1.02–2.38)]. Low WRAP53 RNA levels were associated with almost a three-fold decreased effect of radiotherapy in relation to ipsilateral breast tumor recurrence [IBTR; SHR 0.87 (95% CI 0.44–1.72)] compared with high RNA levels [0.33 (0.19–0.55)], with a significant interaction (P = 0.024). In conclusion, low WRAP53 protein is prognostic for local recurrence and breast cancer-related death. Low WRAP53 RNA is a potential marker for radioresistance.
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20.
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21.
  • Ekberg, Lars, et al. (författare)
  • What margins should be added to the clinical target volume in radiotherapy treatment planning for lung cancer?
  • 1988
  • Ingår i: Radiotherapy and Oncology. - 1879-0887. ; 48:1, s. 71-77
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The planning target volume in radiotherapy treatment planning takes into account both movements of the clinical target volume (CTV) and set-up deviations. MATERIALS AND METHODS: A group of patients who received radiotherapy for lung cancer were studied. In order to measure the CTV movements due to respiration and other internal organ motions, fluoroscopy was performed for 20 patients. To study the accuracy and reproducibility of patient and beam set-up, 553 electronic portal images from 20 patients were evaluated. Discrepancies between planned and actual field positions were measured and the systematic and random errors were identified. The combined effect of these geometrical variations was evaluated. RESULTS: The average CTV movement with quiet respiration was about 2.4 mm in the medio-lateral and dorso-ventral directions. Movement in the cranio-caudal direction was on average 3.9 mm with a range of 0-12 mm. The systematic set-up errors were on average 2.0 mm in the transversal plane and 3.0 mm in the cranio-caudal direction. The random errors can be described by their standard deviations of 3.2 and 2.6 mm. In this study, the combined effect of the two parameters (CTV movement and set-up deviations) varied between 7.5 and 10.3 mm in different anatomical directions. CONCLUSIONS: In our daily clinical routine, we use a margin of 11 mm in the transversal plane and 15 mm cranially and caudally, also taking into account other unquantified variations and uncertainties.
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22.
  • Espinoza, Fredrik, et al. (författare)
  • Intrusiveness management for focused, efficient, and enjoyable activities
  • 2007
  • Ingår i: The Disappearing Computer. - Berlin / Heidelberg : Springer. - 9783540727255 ; , s. 143-157
  • Bokkapitel (refereegranskat)abstract
    • When technologies for distributed activities develop, in particular the rapidly developing mobile technology, a larger part of our time will be spent connected to our various distributed contexts. When we meet physically we bring technology, both artifacts and services, which enable us to participate in these non-local contexts. Potentially this is a threat to focused and efficient activities due to the intrusiveness of the technology. Our aim is to contribute to the restoration of a number of the desirable properties of traditional local technology-free contexts. The intrusiveness itself is caused by at least four typical phenomena that have influenced current technology: • Focus-demanding and clearly distinguishable artifacts like phones or PCs explicitly mediate interaction with the distributed context • The functionality of services is traditionally based upon the assumption that communication is a deterministic flow of passive information, which for example, does not include information of the participants´ current context • Services in general perform individually and without coordinated communication schemes • The switches between contexts introduce a high cognitive load as each distributed context typically has its own system of characteristic objects and rules. In the FEEL project, we have developed a system called “Focused, Efficient and Enjoyable Local Activities with Intrusiveness Management” (FEELIM) that constitutes an intermediate alternative between the technology-dense and technology-free environments, which addresses the problems cited above. This research is based on a collaborative and cooperative setting where problems of intrusiveness management are confounded by several users meeting and cooperating together as opposed to isolated users dealing with similar problems of interruption management (Chen 2004; Ho 2005).
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23.
  • Fransson, Göran, 1968-, et al. (författare)
  • Digitalise and capitalise? : Teachers’ self-understanding in 21st-century teaching contexts
  • 2019
  • Ingår i: Oxford Review of Education. - : Routledge. - 0305-4985 .- 1465-3915. ; 45:1, s. 102-118
  • Tidskriftsartikel (refereegranskat)abstract
    • The digitalisation of educational contexts has changed the practice of teaching and learning. In this, teachers have a key role in enacting digital technologies for this purpose and have different opportunities to do so. This article explores how digitalisation can affect teachers by focusing on: (a) how teachers manage to capitalise on digitalisation; and (b) how digitalisation can affect and reconstruct their self-understanding. Two teacher colleagues of English as a foreign language (EFL) in the same teaching team are interviewed and observed. Drawing on the interplay between self-image, self-esteem, job motivation, and task perception, it is shown how the teachers’ self-understanding is played out and changes due to the call for digitalisation. Whereas one of the teachers has been able to capitalise on digitalisation in a way that has been beneficial both professionally and personally, the other has felt pressurised by it. A conclusion is that a limited or extended use of digital technologies should not be taken as an indicator of teaching quality.
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24.
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25.
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26.
  • Harrison, Philip J., et al. (författare)
  • Exploring the evolution of cellular morphological changes after drug administration based on brightfield image data
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Most image based studies of the morphological effects of compound treatments on cells, such as those for elucidating a compound's mechanism of action, use fixed-cell based approaches whereby the cells are fixated, stained, and imaged with fluorescence microscopy some time after compound administration. This snapshot data, however, cannot uncover any information on the temporal dynamics of the induced morphological changes. For instance regarding the rate at which these changes occur following compound perturbation. Live-cell compatible dyes can be used although are limited by technical difficulties, cytotoxicity and photobleaching. A simpler, cheaper and less harmful option is to use brightfield microscopy. Although brightfield images have less contrast than fluorescence images and cannot separate out the different cellular compartments, we here show that for compounds inducing morphological changes on cells, brightfield data, together with convolutional neural networks and feature projection techniques, can be used to extract such temporal information from time-lapse experiments.
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27.
  • Hellsten, Caroline, et al. (författare)
  • Cervical cancer in Region Skåne, Sweden 2017–2020 after the implementation of primary HPV screening : A quality assurance audit
  • 2024
  • Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - 0001-6349. ; 103:1, s. 129-137
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Primary human papilloma virus (HPV) screening to detect cervical cancer and dysplastic lesions was implemented in Region Skåne 2017 for women aged 30–70. The aim of this study was to characterize the screening history of women diagnosed with cervical cancer to evaluate the performance of the screening program, as well as to assess the cancer treatments given and shortcomings in the follow-up of women with cervical dysplasia. Material and methods: We performed a quality assurance audit. The data was collected from the National Cervical Cancer Prevention Registry, Region Skåne Labmedicin database and the Melior Journal system in 2017–2020. Results: We identified 247 women diagnosed with invasive cervical cancer in Region Skåne in 2017–2020. Of these, 35 (14.2%) had a screening history over at least two screening rounds before diagnosis. There were 25 (10.1%) women diagnosed with cervical cancer in between screening intervals, i.e., interval cancer. The most common screening history in women with cervical cancer was irregular screening (143, 57.9%), followed by women being above screening age (44, 17.8%). HPV was detected in 96% of the cases, either in cervical cytology or in the tumor tissue. The screening program detected the disease in 96 (38.9%) of the patients, 149 (60.3%) were diagnosed through symptoms and two (0.80%) as a result of incidental findings. Conclusions: The most powerful tool in the prevention of cervical cancer is screening program attendance. Prolongation with HPV screening among elderly women will also reduce the incidence of cervical cancer. Today, such cancers are usually discovered when symptoms appear.
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28.
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29.
  • Holmberg, Monica, et al. (författare)
  • Localization of autosomal dominant cerebellar ataxia associated with retinal degeneration and anticipation to chromosome 3p12-p21.1
  • 1995
  • Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 4:8, s. 1441-1445
  • Tidskriftsartikel (refereegranskat)abstract
    • We present linkage analysis on a large Swedish five-generation family of 15 affected individuals with autosomal dominant cerebellar ataxia (ADCA) associated with retinal degeneration and anticipation, Common clinical signs in this family include ataxia, dysarthria and severely impaired vision with the phenotype ADCA type II, Different subtypes of ADCA have proven difficult to classify clinically due to extensive phenotypic variability within and between families. Genetic analysis of a number of ADCA type I families shows that heterogeneity exists also genetically, During the last few years several types of ADCA type I have been localized and to date six genetically distinct forms have been identified including SCA1 (6p), SCA2 (12q), SCA3 and Machado-Joseph disease (MJD) (14q), SCA4 (16q), and finally SCA5 (11), We performed a genome-wide search of the Swedish ADCA type II family using a total of 270 microsatellite markers, Positive lod scores were obtained with a number of microsatellite markers located on chromosome 3p12-p21.1. Three markers gave lod scores over 3 with a maximum lod score of 4.53 achieved with the marker D3S1600. The ADCA type II gene could be restricted to a region of 32 cM by the markers D3S1547 and D3S1274.
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30.
  • Holmberg, Ola, et al. (författare)
  • A method of predicting workload and staffing level for radiotherapy treatment planning as plan complexity changes
  • 2003
  • Ingår i: Clinical Oncology. - 1433-2981. ; 15:6, s. 359-363
  • Tidskriftsartikel (refereegranskat)abstract
    • When assessing the impact on workload from an expanding number of new patients and increasing treatment complexity, radiotherapy clinics find that oversimplified workload parameters, such as number of patients or number of fields, are not suitable for managing and predicting workload and organisational dimension. Although the basic treatment equivalent concept is available for predicting linear accelerator utilisation, no corresponding parameter has been available for radiotherapy treatment planning. In this study, we derive a simple workload indicator for treatment planning. The dose plan unit (DPU) takes the complexity of the treatment plan into account. Categorising plans according to complexity in their production, and measuring corresponding time for completing the plans in these categories, leads to the following baseline values for workload prediction: I DPU (non-computed tomography [CT]), 3 DPU (CT-contour) and 6 DPU (full-CT). The measured average productivity of 0.65 DPU per hour (1 standard deviation, SD=0.08 DPU), or alternatively 1 DPU=92 min, for a dosimetrist in this clinic indicates that 79.0 DPU can be produced by each dosimetrist per month within normal working hours. The predictive power of the DPU is shown in terms of using it to quantify the impact on workload in treatment planning of changing treatment protocols for a particular anatomic treatment site.
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31.
  • Holmberg, Ola (författare)
  • Ensuring the intended volume is given the intended absorbed dose in radiotherapy: Managing geometric variations and treatment hazards
  • 2004
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Methods for ensuring that the intended volume receives the intended absorbed dose in radiotherapy have been investigated. In order to optimise radiation treatment of cancer, geometric variations in the treatment chain need to be controlled. Furthermore, hazards potentially leading to unintended irradiation need to be controlled. While the required methods for optimisation of irradiation are diverse, advances in technology leading to more distinctly defined high dose volumes make the implementation of these methods crucial. Geometric variations are controlled by (a) knowledge of types and magnitude of variations; (b) minimisation of variations; (c) taking into account remaining variations by creating margins around volumes. Set-up variations have been quantified for lung cancer and breast cancer irradiation. Organ motion has also been measured in connection with treatment of lung tumours. While set-up variations are characterised for groups of patients within individual clinics, it is shown that lung tumour motion needs to be measured for the individual patient due to the range of organ positional variation and corresponding impact. Another parameter that has a high impact on the overall accuracy is the delineation variation in the definition of volumes. It is shown that various methods impact on the minimisation of this variation to different degrees. It is also shown that the delineation of clinical target volume (CTV), being different from gross tumour volume (GTV) delineation in that it also can reflect non-biological parameters such as treatment strategy, will call for the recording of CTV delineation strategy in order to capture the required information. Margins should be based on measured values of variations that are combined according to a documented model. A method of enhancing the potential for dose escalation through stratification of margins based on tumour cell density is suggested and analysed. Hazards in the treatment preparation chain are controlled by (a) identification of hazards in combination with frequency and consequence analysis, leading to (b) a risk estimation and (c) reducing these risks by introducing a multilayered system of preventive measures. Hazards in radiotherapy preparation have been identified together with corresponding frequencies. Mistakes in the calculation and creation of information were found with a frequency of 1-3% of treatment courses, while the corresponding numbers for information transfer was found to be 1-2%. Layers of preventive measures include (1) actions where potential deviations from intended dose and geometry can be found before the first irradiation-fraction of the patient; (2) actions where deviations can be found during or after the treatment course; (3) application of safety-technology; (4) application of safety procedures; and (5) actions where contributing factors such as staffing-levels and structure, training and communication are addressed. A method for monitoring workload in treatment preparation is explored in this context.
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32.
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33.
  • Holmberg, Ted, et al. (författare)
  • Dynamic Exhaust Valve Flow 1-D Modelling During Blowdown Conditions
  • 2019
  • Ingår i: SAE Technical Papers. - 400 Commonwealth Drive, Warrendale, PA, United States : SAE International. - 0148-7191.
  • Konferensbidrag (refereegranskat)abstract
    • To conduct system level studies on internal combustionengines reduced order models are required in order tokeep the computational load below reasonable limits.By its nature a reduced order model is a simplification of realityand may introduce modeling errors. However what is of interestis the size of the error and if it is possible to reduce the errorby some method. A popular system level study is gas exchangeand in this paper the focus is on the exhaust valve. Generallythe valve is modeled as an ideal nozzle where the flow lossesare captured by reducing the flow area. As the valve movesslowly compared to the flow the process is assumed to be quasisteady,i.e. interpolation between steady-flow measurementscan be used to describe the dynamic process duringvalve opening. These measurements are generally done at lowpressure drops, as the influence of pressure ratio is assumed tobe negligible. As it is very difficult to measure time-resolvedmass flow it is hard to test validity of these modeling assumptions.Experimental data indicates that the model overestimatesvalve flow during the blowdown event. As the blowdown pulsecontains a significant portion of the energy in the cylinder atexhaust valve opening, it is therefore of importance to modelthis correctly. In this paper experimental results from previouslypublished research have been compared to simulationresults and the deviation from quasi-steady behavior has beenquantified. The deviation appears to be a function of pressureratio over the valve and valve opening speed. A model isproposed to compensate for the observed effects.
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34.
  • Holmberg, Ted, et al. (författare)
  • Impact of Dynamic Exhaust Valve Modelling
  • 2019
  • Konferensbidrag (refereegranskat)abstract
    • A method developed in SAE 2019-01-0058 to correctfor deviations from quasi-steady exhaust valve flow isimplemented on a single-cylinder GT-Power modeland the effects on pumping work and blowdown pulsecharacteristics are investigated. The valve flow area isalways reduced compared to the referencequasi-steady case. It decreases with higher pressureratios over the valve and increases with higherengines speeds. The reduced flow area increasespumping work with load and engine speed, thoughprimarily with engine speed. The magnitude of theblowdown pulse is reduced and the peak is shifted toa later crank angle.
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35.
  • Holmberg, Ulf, 1946-, et al. (författare)
  • Interviewing suspects
  • 2008
  • Ingår i: Forensic psychology. - Chichester : John Wiley & Sons. - 9780470058329 ; , s. 113-132
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)
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36.
  • Holmberg, Ulf, et al. (författare)
  • Interviewing suspects
  • 2008
  • Ingår i: Forensic Psychology. - West Sussex : John Wiley & Sons. - 9780470058329 ; , s. 113-132
  • Bokkapitel (refereegranskat)
  •  
37.
  • Johansson, Jenni, et al. (författare)
  • Expanded CAG repeats in Swedish Spinocerebellar ataxia type 7 (SCA7) patients : effect of repeat length on the clinical manifestation
  • 1998
  • Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 7:2, s. 171-176
  • Tidskriftsartikel (refereegranskat)abstract
    • Spinocerebellar ataxia 7 (SCA7) is a neurodegenerative disorder characterized by degeneration of the cerebellum, brainstem and retina. The gene responsible for SCA7, located on chromosome 3p, recently was cloned and shown to contain a CAG repeat in the coding region of the gene, that is expanded in SCA7 patients of French origin, We examined the SCA7 repeat region in four Swedish SCA7 families as well as in 57 healthy controls, All Swedish SCA7 patients exhibited expanded CAG repeats with a strong negative correlation between repeat size and age of onset, The repeat length in SCA7 patients ranged from 40 to >200 repeats, The largest expansion was observed in a juvenile case with an age of onset of 3 months, and represents the longest polyglutamine stretch ever reported, In patients with 59 repeats or more, visual impairment was the most common initial symptom observed, while ataxia predominates in patients with <59 repeats. Two of the Swedish SCA7 families analysed in this study were shown to be related genealogically, The other two SCA7 families could not be traced back to a common ancestor, All four families shared the same allele on the disease chromosome at a locus closely linked to SCA7, suggesting the possibility of a founder effect in the Swedish population.
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38.
  • Jonsson, Frida, et al. (författare)
  • ATP-binding cassette subfamily A, member 4 intronic variants c.4773+3A > G and c.5461-10T > C cause Stargardt disease due to defective splicing
  • 2018
  • Ingår i: Acta Ophthalmologica. - : John Wiley & Sons. - 1755-375X .- 1755-3768. ; 96:7, s. 737-743
  • Tidskriftsartikel (refereegranskat)abstract
    • PurposeInherited retinal dystrophies (IRDs) represent a group of progressive conditions affecting the retina. There is a great genetic heterogeneity causing IRDs, and to date, more than 260 genes are associated with IRDs. Stargardt disease, type 1 (STGD1) or macular degeneration with flecks, STGD1 represents a disease with early onset, central visual impairment, frequent appearance of yellowish flecks and mutations in the ATP‐binding cassette subfamily A, member 4 (ABCA4) gene. A large number of intronic sequence variants in ABCA4 have been considered pathogenic although their functional effect was seldom demonstrated. In this study, we aimed to reveal how intronic variants present in patients with Stargardt from the same Swedish family affect splicing.MethodsThe splicing of the ABCA4 gene was studied in human embryonic kidney cells, HEK293T, and in human retinal pigment epithelium cells, ARPE‐19, using a minigene system containing variants c.4773+3A>G and c.5461‐10T>C.ResultsWe showed that both ABCA4 variants, c.4773+3A>G and c.5461‐10T>C, cause aberrant splicing of the ABCA4 minigene resulting in exon skipping. We also demonstrated that splicing of ABCA4 has different outcomes depending on transfected cell type.ConclusionTwo intronic variants c.4773+3A>G and c.5461‐10T>C, both predicted to affect splicing, are indeed disease‐causing mutations due to skipping of exons 33, 34, 39 and 40 of ABCA4 gene. The experimental proof that ABCA4 mutations in STGD patients affect protein function is crucial for their inclusion to future clinical trials; therefore, functional testing of all ABCA4 intronic variants associated with Stargardt disease by minigene technology is desirable.
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39.
  • Kolsrud, Oscar, et al. (författare)
  • Renal function and outcome after heart transplantation
  • 2018
  • Ingår i: Journal of Thoracic and Cardiovascular Surgery. - : Elsevier BV. - 0022-5223. ; 155:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To investigate whether measured glomerular filtration rate (mGFR) is a risk factor for death and/or end-stage renal disease (ESRD) after heart transplantation (HTx). Methods: All adult patients (n = 416) who underwent HTx between 1988 and 2010 were included. mGFR was performed both preoperatively and postoperatively as annual follow-up. Eight patients received a concomitant kidney transplant (KTx), and 15 underwent late KTx due to chronic renal failure after HTx. Results: The mean drop in mGFR compared with the preoperative value was 12% during the first year after HTx. Preoperative mGFR was not predictive of mortality or ESRD. Older or the use of a ventricular assist device (VAD) were preoperative predictors of death. Long-term survival was significantly worse in the patients who experienced a >25% decrease in mGFR during the first year after transplantation. The need for acute postoperative renal replacement therapy (RRT) was associated with impaired survival but did not predict ESRD among survivors. On multivariable analyses, previous heart surgery, preoperative VAD, and a lower mGFR were all predictors of RRT. In the most recent period, death without previous ESRD was lower, and the only preoperative factors associated with ESRD by multivariable analyses were mechanical ventilation and diabetes mellitus. Conclusions: Pretransplantation mGFR was not predictive of mortality or ESRD after HTx, but necessitated simultaneous or late-stage KTx in this selected population of patients. However, patients with a decrease in >25% mGFR during the first year post-transplantation, as well as early postoperative dialysis-dependent acute renal dysfunction, had a poor prognosis. We suggest that patients with severely impaired kidney function, irrespective of pretransplantation renal function, still should be considered for HTx, but also encourage careful interpretation of our results given the selection bias involved in this population.
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40.
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41.
  • McGawley, Kerry, 1978-, et al. (författare)
  • No additional benefits of block-over evenly-distributed high-intensity interval training within a polarized microcycle
  • 2017
  • Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 8:JUN, s. 1-12
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: The current study aimed to investigate the responses to block- versus evenly-distributed high-intensity interval training (HIT) within a polarized microcycle. Methods: Twenty well-trained junior cross-country skiers (10 males, age 17.6 ± 1.5 and 10 females, age 17.3 ± 1.5) completed two, 3-week periods of training (EVEN and BLOCK) in a randomized, crossover-design study. In EVEN, 3 HIT sessions (5 × 4-min of diagonal-stride roller-skiing) were completed at a maximal sustainable intensity each week while low-intensity training (LIT) was distributed evenly around the HIT. In BLOCK, the same 9 HIT sessions were completed in the second week while only LIT was completed in the first and third weeks. Heart rate (HR), session ratings of perceived exertion (sRPE), and perceived recovery (pREC) were recorded for all HIT and LIT sessions, while distance covered was recorded for each HIT interval. The recovery-stress questionnaire for athletes (RESTQ-Sport) was completed weekly. Before and after EVEN and BLOCK, resting saliva and muscle samples were collected and an incremental test and 600-m time-trial (TT) were completed. Results: Pre- to post-testing revealed no significant differences between EVEN and BLOCK for changes in resting salivary cortisol, testosterone, or IgA, or for changes in muscle capillary density, fiber area, fiber composition, enzyme activity (CS, HAD, and PFK) or the protein content of VEGF or PGC-1α. Neither were any differences observed in the changes in skiing economy, VO2max or 600-m time-trial performance between interventions. These findings were coupled with no significant differences between EVEN and BLOCK for distance covered during HIT, summated HR zone scores, total sRPE training load, overall pREC or overall recovery-stress state. However, 600-m TT performance improved from pre- to post-training, irrespective of intervention (P = 0.003), and a number of hormonal and muscle biopsy markers were also significantly altered post-training (P < 0.05). Discussion: The current study shows that well-trained junior cross-country skiers are able to complete 9 HIT sessions within 1 week without compromising total work done and without experiencing greater stress or reduced recovery over a 3-week polarized microcycle. However, the findings do not support block-distributed HIT as a superior method to a more even distribution of HIT in terms of enhancing physiological or performance adaptions.
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42.
  • McGibney, C, et al. (författare)
  • Analysis of dose distribution in the 'Rind' - a volume outside the PTV - in 3-dimensional conformal radiation therapy of non-small cell lung cancer
  • 2003
  • Ingår i: Radiotherapy and Oncology. - 1879-0887. ; 66:1, s. 87-93
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and purpose: Appropriate planning target volume (PTV) definition is critical for local disease eradication in the treatment of non-small cell lung cancer (NSCLC). When margins are added to the gross tumour volume (GTV) in the standard way, the PTV formed may be too large to facilitate dose escalation due to normal tissue tolerance. To increase the feasibility of dose escalation with 3-dimensional conformal radiotherapy (3DCRT), this study examines an alternative method for the formation of the PTV in NSCLC. This strategy is based on the reduced probability of tumour cells from the GTV outwards and on the associated lower dose requirements to eradicate such subclinical disease. Materials and methods: 3DCRT plans were generated from the CT scans of 15 patients with NSCLC (stages Ib to IIIb). Each PTV was formed by adding a margin for geometric uncertainties directly onto the GTV. The success of this approach is dependent on the volume immediately outside this smaller PTV, the Rind volume, receiving 50 Gy, the minimum dose requirement that is considered sufficient for eradication of the reduced tumour cell density in this volume. While optimizing the treatment plans for each PTV to 70 Gy, the dose distribution in the Rind volume, and the factors affecting it, were assessed. Results: One hundred percent of each PTV received a minimum of 95% of the prescribed dose. The percentage of the Rind volume receiving 50 Gy or more (V50) had a median value of 94%. The minimum dose in this volume, however, ranged from 5.6 to 32.1 Gy. The V50 was highest for apical tumours (96.1%) and lowest for peripheral tumours (86%) and correlated positively with the size of the PTV (Kendall's rank correlation (Kt) = +0.3, P = 0.05) and the number of beams used (Kt = +0.3, P = 0.03) but not with the conformity index. The average volume outside the Rind which still received 50 Gy (the Wasted 50 Gy) increased significantly with the V50 of the Rind volume and was inversely proportional to the Rind <50 Gy, correlating significantly with the dose to the organs at risk. Conclusions: Using this strategy with standard 3DCRT, all PTVs were irradiated to the required dose with this approach, but none of the corresponding Rind volumes had an acceptable dose distribution. The addition of dual volume planning or the use of intensity modulated radiation therapy may achieve an appropriate dose distribution in the Rind volume while not increasing the dose to the organs at risk and may thereby facilitate dose escalation. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
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43.
  • Nejabati, H. R., et al. (författare)
  • N1-Methylnicotinamide : Is it Time to Consider it as a Dietary Supplement for Athletes?
  • 2022
  • Ingår i: Current pharmaceutical design. - : Bentham Science Publishers Ltd.. - 1381-6128 .- 1873-4286. ; 28:10, s. 800-805
  • Forskningsöversikt (refereegranskat)abstract
    • Exercise is considered to be a “medicine” due to its modulatory roles in metabolic disorders, such as diabetes and obesity. The intensity and duration of exercise determine the mechanism of energy production by various tissues of the body, especially by muscles, in which the requirement for adenosine triphosphate (ATP) increases by as much as 100-fold. Naturally, athletes try to improve their exercise performance by dietary supplementation with, e.g., vitamins, metabolites, and amino acids. MNAM, as a vitamin B3 metabolite, reduc-es serum levels and liver contents of triglycerides and cholesterol, and induces lipolysis. It stimulates gluconeo-genesis and prohibits liver cholesterol and fatty acid synthesis through the expression of sirtuin1 (SIRT1). It seems that MNAM is not responsible for the actions of NNMT in the adipose tissues as MNAM inhibits the activity of NNMT in the adipose tissue and acts as an inhibitor of its activity. NNMT-MNAM axis is more activated in the muscles of individuals undergoing the high-volume-low-intensity exercise and caloric restriction. Therefore, MNAM could be an important myokine during exercise and fasting where it provides the required energy for muscles through the induction of lipolysis and gluconeogenesis in the liver and adipose tissues, respectively. Increased levels of MNAM in exercise and fasting led us to propose that the consumption of MNAM during training, especially endurance training, could boost exercise capacity and improve perfor-mance. Therefore, in this review, we shed light on the potential of MNAM as a dietary supplement in sports medicine. 
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44.
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45.
  • Nicholls, Ian A., et al. (författare)
  • Can we rationally design molecularly imprinted polymers?
  • 2001
  • Ingår i: Analytica Chimica Acta. ; 435:1, s. 9-18
  • Tidskriftsartikel (refereegranskat)abstract
    • The nearly exponential growth in the molecular imprinting literature has to a large extent been fuelled by an increasing awareness of the potential of molecular imprinting based technologies. Despite the acceptance of the technique by cognate disciplines and the demonstration of its usefulness in a number of enabling technologies, relatively little is known about the molecular level events underlying the imprinting process and subsequent recognition events. What rules govern imprint formation? Can we use such rules to rationally design molecularly imprinted polymers?
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46.
  • Oskolov, Nikolay, et al. (författare)
  • GWAS OF HISTOLOGICAL PHENOTYPES PROVIDES INSIGHTS INTO THE GENETIC ARCHITECTURE OF HUMAN SKELETAL MUSCLE
  • 2015
  • Ingår i: ABSTRACT BOOK for the SGGD 2015.
  • Konferensbidrag (refereegranskat)abstract
    • IntroductionAthlete performance depends to some extent on skeletal muscle fiber-type composition, i.e. athletes practicing endurance sports usually have a higher proportion of slow-twitch type I fibers, while fast-twitch type II fibers are more common for athletes in explosive sports. Insulin sensitivity has also been correlated with proportion of type I fibers, i.e. insulin resistant individuals having reduced muscle oxidative capacity with less oxidative type I and more glycolytic type IIx fibers.AimsHere we aimed to identify genetic variation and corresponding biological mechanisms affecting human skeletal muscle histology.MethodsWe performed a genome-wide association meta-analysis in Swedish males from 3 independent cohorts (n=656) with skeletal muscle histological phenotypes, e.g. capillary density, fibre-type distribution and area (measured by ATPas staining). Skeletal muscle microarray expression data (n=77) were used for an eQTL analysis of associated markers. Follow-up of capillary density was done in Swedish elite cross-country skiers (n=15).ResultsWe identified 11 genome-wide significant (p<5x10-8) independent loci (STEAP, NYAP2, ADRA1B, TNFSF11, FAM155A, SLC22A10, FASLG, RBFOX1, FOXJ2, KCNMA1, RAB3GAP2) associated with 6 skeletal muscle phenotypes. eQTL-genes corresponding to the top associated variants were enriched in metabolic pathways. Using a population differentiation neutrality test we show that some of the fibre-type nominally associated loci (p<1x10-6) fall within regions of positive selection (i.e. FHIT, CRISP and ANXA1). The G-allele of rs115660502 (MAF=0.048) was significantly associated (p=2x10-8) with increased capillary density and also decreased expression of the nearby gene RAB3GAP2 (FDR=0.007). The G-allele also had a significantly higher frequency (MAF=0.122, p=0.029) in the cohort of Swedish elite skiers.ConclusionOur results add to our understanding of skeletal muscle architecture and indicate that there is a genetic component to it and that this might contribute to increased endurance performance in sport athletes.
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47.
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48.
  • Pedersen, Lars, et al. (författare)
  • Prognostic factors for outcome after septoplasty in 888 patients from the Swedish National Septoplasty Register
  • 2019
  • Ingår i: European Archives of Oto-Rhino-Laryngology. - : Springer Science and Business Media LLC. - 0937-4477 .- 1434-4726. ; 276:8, s. 2223-2228
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundThe aim of this study was to identify predictors of outcome after septoplasty in 888 patients from the Swedish National Septoplasty Register.MethodologyThis is an observational register study analysing data from patients undergoing septoplasty in Sweden between 2015 and 2016. The patients reported severity of nasal obstruction (mild, moderate, severe) pre- and again 12months postoperatively (none, mild, moderate, severe), unplanned visits within 30days after surgery. The examining doctor reported co-morbidities such as allergic rhinitis and snoring. The primary end-point was one level improvement of the nasal obstruction 12months after surgery.ResultsNasal obstruction had improved in 63% 12months after surgery. Twelve months after surgery, 81% with severe nasal obstruction and 31% with mild nasal obstruction before surgery had improved. Only 56% reported that the results of the surgery were as they had expected. Higher patient age at surgery, no unplanned visits within 1month of surgery and activity limitation before surgery were associated with improvements in nasal breathing in the logistic regression model.ConclusionSeptoplasty should be offered to patients with severe nasal obstruction and surgery should be avoided in mild nasal obstruction confirmed by both an improvement in nasal obstruction and patient expectations in this study.
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49.
  • Robinson, D., et al. (författare)
  • Androgen deprivation therapy for prostate cancer and risk of dementia
  • 2019
  • Ingår i: Bju International. - : Wiley. - 1464-4096 .- 1464-410X. ; 124:1, s. 87-92
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives To study whether androgen deprivation therapy (ADT), the mainstay treatment for advanced and disseminated prostate cancer, is associated with risk of dementia. Methods Risk of dementia in men with prostate cancer primarily managed with ADT or watchful waiting (WW) in the Prostate Cancer Database Sweden, PCBaSe, was compared with that in prostate cancer-free men, matched on birth year and county of residency. We used Cox regression to calculate the hazard ratios (HRs) for Alzheimer's and non-Alzheimer's dementia (vascular dementia, dementia secondary to other diseases or unspecified dementias) for different types and duration of ADT and oral antiandrogens (AAs) as well as for men managed with WW. Results A total of 25 967 men with prostate cancer and 121 018 prostate cancer-free men were followed for a median of 4 years. In both groups 6% of the men were diagnosed with dementia. In men with prostate cancer, gonadotropin-releasing hormone agonist treatment ( HR 1.15, 95% confidence interval [CI] 1.07-1.23) and orchiectomy (HR 1.60, 95% CI 1.32-1.93) were associated with an increased risk of dementia, as compared to no treatment in prostate cancer-free men; however, this increase in risk was only observed for non-Alzheimer's dementia and occurred from year 1-4 after start of ADT. No increase in risk for any type of dementia was observed for men treated with AAs or for men on WW. Conclusion This population-based cohort study does not support previous observations of an increased risk of Alzheimer's dementia for men on ADT; however, there was a small increase in risk of non-Alzheimer's dementia.
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50.
  • Robinson, David, et al. (författare)
  • Ischemic heart disease and stroke before and during endocrine treatment for prostate cancer in PCBaSe Sweden
  • 2012
  • Ingår i: International Journal of Cancer. - Geneve : International union against cancer. - 0020-7136 .- 1097-0215. ; 130:2, s. 478-487
  • Tidskriftsartikel (refereegranskat)abstract
    • In observational studies of men with prostate cancer, men on endocrine treatment (ET) have had an increased risk of ischemic heart disease (IHD) and stroke. However, prostate cancer per se may increase risk of IHD and stroke and men on ET may have been at increased risk already prior to initiation of ET. We assessed the incidence of IHD and stroke in men with prostate cancer before and during different endocrine treatments. The hazard ratio (HR) of IHD and stroke in 39,051 men with prostate cancer vs. a matched control population without prostate cancer was assessed by use of Cox proportion hazard models. An increased risk was found among 30,883 men with prostate cancer who did not receive ET, with a HR of 1.08 (95% CI 1.00–1.18) for IHD and 1.10 (95%CI 1.00–1.21) for stroke. In 8,168 men who initiated ET during the observation period, the risk of IHD was significantly higher (p = 0.014), during ET (HR 1.40, 95% CI 1.17–1.67) compared with before initiation of ET (HR of 0.98, 95% CI 0.72–1.33), whereas no such increase was found for stroke. Regardless of treatment, men with prostate cancer had a small increase in risk of IHD and stroke and initiation of ET was associated with a further increase in risk of IHD. Our data underline the importance of a proper indication for ET because many men with low-risk prostate cancer currently receive ET.
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