Suitability of PSA-detected localised prostate cancers for focal therapy: Experience from the ProtecT study

This article is available through a Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. Copyright @ 2011 Cancer Research UK.Background: Contemporary screening for prostate cancer frequently identifies small volume, low-grade lesions. Some clinicians have advocated focal prostatic ablation as an alternative to more aggressive interventions to manage these lesions. To identify which patients might benefit from focal ablative techniques, we analysed the surgical specimens of a large sample of population-detected men undergoing radical prostatectomy as part of a randomised clinical trial. Methods: Surgical specimens from 525 men who underwent prostatectomy within the ProtecT study were analysed to determine tumour volume, location and grade. These findings were compared with information available in the biopsy specimen to examine whether focal therapy could be provided appropriately. Results: Solitary cancers were found in prostatectomy specimens from 19% (100 out of 525) of men. In addition, 73 out of 425 (17%) men had multiple cancers with a solitary significant tumour focus. Thus, 173 out of 525 (33%) men had tumours potentially suitable for focal therapy. The majority of these were small, well-differentiated lesions that appeared to be pathologically insignificant (38–66%). Criteria used to select patients for focal prostatic ablation underestimated the cancer's significance in 26% (34 out of 130) of men and resulted in overtreatment in more than half. Only 18% (24 out of 130) of men presumed eligible for focal therapy, actually had significant solitary lesions. Conclusion: Focal therapy appears inappropriate for the majority of men presenting with prostate-specific antigen-detected localised prostate cancer. Unifocal prostate cancers suitable for focal ablation are difficult to identify pre-operatively using biopsy alone. Most lesions meeting criteria for focal ablation were either more aggressive than expected or posed little threat of progression.National Institute for Health Researc

Contemporary accuracy of death certificates for coding prostate cancer as a cause of death : Is reliance on death certification good enough? A comparison with blinded review by an independent cause of death evaluation committee

BACKGROUND: Accurate cause of death assignment is crucial for prostate cancer epidemiology and trials reporting prostate cancer-specific mortality outcomes. METHODS: We compared death certificate information with independent cause of death evaluation by an expert committee within a prostate cancer trial (2002-2015). RESULTS: Of 1236 deaths assessed, expert committee evaluation attributed 523 (42%) to prostate cancer, agreeing with death certificate cause of death in 1134 cases (92%, 95% CI: 90%, 93%). The sensitivity of death certificates in identifying prostate cancer deaths as classified by the committee was 91% (95% CI: 89%, 94%); specificity was 92% (95% CI: 90%, 94%). Sensitivity and specificity were lower where death occurred within 1 year of diagnosis, and where there was another primary cancer diagnosis. CONCLUSIONS: UK death certificates accurately identify cause of death in men with prostate cancer, supporting their use in routine statistics. Possible differential misattribution by trial arm supports independent evaluation in randomised trials

Prostate-Specific Antigen Screening and 15-year Prostate Cancer Mortality:A Secondary Analysis of the CAP Randomized Clinical Trial

Key PointsQuestion  In men aged 50 to 69 years, does a single invitation for a prostate-specific antigen (PSA) screening test reduce prostate cancer mortality at 15-year follow-up compared with no invitation for testing?Findings  In this secondary analysis of a randomized clinical trial of 415 357 men aged 50 to 69 years randomized to a single invitation for PSA screening (n = 195 912) or a control group without PSA screening (n = 219 445) and followed up for a median of 15 years, risk of death from prostate cancer was lower in the group invited to screening (0.69% vs 0.78%; mean difference, 0.09%) compared with the control group.Meaning  Compared with no invitation for routine PSA testing, a single invitation for a PSA screening test reduced prostate cancer mortality at a median follow-up of 15 years, but the absolute mortality benefit was small.AbstractIMPORTANCE The Cluster randomized trial of PSA testing for Prostate cancer (CAP) reported no effect of prostate specific antigen (PSA) screening on prostate cancer mortality at median 10-year follow-up (primary outcome), but the long-term effects of PSA screening on prostate cancer mortality remain unclear.OBJECTIVE To evaluate the effect of a single invitation for PSA screening on the pre-specified secondary outcome of prostate cancer-specific mortality at a median of 15 years’ follow-up, compared to a control group not invited for screening. DESIGN, SETTING, PARTICIPANTS Cluster randomized trial of men aged 50-69 identified from 573 primary-care practices in England and Wales. Primary-care practices were randomized between 09/25/2001 and 08/24/2007 and men were enrolled between 01/08/2002 and 01/20/2009. Follow-up was completed on 03/31/2021. INTERVENTION A single invitation for a PSA screening test with subsequent diagnostic tests if PSA≥3.0ng/ml, compared to standard practice (control). MAIN OUTCOMES AND MEASURES The primary outcome was reported previously. Of eight prespecified secondary outcomes, results of four were reported previously. The four remaining pre-specified secondary outcomes at 15-year follow-up were prostate cancer-specific mortality, all-cause mortality, and prostate cancer stage and Gleason grade at diagnosis.RESULTS Of 415,357 randomized men (mean [SD] age: 59.0 [5.6] years), 98% were analyzed in these analyses. Overall, 12,013 and 12,958 men with prostate cancers were diagnosed in the intervention and control groups (15-year cumulative risks 7.1% and 6.9% respectively). At a median 15-year follow-up, 1,199 (0.69%) men in the intervention group and 1,451 (0.78%) men in the control group died of prostate cancer (rate ratio [RR] 0.92 [95% CI 0.85, 0.99]; p=0.03). Compared to the control group, the PSA screening intervention increased detection of low-grade (Gleason score [GS]≤6; 2.2% versus 1.6%;p&lt;0.001) and localized (T1/T2; 3.6% versus 3.1%;p&lt;0.001) disease, but not intermediate (GS=7), high-grade (GS≥8), locally-advanced (T3) or distally-advanced (T4/N1/M1) tumors. There were 45,084 all-cause deaths (23.2%) in the intervention group and 50,336 deaths (23.3%) in the control group respectively (RR 0.97 [95% CI 0.94, 1.01]; p=0.11). Eight deaths in the intervention and seven deaths in the control group were related to a diagnostic biopsy or prostate cancer treatment.CONCLUSIONS AND RELEVANCE A single invitation for PSA screening, compared to standard practice without routine screening, reduced the secondary outcome of prostate cancer deaths at a median follow-up of 15-years. However, the absolute reduction in deaths was small.<br/

Prostate cancer, treatment modalities and complications: an evaluation of the scientific literature

Prostate (PR) cancer (CA) is one of the most common malignant neoplasms in men all over the world. In general, if prostate cancer (PC) is detected early, treatment usually involves either surgical removal of the prostate or radiotherapy (RT). Hormone Therapy (HT) or chemotherapy (CH) is the preferred treatment for more advanced cases of PC or if CA spreads beyond the PT. A number of complications, such as urinary incontinence (IU) or erectile dysfunction (ED), can be associated with some modalities of treatment of the PC. The aim of this work is to evaluate, in PubMed, the number of publications related with prostate cancer and the main modalities of treatment, as well as some clinical complications. The searches were performed in PubMed (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi) in the period 1950 to 2008 using the words: (i) CA, (ii) CA and PR or penis or testis, (iii) CA and PR and RT, CA and PR and surgery (SU), CA and PR and CH and, CA and PR and HT and (iv) CA and PR and RT and IU or ED, CA and PR and SU and IU or ED, CA and PR and CH and IU or ED and, CA and PR and HT and CH and IU or ED, and (V) PC and the same modalities of treatment. The data was obtained on July 20th, 2008. PC, as expected has been cited extensively and surgery has been identified as the most widely referenced modality of treatment. Furthermore, urinary incontinence and erectile dysfunction are important complications that have attracted significant scientific interest. In conclusion, these findings have shown the relevance of the PubMed to analyze quantitatively the publications in cancer and this information could be worthwhile in aiding the comprehension of some clinical aspects related with PC, as well as the development of preventative actions. The analysis of the scientific interest, considering the number of publications in the PubMed, reveals research trends in the field and demonstrates the importance of the surgical procedures in the treatment of the prostate cancer. Moreover, this finding is relevant due to the fact that surgery is the treatment of choice when early detection of PC is achieved. However, it is important to consider clinical complications related to such procedures, such as urinary incontinence and erectile dysfunctions that can reduce the quality of life of the patient

Quantifying Cost-Effectiveness of Controlling Nosocomial Spread of Antibiotic-Resistant Bacteria: The Case of MRSA

BACKGROUND: The costs and benefits of controlling nosocomial spread of antibiotic-resistant bacteria are unknown. METHODS: We developed a mathematical algorithm to determine cost-effectiveness of infection control programs and explored the dynamical interactions between different epidemiological variables and cost-effectiveness. The algorithm includes occurrence of nosocomial infections, attributable mortality, costs and efficacy of infection control and how antibiotic-resistant bacteria affect total number of infections: do infections with antibiotic-resistant bacteria replace infections caused by susceptible bacteria (replacement scenario) or occur in addition to them (addition scenario). Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia was used for illustration using observational data on S. aureus bacteremia (SAB) in our hospital (n = 189 between 2001-2004, all being methicillin-susceptible S. aureus [MSSA]). RESULTS: In the replacement scenario, the costs per life year gained range from 45,912 euros to 6590 euros for attributable mortality rates ranging from 10% to 50%. Using 20,000 euros per life year gained as a threshold, completely preventing MRSA would be cost-effective in the replacement scenario if attributable mortality of MRSA is > or = 21%. In the addition scenario, infection control would be cost saving along the entire range of estimates for attributable mortality. CONCLUSIONS: Cost-effectiveness of controlling antibiotic-resistant bacteria is highly sensitive to the interaction between infections caused by resistant and susceptible bacteria (addition or replacement) and attributable mortality. In our setting, controlling MRSA would be cost saving for the addition scenario but would not be cost-effective in the replacement scenario if attributable mortality would be < 21%

Long-lived magnetism from solidification-driven convection on the pallasite parent body.

Palaeomagnetic measurements of meteorites suggest that, shortly after the birth of the Solar System, the molten metallic cores of many small planetary bodies convected vigorously and were capable of generating magnetic fields. Convection on these bodies is currently thought to have been thermally driven, implying that magnetic activity would have been short-lived. Here we report a time-series palaeomagnetic record derived from nanomagnetic imaging of the Imilac and Esquel pallasite meteorites, a group of meteorites consisting of centimetre-sized metallic and silicate phases. We find a history of long-lived magnetic activity on the pallasite parent body, capturing the decay and eventual shutdown of the magnetic field as core solidification completed. We demonstrate that magnetic activity driven by progressive solidification of an inner core is consistent with our measured magnetic field characteristics and cooling rates. Solidification-driven convection was probably common among small body cores, and, in contrast to thermally driven convection, will have led to a relatively late (hundreds of millions of years after accretion), long-lasting, intense and widespread epoch of magnetic activity among these bodies in the early Solar System.The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013) / ERC Grant Agreement No. 320750, the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 312284, the Natural Environment Research Council, Fundación ARAID and the Spanish MINECO MAT2011-23791.This is the accepted manuscript. The final version is available from Nature at http://www.nature.com/nature/journal/v517/n7535/full/nature14114.html

Work factors and smoking cessation in nurses' aides: a prospective cohort study

BACKGROUND: The prevalence of smoking in nursing personnel remains high. The aim of this study was to identify work factors that predict smoking cessation among nurses' aides. METHODS: Of 2720 randomly selected, Norwegian nurses' aides, who were smoking at least one cigarette per day when they completed a questionnaire in 1999, 2275 (83.6 %) completed a second questionnaire 15 months later. A wide spectrum of work factors were assessed at baseline. Respondents who reported smoking 0 cigarettes per day at follow-up were considered having stopped smoking. The odds ratios and 95 % confidence intervals of stopping smoking were derived from logistic regression models. RESULTS: Compared with working 1–9 hours per week, working 19–36 hours per week (odds ratio (OR) = 0.35; 95 % confidence interval (CI) = 0.13 – 0.91), and working more than 36 hours per week (i.e. more than full-time job) (OR = 0.27; CI = 0.09 – 0.78) were associated with reduced odds of smoking cessation, after adjustments for daily consumption of cigarettes at baseline, age, gender, marital status, and having preschool children. Adjusting also for chronic health problems gave similar results. CONCLUSION: There seems to be a negative association between hours of work per week and the odds of smoking cessation in nurses' aides. It is important that health institutions offer workplace-based services with documented effects on nicotine dependence, such as smoking cessation courses, so that healthcare workers who want to stop smoking, especially those with long working hours, do not have to travel to the programme or to dedicate their leisure time to it

Genomic insights into members of the candidate phylum Hyd24-12 common in mesophilic anaerobic digesters

Members of the candidate phylum Hyd24-12 are globally distributed, but no genomic information or knowledge about their morphology, physiology or ecology is available. In this study, members of the Hyd24-12 lineage were shown to be present and abundant in full-scale mesophilic anaerobic digesters at Danish wastewater treatment facilities. In some samples, a member of the Hyd24-12 lineage was one of the most abundant genus-level bacterial taxa, accounting for up to 8% of the bacterial biomass. Three closely related and near-complete genomes were retrieved using metagenome sequencing of full-scale anaerobic digesters. Genome annotation and metabolic reconstruction showed that they are Gram-negative bacteria likely involved in acidogenesis, producing acetate and hydrogen from fermentation of sugars, and may play a role in the cycling of sulphur in the digesters. Fluorescence in situ hybridization revealed single rod-shaped cells dispersed within the flocs. The genomic information forms a foundation for a more detailed understanding of their role in anaerobic digestion and provides the first insight into a hitherto undescribed branch in the tree of life

Candidate target genes for loss of heterozygosity on human chromosome 17q21

Loss of heterozygosity (LOH) on chromosome 17q21 has been detected in 30% of primary human breast tumours. The smallest common region deleted occurred in an interval between the D17S746 and D17S846 polymorphic sequences tagged sites that are located on two recombinant PI-bacteriophage clones of chromosome 17q21: 122F4 and 50H1, respectively. To identify the target gene for LOH, we defined a map of this chromosomal region. We found the following genes: JUP, FK506BP10, SC65, Gastrin (GAS) and HAP1. Of the genes that have been identified in this study, only JUP is located between D17S746 and D17S846. This was of interest since earlier studies have shown that JUP expression is altered in breast, lung and thyroid tumours as well as cell lines having LOH in chromosome 17q21. However, no mutations were detected in JUP using single-strand conformation polymorphism analysis of primary breast tumour DNAs having LOH at 17q21. We could find no evidence that the transcription promoter for JUP is methylated in tumour DNAs having LOH at 17q21. We suspect that the target gene for LOH in primary human breast tumours on chromosome 17q21 is either JUP and results in a haploinsufficiency for expression or may be an unidentified gene located in the interval between D17S846 and JUP. © 2004 Cancer Research UK

The HOG Pathway Dictates the Short-Term Translational Response after Hyperosmotic Shock

In the global osmoshock translational response in yeast, some gene products were translationally mobilized without transcriptional up-regulation. Conversely, other transcriptionally up-regulated mRNAs were translationally inhibited. Analogous changes occurred on the protein level. These translational responses were strongly dependent on Hog1 and Rck2