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1.
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2.
  • Andersson, Lena, et al. (författare)
  • Quartz and dust exposure in Swedish iron foundries
  • 2009
  • Ingår i: Journal of Occupational and Environmental Hygiene. - Philadelphia, PA : Taylor & Francis. - 1545-9624 .- 1545-9632. ; 6:1, s. 9-18
  • Tidskriftsartikel (refereegranskat)abstract
    • Exposure to respirable quartz continues to be a major concern in the Swedish iron foundry industry. Recommendations for reducing the European occupational exposure limit (EU-OEL) to 0.05 mg/m3 and the corresponding ACGIH® threshold limit value (ACGIH-TLV) to 0.025 mg/m3 prompted this exposure survey. Occupational exposure to respirable dust and respirable quartz were determined in 11 Swedish iron foundries, representing different sizes of industrial operation and different manufacturing techniques. In total, 436 respirable dust and 435 respirable quartz exposure measurements associated with all job titles were carried out and are presented as time-weighted averages. Our sampling strategy enabled us to evaluate the use of respirators in certain jobs, thus determining actual exposure. In addition, measurements using real-time dust monitors were made for high exposure jobs. For respirable quartz, 23% of all the measurements exceeded the EU-OEL, and 56% exceeded the ACGIH-TLV. The overall geometric mean (GM) for the quartz levels was 0.028 mg/m3, ranging from 0.003 to 2.1 mg/m3. Fettler and furnace and ladle repair operatives were exposed to the highest levels of both respirable dust (GM = 0.69 and 1.2 mg/m3; range 0.076-31 and 0.25-9.3 mg/m3 and respirable quartz (GM = 0.041 and 0.052 mg/m3; range 0.004-2.1 and 0.0098-0.83 mg/m3. Fettlers often used respirators and their actual quartz exposure was lower (range 0.003-0.21 mg/m3, but in some cases it still exceeded the Swedish OEL (0.1 mg/m3. For furnace and ladle repair operatives, the actual quartz exposure did not exceed the OEL (range 0.003-0.08 mg/m3, but most respirators provided insufficient protection, i.e., factors less than 200. In summary, measurements in Swedish iron foundries revealed high exposures to respirable quartz, in particular for fettlers and furnace and ladle repair workers. The suggested EU-OEL and the ACGIH-TLV were exceeded in, respectively, 23% and 56% of all measurements regardless of the type of foundry. Further work on elimination techniques to reduce quartz concentrations, along with control of personal protection equipment, is essential.
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3.
  • Aus, Gunnar, 1958, et al. (författare)
  • Individualized screening interval for prostate cancer based on prostate-specific antigen level.
  • 2005
  • Ingår i: Arch Intern Med. ; 165:16, s. 1857-1861
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The aim of the present study was to evaluate the future cumulative risk of prostate cancer in relation to levels of prostate-specific antigen (PSA) in blood and to determine whether this information could be used to individualize the PSA testing interval. Methods The study included 5855 of 9972 men (aged 50-66 years) who accepted an invitation to participate in a prospective, randomized study of early detection for prostate cancer. We used a protocol based on biennial PSA measurements starting from 1995 and 1996. Men with serum PSA levels of 3.0 ng/mL or more were offered prostate biopsies. Results Among the 5855 men, 539 cases of prostate cancer (9.2%) were detected after a median follow-up of 7.6 years (up to July 1, 2003). Cancer detection rates during the follow-up period in relation to PSA levels were as follows: 0 to 0.49 ng/mL, 0% (0/958); 0.50 to 0.99 ng/mL, 0.9% (17/1992); 1.00 to 1.49 ng/mL, 4.7% (54/1138); 1.50 to 1.99 ng/mL, 12.3% (70/571); 2.00 to 2.49 ng/mL, 21.4% (67/313); 2.50 to 2.99 ng/mL, 25.2% (56/222); 3.00 to 3.99 ng/mL, 33.3% (89/267); 4.00 to 6.99 ng/mL, 38.9% (103/265); 7.00 to 9.99 ng/mL, 50.0% (30/60); and for men with an initial PSA of 10.00 ng/mL or higher, 76.8% (53/69). Not a single case of prostate cancer was detected within 3 years in 2950 men (50.4% of the screened population) with an initial PSA level less than 1 ng/mL. Conclusions Retesting intervals should be individualized on the basis of the PSA level, and the large group of men with PSA levels of less than 1 ng/mL can safely be scheduled for a 3-year testing interval.
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4.
  • Aus, Gunnar, 1958, et al. (författare)
  • Prostate cancer screening decreases the absolute risk of being diagnosed with advanced prostate cancer--results from a prospective, population-based randomized controlled trial.
  • 2007
  • Ingår i: Eur Urol. - : Elsevier BV. ; 51:3, s. 659-664
  • Tidskriftsartikel (refereegranskat)abstract
    • Abstract Objectives Randomized controlled trials are currently conducted to assess whether the mortality from prostate cancer is reduced by early detection with the use of prostate-specific antigen (PSA) measurements in serum. To be effective, such a program should be able to reduce the absolute number of men diagnosed with metastatic prostate cancer (for which no cure is available). The aim of the present report is to evaluate whether PSA-based screening reduces the risk of being diagnosed with metastatic prostate cancer. Methods A population-based, prospective, randomized, controlled screening trial for prostate cancer started in 1995 (the Göteborg branch of the European Randomized Study of Screening for Prostate Cancer [ERSPC]). Ten thousand, randomly selected men aged 50–66 yr were invited for biennial PSA testing, with 10,000 men serving as passive controls for whom diagnosis of metastatic prostate cancer was monitored by using the Swedish Cancer Registry. Results After a follow-up of 10 yr, the risk of being diagnosed with metastatic prostate cancer was reduced by 48.9%—that is, decreasing from 47 cases in the control group to 24 cases in the group randomized to PSA-based screening (p = 0.0084). However, the risk of being diagnosed with prostate cancer increased 1.8-fold with PSA-based screening. Conclusions Biennial PSA screening reduces the risk of being diagnosed with metastatic prostate cancer, the first prerequisite for achieving decreased cancer mortality in younger men. This putative benefit is balanced by a 1.8-fold increased risk for diagnosis of prostate cancer. Take Home Message The present randomized, controlled study shows that men taking part in a PSA-based prostate cancer–screening program will have a 50% reduction in the risk of being diagnosed with advanced/metastatic, noncurable prostate cancer.
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5.
  • Aus, Gunnar, et al. (författare)
  • Prostate cancer screening decreases the absolute risk of being diagnosed with advanced prostate cancer - Results from a prospective, population-based randomized controlled trial
  • 2007
  • Ingår i: European Urology. - : Elsevier BV. - 1873-7560. ; 51:3, s. 659-664
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Randomized controlled trials are currently conducted to assess whether the mortality from prostate cancer is reduced by early detection with the use of prostate-specific antigen (PSA) measurements in serum. To be effective, such a program should be able to reduce the absolute number of men diagnosed with metastatic prostate cancer (for which no cure is available). The aim of the present report is to evaluate whether PSA-based screening reduces the risk of being diagnosed with metastatic prostate cancer. Methods: A population-based, prospective, randomized, controlled screening trial for prostate cancer started in 1995 (the Goteborg branch of the European Randomized Study of Screening for Prostate Cancer [ERSPC]). Ten thousand, randomly selected men aged 50-66 yr were invited for biennial PSA testing, with 10,000 men serving as passive controls for whom diagnosis of metastatic prostate cancer was monitored by using the Swedish Cancer Registry. Results: After a follow-up of 10 yr, the risk of being diagnosed with metastatic prostate cancer was reduced by 48.9%-that is, decreasing from 47 cases in the control group to 24 cases in the group randomized to PSA-based screening (p = 0.0084). However, the risk of being diagnosed with prostate cancer increased 1.8-fold with PSA-based screening. Conclusions: Biennial PSA screening reduces the risk of being diagnosed with metastatic prostate cancer, the first prerequisite for achieving decreased cancer mortality in younger men. This putative benefit is balanced by a 1.8-fold increased risk for diagnosis of prostate cancer. (c) 2006 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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6.
  • Grenabo Bergdahl, Anna, et al. (författare)
  • Risk of Dying From Prostate Cancer in Men Randomized to Screening Differences Between Attendees and Nonattendees
  • 2009
  • Ingår i: Cancer. - : Wiley. - 1097-0142 .- 0008-543X. ; 115:24, s. 5672-5679
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Although the true benefits and disadvantages of prostate cancer screening are still not known, the analysis of fatal cases is important for increasing knowledge of the effects of prostate cancer screening on mortality. Who dies from prostate cancer despite participation in a population-based prostate-specific antigen (PSA) screening program? METHODS: From the Goteborg branch of the European Randomized study of Screening for Prostate Cancer, 10,000 men randomly assigned to active PSA-screening every second year formed the basis of the present study. Prostate cancer mortality was attributed to whether the men were attendees in the screening program (attending at least once) or nonattendees. RESULTS: Thirty-nine men died from prostate cancer during the first 13 years. Both overall (34% vs 13 %; P <.0001) and cancer-specific mortality (0.8% vs 0.3 %; P < .005) were found to be significantly higher among nonattendees compared with attendees. Furthermore, the majority of deaths (12 of 18) among screening attendees were in men diagnosed at first screening (prevalent cases). Only 6 deaths (including 3 interval cases) were noted among men complying with the biennial screening program. CONCLUSIONS: Nonattendees in prostate cancer screening constitute a high-risk group for both death from prostate cancer and death from other causes comparable to that described in other cancer screening programs. Cancer 2009;115:5672-9. (C) 2009 American Cancer Society.
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7.
  • Khatami, Ali, 1975, et al. (författare)
  • PSA doubling time predicts the outcome after active surveillance in screening-detected prostate cancer: Results from the European randomized study of screening for prostate cancer, Sweden section
  • 2007
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 120:1, s. 170-174
  • Tidskriftsartikel (refereegranskat)abstract
    • This study reports the outcome of active surveillance in men with PSA screening-detected prostate cancer (PC), and PSA doubling time (PSADT) was evaluated as a predictor of selecting patients to active treatment or surveillance. On December 31, 1994, 10,000 men were randomized to biennial PSA testing. Through to December 2004, a total of 660 men were diagnosed with PC, of whom 270 managed with initial surveillance. Of these 270 patients, 104 (39%) received active treatment during follow-up, 70 radical prostatectomy, 24 radiation and 10 endocrine treatment. Those who received active treatment during follow-up (mean 63 months) were significantly younger (62.6 vs. 65.5 years, p < 0.0001) and had a shorter PSADT (3.7 vs. 12 years, p < 0.0001). PSA relapse was observed in 9 of 70 patients who received RRP during a mean follow-up of 37 months. Seven of these nine PSA relapses were in the patients with preoperative PSADT < 2 years. None of the 37 operated patients with a PSADT > 4 years had a PSA relapse. In a Cox regression analysis adjusted for PSA, ratio-free PSA and amount of cancer in biopsy, only the preoperative PSADT was statistically significant predictor of PSA relapse in p = 0.031. The optimal candidate for surveillance is a man with early, low-grade, low-stage PC and a PSADT > 4 years. In younger men with a PSADT of less than 4 years, surveillance does not seem to be a justified alternative, and patient should be informed about the risk with such an approach. (c) 2006 Wiley-Liss, Inc.
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8.
  • Larsson, Anna-Karin, 1975- (författare)
  • Early life cytokines, viral infections and IgE-mediated allergic disease
  • 2006
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background: The reasons why some individuals become IgE-sensitised and allergic are largely unknown, though genetic- and early life environmental factors seem to be of importance.Objective: The overall aim of this thesis was to investigate the relationship between IgE-sensitisation and allergic disease, viral infections, genetic markers and early life cytokines.Results: IgE-sensitised children were found to have reduced numbers of IL-12 producing cord blood mononuclear cells (CBMC), whereas children diagnosed with eczema were found to have reduced numbers of IFN-γ producing CBMC. When dividing the children into early onset of IgE-sensitisation and late onset of IgE-sensitisation we found that the children with an early onset had low numbers of PHA-induced IL-4, IL-12 and IFN-γ secreting CBMC. At the age of two there was a general exacerbation of cytokine responses in the IgE-sensitised children, and the results were similar for the children with early onset IgE-sensitisation. Children with a late onset IgE-sensitisation were more similar to the non-sensitised children, but with a specific increase in the response to cat allergen (IL-4 and IFN-γ). The mothers of IgE-sensitised children, were just as their children, found to have an exaggerated cytokine response as compared to mothers of non-sensitised children. Maternal responses correlated well to the responses seen in the child, though the samples were taken two years after delivery.Cytomegalovirus (CMV) infection in early life was associated to reduced numbers of IL-4, and increased numbers of IFN-γ producing cells at the age of two. No association between CMV seropositivity and IgE-sensitisation was seen. Epstein-Barr virus (EBV) infection, on the other hand, was inversely correlated with IgE –sensitisation, whereas no statistically significant association to cytokine production could be seen.We also showed that the IL12B 1188 C-allele was associated to having a positive skin prick test at the age of two. The rare alleles of the three SNPs investigated (IL12B 1188C, IL12RB1132C and IRF1 1688A) were all associated to low IL-12 production at birth.Conclusions: Our results indicate that allergic diseases are complex traits, and that both the genetic and the cytokine background differ between the different allergic diseases. We can also conclude that the time of onset seem to play a role when investigating IgE-sensitisation, and that perhaps early and late onset IgE-sensitisation have partly different causes. CMV and EBV infection early in life are associated to a protective cytokine profile and to protection from IgE-sensitisation, respectively, again indicating the heterogeneity and the complexity of allergic diseases.
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10.
  • Nilsson, Caroline, et al. (författare)
  • Does early EBV infection protect against IgE sensitization?
  • 2005
  • Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 116:2, s. 438-444
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: There is indirect evidence that an increased infectious burden is associated with a decreased prevalence of IgE-mediated allergy during childhood. Objective: To determine whether there is a relation between the serostatus of 13 different viruses and parentally reported infections and IgE sensitization in 2-year-old children. To investigate whether there is an interaction between cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in relation to IgE sensitization. Methods: A total of 246 infants were followed prospectively to 2 years of age with clinical examinations, skin prick test, and specific IgE analyses and through analysis of seropositivity against adenovirus, influenza, parainfluenza, respiratory syncytial virus, CMV, EBV, herpes simplex virus, human herpesvirus 6, and varicella-zoster virus. Results: There was some evidence that IgE sensitization (24%) tended to be more common among children who were seropositive against few compared with children who were seropositive against many viruses, but this was not statistically significant, and there was no consistent trend across the groups. IgE sensitization was statistically significantly less prevalent at 2 years of age among infants who were seropositive against EBV but not other viruses (adjusted odds ratio, 0.34; 95% CI, 0.14-0.86). The interaction of seropositivity against both CMV and EBV antibodies indicated a further reduction in the risk for IgE sensitization (adjusted odds ratio for interaction, 0.10; 95% CI, 0.01-0.92), indicating effect modification associated with seropositivity against CMV. Conclusion: Our results indicate that acquisition of EBV infection during the first 2 years of life is associated with a reduced risk of IgE sensitization, and this effect is enhanced by CMV coinfection.
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11.
  • Roobol, Monique J., et al. (författare)
  • Prostate Cancer Mortality Reduction by Prostate-Specific Antigen-Based Screening Adjusted for Nonattendance and Contamination in the European Randomised Study of Screening for Prostate Cancer (ERSPC)
  • 2009
  • Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 56:4, s. 584-591
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Prostate-specific antigen (PSA) based screening for prostate cancer (PCa) has been shown to reduce prostate specific mortality by 20% in an intention to screen (ITS) analysis in a randomised trial (European Randomised Study of Screening for Prostate Cancer [ERSPC]). This effect may be diluted by nonattendance in men randomised to the screening arm and contamination in men randomised to the control arm. Objective: To assess the magnitude of the PCa-specific mortality reduction after adjustment for nonattendance and contamination. Design, setting, and participants: We analysed the occurrence of PCa deaths during an average follow-up of 9 yr in 162 243 men 55-69 yr of age randomised in seven participating centres of the ERSPC. Centres were also grouped according to the type of randomisation (ie, before or after informed written consent). Intervention: Nonattendance was defined as nonattending the initial screening round in ERSPC. The estimate of contamination was based on PSA use in controls in ERSPC Rotterdam. Measurements: Relative risks (RRs) with 95% confidence intervals (Cis) were compared between an ITS analysis and analyses adjusting for nonattendance and contamination using a statistical method developed for this purpose. Results and limitations: In the ITS analysis, the RR of PCa death in men allocated to the intervention arm relative to the control arm was 0.80 (95% CI, 0.68-0.96). Adjustment for nonattendance resulted in a RR of 0.73 (95% CI, 0.58-0.93), and additional adjustment for contamination using two different estimates led to estimated reductions of 0.69 (95% CI, 0.51-0.92) to 0.71 (95% CI, 0.55-0.93), respectively. Contamination data were obtained through extrapolation of single-centre data. No heterogeneity was found between the groups of centres. Conclusions: PSA screening reduces the risk of dying of PCa by up to 31% in men actually screened. This benefit should be weighed against a degree of over diagnosis and overtreatment inherent in PCa screening. (C) 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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12.
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13.
  • Schröder, Fritz H, et al. (författare)
  • Screening and prostate-cancer mortality in a randomized European study.
  • 2009
  • Ingår i: The New England journal of medicine. - 1533-4406 .- 0028-4793. ; 360:13, s. 1320-8
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • The European Randomized Study of Screening for Prostate Cancer was initiated in the early 1990s to evaluate the effect of screening with prostate-specific-antigen (PSA) testing on death rates from prostate cancer.
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14.
  • Stenius, Fredrik, et al. (författare)
  • Comparisons between salivary cortisol levels in six-months-olds and their parents.
  • 2008
  • Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 33:3, s. 352-9
  • Tidskriftsartikel (refereegranskat)abstract
    • Comparisons between salivary cortisol levels in six-months-olds and their parents.Stenius F, Theorell T, Lilja G, Scheynius A, Alm J, Lindblad F.Karolinska Institutet, Department of Clinical Science and Education, Södersjukhuset, Section of Pediatrics, Sachs' Children's Hospital, 118 83 Stockholm, Sweden. fredrik.stenius@sodersjukhuset.seBACKGROUND: There is a close relation between the psychosocial environment of the infant--including the perception of maternal behaviour--and cortisol levels of the infant. One previous study has also demonstrated a correlation between mother and infant mean cortisol levels. In this study, this relation was further explored, also including father cortisol levels. METHODS: Saliva cortisol samples were collected from 51 six-months-olds and their parents on the same day in the morning, afternoon and evening. Analyses were performed with a radioimmunoassay technique. All mothers were at home with their child at this age and 47/51 mothers were breast feeding. RESULTS: Strong correlations were found between mother and child levels on all sampling occasions whereas weaker correlations were found between father and child levels and only in the afternoon and the evening samples. There was also a strong relation between waking up/bedtime-difference in mother and child and a weaker relation between the corresponding measure in father and child. CONCLUSIONS: The stronger mother-infant than father-infant cortisol level correlations probably mirror that mother and infant not only have genetic similarities but also have been exposed to similar environmental conditions to a higher degree than father and infant.
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15.
  • Vickers, AJ, et al. (författare)
  • A panel of kallikrein markers can reduce unnecessary biopsy for prostate cancer: data from the European Randomized Study of Prostate Cancer Screening in Göteborg, Sweden.
  • 2008
  • Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 8:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Prostate-specific antigen (PSA) is widely used to detect prostate cancer. The low positive predictive value of elevated PSA results in large numbers of unnecessary prostate biopsies. We set out to determine whether a multivariable model including four kallikrein forms (total, free, and intact PSA, and human kallikrein 2 (hK2)) could predict prostate biopsy outcome in previously unscreened men with elevated total PSA. Methods The study cohort comprised 740 men in Göteborg, Sweden, undergoing biopsy during the first round of the European Randomized study of Screening for Prostate Cancer. We calculated the area-under-the-curve (AUC) for predicting prostate cancer at biopsy. AUCs for a model including age and PSA (the 'laboratory' model) and age, PSA and digital rectal exam (the 'clinical' model) were compared with those for models that also included additional kallikreins. Results Addition of free and intact PSA and hK2 improved AUC from 0.68 to 0.83 and from 0.72 to 0.84, for the laboratory and clinical models respectively. Using a 20% risk of prostate cancer as the threshold for biopsy would have reduced the number of biopsies by 424 (57%) and missed only 31 out of 152 low-grade and 3 out of 40 high-grade cancers. Conclusion Multiple kallikrein forms measured in blood can predict the result of biopsy in previously unscreened men with elevated PSA. A multivariable model can determine which men should be advised to undergo biopsy and which might be advised to continue screening, but defer biopsy until there was stronger evidence of malignancy.
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16.
  • Vickers, Andrew J., et al. (författare)
  • Prostate-Specific Antigen Velocity for Early Detection of Prostate Cancer: Result from a Large, Representative, Population-based Cohort
  • 2009
  • Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 56:5, s. 753-760
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: It has been suggested that changes in prostate-specific antigen (PSA) over time (ie, PSA velocity [PSAV]) aid prostate cancer detection. Some guidelines do incorporate PSAV cut points as an indication for biopsy. Objective: To evaluate whether PSAV enhances prediction of biopsy outcome in a large, representative, population-based cohort. Design, setting, and participants: There were 2742 screening-arm participants with PSA < 3 ng/ml at initial screening in the European Randomized Study of Screening for Prostate Cancer in Rotterdam, Netherlands, or Goteborg, Sweden, and who were subsequently biopsied during rounds 2-6 due to elevated PSA. Measurements: Total, free, and intact PSA and human kallikrein 2 were measured for 16 screening rounds at intervals of 2 or 4 yr. We created logistic regression models to predict prostate cancer based on age and PSA, with or without free-to-total PSA ratio (%fPSA). PSAV was added to each model and any enhancement in predictive accuracy assessed by area under the curve (AUC). Results and limitations: PSAV led to small enhancements in predictive accuracy (AUC of 0.569 vs 0.531; 0.626 vs 0.609 if %fPSA was included), although not for high-grade disease. The enhancement depended on modeling a nonlinear relationship between PSAV and cancer. There was no benefit if we excluded men with higher velocities, which were associated with lower risk. These results apply to men in a screening program with elevated PSA; men with prior negative biopsy were not evaluated in this study. Conclusions: In men with PSA of about >= 3 ng/ml, we found little justification for formal calculation of PSAV or for use of PSAV cut points to determine biopsy. Informal assessment of PSAV will likely aid clinical judgment, such as a sudden rise in PSA suggesting prostatitis, which could be further evaluated before biopsy. (C) 2009 European Association of Urology. Published by Elsevier B. V. All rights reserved.
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