Overdetection, overtreatment and costs in prostate-specific antigen screening for prostate cancer

Background:Prostate cancer screening with prostate-specific antigen (PSA) has shown to reduce prostate cancer mortality in the European Randomised study of Screening for Prostate Cancer (ERSPC) trial. Overdetection and overtreatment are substantial unfavourable side effects with consequent healthcare costs. In this study the effects of introducing widespread PSA screening is evaluated.Methods:The MISCAN model was used to simulate prostate cancer growth and detection in a simulated cohort of 100 000 men (European standard population) over 25 years. PSA screening from age 55 to 70 or 75, with 1, 2 and 4-year-intervals is simulated. Number of diagnoses, PSA tests, biopsies, treatments, deaths and corresponding costs for 100 000 men and for United Kingdom and United States are compared.Results:Without screening 2378 men per 100 000 were predicted to be diagnosed with prostate cancer compared with 4956 men after screening at 4-year intervals. By introducing screening, the costs would increase with 100% to \[euro]60 695 000. Overdetection is related to 39% of total costs (\[euro]23 669 000). Screening until age 75 is relatively most expensive because of the costs of overtreatment.Conclusion:Introduction of PSA screening will increase total healthcare costs for prostate cancer substantially, of which the actual screening costs will be a small part

Sour Ageusia in Two Individuals Implicates Ion Channels of the ASIC and PKD Families in Human Sour Taste Perception at the Anterior Tongue

BACKGROUND:The perception of sour taste in humans is incompletely understood at the receptor cell level. We report here on two patients with an acquired sour ageusia. Each patient was unresponsive to sour stimuli, but both showed normal responses to bitter, sweet, and salty stimuli. METHODS AND FINDINGS:Lingual fungiform papillae, containing taste cells, were obtained by biopsy from the two patients, and from three sour-normal individuals, and analyzed by RT-PCR. The following transcripts were undetectable in the patients, even after 50 cycles of amplification, but readily detectable in the sour-normal subjects: acid sensing ion channels (ASICs) 1a, 1beta, 2a, 2b, and 3; and polycystic kidney disease (PKD) channels PKD1L3 and PKD2L1. Patients and sour-normals expressed the taste-related phospholipase C-beta2, the delta-subunit of epithelial sodium channel (ENaC) and the bitter receptor T2R14, as well as beta-actin. Genomic analysis of one patient, using buccal tissue, did not show absence of the genes for ASIC1a and PKD2L1. Immunohistochemistry of fungiform papillae from sour-normal subjects revealed labeling of taste bud cells by antibodies to ASICs 1a and 1beta, PKD2L1, phospholipase C-beta2, and delta-ENaC. An antibody to PKD1L3 labeled tissue outside taste bud cells. CONCLUSIONS:These data suggest a role for ASICs and PKDs in human sour perception. This is the first report of sour ageusia in humans, and the very existence of such individuals ("natural knockouts") suggests a cell lineage for sour that is independent of the other taste modalities

Modern approach to numerical modelling of anchored protective structures

radu je opisan suvremeni pristup numeričkom modeliranju sidrenih zaštitnih konstrukcija s osvrtom na iskustva u primjeni računalnog programa Plaxis 2D i modela tla s izotropnim očvršćivanjem. Objašnjena su osnovna obilježja u ponašanju tla u dreniranim i nedreniranim uvjetima za naprezanja koja se pojavljuju pri iskopu građevne jame. Prikazan je primjer simulacije sidrene zaštitne konstrukcije i dane su smjernice za strategiju odabira parametara materijala HSs modela tla.modern approach to numerical modelling of anchored protective structures is presented in the paper, and an overview is given of experience gained in the use of the Plaxis 2D computer program, and soil model with isotropic strengthening. Basic properties of soil in drained and undrained conditions, due to stress occurring during foundation pit excavation, are explained. An example involving simulation of an anchored protective structure is presented, and guidelines for the selection of soil materials for the HSs soil model are given

Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980-2015 : the Global Burden of Disease Study 2015

Background Timely assessment of the burden of HIV/AIDS is essential for policy setting and programme evaluation. In this report from the Global Burden of Disease Study 2015 (GBD 2015), we provide national estimates of levels and trends of HIV/AIDS incidence, prevalence, coverage of antiretroviral therapy (ART), and mortality for 195 countries and territories from 1980 to 2015. Methods For countries without high-quality vital registration data, we estimated prevalence and incidence with data from antenatal care clinics and population-based seroprevalence surveys, and with assumptions by age and sex on initial CD4 distribution at infection, CD4 progression rates (probability of progression from higher to lower CD4 cell-count category), on and off antiretroviral therapy (ART) mortality, and mortality from all other causes. Our estimation strategy links the GBD 2015 assessment of all-cause mortality and estimation of incidence and prevalence so that for each draw from the uncertainty distribution all assumptions used in each step are internally consistent. We estimated incidence, prevalence, and death with GBD versions of the Estimation and Projection Package (EPP) and Spectrum software originally developed by the Joint United Nations Programme on HIV/AIDS (UNAIDS). We used an open-source version of EPP and recoded Spectrum for speed, and used updated assumptions from systematic reviews of the literature and GBD demographic data. For countries with high-quality vital registration data, we developed the cohort incidence bias adjustment model to estimate HIV incidence and prevalence largely from the number of deaths caused by HIV recorded in cause-of-death statistics. We corrected these statistics for garbage coding and HIV misclassification. Findings Global HIV incidence reached its peak in 1997, at 3.3 million new infections (95% uncertainty interval [UI] 3.1-3.4 million). Annual incidence has stayed relatively constant at about 2.6 million per year (range 2.5-2.8 million) since 2005, after a period of fast decline between 1997 and 2005. The number of people living with HIV/AIDS has been steadily increasing and reached 38.8 million (95% UI 37.6-40.4 million) in 2015. At the same time, HIV/AIDS mortality has been declining at a steady pace, from a peak of 1.8 million deaths (95% UI 1.7-1.9 million) in 2005, to 1.2 million deaths (1.1-1.3 million) in 2015. We recorded substantial heterogeneity in the levels and trends of HIV/AIDS across countries. Although many countries have experienced decreases in HIV/AIDS mortality and in annual new infections, other countries have had slowdowns or increases in rates of change in annual new infections. Interpretation Scale-up of ART and prevention of mother-to-child transmission has been one of the great successes of global health in the past two decades. However, in the past decade, progress in reducing new infections has been slow, development assistance for health devoted to HIV has stagnated, and resources for health in low-income countries have grown slowly. Achievement of the new ambitious goals for HIV enshrined in Sustainable Development Goal 3 and the 90-90-90 UNAIDS targets will be challenging, and will need continued efforts from governments and international agencies in the next 15 years to end AIDS by 2030. Copyright (C) The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY licensePeer reviewe

Gleason score and laterality concordance between prostate biopsy and prostatectomy specimens

Objectives: Prostate biopsy involvement and Gleason score guide treatment decisions in prostate cancer. We evaluated concordance in Gleason score and laterality between biopsy and radical retropubic prostatectomy (RRP) specimens and factors that influenced this relationship. Material and Methods: We reviewed 538 prostate cancer diagnoses at a Veterans Affairs medical center (2000-2005) to identify men with prostate biopsy and RRP specimens. During this time there was a move from limited (6 core) to extended (12 core) biopsy schemes. Discordance in Gleason score was defined as any change in Gleason score. Results: 152 men underwent RRP with biopsy showing Gleason < 7 in 56%, 7 in 36%, and > 7 in 8%. Biopsy involvement was unilateral in 59% and bilateral in 41%. Compared to the biopsy, RRP Gleason score was concordant in 76 (50%), higher in 51 (34%), and lower in 25 (16%). Bilateral involvement was concordant in 97%, while unilateral involvement was concordant in only 20%. Both Gleason score and laterality were concordant in only 26%. Gleason concordance was higher in those with 8 or more cores compared to < 8 cores taken (54% vs. 34%, p = 0.046), but concordance was not affected by age, PSA, prostate volume, or length of time from biopsy to RRP. During later years, concordance did not improve despite taking more cores. Conclusions: Prostate biopsy underestimated prostatectomy Gleason score in 34% of men and bilateral involvement in 80% of those with unilateral disease on biopsy. Taking at least eight cores improves the accuracy of the prostate biopsy