Excess cases of prostate cancer and estimated overdiagnosis associated with PSA testing in East Anglia

This study aimed to estimate the extent of 'overdiagnosis' of prostate cancer attributable to prostate-specific antigen (PSA) testing in the Cambridge area between 1996 and 2002. Overdiagnosis was defined conceptually as detection of prostate cancer through PSA testing that otherwise would not have been diagnosed within the patient's lifetime. Records of PSA tests in Addenbrookes Hospital were linked to prostate cancer registrations by NHS number. Differences in prostate cancer registration rates between those receiving and not receiving prediagnosis PSA tests were calculated. The proportion of men aged 40 years or over with a prediagnosis PSA test increased from 1.4 to 5.2% from 1996 to 2002. The rate of diagnosis of prostate cancer was 45% higher (rate ratios (RR) = 1.45, 95% confidence intervals (CI) 1.02-2.07) in men with a history of prediagnosis PSA testing. Assuming average lead times of 5 to 10 years, 40-64% of the PSA-detected cases were estimated to be overdiagnosed. In East Anglia, from 1996 to 2000, a 1.6% excess of cases was associated with PSA testing (around a quarter of the 5.3% excess incidence cases observed in East Anglia from 1996 to 2000). Further quantification of the overdiagnosis will result from continued surveillance and from linkage of incidence to testing in other hospitals

To be screened or not to be screened Modeling the consequences of PSA screening for the individual

Background:Screening with prostate-specific antigen (PSA) can reduce prostate cancer mortality, but may advance diagnosis and treatment in time and lead to overdetection and overtreatment. We estimated benefits and adverse effects of PSA screening for individuals who are deciding whether or not to be screened.Methods:Using a microsimulation model, we estimated lifetime probabilities of prostate cancer diagnosis and death, overall life expectancy and expected time to diagnosis, both with and without screening. We calculated anticipated loss in quality of life due to prostate cancer diagnosis and treatment that would be acceptable to decide in favour of screening.Results:Men who were screened had a gain in life expectancy of 0.08 years but their expected time to diagnosis decreased by 1.53 life-years. Of the screened men, 0.99% gained on average 8.08 life-years and for 17.43% expected time to diagnosis decreased by 8.78 life-years. These figures imply that the anticipated loss in quality of life owing to diagnosis and treatment should not exceed 4.8%, for screening to have a positive effect on quality-adjusted life expectancy.Conclusion:The decision to be screened should depend on personal preferences. The negative impact of screening might be reduced by screening men who are more willing to accept the side effects from treatment

A 16-yr Follow-up of the European Randomized study of Screening for Prostate Cancer

Background: The European Randomized study of Screening for Prostate Cancer (ERSPC) has previously demonstrated that prostate-specific antigen (PSA) screening decreases prostate cancer (PCa) mortality. Objective: To determine whether PSA screening decreases PCa mortality for up to 16 yr and to assess results following adjustment for nonparticipation and the number of screening rounds attended. Design, setting, and participants: This multicentre population-based randomised screening trial was conducted in eight European countries. Report includes 182 160 men, followed up until 2014 (maximum of 16 yr), with a predefined core age group of 162 389 men (55-69 yr), selected from population registry. Outcome measurements and statistical analysis: The outcome was PCa mortality, also assessed with adjustment for nonparticipation and the number of screening rounds attended. Results and limitations: The rate ratio of PCa mortality was 0.80 (95% confidence interval [CI] 0.72-0.89, p 20 ng/ml (9.9% compared with 4.1% in the second round, p <0.001) and higher PCa mortality (hazard ratio = 1.86, p <0.001) than those detected subsequently. Conclusions: Findings corroborate earlier results that PSA screening significantly reduces PCa mortality, showing larger absolute benefit with longer follow-up and a reduction in excess incidence. Repeated screening may be important to reduce PCa mortality on a population level. Patient summary: In this report, we looked at the outcomes from prostate cancer in a large European population. We found that repeated screening reduces the risk of dying from prostate cancer. (C) 2019 Published by Elsevier B.V. on behalf of European Association of Urology.Peer reviewe

Rule-based versus probabilistic selection for active surveillance using three definitions of insignificant prostate cancer

To study whether probabilistic selection by the use of a nomogram could improve patient selection for active surveillance (AS) compared to the various sets of rule-based AS inclusion criteria currently used. We studied Dutch and Swedish patients participating in the European Randomized study of Screening for Prostate Cancer (ERSPC). We explored which men who were initially diagnosed with cT1-2, Gleason 6 (Gleason pattern a parts per thousand currency sign3 + 3) had histopathological indolent PCa at RP [defined as pT2, Gleason pattern a parts per thousand currency sign3 and tumour volume (TV) a parts per thousand currency sign0.5 or TV a parts per thousand currency sign 1.3 ml, and TV no part of criteria (NoTV)]. Rule-based selection was according to the Prostate cancer Research International: Active Surveillance (PRIAS), Klotz, and Johns Hopkins criteria. An existing nomogram to define probability-based selection for AS was refitted for the TV1.3 and NoTV indolent PCa definitions. 619 of 864 men undergoing RP had cT1-2, Gleason 6 disease at diagnosis and were analysed. Median follow-up was 8.9 years. 229 (37 %), 356 (58 %), and 410 (66 %) fulfilled the TV0.5, TV1.3, and NoTV indolent PCa criteria at RP. Discriminating between indolent and significant disease according to area under the curve (AUC) was: TV0.5: 0.658 (PRIAS), 0.523 (Klotz), 0.642 (Hopkins), 0.685 (nomogram). TV1.3: 0.630 (PRIAS), 0.550 (Klotz), 0.615 (Hopkins), 0.646 (nomogram). NoTV: 0.603 (PRIAS), 0.530 (Klotz), 0.589 (Hopkins), 0.608 (nomogram). The performance of a nomogram, the Johns Hopkins, and PRIAS rule-based criteria are comparable. Because the nomogram allows individual trade-offs, it could be a good alternative to rigid rule-based criteria

Scan segments matching for pairwise 3D alignment

Abstract — This paper presents a method for pairwise 3D alignment which solves data association by matching scan segments across scans. Generating accurate segment associa-tions allows to run a modified version of the Iterative Closest Point (ICP) algorithm where the search for point-to-point correspondences is constrained to associated segments. The novelty of the proposed approach is in the segment matching process which takes into account the proximity of segments, their shape, and the consistency of their relative locations in each scan. Scan segmentation is here assumed to be given (recent studies provide various alternatives [10], [19]). The method is tested on seven sequences of Velodyne scans acquired in urban environments. Unlike various other standard versions of ICP, which fail to recover correct alignment when the displacement between scans increases, the proposed method is shown to be robust to displacements of several meters. In addition, it is shown to lead to savings in computational times which are potentially critical in real-time applications. I

Importance of prostate volume in the European Randomised Study of Screening for Prostate Cancer (ERSPC) risk calculators: results from the prostate biopsy collaborative group

OBJECTIVES: To compare the predictive performance and potential clinical usefulness of risk calculators of the European Randomized Study of Screening for Prostate Cancer (ERSPC RC) with and without information on prostate volume. METHODS: We studied 6 cohorts (5 European and 1 US) with a total of 15,300 men, all biopsied and with pre-biopsy TRUS measurements of prostate volume. Volume was categorized into 3 categories (25, 40, and 60 cc), to reflect use of digital rectal examination (DRE) for volume assessment. Risks of prostate cancer were calculated according to a ERSPC DRE-based RC (including PSA, DRE, prior biopsy, and prostate volume) and a PSA + DRE model (including PSA, DRE, and prior biopsy). Missing data on prostate volume were completed by single imputation. Risk predictions were evaluated with respect to calibration (graphically), discrimination (AUC curve), and clinical usefulness (net benefit, graphically assessed in decision curves). RESULTS: The AUCs of the ERSPC DRE-based RC ranged from 0.61 to 0.77 and were substantially larger than the AUCs of a model based on only PSA + DRE (ranging from 0.56 to 0.72) in each of the 6 cohorts. The ERSPC DRE-based RC provided net benefit over performing a prostate biopsy on the basis of PSA and DRE outcome in five of the six cohorts. CONCLUSIONS: Identifying men at increased risk for having a biopsy detectable prostate cancer should consider multiple factors, including an estimate of prostate volume

First principles study of point defects in titanium oxycarbide

We have performed first principles density functional theory calculations to study the formation energy of point defects in TiC, TiO and TiCO compounds. The formation energy of isolated vacancies were obtained for different equilibrium conditions. For binary compounds, we have also calculated the formation energy of antisite defects. It was found that the defect formation energies strongly depend on the chemical environment. Our results show that C vacancies are easily formed in TiC and TiCO. For the TiO compound, Ti vacancies are highly probable to occur and O vacancies are also easily formed under titanium rich atmosphere.Fundação para a Ciência e a Tecnologia (FCT) – Programa Operacional “Ciência , Tecnologia, Inovação” – CONC-REEQ/443/EEI/2005, POCTI/CTM/69362/200

The feasibility and results of a population-based approach to evaluating prostate-specific antigen screening for prostate cancer in men with a raised familial risk

The feasibility of a population-based evaluation of screening for prostate cancer in men with a raised familial risk was investigated by studying reasons for non-participation and uptake rates according to postal recruitment and clinic contact. The levels of prostate-specific antigen (PSA) and the positive predictive values (PPV) for cancer in men referred with a raised PSA and in those biopsied were analysed. First-degree male relatives (FDRs) were identified through index cases (ICs): patients living in two regions of England and diagnosed with prostate cancer at age ⩽65 years from 1998 to 2004. First-degree relatives were eligible if they were aged 45–69 years, living in the UK and had no prior diagnosis of prostate cancer. Postal recruitment was low (45 of 1687 ICs agreed to their FDR being contacted: 2.7%) but this was partly due to ICs not having eligible FDRs. A third of ICs in clinic had eligible FDRs and 49% (192 out of 389) agreed to their FDR(s) being contacted. Of 220 eligible FDRs who initially consented, 170 (77.3%) had a new PSA test taken and 32 (14.5%) provided a previous PSA result. Among the 170 PSA tests, 10% (17) were ⩾4 ng ml−1 and 13.5% (23) tests above the age-related cutoffs. In 21 men referred, five were diagnosed with prostate cancer (PPV 24%; 95% CI 8, 47). To study further the effects of screening, patients with a raised familial risk should be counselled in clinic about screening of relatives and data routinely recorded so that the effects of screening on high-risk groups can be studied

Reduction of Malaria Transmission to Anopheles Mosquitoes with a Six-Dose Regimen of Co-Artemether

BACKGROUND: Resistance of malaria parasites to chloroquine (CQ) and sulphadoxine-pyrimethamine (SP) is increasing in prevalence in Africa. Combination therapy can both improve treatment and provide important public health benefits if it curbs the spread of parasites harbouring resistance genes. Thus, drug combinations must be identified which minimise gametocyte emergence in treated cases, and so prevent selective transmission of parasites resistant to any of the partner drugs. METHODS AND FINDINGS: In a randomised controlled trial, 497 children with uncomplicated falciparum malaria were treated with CQ and SP (three doses and one dose respectively; n = 91), or six doses of artemether in fixed combination with lumefantrine (co-artemether [Coartem, Riamet]) (n = 406). Carriage rates of Plasmodium falciparum gametocytes and trophozoites were measured 7, 14, and 28 d after treatment. The infectiousness of venous blood from 29 children carrying P. falciparum gametocytes 7 d after treatment was tested by membrane-feeding of Anopheles mosquitoes. Children treated with co-artemether were significantly less likely to carry gametocytes within the 4 weeks following treatment than those receiving CQ/SP (30 of 378 [7.94%] versus 42 of 86 [48.8%]; p < 0.0001). Carriers in the co-artemether group harboured gametocytes at significantly lower densities, for shorter periods (0.3 d versus 4.2 d; p < 0.0001) and were less infectious to mosquitoes at day 7 (p < 0.001) than carriers who had received CQ/SP. CONCLUSIONS: Co-artemether is highly effective at preventing post-treatment transmission of P. falciparum. Our results suggest that co-artemether has specific activity against immature sequestered gametocytes, and has the capacity to minimise transmission of drug-resistant parasites